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Article ; Online: Combined BRAF, MEK, and heat-shock protein 90 inhibition in advanced BRAF V600-mutant melanoma.

Eroglu, Zeynep / Chen, Y Ann / Smalley, Inna / Li, Jiannong / Markowitz, Joseph K / Brohl, Andrew S / Tetteh, Leticia / Taylor, Hayley / Sondak, Vernon K / Khushalani, Nikhil I / Smalley, Keiran S M

Cancer

2023 Volume 130, Issue 2, Page(s) 232–243

Abstract: Background: Resistance to BRAF and MEK inhibitors in BRAF V600-mutant melanoma is common. Multiple resistance mechanisms involve heat-shock protein 90 (HSP90) clients, and a phase 1 study of vemurafenib with the HSP90 inhibitor XL888 in patients with ... ...

Abstract	Background: Resistance to BRAF and MEK inhibitors in BRAF V600-mutant melanoma is common. Multiple resistance mechanisms involve heat-shock protein 90 (HSP90) clients, and a phase 1 study of vemurafenib with the HSP90 inhibitor XL888 in patients with advanced melanoma showed activity equivalent to that of BRAF and MEK inhibitors. Methods: Vemurafenib (960 mg orally twice daily) and cobimetinib (60 mg orally once daily for 21 of 28 days) with escalating dose cohorts of XL888 (30, 45, 60, or 90 mg orally twice weekly) was investigated in a phase 1 trial of advanced melanoma, with a modified Ji dose-escalation design. Results: Twenty-five patients were enrolled. After two dose-limiting toxicities (DLTs) (rash and acute kidney injury) in the first cohort, lower doses of vemurafenib (720 mg) and cobimetinib (40 mg) were investigated with the same XL888 doses. Three DLTs (rash) were observed in 12 patients in the XL888 60-mg cohort, and this was determined as the maximum tolerated dose. Objective responses were observed in 19 patients (76%), and the median progression-free survival was 7.6 months, with a 5-year progression-free survival rate of 20%. The median overall survival was 41.7 months, with a 5-year overall survival rate of 37%. Single-cell RNA sequencing was performed on baseline and on-treatment biopsies; treatment was associated with increased immune cell influx (CD4-positive and CD8-positive T cells) and decreased melanoma cells. Conclusions: Combined vemurafenib and cobimetinib plus XL888 had significant toxicity, requiring frequent dose reductions, which may have contributed to the relatively low progression-free survival despite a high tumor response rate. Given overlapping toxicities, caution must be used when combining HSP90 inhibitors with BRAF and MEK inhibitors.
MeSH term(s)	Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Vemurafenib ; Proto-Oncogene Proteins B-raf ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Protein Kinase Inhibitors/adverse effects ; Exanthema/chemically induced ; Exanthema/drug therapy ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/therapeutic use ; Mitogen-Activated Protein Kinase Kinases/genetics ; Mutation ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology
Chemical Substances	Vemurafenib (207SMY3FQT) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors ; Heat-Shock Proteins ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; BRAF protein, human (EC 2.7.11.1)
Language	English
Publishing date	2023-09-30
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35029
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Article ; Online: Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland.

Song, E A C / Smalley, K / Oyelakin, A / Horeth, E / Che, M / Wrynn, T / Osinski, J / Romano, R A / Sinha, S

Journal of dental research

2022 Volume 102, Issue 3, Page(s) 340–348

Abstract: Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell ... ...

Abstract	Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of
MeSH term(s)	Male ; Mice ; Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Transcription Factors/metabolism ; Salivary Glands/metabolism
Chemical Substances	DNA-Binding Proteins ; Transcription Factors
Language	English
Publishing date	2022-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80207-4
ISSN	1544-0591 ; 0022-0345
ISSN (online)	1544-0591
ISSN	0022-0345
DOI	10.1177/00220345221130258
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Ul III Zs.75: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Computed Tomography Utilization for Patients Presenting with Chest Pain.

Simon, Erin L / Krizo, Jessica / Septaric, Kristen / Citozi, Enri / Smalley, Courtney M / Shaffer, Austin / Mangira, Caroline / Fertel, Baruch S

The American journal of emergency medicine

2023 Volume 74, Page(s) 100–103

Abstract: Introduction: Computed tomography (CT) is routinely used in the emergency department (ED) due to its ease of access and its ability to rapidly rule in or out many serious conditions. Freestanding emergency departments (FSEDs) have become increasingly ... ...

