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1.
Am J Emerg Med ; 84: 59-67, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39094242

RESUMO

BACKGROUND: The benefit of virtual emergency department observation unit (EDOU) care relative to traditional observation care in an inpatient bed is unknown. OBJECTIVE: To determine if virtual observation care in an EDOU is associated with improved length of stay, cost, inpatient admission rate, and adverse events relative to traditional observation care in non-observation unit (NOU) inpatient bed. METHODS: This is a retrospective observational cohort study of observation patients managed over 24 months in two urban teaching hospitals. Following an ED visit, observation care occurred in a virtual-EDOU or NOU inpatient setting based on bed availability, physician discretion, and observation guidelines. Primary outcomes were length of stay, total cost, inpatient admission rate, and adverse events (death or ICU admission). Hospital cost and clinical databases were used. Analysis with a doubly-robust regression with entropy balancing and propensity scores was used to control for subgroup differences. RESULTS: 30,191 observation patients were divided into 13,753 NOU patients and 16,438 EDOU patients with similar distributions for age and gender, and differences in health insurance and diagnosis. For both discharged and admitted patients, the mean cost was higher in the NOU setting at $7989 than the virtual-EDOU setting at $4876 with an adjusted difference of $1951 (95% CI: $1762-$2133). The mean total length of stay was higher in the NOU setting (60.5 h) than the virtual-EDOU setting (36.4 h) with an adjusted difference of 20.4 h (95% CI: 19.2 h - 21.3 h). NOU inpatient admission rates were higher (25.3% vs 18.4%). Cost and length of stays were lower in discharged observation patients, with differences favoring the virtual-EDOU group. Adverse events were higher in the NOU setting (2.1% vs 0.8%). 30-day ED recidivism did not differ significantly between NOU and virtual-EDOU study groups. The virtual-EDOU saved the two hospitals $16,036,913 and 6986 bed-days annually. CONCLUSION: Management of observation patients in a virtual-EDOU setting is superior to care in a traditional inpatient setting in terms of costs, length of stays, inpatient admission and adverse events rates.


Assuntos
Unidades de Observação Clínica , Serviço Hospitalar de Emergência , Tempo de Internação , Humanos , Feminino , Masculino , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/economia , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Custos Hospitalares , Adulto , Hospitais de Ensino
3.
Am J Respir Crit Care Med ; 209(6): 703-715, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37972349

RESUMO

Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca2+ channel involved in store-operated Ca2+ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Pneumonia Bacteriana , Síndrome do Desconforto Respiratório , Humanos , Camundongos , Animais , Canais de Cálcio/metabolismo , Canais de Cálcio/farmacologia , Cálcio/metabolismo , Células HEK293 , Staphylococcus aureus Resistente à Meticilina/metabolismo , Sinalização do Cálcio , Inflamação/tratamento farmacológico , Pulmão/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Proteína ORAI1/metabolismo , Proteína ORAI1/farmacologia
4.
Allergy ; 79(2): 432-444, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37804001

RESUMO

BACKGROUND: Environmental exposure to peanut through non-oral routes is a risk factor for peanut allergy. Early-life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model. METHODS: C57BL/6J mice were co-exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut-specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM-induced peanut allergy. RESULTS: Airway co-exposure to peanut and either UPM- or DEP-induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut-specific CD4+ Th cells. UPM- and DEP-induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM- and DEP-induced peanut allergy, whereas TLR4 signaling was dispensable. DEP-induced peanut allergy and Tfh-cell differentiation depended on IL-1 but not IL-33 signaling, whereas neither cytokine alone was necessary for UPM-mediated sensitization. CONCLUSION: Environmental co-exposure to peanut and PM induces peanut-specific Tfh cells and peanut allergy in mice.


Assuntos
Anafilaxia , Hipersensibilidade a Amendoim , Camundongos , Animais , Camundongos Endogâmicos C57BL , Poeira , Citocinas/metabolismo , Material Particulado/efeitos adversos
5.
J Neurointerv Surg ; 16(4): 359-364, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-37290918

RESUMO

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.


