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Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood. In this retrospective, multinational study, real-world data were collected from 14 different sites in Germany, Austria and Switzerland on 88 patients receiving 93 2nd-generation CAR therapies. Bridging therapy was classified into the categories 1) no systemic therapy (15/93 treatments), 2) low-intensity therapy (38/93 treatments) and 3) high-intensity therapy (39/93 treatments). We analyzed the impact of bridging regimens on clinical outcome. Patients receiving a high-intensity bridging therapy had a significantly higher tumor burden at time of eligibility compared to patients treated with a low-intensity or no systemic bridging therapy. They suffered significantly more from bacterial adverse events and mucositis. Overall survival was significantly better for patients who did not receive any bridging therapy in comparison to patients who had been treated with a low- or high-intensity bridging regimen. In conclusion, in this retrospective cohort, high-intensity bridging therapy has not improved the outcome in terms of overall and progression-free survival in comparison to a low-intensity therapy. Yet, high-intensity bridging therapy was associated with more adverse events. Our study suggests that a low-intensity bridging regimen may be preferred whenever tumor burden and disease kinetics allow this treatment strategy., (© 2025. The Author(s).)

Objectives: Disorders of the gut-brain interaction (DGBI) arise from a complex interplay of psychosocial factors, altered physiology, and early life factors. In adults, adverse childhood experiences (ACEs) have been associated with DGBI. While both ACEs and DGBI are prevalent among children, the relationship between ACEs and DGBI in childhood is not well understood., Methods: Retrospective review of patients aged 3-18 years with ACE scores documented between October 1, 2019 and April 30, 2022 who were divided into three comparison groups: (1) not referred to pediatric gastroenterology (GI); (2) referred to GI and diagnosed with a DGBI; and (3) referred to GI and not diagnosed with a DGBI., Results: Of 29,490 patients with ACE scores documented during the study period, 897 completed a GI consultation. Four hundred and one (44.7%) were diagnosed with a DGBI. With each additional adverse experience, patients were 1.09 times more likely to have a DGBI diagnosis (95% confidence interval [CI] = 1.056-1.163; p ≤ 0.001). An anxiety diagnosis mediated 73% of this relationship (p = 0.012)., Conclusions: Among patients receiving pediatric GI specialty care, higher ACE scores were associated with a higher likelihood of a DGBI diagnosis. Anxiety largely mediates this relationship, suggesting potential avenues for targeted, multidisciplinary interventions in both primary and specialty care settings., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Health and racial disparities can limit access to preventative, trauma, and chronic disease care but have not been addressed in burn resuscitation. Over- and under-resuscitation contribute to increased overall hospital costs, and morbidity and mortality rates. The primary objective of this study was to identify potential racial disparities that may exist during the initial fluid resuscitation after burn injury. This was a retrospective review of all burn patients > 14 years of age admitted between January 1, 2020 and December 31, 2022 to a county safety net hospital. Patients were excluded if they transitioned to comfort care within 24 hours of admission. Data collected included baseline demographics, relevant burn injury information, and laboratory parameters. Outcomes included hospital and ICU length of stay, duration of mechanical ventilation, payor status, and mortality. Patients were divided into white (59 %) vs. African American-Hispanic (AA-HIS) (41 %) and included 105 patients. The median age (IQR) was 44.5(30) for whites vs 34(36) for AA-HIS. There were no statistically significant differences in severity of burn injury, cause of burn injury, rates of inhalation injury, or ICU or hospital lengths of stay. In both groups 55 % of the patients required mechanical ventilation while 18 % required renal replacement therapy. Overall mortality was not higher in the AA-HIS group at 32.6 % vs 17.7 % (p = 0.081). There were no differences in amount of fluid administered, urine output, laboratory values during resuscitation, or patient outcomes between the groups. The use of protocols for burn resuscitation can be instrumental in protecting against racial and ethnic disparities., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Smoking while using home oxygen leads to explosions, which cause cutaneous burns, death, and loss of property. Thermal fuses interrupt the propagation of ignited oxygen lines and reduce the risk of injury. Prior to mandating thermal fuses for all home oxygen users in the United States, cost-effectiveness analysis should be performed. A Markov model was constructed for suffering a thermal injury while smoking on home oxygen. Societal and Medicare perspectives were adopted, evaluating the costs of a federal policy, including purchasing/shipping thermal fuses to all home oxygen users. Costs included the healthcare required to treat burn patients and extend lives in advanced chronic obstructive pulmonary disease. Cost savings included the avoided property loss. Effectiveness was measured in gains in quality adjusted life years (QALYs). In the status quo, the 10-year societal cost was $28.67 billion compared to $28.36 billion in the policy mandate (saving $305.40 million at 10 years). 1812 QALYs were gained with the policy mandate, yielding, and incremental cost-effectiveness ratio (ICER) of -$160 317. From the Medicare payor perspective, the ICER was $64 981. Deterministic and probabilistic sensitivity analyses showed little variation in the ICER under multiple scenarios. The discrepancy between the dominant ICER for a societal perspective and the cost-effective ICER for a Medicare perspective reflected savings from averted property loss not realized by Medicare. A national policy mandating and paying for thermal fuses for all home oxygen users is dominant from a societal perspective and cost-effective from a Medicare perspective. The US government should adopt such a policy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Research is one of the American Burn Association's (ABA) strategic priorities. Advocacy is required not only to promote burn research, but also, the ABA's other strategic priorities (Prevention, Quality, and Education). The ABA convened a two-day Research and Advocacy (R&A) Summit in September 2023, to develop a roadmap for the organization's research and advocacy efforts. The in-person summit identified fourteen key R&A initiatives. A multidisciplinary workgroup then developed strategies to achieve each initiative. The initiatives and strategies were then approved by the ABA's Board of Trustees as our organization's roadmap for research and advocacy. The next task will be to implement the initiatives. This will require not only oversight from the ABA's Board of Trustees, but also, effort from and collaboration between several of the ABA's committees and panels, including the Burn Science Advisory panel (BSAP), the Research Committee, the Prevention Committee, The Governmental Affairs Committee, The Organization and Delivery of Burn care Committee, the Quality and Burn Registry Committee, the ad hoc Coding Committee, and the ABA's Central Office., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The COVID-19 pandemic affected daily life significantly and had massive consequences for healthcare systems with tremendous regional differences. This retrospective study aimed to investigate whether the pandemic and resulting societal changes impacted the diagnosis of pediatric malignancies in a distinct region. Pediatric cancer cases in Bavaria (2016-2021) and SARS-CoV-2 proceedings during the peak phase of the pandemic (2020-2021) were retrospectively analyzed. All new diagnoses of pediatric malignancies reported from cancer centers in Bavaria were included. Clinical data from pre-pandemic years was compared to diagnoses made during the pandemic. Official SARS-CoV-2 reports were received from the Bavarian Health and Food Safety Authority and data on regional pandemic measures were obtained from the Healthcare Data Platform. With this design, a comprehensive analysis of the pandemic proceedings was performed. We found significantly decreased incidence-rate ratios for pediatric cancer diagnosis during the early spring peak of SARS-CoV-2 as it was observed in May during the pandemic, followed by non-significantly increased metastatic cancer diagnosis two months later. Additionally, the time-to-diagnosis of pediatric malignancies was significantly prolonged during the pandemic, and outpatient contacts were significantly reduced, although the availability of consultations remained the same. From our findings, we may hypothesize that there have been effects on pediatric cancer diagnosis during the COVID-19 pandemic at vulnerable times. Interpretation of changes remains speculative with potential causes from behavior patterns, such as hesitation, concerns, and potential societal changes during phases of public restrictions, rather than overwhelmed medical capacities. Nevertheless, specific awareness is needed to protect this patient population during potential future pandemics.

