Optimized Enzyme-Linked Immunosorbent Assay for Anti-PEG Antibody Detection in Healthy Donors and Patients Treated with PEGylated Liposomal Doxorubicin.

There is considerable interest in quantifying anti-PEG antibodies, given their potential involvement in accelerated clearance, complement activation, neutralization, and acute reactions associated with drug delivery systems. Published and commercially available anti-PEG enzyme-linked immunosorbent assays (ELISAs) differ significantly in terms of reagents and conditions, which could be confusing to users who want to perform in-house measurements. Here, we optimize the ELISA protocol for specific detection of anti-PEG IgG and IgM in sera from healthy donors and in plasma from cancer patients administered with PEGylated liposomal doxorubicin. The criterion of specificity is the ability of free PEG or PEGylated liposomes to inhibit the ELISA signals. We found that coating high-binding plates with monoamine methoxy-PEG5000, as opposed to bovine serum albumin-PEG20000, and blocking with 1% milk, as opposed to albumin or lysozyme, significantly improve the specificity, with over 95% of the signal being blocked by competition. Despite inherent between-assay variability, setting the cutoff value of the optical density at the 80th percentile consistently identified the same subjects. Using the optimized assay, we longitudinally measured levels of anti-PEG IgG/IgM in cancer patients before and after the PEGylated liposomal doxorubicin chemotherapy cycle (1 month apart, three cycles total). Antibody titers did not show any increase but rather a decrease between treatment cycles, and up to 90% of antibodies was bound to the infused drug. This report is a step toward harmonizing anti-PEG assays in human subjects, emphasizing the cost-effectiveness and optimized specificity.

Validation of dot blot immunoassay for measurement of complement opsonization of nanoparticles.

Complement plays a critical role in the immune response toward nanomaterials. The complement attack on a foreign surface results in the deposition of C3, assembly of C3 convertases, the release of anaphylatoxins C3a and C5a, and finally, the formation of membrane attack complex C5b-9. Various technologies can measure complement activation markers in the fluid phase, but measurements of surface C3 deposition are less common. Previously, we developed an ultracentrifugation-based dot blot immunoassay (DBI) to measure the deposition of C3 and other protein corona components on nanoparticles. Here, we validate the repeatability of the DBI and its correlation with pathway-specific and common fluid phase markers. Moreover, we discuss the advantages of DBI, such as cost-effectiveness and versatility, while addressing potential limitations. This study provides insights into complement activation at the nanosurface level, offering a valuable tool for nanomedicine researchers in the field.

Provider Perceptions of Oxygenation Strategies for Critically Ill Trauma Patients With and Without Moderate-to-Severe Traumatic Brain Injury.

BACKGROUND: Hypoxia and hyperoxia (pulse oximetry [SpO2] > 96%) are associated with increased mortality in critically ill patients. However, provider practices regarding oxygenation in traumatic brain injury (TBI) patients are unknown. This study assesses views on oxygenation of critically ill trauma patients with and without TBI and how this varies between Neurological ICU (NeuroICU) and Surgical-Trauma ICU (STICU) providers. METHODS: This is a cross-sectional survey of Level I trauma center's NeuroICU and STICU providers. We used Likert scales, yes-no questions, and multiple-choice case-based scenarios to characterize provider views on oxygenation with descriptive statistics to characterize responses. Significant differences regarding TBI and non-TBI patients or NeuroICU and STICU providers were determined using Fisher's exact test and a P-value of .05. RESULTS: A total of 83 providers initiated the survey, and 53 providers completed it. Most providers identified a threshold SpO2 < 92% for the administration of supplemental oxygen in critically ill TBI patients. A total of 9% of providers "somewhat or completely agreed" that they were more likely to give supplemental oxygen to a critically ill trauma patient with TBI than one without TBI and the same SpO2. A total of 48% of providers selected an SpO2 < 90% as the point at which supplemental oxygen should be initiated in patients without TBI, compared to 27% of providers in patients with TBI (P < .01). This threshold for supplemental oxygen use varied by provider type for non-TBI patients, but not for TBI patients (30% NeuroICU and 69% STICU providers selected SpO2 < 90% in non-TBI, P < .05; 30% NeuroICU and 35% STICU providers selected SpO2 < 90% in TBI, P = .85). CONCLUSIONS: Critical care providers at UCHealth University of Colorado Hospital approach the oxygenation of critically ill trauma patients with and without TBI differently. Specifically, critical care respondents accepted a different lower oxygen saturation threshold for TBI and non-TBI patients. NeuroICU and STICU respondents differed in their threshold for the down-titration of supplemental oxygen. Targeted education for critical care providers may reduce these discrepancies and optimize oxygen use.