Assuntos
Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Procedimentos Endovasculares/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas , Distribuição Aleatória , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Resultado do Tratamento , Ensaios Clínicos como Assunto
6.
Front Allergy ; 4: 1219268, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528863

RESUMO

Background: Early dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains. Objective: We aimed to determine whether environmental adjuvant-driven airway sensitization and oral tolerance to peanut could be induced in various genetically diverse mouse strains. Methods: C57BL/6J and 12 Collaborative Cross (CC) mouse strains were fed regular chow or ad libitum peanut butter to induce tolerance. Tolerance was tested by attempting to sensitize mice via intratracheal exposure to peanut and lipopolysaccharide (LPS), followed by intraperitoneal peanut challenge. Peanut-specific immunoglobulins and peanut-induced anaphylaxis were assessed. Results: Without oral peanut feeding, most CC strains (11/12) and C57BL/6J induced peanut-specific IgE and IgG1 following airway exposure to peanut and LPS. With oral peanut feeding none of the CC strains nor C57BL/6J mice became sensitized to peanut or experienced anaphylaxis following peanut challenge. Conclusion: Allergic sensitization and oral tolerance to peanut can be achieved across a range of genetically diverse mice. Notably, the same strains that became allergic via airway sensitization were tolerized by feeding high doses of peanut butter before sensitization, suggesting that the order and route of peanut exposure are critical for determining the allergic fate.

7.
Clin Exp Allergy ; 53(9): 930-940, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37437951

RESUMO

BACKGROUND: Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance. METHODS: To determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low-dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high-dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high-dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut-specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut-specific CD4+ memory T cells (CD4+ TCRß+ CD44hi CD154+ ) were quantified in mediastinal lymph nodes following airway priming. RESULTS: Mice co-exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low-dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high-dose peanut prior to airway sensitization. In contrast, mice fed high-dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut-specific CD4+ memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance. CONCLUSIONS: A single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high-dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non-oral priming event.


Assuntos
Arachis , Hipersensibilidade a Amendoim , Camundongos , Animais , Citocinas/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos , Poeira , Tolerância Imunológica , Alérgenos
8.
Respir Res ; 24(1): 153, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296458

RESUMO

Among asthmatics, there is significant heterogeneity in the clinical presentation and underlying pathophysiological mechanisms, leading to the recognition of multiple disease endotypes (e.g., T2-high vs. T2-low). This heterogeneity extends to severe asthmatics, who may struggle to control symptoms even with high-dose corticosteroid treatment and other therapies. However, there are limited mouse models available to model the spectrum of severe asthma endotypes. We sought to identify a new mouse model of severe asthma by first examining responses to chronic allergen exposure among strains from the Collaborative Cross (CC) mouse genetics reference population, which contains greater genetic diversity than other inbred strain panels previously used for models of asthma. Mice from five CC strains and the often-used classical inbred strain BALB/cJ were chronically exposed to house dust mite (HDM) allergen for five weeks followed by measurements of airway inflammation. CC strain CC011/UncJ (CC011) exhibited extreme responses to HDM including high levels of airway eosinophilia, elevated lung resistance, and extensive airway wall remodeling, and even fatalities among ~ 50% of mice prior to study completion. Compared to BALB/cJ mice, CC011 mice had stronger Th2-mediated airway responses demonstrated by significantly elevated total and HDM-specific IgE and increased Th2 cytokines during tests of antigen recall, but not enhanced ILC2 activation. Airway eosinophilia in CC011 mice was completely dependent upon CD4+ T-cells. Notably, we also found that airway eosinophilia in CC011 mice was resistant to dexamethasone steroid treatment. Thus, the CC011 strain provides a new mouse model of T2-high, severe asthma driven by natural genetic variation likely acting through CD4+ T-cells. Future studies aimed at determining the genetic basis of this phenotype will provide new insights into mechanisms underlying severe asthma.