Abstract	Introduction: Computed tomography (CT) is routinely used in the emergency department (ED) due to its ease of access and its ability to rapidly rule in or out many serious conditions. Freestanding emergency departments (FSEDs) have become increasingly used as an alternative to hospital-based emergency departments (HBEDs). The objective of this study was to investigate if the utilization rate of CT differs between FSEDs and HBEDs for chest pain. Methods: A retrospective evaluation of patients presenting to 17 EDs within a large integrated healthcare system between May 1, 2019 - April 30, 2021 with a chief complaint chest pain. Categorical variables are presented as frequencies and percentages. Continuous variables are presented as mean and standard deviation. Multiple logistic regression was used to assess the effect of facility on CT utilization for chest pain. Results: There were 67,084 patient encounters included in the study. Patients were predominately female (55%), white (61%), and insured through Medicare/Medicaid (59%). After controlling for predictive variables which included Charlson Comorbidity Index, ESI, age, sex, and race, patients who presented to FSEDs with chest pain were less likely to have a CT than those who presented to a HBED (AOR = 0.85, CI (0.81-0.90). Conclusion: CT scans of the chest are utilized less frequently at FSEDs compared to HBEDs for patient presenting with chest pain.
MeSH term(s)	Humans ; United States ; Female ; Aged ; Retrospective Studies ; Medicare ; Tomography, X-Ray Computed ; Chest Pain/diagnostic imaging ; Chest Pain/etiology ; Thorax ; Emergency Service, Hospital
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2023.09.038
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Article: Potential of Zero Charge and Its Temperature Derivative for Au(111) Electrode|Alkanethiol SAM|1.0 M Aqueous Electrolyte Solution Interfaces: Impact of Electrolyte Solution Ionic Strength and Its Effect on the Structure of the Modified Electrode|Electrolyte Solution Interface

Smalley, John F

The Journal of Physical Chemistry C. 2017 May 04, v. 121, no. 17

2017

Abstract: ... ionic strength (i.e., 1.0 M) aqueous electrolyte solutions. The Eₚzc’s measured for two different types of SAMs ... Nevertheless, an analysis based upon the value of dEpzcdT (= (0.51 ± 0.12) mV/K, essentially the same for SAMs made ...

Abstract	We demonstrate how small and rapid temperature perturbations (produced by the indirect laser-induced temperature jump (ILIT) technique) of solid metal electrode\|electrolyte solution interfaces may be used to determine the potential of zero (total) charge (Eₚzc) and its temperature derivative (dEpzcdT) of Au(111) electrode surfaces modified by alkanethiol self-assembled monolayers in contact with high ionic strength (i.e., 1.0 M) aqueous electrolyte solutions. The Eₚzc’s measured for two different types of SAMs (made from either HS(CH₂)ₙ₋₁CH₃ (5 ≤ n ≤ 12, Eₚzc = −(0.99 ± 0.12) V vs SSCE) or HS(CH₂)ₙOH (3 ≤ n ≤ 16, Eₚzc = (0.46 ± 0.22) V vs SSCE)) are considerably different than those measured previously at much lower electrolyte solution ionic strengths. For mixed monolayers made from both HS(CH₂)ₙ₋₁CH₃ and HS(CH₂)ₙFc (where Fc refers to ferrocene), the difference in Eₚzc decreases as a function of the surface concentration of the Fc moiety (i.e., [Fc]), and it completely disappears at a surprisingly small [Fc] (∼4.0 × 10–¹¹ mol cm–²). These observations for the Au(111)\|hydrophobic (neat and mixed) SAM\|aqueous electrolyte solution interfaces, along with the surface potentials (gₘₗS(dip)) evaluated for the contacting electrolyte solution surfaces of these interfaces, are consistent with a structure for the water molecule components of these surfaces where there is a net orientation of the dipoles of these molecules. Accordingly, the negative (oxygen) ends of these molecules point toward the SAM surface. The positive values of gₘₗS(dip) evaluated for hydrophilic SAM (e.g., made from HS(CH₂)ₙOH)\|aqueous electrolyte solution interfaces) also indicate that the structure of these interfaces is similar to that of the hydrophobic interfaces. However, gₘₗS(dip) decreases with increasing ionic strength for the hydrophilic interfaces, while it increases with increasing ionic strength for the hydrophobic interfaces. The data (and calculations) reported in the present work and other studies of hydrophobic (and hydrophilic)\|aqueous solution interfaces are as yet insufficient to support a complete explanation for the effects of ionic strength observed in the present study. Nevertheless, an analysis based upon the value of dEpzcdT (= (0.51 ± 0.12) mV/K, essentially the same for SAMs made from both HS(CH₂)ₙ₋₁CH₃ and HS(CH₂)ₙOH), determined in the present study provides a further indication that upon formation of the SAM there is a partial charge transfer of electrons from the relevant gold atoms on the Au(111) surface to the sulfur atoms of the alkanethiols.
Keywords	electrodes ; electrolytes ; electrons ; gold ; hydrophilicity ; hydrophobicity ; ionic strength ; moieties ; oxygen ; sulfur ; temperature
Language	English
Dates of publication	2017-0504
Size	p. 9260-9272.
Publishing place	American Chemical Society
Document type	Article
ISSN	1932-7455
DOI	10.1021%2Facs.jpcc.6b10954
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Differential requirements for CD4+ T cells in the efficacy of the anti-PD-1+LAG-3 and anti-PD-1+CTLA-4 combinations in melanoma flank and brain metastasis models.