Sex differences in acute ischemic stroke presentation are a matter of infarct location.

INTRODUCTION: Recognition of stroke by Emergency Medical Services (EMS) is critical to initiate rapid emergency department treatment. Most prehospital stroke screening tools rely heavily on presentation with the classic symptoms of facial droop, speech changes, unilateral weakness. However, women may be less likely to present with classic symptoms and may also have different distributions of stroke by anatomical location. This study seeks to determine the association between biological sex, presentation with classic symptoms, and the location of the infarcted tissue. METHODS: This is a retrospective cohort study. Data from electronic health records were extracted for patients with acute ischemic stroke who presented via EMS to a single Comprehensive Stroke Center between January 1, 2018 and December 31, 2020. We used descriptive statistics characterize the cohort. Multivariable logistic regression identified factors associated with classic symptom presentation (facial droop, speech changes, and/or unilateral weakness). Biological sex, location of the infarct, stroke etiology, age and the interaction between sex and infarct location were assessed as covariates. RESULTS: There were 364 (58.6%) males and 257 (41.1%) females with an acute ischemic stroke included in this study. EMS documented one or more classic symptoms in 125 (72.3%) males and 161 (67.9%) females. There were no baseline differences in infarct location or presentation with classic symptoms as documented by EMS comparing males and females. Multivariate logistic regression found no association between biological sex and presentation with classic symptoms (Odds Ratio 1.08; 95% CI 0.58 to 1.55) after controlling for age, stroke location, etiology of stroke or the interaction between sex and infarct location. Presence of an anterior circulation infarct compared to posterior circulation infarct was positively associated with a classic presentation to EMS (Odds Ratio 3.41; 95% CI 2.15 to 5.41). CONCLUSIONS: This study found no difference in the frequency of patient presentation with classic stroke symptoms based on biological sex alone, nor a significant different in distribution of infarcts between males and females. Infarct location (i.e., involving the anterior circulation) was associated with a classic presentation. This suggests that the likelihood of presenting with classic stroke symptoms is not influenced by sex, but rather the location of the infarct.

A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation.

BACKGROUND: Acetaminophen (APAP) is the most common cause liver injury following alcohol in US patients. Predicting liver injury and subsequent hepatic regeneration in patients taking therapeutic doses of APAP may be possible using new 'omic methods such as metabolomics and genomics. Multi'omic techniques increase our ability to find new mechanisms of injury and regeneration. METHODS: We used metabolomic and genomic data from a randomized controlled trial of patients administered 4 g of APAP per day for 14 days or longer with blood samples obtained at 0 (baseline), 4, 7, 10, 13 and 16 days. We used the highest ALT as the clinical outcome to be predicted in our integrated analysis. We used penalized regression to model the relationship between genetic variants and day 0 metabolite level, and then performed a metabolite-wide colocalization scan to associate the genetically regulated component of metabolite expression with ALT elevation. Genome-wide association study (GWAS) analyses were conducted for ALT elevation and metabolite level using linear regression, with age, sex, and the first five principal components included as covariates. Colocalization was tested via a weighted sum test. RESULTS: Out of the 164 metabolites modeled, 120 met the criteria for predictive accuracy and were retained for genetic analyses. After genomic examination, eight metabolites were found to be under genetic control and predictive of ALT elevation due to therapeutic acetaminophen. The metabolites were: 3-oxalomalate, allantoate, diphosphate, L-carnitine, L-proline, maltose, and ornithine. These genes are important in the tricarboxylic acid cycle (TCA), urea breakdown pathway, glutathione production, mitochondrial energy production, and maltose metabolism. CONCLUSIONS: This multi'omic approach can be used to integrate metabolomic and genomic data allowing identification of genes that control downstream metabolites. These findings confirm prior work that have identified mitochondrial energy production as critical to APAP induced liver injury and have confirmed our prior work that demonstrate the importance of the urea cycle in therapeutic APAP liver injury.

