14-3-3σ/Stratifin and p21 limit AKT-related malignant progression in skin carcinogenesis following MDM2-associated p53 loss.

To study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of 14-3-3σ (Stratifin) was analyzed in skin carcinogenesis driven by activated rasHa/fos expression (HK1.ras/fos) and ablation of PTEN-mediated AKT regulation (K14.creP/Δ5PTENflx/flx). Consistent with 14-3-3σ roles in epidermal differentiation, HK1.ras hyperplasia and papillomas displayed elevated 14-3-3σ expression in supra-basal keratinocytes, paralleled by supra-basal p-MDM2166 activation and sporadic p-AKT473 expression. In bi-genic HK1.fos/Δ5PTENflx/flx hyperplasia, basal-layer 14-3-3σ expression appeared, and alongside p53/p21, was associated with keratinocyte differentiation and keratoacanthoma etiology. Tri-genic HK1.ras/fos-Δ5PTENflx/flx hyperplasia/papillomas initially displayed increased basal-layer 14-3-3σ, suggesting attempts to maintain supra-basal p-MDM2166 and protect basal-layer p53. However, HK1.ras/fos-Δ5PTENflx/flx papillomas exhibited increasing basal-layer p-MDM2166 activation that reduced p53, which coincided with malignant conversion. Despite p53 loss, 14-3-3σ expression persisted in well-differentiated squamous cell carcinomas (wdSCCs) and alongside elevated p21, limited malignant progression via inhibiting p-AKT1473 expression; until 14-3-3σ/p21 loss facilitated progression to aggressive SCC exhibiting uniform p-AKT1473. Analysis of TPA-promoted HK1.ras-Δ5PTENflx/flx mouse skin, demonstrated early loss of 14-3-3σ/p53/p21 in hyperplasia and papillomas, with increased p-MDM2166/p-AKT1473 that resulted in rapid malignant conversion and progression to poorly differentiated SCC. In 2D/3D cultures, membranous 14-3-3σ expression observed in normal HaCaT and SP1ras61 papilloma keratinocytes was unexpectedly detected in malignant T52ras61/v-fos SCC cells cultured in monolayers, but not invasive 3D-cells. Collectively, these data suggest 14-3-3σ/Stratifin exerts suppressive roles in papillomatogenesis via MDM2/p53-dependent mechanisms; while persistent p53-independent expression in early wdSCC may involve p21-mediated AKT1 inhibition to limit malignant progression.

Wound Management of Pediatric Burns.

The goal for treating pediatric burns is to allow the patient to heal with as little scarring as possible. Compared to older children and adults, very small children have anatomic differences that alter their treatment. They have thinner skin that leads to a higher risk for full-thickness burns. Children also tend to freeze when touching a hot item, so that the prolonged contact also leads to deeper burns. Two healing strategies are needed to treat these wounds. One must optimize reepithelialization in superficial burns to reduce scarring. Deeper burns require skin grafting, but there are techniques, such as the use of "sheet" autograft skin that lead to excellent outcomes. Strategies to treat the massive pediatric burn will also be covered. Finally, there are instances where different strategies are needed to cover exposed bone or tendon. The ultimate goal is to return the skin to as normal a state as possible.

American Burn Association Clinical Practice Guidelines on Burn Shock Resuscitation.

This Clinical Practice Guideline (CPG) addresses the topic of acute fluid resuscitation during the first 48 hours following a burn injury for adults with burns ≥20% of the total body surface area (%TBSA). The listed authors formed an investigation panel and developed clinically relevant PICO (Population, Intervention, Comparator, Outcome) questions. A systematic literature search returned 5978 titles related to this topic and after 3 levels of screening, 24 studies met criteria to address the PICO questions and were critically reviewed. We recommend that clinicians consider the use of human albumin solution, especially in patients with larger burns, to lower resuscitation volumes and improve urine output. We recommend initiating resuscitation based on providing 2 mL/kg/% TBSA burn in order to reduce resuscitation fluid volumes. We recommend selective monitoring of intra-abdominal and intraocular pressure during burn shock resuscitation. We make a weak recommendation for clinicians to consider the use of computer decision support software to guide fluid titration and lower resuscitation fluid volumes. We do not recommend the use of transpulmonary thermodilution-derived variables to guide burn shock resuscitation. We are unable to make any recommendations on the use of high-dose vitamin C (ascorbic acid), fresh frozen plasma (FFP), early continuous renal replacement therapy, or vasopressors as adjuncts during acute burn shock resuscitation. Mortality is an important outcome in burn shock resuscitation, but it was not formally included as a PICO outcome because the available scientific literature is missing studies of sufficient population size and quality to allow us to confidently make recommendations related to the outcome of survival at this time.