Phadke, Manali S / Li, Jiannong / Chen, Zhihua / Rodriguez, Paulo C / Mandula, Jessica K / Karapetyan, Lilit / Forsyth, Peter A / Chen, Y Ann / Smalley, Keiran S M

Journal for immunotherapy of cancer

2023 Volume 11, Issue 12

Abstract: Background: Although the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combinations are effective in advanced melanoma, it remains unclear whether their mechanisms of action overlap.: Methods: We used single cell (sc) RNA-seq, flow cytometry and IHC ... ...

Abstract	Background: Although the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combinations are effective in advanced melanoma, it remains unclear whether their mechanisms of action overlap. Methods: We used single cell (sc) RNA-seq, flow cytometry and IHC analysis of responding SM1, D4M-UV2 and B16 melanoma flank tumors and SM1 brain metastases to explore the mechanism of action of the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combination. CD4+ and CD8+ T cell depletion, tetramer binding assays and ELISPOT assays were used to demonstrate the unique role of CD4+T cell help in the antitumor effects of the anti-PD-1+LAG-3 combination. Results: The anti-PD-1+CTLA-4 combination was associated with the infiltration of FOXP3+regulatory CD4+ cells (Tregs), fewer activated CD4+T cells and the accumulation of a subset of IFNγ secreting cytotoxic CD8+T cells, whereas the anti-PD-1+LAG-3 combination led to the accumulation of CD4+T helper cells that expressed CXCR4, TNFSF8, IL21R and a subset of CD8+T cells with reduced expression of cytotoxic markers. T cell depletion studies showed a requirement for CD4+T cells for the anti-PD-1+LAG-3 combination, but not the PD-1-CTLA-4 combination at both flank and brain tumor sites. In anti-PD-1+LAG-3 treated tumors, CD4+T cell depletion was associated with fewer activated (CD69+) CD8+T cells and impaired IFNγ release but, conversely, increased numbers of activated CD8+T cells and IFNγ release in anti-PD-1+CTLA-4 treated tumors. Conclusions: Together these studies suggest that these two clinically relevant immune checkpoint inhibitor (ICI) combinations have differential effects on CD4+T cell polarization, which in turn, impacted cytotoxic CD8+T cell function. Further insights into the mechanisms of action/resistance of these clinically-relevant ICI combinations will allow therapy to be further personalized.
MeSH term(s)	Animals ; Humans ; CD4-Positive T-Lymphocytes ; CTLA-4 Antigen ; T-Lymphocytes, Cytotoxic/metabolism ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Melanoma, Experimental
Chemical Substances	CTLA-4 Antigen
Language	English
Publishing date	2023-12-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-007239
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Article ; Online: BRAF-MEK inhibition in melanoma brain metastases: a new hope.

Forsyth, Peter A / Smalley, Keiran S M / Sondak, Vernon K

The Lancet. Oncology

2017 Volume 18, Issue 7, Page(s) 836–837

MeSH term(s)	Brain Neoplasms ; Cell Line, Tumor ; Humans ; Melanoma ; Mutation ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf/genetics
Chemical Substances	Protein Kinase Inhibitors ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2017-09-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(17)30449-7
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Agricultural Safety Education: Formative Assessment of a Curriculum Integration Strategy.