Assuntos
Asma , Imunidade Inata , Camundongos , Animais , Citocinas , Linfócitos , Asma/tratamento farmacológico , Pulmão , Alérgenos , Pyroglyphidae , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Células Th2
9.
J Hosp Med ; 18(8): 670-676, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37286190

RESUMO

BACKGROUND: Stigma surrounding opioid use disorder (OUD) is a barrier to treatment. The use of stigmatizing language may be evidence of negative views toward patients. OBJECTIVE: We aimed to identify associations between language and clinical outcomes in patients admitted for infectious complications of OUD. DESIGNS: We performed a retrospective medical record review. SETTINGS AND PARTICIPANTS: Four U.S. academic health systems. Participants were patients with OUD admitted for infectious complications of injection opioid use from January 1, 2018, to December 31, 2018, identified through international classification of diseases, 10th revision codes consistent with OUD and acute bacterial/fungal infection. MAIN OUTCOME AND MEASURES: Discharge summaries were reviewed for language, specifically: abuse, addiction, dependence, misuse, use disorder, intravenous drug use, and others. Binary outcomes including medication for OUD, planned discharge, naloxone provision, and an OUD treatment plan were evaluated using logistic regressions and admission duration was evaluated using Gamma regression. RESULTS: A total of 1285 records were reviewed and 328 met inclusion criteria. Of those, 191 (58%) were male, with a median age of 38 years. The most common term was "abuse" (219, 67%), whereas "use disorder" was recorded in 75 (23%) records. Having "use disorder" in the discharge summary was associated with increased odds of having a documented plan for ongoing OUD treatment (adjusted odds ratio [AOR]: 4.11, 95% confidence interval [CI]: 1.89-8.93) and having a documented plan for addiction-specific follow-up care (AOR: 2.31, 95% CI: 1.30-4.09). CONCLUSIONS: Stigmatizing language was common in this study of patients hospitalized for infectious complications of OUD. Best-practice language was uncommon, but when used was associated with increased odds of addiction treatment and specialty care referrals.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seguimentos , Hospitalização , Transtornos Relacionados ao Uso de Opioides/terapia , Estudos Retrospectivos , Resultado do Tratamento , Idioma
10.
Curr Opin Allergy Clin Immunol ; 23(2): 164-171, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728313

RESUMO

PURPOSE OF REVIEW: The increasing global prevalence of food allergy indicates that environmental exposures are likely contributing to food allergy development. This review summarizes recent studies on how specific factors within the external exposome may impact the development of food allergy. RECENT FINDINGS: There is strong evidence that nonoral exposure to food allergens within the living environment is a risk factor for food sensitization and food allergy. The role of air pollution in food allergy development remains unclear, as cohort studies have not found consistent relationships between air pollutant exposure and food sensitization. Early-life microbial exposures linked to a rural lifestyle are likely protective against food allergy development, possibly through alteration of the infant microbiome. In contrast, factors associated with urbanization and decreased exposure to microbes may contribute to food allergy development. Recent studies on the role of residential greenness in food allergy development suggest either no relationship or a possible increased risk for food allergy. SUMMARY: The external exposome comprises a number of exposures that can modify food allergy risk. Improved understanding of how complex environmental exposures interact with genetic factors will be necessary for developing effective interventions aimed at preventing food allergy development in children.


Assuntos
Poluição do Ar , Expossoma , Hipersensibilidade Alimentar , Criança , Lactente , Humanos , Hipersensibilidade Alimentar/epidemiologia , Alérgenos , Fatores de Risco , Exposição Ambiental/efeitos adversos
11.
Inj Prev ; 29(3): 253-258, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36854627

RESUMO

BACKGROUND: Individuals with non-English language preferences (NELP) represent a growing proportion of the USA population. Prior studies demonstrate disparate health outcomes related to NELP status; however, this patient population is often excluded from medical research. There is a paucity of literature describing the impact of NELP status on trauma, specifically injury and outcomes related to vehicle occupants injured during motor vehicle collisions (MVCs). The goal of this study was to evaluate the representation of patients with NELP in both emergency medicine and trauma literature. METHODS: We conducted a systematic search of US-based publications from 2010 to 2021. Titles, abstracts and full texts of eligible articles were evaluated. Data were extracted using an a priori determined standardised reporting tool to evaluate language as study inclusion/exclusion criteria, manuscript reporting of language, assessment of language as a primary variable and consideration of language in study methodology. RESULTS: A total of 82 studies met inclusion criteria. Twenty-three studies (28%) excluded NELP populations and only one study explicitly included the NELP population. None of the studies evaluated language as a primary outcome of the study or included language as a variable in the analysis. Over half of the studies (53.6%) used a public data set or registry. CONCLUSION: NELP populations are routinely excluded from and are difficult to identify in MVC trauma research. Without appropriate inclusion and identification, it will be difficult to understand the prevalence and outcomes of traumatic injury in NELP patients and to develop culturally and linguistically appropriate interventions.