Surviving Sepsis After Burn Campaign.

INTRODUCTION: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. METHODS: The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. RESULTS: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. CONCLUSION: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

Comparison of Different Methods of Measuring Finger Range of Motion via Telehealth.

PURPOSE: This study examined the accuracy and reliability of measuring total motion of the fingers via telehealth using the following three different methods: (1) goniometry, (2) visual estimation, and (3) electronic protractor. Measurements were compared with in-person measurement, which was assumed to be the reference standard. METHODS: Thirty clinicians measured finger range of motion from prerecorded videos of a mannequin hand with articulating fingers, which was posed in extension and flexion that simulated a telehealth visit, using a goniometer with results blinded to the clinician (blinded goniometry), visual estimation, and an electronic protractor, in random order. Total motion was calculated for each finger and for all four fingers in sum. The experience level, familiarity with measuring finger range of motion, and opinions of measurement difficulty were assessed. RESULTS: Measurement with the electronic protractor was the only method equivalent to the reference standard within 20°. Remote goniometer and visual estimation did not fall within the acceptable error margin of equivalence, and both underestimated total motion. Electronic protractor also had the highest interrater reliability (intraclass correlation [upper limit, lower limit], 0.95 [0.92, 0.95]); goniometry (intraclass correlation, 0.94 [0.91, 0.97]) was nearly identical, whereas visual estimation (intraclass correlation, 0.82 [0.74, 0.89]) was much lower. Clinicians' experience and familiarity with range of motion measurements had no relationship with the findings. Clinicians reported visual estimation as the most difficult (80%) and electronic protractor as the easiest method (73%). CONCLUSIONS: This study showed that traditional in-person forms of measurement underestimate finger range of motion via telehealth; a new computer-based method (ie, electronic protractor) was found to be more accurate. CLINICAL RELEVANCE: The use of an electronic protractor can be beneficial to clinicians measuring range of motion in patients virtually.

Use of Cultured Epithelial Autograft in Conjunction with Biodegradable Temporizing Matrix in Massive Burns: A Case Series.

Intensive care for massively burn patients has increased survival and highlights the need for a solution to the problem of insufficient donor sites for autologous skin coverage. In this case series, we present 10 patients with average burn size of 81% TBSA and mean age of 24 years old, who underwent burn excision followed by either immediate or delayed biodegradable temporizing matrix (BTM) placement. After an integration period, the BTM was delaminated either the day before or immediately prior to placement of cultured epithelial autografts over a widely meshed (4:1 or 6:1) split thickness skin graft. One patient had cultured epithelial autografts alone, without split thickness skin graft, placed on integrated BTM and had successful take. Seven patients survived to discharge and had average 95% wound closure at 135 ± 35 days. The patients had on average 10.4 total operations and 8.7 excision and grafting operations. Five patients had complications related to the BTM requiring removal or replacement including three fungal infections, one bacterial infection and one with bleeding and a large clot burden. In conclusion, this surgical strategy is a viable option for patients with massive burns and insufficient donor for autologous skin grafting.

Infections in Burn Patients.

Infections are the leading cause of mortality in burn patients who survive their initial resuscitation. Burn injury leads to immunosuppression and a dysregulated inflammatory response which can have a prolonged impact. Early surgical excision along with support of the multidisciplinary burn team has improved mortality in burn patients. The authors review diagnostic and therapeutic challenges as well as strategies for management of burn related infections.