Pate, M L / Lawver, R G / Smalley, S W / Perry, D K / Stallones, L / Shultz, A

Journal of agricultural safety and health

2020 Volume 25, Issue 2, Page(s) 63–76

Abstract: The purpose of this study was to assess an agricultural tractor and machinery safety curriculum for teacher training that focused on hands-on integration activities to assist with training youth in machinery safety skills. Teachers attended a single ten- ... ...

Abstract	The purpose of this study was to assess an agricultural tractor and machinery safety curriculum for teacher training that focused on hands-on integration activities to assist with training youth in machinery safety skills. Teachers attended a single ten-hour summer training seminar hosted in Montana, South Dakota, or Utah during 2017. Teachers completed the National Tractor and Machinery Safe Operation (NSTMOP) exam to measure their existing knowledge prior to beginning the training. Upon seminar completion, teachers took an NSTMOP post-test to measure their knowledge gain of agricultural safety practices and hazard recognition associated with machinery and tractors. A total of 116 teachers completed the training. Fifty-three participants (45.7%) identified as female, and 63 (54.3%) identified as male. The average participant was 35 years old (SD = 11.3) and had 9.5 years of teaching experience (SD = 9.2). The average NSTMOP pre-test score was 35.2 out of 48 (SD = 3.3), and the average NSTMOP post-test score was 40.3 out of 48 (SD = 4.1). Participants' scores increased by ten percentage points. A paired-samples t-test was used to determine statistical significance. The difference between pre-test and post-test was significant (t(109) = 11.9, p < 0.001). Open responses indicated continuation of hands-on activities that focused on "how to teach" skills training that is relevant to the students. Teachers suggested developing new activities each year with a rotation of topics for upcoming seminars. Research is needed to determine the training's influence on the behaviors of young workers in agriculture.
MeSH term(s)	Adult ; Agriculture/education ; Curriculum ; Female ; Humans ; Male ; Safety ; Students ; Utah
Language	English
Publishing date	2020-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1501979-2
ISSN	1943-7846 ; 1074-7583
ISSN (online)	1943-7846
ISSN	1074-7583
DOI	10.13031/jash.13113
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Article ; Online: PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy.

The Journal of experimental medicine

2024 Volume 221, Issue 3

Abstract: ... and reduces monocytic myeloid-derived suppressor cells (m-MDSC), all of which are known to be ...

Abstract	An effective cancer therapy requires killing cancer cells and targeting the tumor microenvironment (TME). Searching for molecules critical for multiple cell types in the TME, we identified NR4A1 as one such molecule that can maintain the immune suppressive TME. Here, we establish NR4A1 as a valid target for cancer immunotherapy and describe a first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades NR4A1 within hours in vitro and exhibits long-lasting NR4A1 degradation in tumors with an excellent safety profile. NR-V04 inhibits and frequently eradicates established tumors. At the mechanistic level, NR-V04 induces the tumor-infiltrating (TI) B cells and effector memory CD8+ T (Tem) cells and reduces monocytic myeloid-derived suppressor cells (m-MDSC), all of which are known to be clinically relevant immune cell populations in human melanomas. Overall, NR-V04-mediated NR4A1 degradation holds promise for enhancing anticancer immune responses and offers a new avenue for treating various types of cancers such as melanoma.
MeSH term(s)	Humans ; Cell Line, Tumor ; Immunotherapy ; Melanoma/pathology ; Myeloid-Derived Suppressor Cells/pathology ; Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism ; Tumor Microenvironment ; Proteolysis Targeting Chimera
Chemical Substances	NR4A1 protein, human ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Proteolysis Targeting Chimera
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20231519
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Ua VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 45: Show issues

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Article ; Online: Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy.

Li, Jiannong / Smalley, Inna / Chen, Zhihua / Wu, Jheng-Yu / Phadke, Manali S / Teer, Jamie K / Nguyen, Thanh / Karreth, Florian A / Koomen, John M / Sarnaik, Amod A / Zager, Jonathan S / Khushalani, Nikhil I / Tarhini, Ahmad A / Sondak, Vernon K / Rodriguez, Paulo C / Messina, Jane L / Chen, Y Ann / Smalley, Keiran S M

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 10, Page(s) 2131–2146

Abstract: Purpose: Acral melanoma is a rare subtype of melanoma that arises on the non-hair-bearing skin of the palms, soles, and nail beds. In this study, we used single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and ... ...