Introduction: African Americans are at increased risk of hepatocellular carcinoma (HCC) compared to other racial and ethnic groups. We investigated the associations of four urinary biomarkers of prostaglandin E 2 (PGE-M), prostacyclin (PGI-M), and thromboxane (11dTxB 2 ) synthesis and the ratio of PGI-M to 11dTXB 2 with HCC risk in a cohort of predominantly African American populations., Methods: We conducted a nested case-control study (50 cases; 43 with HCC, 151 controls) in the Southern Community Cohort Study (SCCS), a large prospective cohort study including over 80,000 study participants, of whom two-thirds are African Americans. Urine samples were collected at enrollment and subsequently analyzed to assess biomarker levels. Multivariable regression models adjusted for age, race, sex, BMI, smoking status, NSAID use, education level, income, and alcohol consumption were used to assess the relationship between the biomarker and HCC risk., Results: Only 11dTxB 2 (OR = 11.50; 95% CI [2.34-56.47] for highest tertile vs. lowest tertile, p = 0.004) and the PGI-M/11dTXB 2 ratio of the second quartile (0.25-0.49) (OR = 5.16; 95% CI [1.44-18.47]; p = 0.01) were significantly associated with increased risk of liver cancer., Conclusion: 11dTXB 2 and PGI-M/11dTXB 2 ratio may be urinary markers of HCC risk, particularly among African Americans, and future prospective studies are needed to evaluate this finding further and to develop accessible methods., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426-21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Opioids are the most frequently used pain medications by US burn centers to control severe procedural pain during wound care. Concerns for long-term opioid use have prompted the exploration of non-pharmaceutical interventions, such as virtual reality (VR), for procedural pain management. The primary objective of this pilot study was to evaluate the feasibility and efficacy of VR pain alleviation treatment in reducing adult burn patients' perceived pain during burn dressing changes. Adult patients aged 18-70 years were recruited from the inpatient unit of a single American Burn Association-verified burn center between May 2019 and February 2020 and randomly assigned to one of three arms. Active VR participants played four VR games; passive VR participants were immersed in the same VR environment without the interaction elements; and a standard of care control group. 71 patients were screened for eligibility and 33 were deemed eligible to approach for informed consent, with 14 agreeing to participate in this study. Of these 14 patients, 4 were randomly assigned to the active VR, 4 to the passive VR, and 6 to the control group. Self-reported overall pain was lowest among participants in the active VR (dressing 1 = 41.3, dressing 2 = 61.0, and dressing 3 = 72.7) and highest among participants in the passive VR (dressing 1 = 58.3, dressing 2 = 74.5, and dressing 3 = 89.0) across all three dressing changes. Self-reported worst pain was lowest among the active VR at the first and last dressing (64.3 and 92.2, respectively), but the control group has the lowest self-reported worst pain at the second dressing (71.3). VR is a useful non-pharmacological tool for pain distraction but designing and implementing clinical research studies face many challenges in real-world medical settings. Lessons from this study have important implications for future VR studies by other researchers. Trial Registration: ClinicalTrials.gov Identifier: NCT04545229., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Armstrong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication., Methods and Analysis: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival., Ethics and Dissemination: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications., Trial Registration Number: ANZCTR ACTRN12619001735145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The epidermal growth factor receptor (EGFR) plays a role in cell proliferation and differentiation during healthy development and tumor growth; however, its requirement for brain development remains unclear. Here we used a conditional mouse allele for Egfr to examine its contributions to perinatal forebrain development at the tissue level. Subtractive bulk ventral and dorsal forebrain deletions of Egfr uncovered significant and permanent decreases in oligodendrogenesis and myelination in the cortex and corpus callosum. Additionally, an increase in astrogenesis or reactive astrocytes in effected regions was evident in response to cortical scarring. Sparse deletion using mosaic analysis with double markers (MADM) surprisingly revealed a regional requirement for EGFR in rostrodorsal, but not ventrocaudal glial lineages including both astrocytes and oligodendrocytes. The EGFR-independent ventral glial progenitors may compensate for the missing EGFR-dependent dorsal glia in the bulk Egfr -deleted forebrain, potentially exposing a regenerative population of gliogenic progenitors in the mouse forebrain., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Identifying factors related to expulsion risk is of great need due to the high and disparate rates of young children routinely excluded from preschool classrooms. This study aimed to explore the pathways to expulsion risk among a sample of 88 preschool children from 22 Head Start classrooms. Data were collected on children's inhibitory control using the Child Behavior Questionnaire, the closeness subscale of the Student-Teacher Relationship Scale, and on children's overall expulsion risk using the Preschool Expulsion Risk Measure. Direct pathways from children's inhibitory control and student-teacher closeness to expulsion risk were significant. Results indicated that student-teacher closeness mediated the relationship between children's inhibitory control and expulsion risk, indicating the importance of supporting positive relationships in preschool classrooms to disrupt pathways to expulsion. Implications for practices and future research to prevent expulsion are discussed., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Introduction: Teleconsultation is used in tertiary care hospitals to evaluate neonatal encephalopathy. Neonates born in community hospitals, however, often experience delayed evaluation due to transport to the tertiary care center. We studied teleconsultations in community hospitals to decrease this disparity., Methods: Prospective observational study in 9 community hospitals and 1 neonatal intensive care unit. Inclusion criteria: gestational age greater than or equal to 35 weeks and one of the following: umbilical cord pH less than or equal to 7.2, 5-minute Apgar less than 7, prolonged respiratory support, perinatal event, or abnormal neurological exam. We performed synchronized, unscheduled telemedicine consults with the main outcome of time to teleconsultation., Results: From April 2018 to September 2020, we performed 53 teleconsultations: 34 (64%) in community hospitals and 19 (36%) in the tertiary care center. Teleconsultations occurred at a median of 98 minutes (IQR, 76-127) in community hospitals versus 68 minutes (IQR, 43-91) in the tertiary care center ( p = .004). Nine (26%) neonates born in a community hospital remained with their parents and were not transferred to the tertiary care center for further assessment., Discussion: Neonates born in rural community hospitals have slightly later teleconsultations than neonates born in the tertiary care center. Telemedicine use reduced this disparity from nearly 5 hours in our prior study to 98 minutes in this study by permitting evaluation of neonates in community hospitals without transporting them to the tertiary care center., Conclusions: Teleconsultations to evaluate neonatal encephalopathy are a feasible, accessible, and reliable way to bring expert-level care into rural community hospitals., Competing Interests: Conflicts of interest None

