Regional Burn Review: Neither Parkland Nor Brooke Formulas Reach 85% Accuracy Mark for Burn Resuscitation.

Prolonged resuscitation can result in burn wound conversion and other complications. Our team switched from using Parkland formula (PF) to the modified Brooke formula (BF) in January 2020. Secondary to difficult resuscitations using BF, we sought to review our data to identify factors associated with resuscitation requiring greater than predicted resuscitation with either formula, defined as 25% or more of predicted, hereafter referred to as over-resuscitation. Patients admitted to the burn unit between January 1, 2019 and August 29, 2021 for a burn injury with a percentage of total body surface area (%TBSA) ≥15% were included. Subjects <18 years, or weighing <30 kg, and those who died or had care withdrawn within 24 hours of admission were excluded. Demographics, injury information, and resuscitation information were collected. Univariate and multivariate analyses were performed to identify factors associated with over-resuscitation by either formula. P < .05 was considered significant. Sixty-four patients were included; 27 were resuscitated using BF and 37 using PF. No significant differences were observed in demographics and burn injury between the groups. Patients required a median of 3.59 ml/kg/%TBSA for BF and 3.99 ml/kg/%TBSA for PF to reach maintenance (P = .32). Over-resuscitation was more likely to occur when using BF compared to PF (59.3% vs 32.4%, P = .043). Over-resuscitation was associated with longer time to reach maintenance (OR = 1.179 [1.042-1.333], P = .009) and arrival via ground transportation (OR = 10.523 [1.171-94.597], P = .036). Future studies are warranted to identify populations in which BF under-performs and sequelae associated with prolonged resuscitation.

Investigating Healthcare Provider Bias Toward Patients Who Use Drugs Using a Survey-based Implicit Association Test: Pilot Study.

OBJECTIVES: Negative bias against people who use illicit drugs adversely affects the care that they receive throughout the hospital. We hypothesized that emergency providers would display stronger negative bias toward these patients due to life-threatening contexts in which they treat this population. We also hypothesized that negative implicit bias would be associated with negative explicit bias. METHODS: Faculty, nurses, and trainees at a midwestern tertiary care academic hospital were invited (June 26, 2019-September 5, 2019) to complete an online implicit association test and explicit bias survey. RESULTS: Mean implicit association test results did not vary across demographics (n = 79). There were significant differences in explicit bias scores between departments regarding whether patients who use drugs deserve quality healthcare access (P = 0.017). We saw no significant associations between implicit and explicit bias scores. CONCLUSION: Though limited by sample size, the results indicate that emergency and obstetrics/gynecology providers display more negative explicit bias toward this patient population than other providers.

Understanding Symptom Burden in Patients With Advanced Cancer Living in Rural Areas.

OBJECTIVES: To evaluate the feasibility of using a biobehavioral approach to examine symptom burden in rural residents with advanced cancer. SAMPLE & SETTING: 21 patients with advanced lung, colorectal, or pancreatic cancer were enrolled at the University of Iowa in Iowa City. METHODS & VARIABLES: Using Cleeland's cytokine-immunologic model of symptom expression, symptom burden (i.e., severity, count, and interference) and inflammatory cytokines were measured for 24 weeks. Potential predictors included demographics, clinical characteristics, optimism, social support, and cancer-related stress. Descriptive statistics, Wilcoxon rank-sum, and Fisher's exact test were used for analysis. RESULTS: Recruitment and retention rates were similar for rural and nonrural patients. Demographics, optimism, and social support were no different between groups. The cancer-related stress total score for rural patients was nearly half of the score of nonrural patients, with rural patients reporting significantly less avoidance. Symptom severity for the five worst symptoms remained moderate during the 24 weeks, whereas nonrural residents reported steady declines in severity of their five worst symptoms. Significant differences in inflammatory cytokines between groups were only found at one time point. IMPLICATIONS FOR NURSING: Rural residents who seek care at a cancer center may be clinically and demographically more similar to their nonrural counterparts than to rural residents seeking local care.

Scoring disease in an animal model of multiple sclerosis using a novel infrared-based automated activity-monitoring system.

Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS). Its corresponding animal model, experimental autoimmune encephalomyelitis (EAE), is widely used to understand disease pathogenesis and test novel therapeutic agents. However, existing methods to score EAE disease severity are subjective and often vary between individual researchers, making it difficult to translate findings across different studies. An enhanced automated method of disease scoring would eliminate subjectivity and reduce operator-dependent errors. Here, we used an Infra-Red Activity Monitoring System (IRAMS) to measure murine locomotor activity as a surrogate measure of disease severity and compared it to standard EAE scoring methods. In mice immunized with CNS-specific myelin antigens, we observed an inverse correlation between disease severity and mouse activity, with the IRAMS showing enhanced disease scoring compared to standard EAE scoring methods. Relative to standard EAE scoring methods, IRAMS showed comparable measurement of disease relapses and remissions in the SJL/J-relapsing-remitting model of EAE, and could comparably assess the therapeutic efficiency of the MS drug, Copaxone (Glatiramer acetate-GA). Thus, the IRAMS is a method to measure disease severity in EAE without subjective bias and is a tool to consistently assess the efficacy of novel therapeutic agents for MS.

Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma.

BACKGROUND: Despite the high prevalence of epidermal growth factor receptor (EGFR) overexpression in head and neck squamous cell carcinomas (HNSCCs), incorporation of the EGFR inhibitor cetuximab into the clinical management of HNSCC has not led to significant changes in long-term survival outcomes. Therefore, the identification of novel therapeutic approaches to enhance the clinical efficacy of cetuximab could lead to improved long-term survival for HNSCC patients. Our previous work suggests that EGFR inhibition activates the interleukin-1 (IL-1) pathway via tumor release of IL-1 alpha (IL-1α), although the clinical implications of activating this pathway are unclear in the context of cetuximab therapy. Given the role of IL-1 signaling in anti-tumor immune response, we hypothesized that increases in IL-1α levels would enhance tumor response to cetuximab. METHODS: Parental and stable myeloid differentiation primary response gene 88 (MyD88) and IL-1 receptor 1 (IL-1R1) knockdown HNSCC cell lines, an IL-1R antagonist (IL-1RA), neutralizing antibodies to IL-1α and IL-1ß, and recombinant IL-1α and IL-1ß were used to determine cytokine production (using ELISA) in response to cetuximab in vitro. IL-1 pathway modulation in mouse models was accomplished by administration of IL-1RA, stable overexpression of IL-1α in SQ20B cells, administration of rIL-1α, and administration of a polyanhydride nanoparticle formulation of IL-1α. CD4+ and CD8+ T cell-depleting antibodies were used to understand the contribution of T cell-dependent anti-tumor immune responses. Baseline serum levels of IL-1α were measured using ELISA from HNSCC patients treated with cetuximab-based therapy and analyzed for association with progression free survival (PFS). RESULTS: Cetuximab induced pro-inflammatory cytokine secretion from HNSCC cells in vitro which was mediated by an IL-1α/IL-1R1/MyD88-dependent signaling pathway. IL-1 signaling blockade did not affect the anti-tumor efficacy of cetuximab, while increased IL-1α expression using polyanhydride nanoparticles in combination with cetuximab safely and effectively induced a T cell-dependent anti-tumor immune response. Detectable baseline serum levels of IL-1α were associated with a favorable PFS in cetuximab-based therapy-treated HNSCC patients compared to HNSCC patients with undetectable levels. CONCLUSIONS: Altogether, these results suggest that IL-1α in combination with cetuximab can induce a T cell-dependent anti-tumor immune response and may represent a novel immunotherapeutic strategy for EGFR-positive HNSCCs.

Behavioral effects of mefloquine in tail suspension and light/dark tests.

Mefloquine hydrochloride has been used widely in the past few decades for malaria prophylaxis and treatment. However, in recent years, it has fallen out of favor due to reports of exposure being linked to numerous neuropsychiatric effects, including emotional disturbances. In this study we examined the effects of different doses (5, 25, or 100 mg/kg) of mefloquine relative to vehicle on male C57BL/6 J mice in two tests of emotional behavior, the light-dark box and the tail suspension test. It was found that mefloquine exposure reduced anxiety-linked behaviors in the light-dark box and reduced total immobility times in the tail suspension test, especially at higher doses. Our results lend support to the notion that mefloquine exposure could induce emotional disinhibition.