Abstract	Purpose: Acral melanoma is a rare subtype of melanoma that arises on the non-hair-bearing skin of the palms, soles, and nail beds. In this study, we used single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets. Experimental design: We performed scRNA-seq on nine clinical specimens (five primary, four metastases) of acral melanoma. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by analysis of The Cancer Genome Atlas (TCGA) and single-cell datasets. Cell-cell interactions were inferred and compared with those in nonacral cutaneous melanoma. Results: Multiple phenotypic subsets of T cells, natural killer (NK) cells, B cells, macrophages, and dendritic cells with varying levels of activation/exhaustion were identified. A comparison between primary and metastatic acral melanoma identified gene signatures associated with changes in immune responses and metabolism. Acral melanoma was characterized by a lower overall immune infiltrate, fewer effector CD8 T cells and NK cells, and a near-complete absence of γδ T cells compared with nonacral cutaneous melanomas. Immune cells associated with acral melanoma exhibited expression of multiple checkpoints including PD-1, LAG-3, CTLA-4, V-domain immunoglobin suppressor of T cell activation (VISTA), TIGIT, and the Adenosine A2A receptor (ADORA2). VISTA was expressed in 58.3% of myeloid cells and TIGIT was expressed in 22.3% of T/NK cells. Conclusions: Acral melanoma has a suppressed immune environment compared with that of cutaneous melanoma from nonacral skin. Expression of multiple, therapeutically tractable immune checkpoints were observed, offering new options for clinical translation.
MeSH term(s)	Humans ; Immunologic Factors/therapeutic use ; Immunotherapy ; Melanoma/drug therapy ; Melanoma/therapy ; Neoplasms, Second Primary ; Skin/pathology ; Skin Neoplasms/drug therapy ; Skin Neoplasms/therapy ; Melanoma, Cutaneous Malignant
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-3145
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Zs.A 4223: Show issues

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Article ; Online: Reduced mortality and faster treatment in sepsis seen at freestanding vs. hospital-based emergency departments.

Griffin, Gregory / Smalley, Courtney M / Fertel, Baruch S / Mo, Kevin / Krizo, Jessica / Mangira, Caroline / Simon, Erin

The American journal of emergency medicine

2022 Volume 54, Page(s) 249–252

Abstract: Introduction: Freestanding Emergency Departments (FEDs) have grown in number and understanding their impact on the healthcare system is important. Sepsis causes significant morbidity and mortality and identifying how FEDs impact sepsis morbidity and ... ...

Abstract	Introduction: Freestanding Emergency Departments (FEDs) have grown in number and understanding their impact on the healthcare system is important. Sepsis causes significant morbidity and mortality and identifying how FEDs impact sepsis morbidity and mortality has not been studied. The objective of this study was to determine if there is a difference in in-hospital mortality for sepsis patients who present initially to FEDs compared to a hospital-based ED. Methods: This was a retrospective cohort of adult patients seen at a hospital-based ED or one of three FEDs within a large hospital system from 1/1/2018-10/31/2020. We included those who were diagnosed with sepsis, severe sepsis or septic shock and evaluated ED throughput measures, in-hospital mortality, and hospital length of stay. Categorical variables are presented as frequencies and percentages. Continuous variables are presented as mean and standard deviations or median and quartiles depending on distribution. Multiple logistic regression was fit to compare in-hospital mortality rates between the two groups. Variables controlled for included Charlson Comorbidity Index, race, gender, insurance, and sepsis severity. Wilcoxon rank sum tests were used to compare the time metrics. Results: There were 1955 patients included in the study. Mean age of participants was 61.9 at the FEDs vs 63.7 at the HBED. Majority of the participants were white; 88.2% at the FED vs. 77.3% at the HBED; and male 49.0% at the FED vs. 51.1% at the HBED. Most patients had Medicare; 45.4% at the FED vs. 58.3% at the HBED. In-patient mortality rate was significantly lower for patients that presented to FEDs compared to HBED (95%CI 0.13-0.46) adjusted odds ratio 0.24. Time to IV fluids, time to lactate, time to blood cultures, time to ED disposition, ED LOS, time to arrival on the inpatient unit were all significantly lower for FEDs vs HBED (p < 0.05). Conclusion: Patients presenting to FEDs for sepsis, severe sepsis and septic shock had lower inpatient mortality, quicker treatment times, and were transferred and admitted to the hospital faster than patients seen at a HBED.
MeSH term(s)	Adult ; Aged ; Emergency Service, Hospital ; Hospital Mortality ; Hospitals ; Humans ; Length of Stay ; Male ; Medicare ; Retrospective Studies ; Sepsis ; Shock, Septic/therapy ; United States
Language	English
Publishing date	2022-02-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2022.02.005
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