Chemically induced proximity between certain endogenous enzymes and a protein of interest (POI) inside cells may cause post-translational modifications to the POI with biological consequences and potential therapeutic effects. Heterobifunctional (HBF) molecules that bind with one functional part to a target POI and with the other to an E3 ligase induce the formation of a target-HBF-E3 ternary complex, which can lead to ubiquitination and proteasomal degradation of the POI. Targeted protein degradation (TPD) by HBFs offers a promising approach to modulate disease-associated proteins, especially those that are intractable using other therapeutic approaches, such as enzymatic inhibition. The three-way interactions among the HBF, the target POI, and the ligase-including the protein-protein interaction between the POI and the ligase-contribute to the stability of the ternary complex, manifested as positive or negative binding cooperativity in its formation. How such cooperativity affects HBF-mediated degradation is an open question. In this work, we develop a pharmacodynamic model that describes the kinetics of the key reactions in the TPD process, and we use this model to investigate the role of cooperativity in the ternary complex formation and in the target POI degradation. Our model establishes the quantitative connection between the ternary complex stability and the degradation efficiency through the former's effect on the rate of catalytic turnover. We also develop a statistical inference model for determining cooperativity in intracellular ternary complex formation from cellular assay data and demonstrate it by quantifying the change in cooperativity due to site-directed mutagenesis at the POI-ligase interface of the SMARCA2-ACBI1-VHL ternary complex. Our pharmacodynamic model provides a quantitative framework to dissect the complex HBF-mediated TPD process and may inform the rational design of effective HBF degraders., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Erythroferrone (ERFE) is an erythroblast-secreted regulator of iron metabolism. The production of ERFE increases during stress erythropoiesis, leading to decreased hepcidin expression and mobilization of iron. Pregnancy requires a substantial increase in iron availability to sustain maternal erythropoietic expansion and fetal development and is commonly affected by iron deficiency. To define the role of ERFE during iron-replete or iron-deficient pregnancy, we utilized mouse models expressing a range of ERFE levels: transgenic (TG) mice overexpressing ERFE, wild-type (WT), and ERFE knockout (KO) mice. We altered maternal iron status using diets with low or standard iron content and performed the analysis at E18.5. Iron deficiency increased maternal ERFE in WT pregnancy. Comparing different maternal genotypes, ERFE TG dams had lower hepcidin relative to their liver iron load but similar hematological parameters to WT dams on either diet. In ERFE KO dams, most hematologic and iron parameters were comparable to WT, but mean corpuscular volume (MCV) was decreased under both iron conditions. Similar to dams, TG embryos had lower hepcidin on both diets, but their hematologic parameters did not differ from those of WT embryos. ERFE KO embryos had lower MCV than WT embryos on both diets. The effect was exacerbated under iron-deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct, and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis., (© 2022 Wiley Periodicals LLC.)