Impact of tetravalent dengue vaccination with screening, ADE, and altered infectivity on single-serotype dengue and Zika transmission.

Acquired immunity to a dengue virus serotype (whether by infection or the only licensed dengue vaccine) can produce antibody-dependent enhancement (ADE) in later infections with another dengue serotype, resulting in higher viral loads and more severe symptoms such as dengue hemorrhagic fever, unless the person already has immunity to multiple dengue serotypes. Screening to confirm dengue seropositivity is therefore recommended before vaccination. Recent studies suggest that the closely-related Zika virus may also interact with dengue through ADE. This study uses a mathematical model to evaluate the likely impact of imperfect screening and dengue vaccination on the spread of both viruses in a population where only one dengue serotype circulates, although the vaccine may take against any or all of the four recognized serotypes. Analysis focuses on the reproductive numbers of the viruses. Results indicate that vaccination increases the spread of Zika through induced ADE, while its impact on the spread of dengue depends on screening specificity and serotype-specific vaccine efficacies, as well as the intensity of ADE. Numerical analysis identifies the roles played by age-in and catch-up vaccination as well as screening characteristics and prior dengue exposure.

Poverty and Frailty Are Not Related to Each Other With Regard to Outcomes in Middle-Aged and Older Patients with Burn Injuries.

The purpose of this study was to determine the relationship between frailty and poverty in burn patients ≥50 years old, and their association with patient outcomes. This was a single-center retrospective chart review from 2009 to 2018 of patients ≥50 years old admitted with acute burn injuries. Frailty was assigned using the Canadian Study of Health and Aging Clinical Frailty Scale. Poverty was defined as a patient from a zip code that had >20% of people living in poverty. The relationship between frailty and poverty, as well as each variable independently on mortality, length of stay (LOS), and disposition location, was examined. Of 953 patients, the median age was 61 years, 70.8% were male, and the median total body surface area burn was 6.6%. Upon admission, 26.4% and 35.2% of patients were frail and from impoverished neighborhoods, respectively. The mortality rate was 8.8%. Univariate analysis demonstrated that nonsurvivors had significantly higher chances of living in poverty (P = .02) and were more likely to be frail compared to survivors. There was no significant correlation between poverty and frailty (P = .08). Multivariate logistic regression confirmed the relationship between lack of poverty and mortality (OR .47, 95% CI 0.25-0.89) and frailty and mortality (OR 1.62, 95% CI 1.24-2.12). Neither poverty (P = .26) nor frailty (P = .52) was associated with LOS. Both poverty and frailty were associated with a patient's discharge location (P = .03; P < .0001). Poverty and frailty each independently predict mortality and discharge destination in burn patients ≥50, but they are not associated with LOS nor each other.

Optimizing the timing of renal replacement therapy in burn patients with acute kidney injury.

Acute kidney injury is a common complication in burn ICU patients and is associated with a high mortality rate. The optimal timing for starting renal replacement therapy (RRT) remains unknown; there is no established universal definition for early and late RRT initiation. The aims of the present narrative review are to briefly analyze the available recently published data on the timing of initiation of RRT in critically ill patients and to discuss the optimal timing of RRT in critically ill burn patients with acute kidney injury. When considering renal replacement therapy for acute kidney injury patients, physicians face the dilemma of balancing the hazards of starting too early, exposing patient to an unnecessary therapy with possible complications and costs related to treatment, and preventing a significant proportion of patients from spontaneous recovery of their renal function against the potential life-threatening harm of initiating RRT) too late. Evidence suggests that with appropriate care up to 80% of burn patients experience recovery of kidney function and the need for RRT seems to be very rare after hospital discharge. In the absence of life-threatening complications, the optimal time and thresholds for starting RRT in burn patients are uncertain. High heterogeneity exists between studies on RRT timing in burn patients.

Massive Pediatric Burn Injury: A 10-Year Review.