Assuntos
Lesões Acidentais , Pesquisa Biomédica , Humanos , Acidentes de Trânsito , Veículos Automotores
13.
Adv Emerg Nurs J ; 44(1): 63-73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35089284

RESUMO

The objectives of this study were to measure perceived stress, burnout, and utilization and perceived benefit of wellness practices among emergency medicine (EM) nurse practitioners (NPs) and physician assistants (PAs). An additional aim was to evaluate attributions of stress to racism and the COVID-19 pandemic. A 28-item electronic survey of ED NPs/PAs at 3 hospitals was used to measure respondents' perceived stress (Perceived Stress Scale), stress attributed to COVID-19 and systemic racism, burnout (2-item measure), and utilization and helpfulness of wellness practices. The sample consisted of 53 ED NPs/PAs respondents (response rate 42.4%). More than one half (58.5%) reported burnout from their job, and a majority (58.5%) reported moderate to high stress. Burnout was reported by 70% of female respondents compared with 30.8% of male respondent (p = 0.002). A large majority (70%) of Black respondents reported concerns about experiencing racism at work, and 58.8% reported higher levels of stress attributed to racism. Respondents reported meals during shifts, community donated personal protective equipment, flexible work hours, and societal offerings of financial support (e.g., Internal Revenue Service stimulus check) as helpful. The COVID-19 pandemic and the impact of systemic racism are significant contributors to the stress and burnout of NPs/PAs. Female ED NPs/PAs disproportionally share the burden of burnout. Strategies to reduce burnout should be prioritized by institutional leadership. In addition, a majority of Black ED NPs/PAs are concerned about experiencing racism at work and report moderate to high stress associated with racism in general. There is an urgent need to address racism in the workplace with training on implicit bias, systemic racism, and allyship behavior.


Assuntos
Esgotamento Profissional , COVID-19 , Medicina de Emergência , Profissionais de Enfermagem , Assistentes Médicos , Viés Implícito , Esgotamento Profissional/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Racismo Sistêmico
14.
Disaster Med Public Health Prep ; 16(1): 170-176, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-32958096

RESUMO

OBJECTIVES: The Radiation Injury Treatment Network (RITN) is prepared to respond to a national disaster resulting in mass casualties with marrow toxic injuries. How effective existing RITN workforce education and training is, or whether health-care providers (HCPs) at these centers possess the knowledge and skills to care for patients following a radiation emergency is unclear. HCP knowledge regarding the medical effects and medical management of radiation-exposed patients, along with clinical competence and willingness to care for patients following a radiation emergency was assessed. METHODS: An online survey was conducted to assess level of knowledge regarding the medical effects of radiation, medical/nursing management of patients, self-perception of clinical competence, and willingness to respond to radiation emergencies and nuclear events. RESULTS: Attendance at previous radiation emergency management courses and overall knowledge scores were low for all respondents. The majority indicated they were willing to respond to a radiation event, but few believed they were clinically competent to do so. CONCLUSIONS: Despite willingness to respond, HCPs at RITN centers may not possess adequate knowledge of medical management of radiation patients, and appropriate response actions during a radiation emergency. RITN should increase the awareness of the importance of radiation education and training.