In February 2020, burn prevention experts from a variety of professional backgrounds gathered for a national Burn Prevention Summit. Through lively discussion and debate, this group came to a consensus on several core burn prevention concepts in order to create a framework for burn prevention program planning. The resulting document includes components of a successful program, a five-step process for program planning, best practices in messaging, and general advice from the summit attendees. This framework is designed for both novice professionals who are new to burn prevention programming development and experienced professionals who would like to strengthen existing programming., (© American Burn Association 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The hormone erythroferrone (ERFE) is produced by erythroid cells in response to hemorrhage, hypoxia, or other erythropoietic stimuli, and it suppresses the hepatic production of the iron-regulatory hormone hepcidin, thereby mobilizing iron for erythropoiesis. Suppression of hepcidin by ERFE is believed to be mediated by interference with paracrine bone morphogenetic protein (BMP) signaling that regulates hepcidin transcription in hepatocytes. In anemias with ineffective erythropoiesis, ERFE is pathologically overproduced, but its contribution to the clinical manifestations of these anemias is not well understood. We generated 3 lines of transgenic mice with graded erythroid overexpression of ERFE and found that they developed dose-dependent iron overload, impaired hepatic BMP signaling, and relative hepcidin deficiency. These findings add to the evidence that ERFE is a mediator of iron overload in conditions in which ERFE is overproduced, including anemias with ineffective erythropoiesis. At the highest levels of ERFE overexpression, the mice manifested decreased perinatal survival, impaired growth, small hypofunctional kidneys, decreased gonadal fat depots, and neurobehavioral abnormalities, all consistent with impaired organ-specific BMP signaling during development. Neutralizing excessive ERFE in congenital anemias with ineffective erythropoiesis may not only prevent iron overload but may have additional benefits for growth and development., (© 2022 by The American Society of Hematology.)

Extracted human teeth provide the closest approximation to teeth in situ and play important roles in dental education and materials research. Since extracted teeth are potentially infectious, the Centers for Disease Control recommend their sterilization by autoclaving or disinfection by formalin immersion to ensure safe handling. However, autoclaving is not recommended for teeth with amalgam fillings and formalin is hazardous. The goal of the present study was to investigate the potential of peracetic acid (PA) as an alternative method to achieve reliable disinfection of freshly extracted teeth. A total of 80 extracted teeth were collected for this study. Whole teeth were incubated in one of four solutions for defined periods of time: sterile water (2 weeks), formalin (2 weeks), PA 1000 ppm (2 weeks), and PA 2000 ppm (1 week). After sectioning, the crown and root fragments were transferred into separate tubes containing brain-heart infusion broth and incubated at 37 °C under anaerobic conditions for 72 h. Absence of broth turbidity was used to assess effectiveness of disinfection. No turbidity was observed in any of the formalin-treated or peracetic acid-treated samples, signifying complete disinfection. Our results indicate that PA can effectively disinfect extracted human teeth, providing a reliable alternative to formalin and autoclaving.

The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here, we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA and DNA interactions with the broadly expressed Runt-related transcription factor 1 (RUNX1), we identified the long noncoding RNA (lncRNA) originating from the upstream regulatory element of PU.1 (LOUP). This myeloid-specific and polyadenylated lncRNA induces myeloid differentiation and inhibits cell growth, acting as a transcriptional inducer of the myeloid master regulator PU.1. Mechanistically, LOUP recruits RUNX1 to both the PU.1 enhancer and the promoter, leading to the formation of an active chromatin loop. In t(8;21) acute myeloid leukemia (AML), wherein RUNX1 is fused to ETO, the resulting oncogenic fusion protein, RUNX1-ETO, limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression. These findings highlight the important role of the interplay between cell-type-specific RNAs and transcription factors, as well as their oncogenic derivatives in modulating lineage-gene activation and raise the possibility that RNA regulators of transcription factors represent alternative targets for therapeutic development., (© 2021 by The American Society of Hematology.)

Diabetes has been associated with poor outcomes following burn injury. There is limited data related to prediabetes in burn injury, and no studies to date have compared clinical outcomes inpatients without diabetes, with prediabetes, and with diabetes. Therefore, this study aimed to compare clinical outcomes after burn injury across the continuum of pre-injury glucose control. A propensity score weighted cohort study of adult patients admitted for initial management of burn injury was performed. Patients were categorized as no diabetes, prediabetes or diabetes based on their admission hemoglobin A1c and past medical history. The primary outcome was length of stay per percent Total Body Surface Area (TBSA) burn. Secondary outcome measures included length of stay, all-cause hospital mortality, disposition at discharge, re-grafting of same site, and amputations. A total of 2450 patients were screened; 1137 patients were included for evaluation (236 diabetes, 191 prediabetes, 710 no diabetes). After inverse probability weighing to adjust for potentially confounding factors, patients in the diabetes group had longer length of stay/%TBSA burn than both the no diabetes group (ratio of geometric means (95% CI) = 1.65 (1.25, 2.18), p < 0.001) and the prediabetes group (ratio (95% CI) = 1.49 (1.10, 2.02), p = 0.01). No statistically significant differences in secondary outcomes were observed between groups other than a higher rate of amputations in the diabetes group (2.7%) compared to the no diabetes (0.7%, p = 0.047) and prediabetes (0%, p = 0.04) groups. Further studies are needed to delineate the differences across the continuum of pre-injury glucose control in order to identify mechanisms to optimize burn-related outcomes., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Fluid resuscitation in the first 48 hours postburn is crucial in the management of burn shock. The primary purpose of this study was to evaluate nurses' adherence to a nurse-driven fluid resuscitation protocol at one adult burn center. Their secondary goal was to establish that the use of a nursing-driven protocol did not result in over resuscitation. Following implementation of a nurse-driven burn resuscitation protocol, a 48-hour data resuscitation data collection tool was developed by the burn physicians and nurses. All resuscitations were reviewed in real-time and in burn leadership meeting to identify opportunities for improvement. Follow-up with nursing staff was done in real time by the clinical nurse specialist following each burn resuscitation. Twenty-two patients requiring formal fluid resuscitation were included in the review. Patients had a median age of 36.5(IQR: 38.74) years and were predominantly male. They found that in the first 24 hours that patients received 3.47 ml/kg/hr and then in the next 24 hours they received an average of 2.68 ml/kg/hr. All 22 patients' resuscitation was initiated using the Parkland formula in the emergency department, and nurses were successful in consistently adjusting fluid infusions consistent with the protocol. Using a multidisciplinary approach and preparatory and real-time education processes, burn nurses can successfully guide burn resuscitation. Providing education and follow-up in real time can improve the process., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anxiety is common among patients with burn injury, occurring frequently surrounding wound care. Few pharmacologic interventions targeting anxiety in burn injury have been evaluated. This study aimed to evaluate patient-controlled anxiolysis using dexmedetomidine (PCA-DEX) in patients undergoing burn dressing changes. This was a prospective, open-label, single-arm pilot study to determine the feasibility, safety, and acceptability of PCA-DEX. PCA-DEX included a loading dose, continuous infusion, and patient-administered boluses during dressing changes for up to 5 days. Vital signs were monitored throughout PCA-DEX. Procedural pain and anxiety were evaluated before and after each dressing change. Nursing and patient satisfaction were evaluated after each dressing change. Twenty patients were included; 9 (45%) males and 11 females (55%) with a mean age of 45.1 ± 16.9 years and median total body surface area burn injury of 7 [IQR 4-9.5]%. Median heart rate and systolic blood pressure prior to PCA-DEX on day 1 were 82 [75-97] bpm and 147 [128-170] mmHg. Overall PCA-DEX was tolerated well with a median heart rate of 72 [66-82] bpm and systolic blood pressure 115 [99-141] mmHg after PCA-DEX. One patient was withdrawn due to severe bradycardia (heart rate < 45 bpm) not attributed to PCA-DEX; 4 patients experienced mild hypotension (systolic blood pressure 85-89/diastolic blood pressure 45-49 mmHg), all of which resolved without intervention. The majority of both nurses and patients were either satisfied or highly satisfied with PCA-DEX overall (78.1% for nursing, 86.5% for patients). PCA-DEX is a novel, safe and feasible method of anxiolysis during burn dressing changes with high patient and nurse satisfaction rates. A randomized, controlled trial is warranted to confirm the efficacy of PCA-DEX., Competing Interests: None., (IJBT Copyright © 2020.)