Advances in the care of burn-injured pediatric patients have improved mortality over the last 20 years. However, massive burn injuries (50% TBSA or greater) in pediatric patients, while overall rare, have a significant morbidity and mortality. The primary aim for this study is to analyze treatment and outcomes in massive pediatric burn injuries. A retrospective study of children with burn injuries 50% TBSA or greater who were admitted to Shriners Hospital for Children Northern California, from May 1, 2009 to May 22, 2020, was conducted. Data were collected from the electronic health records through a comprehensive chart review that included: patient demographics, past medical history, treatment interventions, and outcomes. This study included 69 patients (59.4% male) with a mean age of 8.7 ± 6 years. The median time from injury to admission was 2 (1-4) days. In this study, 63.8% of patients were from Mexico, 34.8% were from the United States, and 1% patient was from American Samoa. The median time from injury to admission was 2 (1-4) days. Mean TBSA was 66% ± 12%. The median TBSA of second-degree burns was 0 (0-6) %, and the mean TBSA of third-degree burns was 60% ± 16%. Forty percent of patients suffered an inhalation injury and 83% of patients received a tracheostomy. The median number of days requiring ventilator assistance was 26 (12-58) days. Mean length of hospitalization was 90 ± 60 days, with 61 ± 41 days spent in the intensive care unit. The mean number of surgical procedures was 6 ± 4. The time between surgical procedures was 12 ± 6 days. The median time from admission to the first surgical procedure was 1 (0-2) day. At the first procedure, a mean of 42% ± 15% TBSA of the burn injury was excised. Sixty-two percent of patients received autografting (22% ± 11% TBSA) and 52% of patients received allografting (27% ± 17% TBSA) during the first procedure. For survivors, the median number of inpatient occupational therapy encounters was 143.5 (83-215) and inpatient physical therapy encounters was 139.5 (81-215). Twenty-five percent of the patients included in this study died as a result of their burn injury. Multivariate regression revealed that sustaining an inhalation injury was a significant and independent predictor of death (odds ratio: 3.4, 95% confidence interval: 1.05 to 11, P = .04). Massive burn injuries in children required a very high number of surgical procedures and hospital resources. Most children who died as a result of their massive burn injury died within the first month of admission. Inhalation independently increases the risk of dying in pediatric patients with a massive burn injury.

Burn Resuscitation Practices in North America: Results of the Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT).

OBJECTIVES: ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial. SUMMARY BACKGROUND DATA: No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation. METHODS: Patients ≥18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols. RESULTS: Of 379 enrollees, two-thirds (253) were resuscitated with albumin and one-third (126) were resuscitated with crystalloid alone. Albumin patients received more total fluid than Crystalloid patients (5.2 ± 2.3 vs 3.7 ± 1.7 mL/kg/% TBSA burn/24 hours), but patients in the Albumin Group were older, had larger burns, higher admission Sequential Organ Failure Assessment (SOFA) scores, and more inhalation injury. Albumin lowered the in-to-out (I/O) ratio and was started ≤12 hours in patients with the highest initial fluid requirements, given >12 hours with intermediate requirements, and avoided in patients who responded to crystalloid alone. CONCLUSIONS: Albumin use is associated with older age, larger and deeper burns, and more severe organ dysfunction at presentation. Albumin supplementation is started when initial crystalloid rates are above expected targets and improves the I/O ratio. The fluid received in the first 24 hours was at or above the Parkland Formula estimate.

Understanding Factors in Burn Patient Follow-up.