Assuntos
Planejamento em Desastres , Incidentes com Feridos em Massa , Lesões por Radiação , Atitude do Pessoal de Saúde , Competência Clínica , Humanos , Lesões por Radiação/terapia , Inquéritos e Questionários , Recursos Humanos
15.
Immun Inflamm Dis ; 10(3): e575, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861108

RESUMO

BACKGROUND: Asthma is a heterogenous disease that can be classified into eosinophilic (type 2-high) and noneosinophilic (type 2-low) endotypes. The type 2-low endotype of asthma can be characterized by the presence of neutrophilic airway inflammation that is poorly responsive to corticosteroids. Dysregulated innate immune responses to microbial products including Toll-like receptor (TLR) ligands have been associated with the pathogenesis of neutrophilic asthma. The key molecules that regulate inflammatory responses in individuals with neutrophilic asthma remain unclear. We previously reported that the immunoregulatory receptor neuropilin-2 (NRP2) is expressed by murine and human alveolar macrophage (AM) and suppresses lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. METHODS: Here, we investigated the immunoregulatory role of NRP2 in a mouse model of neutrophilic asthma. RESULTS: We found that TLR ligands, but not T helper 2 (Th2)-promoting adjuvants, induced NRP2 expression by AM. Using an LPS-mediated model of neutrophilic asthma, we demonstrate that NRP2 was increased in AM and other lung antigen-presenting cells following airway challenge with antigen. Conditional deletion of NRP2 in myeloid cells exacerbated airway inflammation in a neutrophilic asthma model. In contrast, myeloid-specific ablation of NRP2 did not affect airway inflammation in a Th2-mediated eosinophilic asthma model. Myeloid-specific ablation of NRP2 did not affect Th1/Th17 responses to inhaled antigens or expression of neutrophil chemokines but rather resulted in impaired efferocytosis by AM, which is necessary for effective resolution of airway inflammation. CONCLUSION: Our findings suggest that NRP2 is a negative regulator of airway inflammation associated with neutrophilic asthma.


Assuntos
Asma , Neuropilina-2 , Animais , Asma/imunologia , Inflamação , Camundongos , Neuropilina-2/genética , Neuropilina-2/metabolismo , Neutrófilos/imunologia , Células Th17/imunologia , Células Th2/imunologia
16.
Am J Physiol Lung Cell Mol Physiol ; 322(1): L33-L49, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34755540

RESUMO

Acute ozone (O3) exposure is associated with multiple adverse cardiorespiratory outcomes, the severity of which varies across individuals in human populations and inbred mouse strains. However, molecular determinants of response, including susceptibility biomarkers that distinguish who will develop severe injury and inflammation, are not well characterized. We and others have demonstrated that airway macrophages (AMs) are an important resident immune cell type that are functionally and transcriptionally responsive to O3 inhalation. Here, we sought to explore influences of strain, exposure, and strain-by-O3 exposure interactions on AM gene expression and identify transcriptional correlates of O3-induced inflammation and injury across six mouse strains, including five Collaborative Cross (CC) strains. We exposed adult mice of both sexes to filtered air (FA) or 2 ppm O3 for 3 h and measured inflammatory and injury parameters 21 h later. Mice exposed to O3 developed airway neutrophilia and lung injury with strain-dependent severity. In AMs, we identified a common core O3 transcriptional response signature across all strains, as well as a set of genes exhibiting strain-by-O3 exposure interactions. In particular, a prominent gene expression contrast emerged between a low- (CC017/Unc) and high-responding (CC003/Unc) strain, as reflected by cellular inflammation and injury. Further inspection indicated that differences in their baseline gene expression and chromatin accessibility profiles likely contribute to their divergent post-O3 exposure transcriptional responses. Together, these results suggest that aspects of O3-induced respiratory responses are mediated through altered AM transcriptional signatures and further confirm the importance of gene-environment interactions in mediating differential responsiveness to environmental agents.


Assuntos
Pulmão/patologia , Macrófagos/metabolismo , Ozônio/efeitos adversos , Animais , Cromatina/metabolismo , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/efeitos dos fármacos
18.
Acad Emerg Med ; 28(9): 974-981, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358387