Ethyl carbamate (EC) is a fermentation byproduct in foods and beverages and classified as a Group 2A probable human carcinogen. Each year, greater than 40 million metric tons of fermentation co-products from the U.S. ethanol industry are fed to food animals. A gas chromatography-mass spectrometry assay was developed to quantify EC extracted from various distillers grains co-products with a limit of detection at 0.7 ng/g (on an as-fed basis). EC was detected in all the distillers grains co-products surveyed in this study. Corn condensed distillers solubles contained the highest concentration of EC, ranging from 1618 to 2956 ng/g. Concentrations of EC in other types of distillers grains co-products varied from 17 to 917 ng/g. Cattle fed distillers grains co-products that constituted 19-38% of the total feed (as-fed) were found to contain 2-3 ng/mL of EC in blood plasma. No EC was detected in blood plasma from grass-fed control cattle.

The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required growth response mediated by cell division control 42 (Cdc42) and Cdc42-deficient enteroids to undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated, receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiologically, but nonconventionally, spliced Cdc42 variant 2 (V2) exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration, and elevating this signaling cascade is capable of initiating protection from genotoxic injury.

Introduction: Recent advances in burn care have resulted in the transition of care from inpatient to outpatient. There is a growing appreciation that with improved survival, meaningful markers of quality need to include recovery of form, function, and reconstruction. Capture of the data describing care delivered in the outpatient setting is being missed., Methods: Development of our outpatient database included providers, registrar, program manager, and outpatient nursing staff. Data points were included if they described the population, and epidemiology of our patients, were useful for programmatic changes and improvements as well as anticipated research focus areas., Results: The database platform chosen was Midas+™ because it was in use by hospital quality and integrated with the electronic medical record. Fields were customized based on changing program needs and are updated for new programs or outcomes measures. Reports can be easily built and both outpatients and inpatients are included. This allows for longitudinal tracking of burn patients. Ongoing additions to original data points include variables to track outcomes related to laser therapy for scar management, time to custom garment donning, and to track functional outcomes. Epidemiologic data collected is used to target high-risk populations for prevention and outreach efforts. Outcome data is used for evaluation of programs and care., Conclusions: High quality databases serve to measure effectiveness of care and offer insight for areas of improvement. There is a clear need for inclusion of outpatient activity in the National Burn Registry (NBR)., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: Patients with thermal burns become zinc deficient due to exudative losses, increased urinary excretion, and reduction of carrier proteins which results in impaired immunity, wound healing and glucose control. Previous trials have demonstrated improved wound healing utilizing fixed zinc supplementation, but none have assessed the potential benefits associated with normalizing serum zinc concentrations. The objective of this study was to compare the impact of zinc normalization on clinical outcomes in patients with severe thermal burns., Methods: This retrospective, single-center study of patients with at least 10% total body surface area (TBSA) burn and three serum zinc concentrations compared the ratio of hospital length of stay (LOS) over TBSA burned (LOS/TBSA index) between those with normal (≥60 mcg/mL) and non-normal (<60 mcg/mL) serum zinc concentrations; delineated by the third measurement. Secondary outcomes were time to 90% epithelialization, infection incidence, and percentage of blood glucose values greater than 180 mg/dL. Data are reported as median [25-75% interquartile range] for continuous variables and frequency (percent) for categorical variables., Results: A total of 56 patients were included for evaluation (11 normal and 45 non-normal). Burn size was 20.5% TBSA [11-29] for those with normal zinc and 27.3% [22-36] for non-normal; number of grafts for each group was 1 [0-1] vs 2 [1-3] respectively. LOS/TBSA index did not differ significantly between groups (1.10 normal vs. 1.21 non-normal, unadjusted p = 0.69; p = 0.75 adjusting for number of grafts). Time to 90% epithelialization was reduced in the normal group (27.5 vs. 57 days, p = 0.02), but this did not remain statistically significant after adjustment for %TBSA and number of grafts (p = 0.18). The groups did not differ significantly in incidence of infection or hyperglycemia in either unadjusted or adjusted analyses., Conclusions: This was the first study, to our knowledge, to assess the clinical impact of normalizing serum zinc levels in patients with severe burns. Our results suggest the normalization of serum zinc levels through individualized zinc supplementation is not associated with improvement in clinical outcomes during hospitalization and therefore fixed-dose zinc supplementation without acquisition of serum zinc measurements should be considered., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Anticipated future hydroclimatic changes are expected to alter the transport and survival of fecally-sourced waterborne pathogens, presenting an increased risk of recreational water quality impairments. Managing future risk requires an understanding of interactions between fecal sources, hydroclimatic conditions and best management practices (BMPs) at spatial scales relevant to decision makers. In this study we used the Hydrologic Simulation Program FORTRAN to quantify potential fecal coliform (FC - an indicator of the potential presence of pathogens) responses to a range of mid-century climate scenarios and assess different BMP scenarios (based on reduction factors) for reducing the risk of water quality impairment in two, small agricultural watersheds - the Chippewa watershed in Minnesota, and the Tye watershed in Virginia. In each watershed, simulations show a wide range of FC responses, driven largely by variability in projected future precipitation. Wetter future conditions, which drive more transport from non-point sources (e.g. manure application, livestock grazing), show increases in FC loads. Loads typically decrease under drier futures; however, higher mean FC concentrations and more recreational water quality criteria exceedances occur, likely caused by reduced flow during low-flow periods. Median changes across the ensemble generally show increases in FC load. BMPs that focus on key fecal sources (e.g., runoff from pasture, livestock defecation in streams) within a watershed can mitigate the effects of hydroclimatic change on FC loads. However, more extensive BMP implementation or improved BMP efficiency (i.e., higher FC reductions) may be needed to fully offset increases in FC load and meet water quality goals, such as total maximum daily loads and recreational water quality standards. Strategies for managing climate risk should be flexible and to the extent possible include resilient BMPs that function as designed under a range of future conditions.