Follow-up rates are concerningly low among burn-injured patients. This study investigates the factors associated with low follow-up rates and missed appointments. We hypothesize that patients who are homeless, use illicit substances, and have psychiatric comorbidities will have lower rates of follow-up and more missed appointments. Data from a discharge-planning survey of 281 burn-injured patients discharged from September 2019 to July 2020 were analyzed and matched with patients' electronic medical records for a retrospective chart review. Data collected included general demographics, burn characteristics, hospitalization details, follow-up visits, missed appointments, homeless status, substance use, major psychiatric illness, and survey responses. Data analysis used chi-square, Fisher's exact test, Student's t-test, Wilcoxon rank sum test, and multivariate regression analysis. Overall, 37% of patients had no follow-up in clinic and 46% had one or more missed appointment. On multivariate regression analysis, homeless patients were more likely to never follow-up, odds ratio (OR) = 0.23 (95% confidence interval [CI] = 0.11-0.49), as were patients who anticipated experiencing transportation difficulties, OR = 0.28 (95% CI = 0.15-0.50). Homeless patients were more likely to have missed appointments, OR = 0.23 (95% CI = 0.1-0.54). On univariate analysis, patients with one or more documented major psychiatric illness had lower follow-up rates, with 50.62% having no follow-up (P < .01). Among patients who responded to the survey that they were current drug users, 52% had no follow-up as compared to 28% of patients who responded that they did not use drugs (P < .01).

Suicide by self-inflicted burns - A persistent psychiatric problem.

Self-inflicted burns are a relatively uncommon but profound attempt at suicide. Twenty years ago, we first reviewed our experience with self-inflicted burns. With this current study, we sought to determine whether there had been any change in the incidence or outcomes of self-inflicted burns. All burn patients admitted between January 1, 2012, and December 31, 2021, with self-inflicted burns were compared with all other admissions. The frequency of self-inflicted burns and confounding risk factors of patients with self-inflicted burns remained unchanged. A large proportion (87.4 %) of the patients had psychiatric disease. They also had larger burns and higher mortality than accidental burns. Unexpectedly, logistic regression analysis that controlled for age, total percent total body surface area (TBSA) burn, sex, and inhalation injury revealed that those patients with self-inflicted burns had 72 % lower odds of dying than the general population. In conclusion, there has been no improvement in the incidence of self-inflicted burns. They result in very severe injuries, but when age, burn size, gender, and inhalation injury are controlled for, they have at least as good a chance for survival as the general burn population.

Modified Frailty Index is an Independent Predictor of Death in the Burn Population: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) Study.

Frailty can increase the risk of dying after suffering a severe injury. The Modified Frailty Index (MFI) was developed by the American College of Surgeons National Surgical Quality Improvement Program to determine the impact of frailty on outcomes. Our aim was to correlate frailty with survival following a burn injury using the 11-item and 5-item MFI. We performed a secondary analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) study. Data including, age, gender, medical history, extent and severity of burn injury, inhalation injury and discharge disposition was collected from the TRIBE database. The 11-item MFI (MFI-11) and 5-item MFI (MFI-5) scores were calculated for all patients in the TRIBE database. The TRIBE database included 347 patients. The mean age of subjects was 43 ± 17 years. Mean total body surface area burn (TBSA) was 38 ± 18%, and 23% had inhalation injury. Multivariate logistic regression analysis determined that both MFI-5 (OR 1.86; 95% CI: 1.11-3.11; P-value .02) and MFI-11 (OR 1.83; 95% CI: 1.18-2.8; P-value .007) were independent predictors for mortality. Additionally, MFI-11 scores that are >1 were independently associated with a markedly increased risk of dying after a burn injury (OR 2.91; 95% CI: 1.1-7.7; P-value .03). The MFI can be used to identify vulnerable burn injured patients who are at high risk of dying.

BACTERIAL PATHOGEN-ASSOCIATED MOLECULAR PATTERNS UPREGULATE HUMAN GLUCOCORTICOID RECEPTOR EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS.