Hyperoxia is associated with a greater risk for mortality in critically ill traumatic brain injury patients than in critically ill trauma patients without brain injury.

OBJECTIVE: The role of hyperoxia in patients with traumatic brain injury (TBI) remains controversial. The objective of this study was to determine the association between hyperoxia and mortality in critically ill TBI patients compared to critically ill trauma patients without TBI. DESIGN: Secondary analysis of a multicenter retrospective cohort study. SETTING: Three regional trauma centers in Colorado, USA, between October 1, 2015, and June 30, 2018. PATIENTS: We included 3464 critically injured adults who were admitted to an intensive care unit (ICU) within 24 h of arrival and qualified for inclusion into the state trauma registry. We analyzed all available SpO2 values during the first seven ICU days. The primary outcome was in-hospital mortality. Secondary outcomes included the proportion of time spent in hyperoxia (defined as SpO2 > 96%) and ventilator-free days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In-hospital mortality occurred in 163 patients (10.7%) in the TBI group and 101 patients (5.2%) in the non-TBI group. After adjusting for ICU length of stay, TBI patients spent a significantly greater amount of time in hyperoxia versus non-TBI patients (p = 0.024). TBI status significantly modified the effect of hyperoxia on mortality. At each specific SpO2 level, the risk of mortality increases with increasing FiO2 for both patients with and without TBI. This trend was more pronounced at lower FiO2 and higher SpO2 values, where a greater number of patient observations were obtained. Among patients who required invasive mechanical ventilation, TBI patients required significantly more days of ventilation to day 28 than non-TBI patients. CONCLUSIONS: Critically ill trauma patients with a TBI spend a greater proportion of time in hyperoxia compared to those without a TBI. TBI status significantly modified the effect of hyperoxia on mortality. Prospective clinical trials are needed to better assess a possible causal relationship.

Sex as a biological variable in determining the metabolic changes influencing acute ischemic stroke outcomes-Where is the data: A systematic review.

Women continue to face a greater lifetime morbidity and mortality from stroke and have been shown to respond differently to stroke treatments compared to men. Since 2016, updated National Institutes of Health (NIH) policies require research studies to consider sex as a biological variable. However, the way in which this policy affects study design, analysis, and reporting is variable, with few studies performing and reporting a subgroup analysis based on biological sex. In acute ischemic stroke, the underlying biological explanation for sex-based differences in patient outcomes and response to treatments remains understudied. We performed a systematic review of preclinical and clinical research studies that explored sex differences in the metabolic response to acute ischemic stroke as it relates to neurological outcomes. Through a literature search in Ovid Medline, Embase, and Web of Science, 1,004 potential references were identified for screening. After abstract and full-text review, we identified only two studies which assessed metabolic response to acute ischemic stroke (within 72 h of last known well) and neurological outcome [Barthel Index, modified Rankin Scale (mRS) or an equivalent in preclinical models] and reported results based on biological sex. One article was a preclinical rat model and the other a clinical cohort study. In both studies, metabolites involved in amino acid metabolism, energy metabolism, fat metabolism, or oxidative stress were identified. We review these results and link to additional articles that use metabolomics to identify metabolites differentially expressed by sex or regulated based on stroke outcomes, but not both. The results of this systematic review should not only help identify targets in need of further investigation to improve the understanding of sex differences in the pathophysiology of acute ischemic stroke, but also highlight the critical need to expand the incorporation of sex as a biological variable in acute stroke research beyond simply including both sexes and reporting the proportion of males/females in each population studied.

Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences.