Anticipated future increases in air temperature and regionally variable changes in precipitation will have direct and cascading effects on U.S. water quality. In this paper, and a companion paper by Coffey et al. (2019), we review technical literature addressing the responses of different water quality attributes to historical and potential future changes in air temperature and precipitation. The goal is to document how different attributes of water quality are sensitive to these drivers, to characterize future risk to inform management responses and to identify research needs to fill gaps in our understanding. Here we focus on potential changes in streamflow, water temperature, and salt water intrusion (SWI). Projected changes in the volume and timing of streamflow vary regionally, with general increases in northern and eastern regions of the U.S., and decreases in the southern Plains, interior Southwest and parts of the Southeast. Water temperatures have increased throughout the U.S. and are expected to continue to increase in the future, with the greatest changes in locations where high summer air temperatures occur together with low streamflow volumes. In coastal areas, especially the mid-Atlantic and Gulf coasts, SWI to rivers and aquifers could be exacerbated by sea level rise, storm surges, and altered freshwater runoff. Management responses for reducing risks to water quality should consider strategies and practices robust to a range of potential future conditions.

Objective: Compression therapy (CT) has been an important, but debated, treatment for burn scars. To better understand one source of variation in observed outcomes after CT, an evaluation of CT timing of application is needed., Materials and Methods: Following IRB approval, 126 burn centers were contacted to complete a 17-question survey regarding the center's practice pattern for compression garment therapy. Locally, study subjects were identified between March 1, 2014 and December 31, 2015 and medical records examined for timing of garment ordering, delivery and fitting., Results: The majority believed that compression therapy is beneficial. Most centers reported using custom-fit and pre-fabricated garments, and a goal time of application between 2-4 weeks (42%) and 4-6 weeks (36%). After the garments are ordered, 61% of centers estimate that it takes 2-4 weeks for them to arrive. No significant differences in practices were found among centers treating pediatric patients only, adults only or both. Locally, the mean number of weeks between the date of original injury and garment order placement was 9.1 weeks with an additional 8.7 weeks between the date of order and date of delivery., Conclusions: The current study identified that although the national reporting of time to garment application is estimated to be between 2-6 weeks at the majority of burn centers including our own, we found our center to be well in excess of 17 weeks. The findings offer an opportunity for local improvement, and raise the possibility of similar incongruity between goals and practice at other centers., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis. This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded. Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups. Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Background: The primary objective of the study was to evaluate the efficacy of 300 milligrams (mg) and 600 mg of pregabalin compared to placebo in the reduction of pain in patients with noncritical partial and full thickness burn injuries., Methods: A prospective, randomized, double-blinded, single center, placebo-controlled trial was conducted. Simple randomization method was used in this trial. After subjects met all the inclusion and none of the exclusion criteria, they were randomized and assigned to 1 of the 3 18-day treatments groups: Pregabalin 300 group, Pregabalin 600 group, or Placebo group. Demographics and clinical characteristics were recorded. The severity of pain was assessed by using the visual analog scale for pain intensity at baseline on day 3, day 9 ± 3, day 25 ± 7, day 90 ± 6, and day 180 ± 12., Results: A total of 54 subjects were randomly assigned, and 51 were included in the data analysis. Demographics and clinical characteristics did not differ significantly between the 3 groups. There was a statistically significant difference in pain between the Pregabalin 300 and Pregabalin 600 groups (P-value = .0260). The Pregabalin 300 group had 17.93 units (95% confidence interval: 1.83-34.04) higher pain scores on average than the Pregabalin 600 group, regardless of time. The adjusted P-value comparing 0 to 300 was .1618, while the adjusted P-value for 0 versus 600 was .5304. There was an overall difference in pain across time regardless of study group (P-value = <.0001). An overall difference in opioid consumption (P-value = .0003) and BSHS (P-value = .0013) across time regardless of study group was noted., Conclusions: Pregabalin could be part of a promising multimodal analgesic regimen in noncritical burn population. Future placebo-controlled studies assessing the use of pregabalin in burn victim patients may further endorse our findings.