ABSTRACT: It is well known that bacterial components (pathogen-associated molecular patterns [PAMPs]) induce a proinflammatory response through pattern recognition receptor signaling. What is not known, however, is how the inflammatory response is downregulated. We hypothesize that bacterial products initiate compensatory anti-inflammatory responses by inducing expression of the human glucocorticoid receptor (hGR). Peripheral blood mononuclear cells (PBMCs) were isolated from leukocytes concentrated from single human donors (Leukopaks). PBMCs were treated with a gram-negative bacterial component, LPS, or gram-positive bacterial components, lipoteichoic acid (LTA) or peptidoglycan (PGN), for 1, 3, or 13 h. Protein expression of hGR was evaluated by Western blot analysis. RNA was extracted from similarly treated cells for reverse transcription-polymerase chain reaction analysis of hGR and cytokine expression. At 13 h after LPS treatment, there was an increase in the reference hGR protein (hGRα) expressed within some but not all PBMCs isolated from Leukopaks. There was also a dose-dependent increase in hGRα expression with increasing concentrations of PGN (10 and 50 µg/mL). LTA, however, did not affect hGRα expression. PGN also increased the mRNA expression of an hGR splice variant, hGR-B(54). The mRNA expression changes for the inflammatory cytokines were Leukopak specific. We found that cell wall components of both gram-positive and gram-negative bacteria can increase the expression of hGRα. Although these PAMPs augment the inflammatory response, it seems that there is a simultaneous upregulation of hGRα expression. Because binding of cortisol to hGRα typically induces anti-inflammatory proteins, the same PAMPs that induce an inflammatory response seem to also initiate a negative feedback system by inducing hGRα expression in PBMCs.

Evaluation of a mosquito home system for controlling Aedes aegypti.

BACKGROUND: Dengue is a significant public health issue that is caused by Aedes spp. mosquitoes. The current vector control methods are unable to effectively reduce Aedes populations and thus fail to decrease dengue transmission. Hence, there is an urgent need for new tools and strategies to reduce dengue transmission in a wide range of settings. In this study, the Mosquito Home System (MHS) and Mosquito Home Aqua (MHAQ) formulations were assessed as commercial autodissemination traps in laboratory and small-scale field trials. METHOD: Multiple series of laboratory and small-scale field trials were performed to assess the efficacy of MHS and MHAQ exposed to Ae. aegypti. In the laboratory trials, various parameters such as fecundity, fertility, wing size, oviposition preferences, residual effects, and MHAQ transference to other containers through controlled experiments were tested. For small-scale field trials, the efficacy of the MHS and MHAQ approaches was determined to ascertain whether wild mosquitoes could transfer the MHAQ formulation from MHS stations to ovitraps. RESULTS: The data revealed that Ae. aegypti was highly susceptible to low concentrations of MHAQ formulations and had a residual effect of up to 3 months, with MHAQ exposure affecting fecundity, fertility, and mosquito wing size. In the oviposition studies, gravid females strongly preferred the hay infusion compared to tap water and MHAQ during egg-laying in the laboratory. Nevertheless, the use of commercial MHAQ by MHS was highly attractive in field settings compared to conventional ovitraps among local Aedes spp. mosquitoes. In addition, MHAQ horizontal transfer activities in the laboratory and small-scale field trials were demonstrated through larval bioassays. These findings demonstrated the potential of MHAQ to be transferred to new containers in each study site. CONCLUSION: This study provided proof of principle for the autodissemination of MHAQ. Through further refinement, this technique and device could become an effective oviposition trap and offer an alternative preventive tool for vector control management.

A Novel Human Glucocorticoid Receptor Variant, G459V, is Hyperactive in Response to Steroids.

ABSTRACT: A potential cause of the variable response to injury and sepsis is the variability of a patient's human glucocorticoid receptor (hGR) profile. To identify hGR variants, blood samples were collected on admission and biweekly thereafter from hospitalized patients who sustained at least a 20% total body surface area burn injury. A hyperactive G1376T single-nucleotide polymorphism (SNP) isoform was identified. This SNP led to a single amino acid change of glutamine to valine at site 459, "G459V," in the DNA-binding domain. The isoform's activity was tested in a reporter assay after treatment with steroids, the hGR antagonist RU486 (mifepristone) alone, or RU486 followed by steroids. When treated with hydrocortisone, the hGR G459V isoform had a hyperactive response; its activity was over 30 times greater than the reference hGRα. Unexpectedly, G459V had significantly increased activity when treated with the hGR antagonist RU486. With the combination of both RU486 and hydrocortisone, G459V activity was repressed, but greater than that of RU486 alone. Finally, when hGRα was cotransfected with G459V to simulate isoform interaction, the activity was closer to that of the hGRα profile than the G459V isoform. The unique activity of the G459V isoform shows that some variants of hGR have the potential to alter a person's response to stress and steroid treatment and may be a factor as to why mitigating the clinical response to sepsis and other stressors has been so elusive.