RESUMO

INTRODUCTION: Discrimination based on race is a known source of stress in individuals and is a contributor to poor health outcomes in patients. However, less is known about how the experiences of racism impact the stress levels of emergency health care workers (EHCWs). OBJECTIVES: The goal of this study was to assess the impact that racism has on the stress of EHCWs. METHODS: An anonymous electronic cross-sectional survey of EHCWs including attending physicians, resident physicians, advanced practice providers, nurses, and staff at three large metropolitan hospitals was administered in the summer of 2020. The survey evaluated the stress related to systemic racism and the COVID-19 pandemic in addition to the wellness measures utilized to cope with these stressors. The focus of this article is the impact of systemic racism on EHCWs. RESULTS: Of the 576 eligible participants, the total number of respondents utilized for analysis was 260. Overall, 64% of participants were very concerned about the state of racism in the United States, and 30% reported moderate-high or high stress resulting from racism. When stratified by race, 46% of Black participants reported moderate-high or high stress resulting from racism, compared to 31% of other participants of color and 23% of White participants (p = 0.002). CONCLUSION: Systemic racism is a significant concern and source of stress for EHCWs. Additional research about systemic racism, its impact on medical providers, and more importantly, active strategies to reduce and ultimately eliminate it in health care is needed.


Assuntos
COVID-19 , Racismo , Estudos Transversais , Pessoal de Saúde , Humanos , Pandemias , SARS-CoV-2 , Estados Unidos
19.
Artigo em Inglês | MEDLINE | ID: mdl-34281013

RESUMO

BACKGROUND: Emergency departments (EDs) have seen dramatic surges in patients infected with COVID-19 and are high-risk transmission environments. Knowledge, attitudes and practice regarding personal protective equipment (PPE) among ED health care workers (HCWs) during the COVID-19 pandemic have not been studied, thus this study examines this knowledge gap. METHODS: This was a cross-sectional survey of 308 HCWs in two urban EDs in Atlanta, Georgia in April and May of 2020. RESULTS: We surveyed 308 HCWs; 137 responded (44% response rate). All HCWs reported adequate knowledge and 96% reported compliance with PPE guidelines. Reported sources of PPE information: 56.7% charge nurse, 67.3% the institutional COVID-19 website. Frequency of training was positively associated with understanding how to protect themselves and patients (OR = 1.7, 95% CI: 1.0-2.9). CONCLUSIONS: Few HCWs are willing to care for patients without PPE, and therefore we should aim for resiliency in the PPE supply chain. EDs should consider multiple communication strategies, including a website with concise information and enhanced training for key personnel, particularly the charge nurse. Attention to frequency in HCW training may be key to improve confidence in protecting themselves and patients. Findings can be leveraged by EDs to implement effective PPE training.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Médicos , Estudos Transversais , Serviço Hospitalar de Emergência , Georgia , Pessoal de Saúde , Humanos , Pandemias , Equipamento de Proteção Individual , SARS-CoV-2 , Autorrelato
20.
Acad Emerg Med ; 28(12): 1399-1408, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34133829

RESUMO

BACKGROUND: Human trafficking (HT) is a human rights violation and public health issue. People with a history of HT are likely to see a physician during their exploitation. A screening tool was developed and implemented in a busy urban emergency department (ED) to aid in the identification of this population. OBJECTIVE: The objective was to retrospectively assess a HT screening tool implemented in an urban ED and evaluate the feasibility of the tool as a component of standard emergency care. METHODS: This was a retrospective observational study conducted at an urban adult ED after the implementation of an original 11-item HT screening tool. Adult patients 18 years and older were screened based on high-risk chief complaints, "red flag" risk factors, or provider gestalt. All patients with a positive screen were offered the opportunity to speak to a social worker, who then determined the patients' likely trafficking status. Data analysis was performed on this group of patients. RESULTS: A total of 26,974 patients were screened in the ED during 2019. Of these patients, 189 of them had a positive screen. A total of 37 patients were confirmed to have a likely sex trafficking status based on the federal definition. Eight of these patients elected to go to a community partner safe house. Positive responses to eight of the questions were significantly associated with likely sex trafficking status. Through regularized regression analysis, the predictive power of the screen was found to be derived from seven of the questions. CONCLUSION: Through the implementation of this screening tool, providers in a busy urban ED were able to identify patients with an experience of sex trafficking and offer them resources using a trauma-informed approach. This study demonstrates the feasibility of implementation of screening in the ED and identifies seven of the questions used as predictive of likely sex trafficking.


Assuntos
Tráfico de Pessoas , Adulto , Serviço Hospitalar de Emergência , Estudos de Viabilidade , Humanos , Programas de Rastreamento , Estudos Retrospectivos
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