Background: Previous research suggests that relatively few hospitalized patients with opioid-related conditions receive substance use treatment during their inpatient stay. Without treatment, these individuals may be more likely to have subsequent hospitalizations for continued opioid use disorder., Objective: To evaluate the relationship between receipt of inpatient drug detoxification and/or rehabilitation services and subsequent opioid-related readmission., Methods: This study used combined hospital inpatient discharge and emergency department visit data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. Our sample consisted of 329,037 patients from seven states with an opioid-related index hospitalization occurring between March 2010 and September 2013. Multivariate analysis was conducted to examine the relationship between opioid-related readmission and the receipt of inpatient drug detoxification and/or rehabilitation during the index visit., Results: A relatively small percentage (19.4%) of patients with identified opioid-related conditions received treatment for drug use during their hospital inpatient stay. Patients who received drug rehabilitation, but not drug detoxification, during an opioid-related index hospitalization had lower odds of an opioid-related readmission within 90 days of discharge (odds ratio = 0.60, 95% confidence interval = 0.54-0.67) compared with patients with no inpatient drug detoxification or rehabilitation. Conclusions/Importance: A low percentage of patients receive inpatient services for drug use during an index stay involving an opioid-related diagnosis. Our findings indicate that receipt of drug rehabilitation services in acute care hospitals is associated with a lower 90-day readmission rate. Further research is needed to understand factors associated with the receipt of inpatient services and readmissions.

In this paper we review the published, scientific literature addressing the response of nutrients, sediment, pathogens and cyanobacterial blooms to historical and potential future changes in air temperature and precipitation. The goal is to document how different attributes of water quality are sensitive to these drivers, to characterize future risk, to inform management responses and to identify research needs to fill gaps in our understanding. Results suggest that anticipated future changes present a risk of water quality and ecosystem degradation in many U.S. locations. Understanding responses is, however, complicated by inherent high spatial and temporal variability, interactions with land use and water management, and dependence on uncertain changes in hydrology in response to future climate. Effects on pollutant loading in different watershed settings generally correlate with projected changes in precipitation and runoff. In all regions, increased heavy precipitation events are likely to drive more episodic pollutant loading to water bodies. The risk of algal blooms could increase due to an expanded seasonal window of warm water temperatures and the potential for episodic increases in nutrient loading. Increased air and water temperatures are also likely to affect the survival of waterborne pathogens. Responding to these challenges requires understanding of vulnerabilities, and management strategies to reduce risk.

This study characterizes adult burn readmissions in the United States using a nationally representative hospital inpatient sample. Readmission rates, diagnoses, and risk factors are discussed. We analyzed the 2013 and 2014 Nationwide Readmission Database for adult burn patients. The data were weighted to estimate national 30-day readmission rates. Principal readmission diagnoses were sorted into burn-specific or other readmission categories. We used multivariable logistic regression to assess the effects of patient and hospital stay risk factors on readmissions. An estimated 42,957 U.S. adult burn patients were discharged between January and November of 2013 and 2014. Of these patients, an estimated 3203 had unscheduled readmissions within 30 days (all-cause readmission rate: 7.5%, 95% CI: 6.7-8.2). An estimated 55.4 per cent of unplanned readmissions were for burn-specific principal readmission diagnoses. Burn-specific readmission was associated with burn severity and increased with both patient age and the number of comorbidities. Patients whose length of stay was less than 1 day per % total body surface area (%TBSA) burned had higher readmission risk (Adjusted odds ratio = 2.10, 95% CI = 1.48-2.99). The results of logistic regression models were similar for burn-specific readmissions and all-cause readmissions. In a nationally representative sample of adult burn patients, 4.1 per cent had unplanned 30-day readmissions for burn-specific reasons; 7.5 per cent were readmitted for any reason. Patient comorbidities and discharge before 1 day per %TBSA from the hospital impact readmission risk. Healthcare providers can use this information to identify at-risk patients, modify their treatment plans, and prevent readmissions.