Face Burns: A 4-Year Experience.

Burns on the face pose unique management challenges because they are in a place that is constantly visible, so scars are hard to hide. The goal of this study was to review our experience of adult patients who had face burns. We performed a retrospective review of adult patients (≥18 years old) who were admitted to a regional burn center from July 2015 to June 2019 with face burns. Sex, age, ethnicity, burn etiology, burn size, and discharge status were collected from electronic medical records of the patients who met study criteria. Descriptive statistics, Student's t-tests, and chi-square tests were performed in Stata/SE 16.1. Significance was defined as a P-value < .05. In 4 years, 595/1705 patients (~35% of admissions) were admitted with face burns. The mean age was 44.9 ± 17.0 (mean ± SD) years, with the majority being men (475, 80%). The mean burn size was 19.8 ± 20.9% TBSA with 10.1 ± 19.8% TBSA being third degree. The mean head burn size for any face burn was 2.8 ± 1.8% TBSA. The majority of burns were due to flames (478, 80%) and of those 122 (21%) were from accelerant use and 43 (7%) resulted from propane or butane use. Scalds caused 53 (9%), electric 25 (4%), hot tar 5 (1%), and chemical 5 (1%). Overall, 208 (35%) patients had grafting of some portion of their body, but only 31 patients (5.2%) had face grafting. The mean age of those with face grafting compared with patients who did not need grafting was 45.9 ± 13.8 and 44.9 ± 17.2 years, respectively. Patients who needed grafting had a mean third-degree burn size of 31.7 ± 25.4% TBSA and a mean head (including face) burn size of 4.7 ± 2.0% TBSA, whereas patients who did not need grafting had a mean third-degree burn size of 8.9 ± 18.7% TBSA and a mean head burn size of 2.7 ± 1.8% head TBSA. Patients requiring face grafts had longer lengths of stay, intensive unit stays, ventilator days, and mortality than those whose face burns healed spontaneously. Overall, head burns in adults were common within the 4-year time span we studied, but only a small fraction (5%) had face grafts. The patients who needed grafting for their head burns had significantly larger total body and face burns and had a 2.4-fold higher mortality rate compared to patients who did not need grafting. Most face burns were caused by flame, especially the use of accelerants or flammable gases. Prevention efforts should focus on avoiding the use of accelerants and being careful with flammable gases.

Wildfire Burn Patients: A Unique Population.

In the past ten years wildfires have burned an average of 6.8 million acres per year and this is expected to increase with climate change. Wildfire burn patient outcomes have not been previously well characterized. Wildfire burn patients from the Tubbs or Camp wildfires and non-wildfire burn matched controls were identified from the burn center database and outcomes were compared. The primary outcome was mortality. Secondary outcomes included length of stay (LOS), intensive care unit (ICU) LOS, readmission and development of wound infections. Time of presentation and operating room use after wildfires was evaluated. Sixteen wildfire burn patients were identified and matched with 32 controls. Wildfire burn patients trended towards higher mortality (19% wildfire vs. 9% non-wildfire, p=0.386), longer LOS (18 days wildfire vs. 15 days non-wildfire, p=0.406), longer ICU LOS (17 days wildfire vs. 11 days non-wildfire, p=0.991), increased readmission (19% wildfire vs. 3% non-wildfire, p=0.080) and higher rates of wound infection (31% wildfire vs. 19% non-wildfire, p=0.468). The majority of wildfire patients (88%) presented within 24 hours of the wildfire reaching a residential area. Operating room time within the first week was 13 hours 44 minutes for the Tubbs Fire and 19 hours 1 minute for the Camp Fire. Patients who sustain burns in wildfires are potentially at increased risk of mortality, prolonged LOS, wound infection and readmission.