Erythropoietin (EPO) acts on erythroid progenitor cells to promote their survival and differentiation to mature erythrocytes. Along with this canonical role, EPO is also reported to modulate energy metabolism, resulting in improved glucose tolerance and insulin sensitivity. EPO also stimulates the production of the hormone erythroferrone (ERFE) which acts to suppress hepcidin production, thus increasing dietary iron absorption and mobilizing stored iron for use in erythropoiesis. ERFE (initially termed myonectin) was also reported have an effect on systemic lipid metabolism by promoting the clearance of nonesterifed fatty acids (NEFA) from circulation. As increased levels of circulating NEFA blunt insulin sensitivity and impair glucose tolerance, ERFE-induced clearance of NEFA after EPO administration would have a beneficial effect on glucose metabolism. The aim of this study was to determine if the known metabolic effect of EPO treatment on glucose homeostasis is mediated by ERFE, produced in response to EPO. Mice lacking Erfe did not differ from wild-type mice in blood lipid parameters, blood glucose, and glucose or insulin tolerance at baseline or after chronic EPO treatment. Additionally, hepcidin suppression and the response of erythrocyte parameters to chronic EPO treatment were unaffected by the absence of Erfe. These findings suggest that the known beneficial effects of EPO on glucose metabolism are not attributable to an accompanying increase in ERFE production, and that Erfe is dispensable for normal glucose homeostasis. Furthermore, our data indicate that ERFE-independent mechanisms can suppress hepcidin in response to chronically elevated EPO levels., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Iron homeostasis ensures adequate iron for biological processes while preventing excessive iron accumulation, which can lead to tissue injury. In mammalian systems, iron availability is controlled by the interaction of the iron-regulatory hormone hepcidin with ferroportin, a molecule that functions both as the hepcidin receptor as well as the sole known cellular exporter of iron. By reducing iron export through ferroportin to blood plasma, hepcidin inhibits the mobilization of iron from stores and the absorption of dietary iron. Among the many processes requiring iron, erythropoiesis is the most iron-intensive, consuming most iron circulating in blood plasma. Under conditions of enhanced erythropoiesis, more iron is required to provide developing erythroblasts with adequate iron for heme and hemoglobin synthesis. Here the hormone erythroferrone, produced by erythroblasts, acts on hepatocytes to suppress hepcidin production, and thereby increase dietary iron absorption and mobilization from stores. This review focuses on the discovery of erythroferrone and recent advances in understanding the role of this hormone in the regulation of iron homeostasis during states of increased erythropoietic demand. Gaps in our understanding of the role of erythroferrone are highlighted for future study., (Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Objectives: As sepsis hospitalizations have increased, in-hospital sepsis deaths have declined. However, reported rates may remain higher among racial/ethnic minorities. Most previous studies have adjusted primarily for age and sex. The effect of other patient and hospital characteristics on disparities in sepsis mortality is not yet well-known. Furthermore, coding practices in claims data may influence findings. The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004-2013 trends in risk-adjusted in-hospital sepsis mortality rates by race/ethnicity to inform efforts to reduce disparities in sepsis deaths., Design: Retrospective, repeated cross-sectional study., Setting: Acute care hospitals in the Healthcare Cost and Utilization Project State Inpatient Databases for 18 states with consistent race/ethnicity reporting., Patients: Patients diagnosed with septicemia, sepsis, organ dysfunction plus infection, severe sepsis, or septic shock., Measurements and Main Results: In-hospital sepsis mortality rates adjusted for patient and hospital factors by race/ethnicity were calculated. From 2004 to 2013, sepsis hospitalizations for all racial/ethnic groups increased, and mortality rates decreased by 5-7% annually. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white (92.0 per 1,000 sepsis hospitalizations), black (94.0), and Hispanic (93.5) patients but remained elevated for Asian/Pacific Islander (106.4) and "other" (104.7; p < 0.001) racial/ethnic patients., Conclusions: Our results indicate that hospital characteristics contribute to higher rates of sepsis mortality for blacks and Hispanics. These findings underscore the importance of ensuring that improved sepsis identification and management is implemented across all hospitals, especially those serving diverse populations.

The regulation of iron metabolism in biological systems centers on providing adequate iron for cellular function while limiting iron toxicity. Because mammals cannot excrete iron, mechanisms have evolved to control iron acquisition, storage, and distribution at both systemic and cellular levels. Hepcidin, the master regulator of iron homeostasis, controls iron flows into plasma through inhibition of the only known mammalian cellular iron exporter ferroportin. Hepcidin is feedback-regulated by iron status and strongly modulated by inflammation and erythropoietic demand. This review highlights recent advances that have changed our understanding of iron metabolism and its regulation., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

It is generally agreed that patients with large burns will be referred to organized burn centers, however, the referral of patients with smaller burns is less certain. A two-part survey was conducted to identify referral patterns for burn patients that meet American Burn Association referral criteria, and any effect insurance type might have on the referral patterns. The emergency departments of our state hospital association's member hospitals were contacted seeking a referral for a fictitious patient with a third-degree scald of the dominant hand. The referral sites were contacted twice, first stating that the patient had commercial insurance, next stating that the patient had Medicaid. Data collected included wait time for an appointment or reasons for denial of an appointment. Of 218 hospitals, 46 were excluded because they did not offer emergency care, and eight because they were listed as burn centers on the American Burn Association website. Of the remaining 164, 119 (73%) would refer to a burn center, 21 (13%) to a plastic surgeon, 10 (6%) to a hand surgeon, 7 (4%) to a wound center, 7 (4%) to another nonburn physician resource. There was no difference in wait time to the first available appointment with regards to insurance type (6.56 ± 4.68 vs 6.53 ± 5.05 days). Our state's referral pattern gives us insight into the regional referral pattern. This information will be used to guide a focused education and communication program to provide better service for the burn victims of our state.

Study Objective: We assess whether the opening of retail clinics near emergency departments (ED) is associated with decreased ED utilization for low-acuity conditions., Methods: We used data from the Healthcare Cost and Utilization Project State Emergency Department Databases for 2,053 EDs in 23 states from 2007 to 2012. We used Poisson regression models to examine the association between retail clinic penetration and the rate of ED visits for 11 low-acuity conditions. Retail clinic "penetration" was measured as the percentage of the ED catchment area that overlapped with the 10-minute drive radius of a retail clinic. Rate ratios were calculated for a 10-percentage-point increase in retail clinic penetration per quarter. During the course of a year, this represents the effect of an increase in retail clinic penetration rate from 0% to 40%, which was approximately the average penetration rate observed in 2012., Results: Among all patients, retail clinic penetration was not associated with a reduced rate of low-acuity ED visits (rate ratio=0.999; 95% confidence interval=0.997 to 1.000). Among patients with private insurance, there was a slight decrease in low-acuity ED visits (rate ratio=0.997; 95% confidence interval=0.994 to 0.999). For the average ED in a given quarter, this would equal a 0.3% reduction (95% confidence interval 0.1% to 0.6%) in low-acuity ED visits among the privately insured if retail clinic penetration rate increased by 10 percentage points per quarter., Conclusion: With increased patient demand resulting from the expansion of health insurance coverage, retail clinics may emerge as an important care location, but to date, they have not been associated with a meaningful reduction in low-acuity ED visits., (Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)