BACKGROUND: Acetaminophen (APAP)-associated transaminase elevation, induced by N-acetyl-p-benzoquinone imine (NAPQI) protein adduction, remains an area of research interest. Distinct from known genetic, physiologic, and dosage associations dictating severity of hepatic injury, no known factors predict an absence of protein adduct formation at therapeutic APAP dosing. HYPOTHESIS: Sex-based physiology is predictive of APAP-induced protein adduct formation and differential metabolite expression at therapeutic doses. METHODS: This retrospective study interrogated serum samples collected for a prior study investigating fluctuations of alanine aminotransferase (ALT) over time with 4G daily APAP dosing for ≥ 16 days in subjects from Denver, Colorado. Subjects were grouped by adduct formation (n = 184) vs no adducts (n = 20). Samples were run on ultra-high-performance liquid chromatography mass spectrometry from study days 0, 7, 16, and 31. Significant metabolite expressions were identified using t-tests with false discovery rate correction (FDR), partial least squares discriminant, and ANOVA simultaneous comparison analyses. Demographic and clinical data were explored using t-tests with FDR (age, weight, BMI, ALT) and Chi-square (sex, ethnicity, race) analyses. RESULTS: In pre-treatment samples, relative quantitation caprylic acid was expressed ninefold higher and 6-carboxyhexanoate was expressed threefold lower in subjects who did not develop adducts. Lactate had greater expression in the no adducts group (p = 0.001). Using absolute quantitation, glutathione was expressed 2.6-fold greater among no adduct subjects. Odds of males developing NAPQI protein adducts at therapeutic APAP dosing were 5.91 times lower than females (95% CI = 2.3-14.9; p = 0.0001). CONCLUSION: Multiple metabolites were differentially expressed based on adduct group and sex. Metabolites were identified unique to adduct development independent of sex. At therapeutic APAP dosing, males were less likely to develop APAP protein adducts. Further research into lipid biosynthesis and metabolism may provide further insight into physiology associated with adduct production.

Analysis of Stroke Care Among 2019-2020 National Emergency Medical Services Information System Encounters.

OBJECTIVES: Emergency Medicine Service (EMS) providers play a pivotal role in early identification and initiation of treatment for stroke. The objective of this study is to characterize nationwide EMS practices for suspected stroke and assess for gender-based differences in compliance with American Stroke Association (ASA) guidelines. MATERIALS AND METHODS: Using the 2019-2020 National Emergency Medical Services Information System (NEMSIS) Datasets, we identified encounters with an EMS designated primary impression of stroke. We characterized patient characteristics and EMS practices and assessed compliance with eight metrics for "guideline-concordant" care. Multivariable logistic regression modeled the association between gender and the primary outcome (guideline-concordant care), adjusted for age, EMS level of service, EMS geographical region, region type (i.e. urban or rural), and year. RESULTS: Of 693,177 encounters with a primary impression of stroke, overall compliance with each performance metric ranged from 18% (providing supplemental oxygen when the pulse oximetry is less than 94%) to 76% (less than 90sec from incoming call to EMS dispatch). 2,382 (0.39%) encounters were fully guideline-concordant. Women were significantly less likely than men to receive guideline-concordant care (adjusted OR 0.82, 95% CI 0.75-0.89; 0.36% women, 0.43% men with guideline-concordant care). CONCLUSIONS: A minority of patients received prehospital stroke care that was documented to be compliant with ASA guidelines. Women were less likely to receive fully guideline-compliant care compared to men, after controlling for confounders, although the difference was small and of uncertain climical importance. Further studies are needed to evaluate the underlying reasons for this disparity, its impact on patient outcomes, and to identify potential targeted interventions to improve prehospital stroke care.

A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial.

BACKGROUND: Targeted normoxia (SpO2 90-96% or PaO2 60-100 mmHg) may help to conserve oxygen and improve outcomes in critically ill patients by avoiding potentially harmful hyperoxia. However, the role of normoxia for critically ill trauma patients remains uncertain. The objective of this study is to describe the study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients (SAVE-O2) clinical trial. METHODS: Design, setting, and participants: Protocol for a multicenter cluster randomized, stepped wedge implementation trial evaluating the effectiveness of a multimodal intervention to target normoxia in critically ill trauma patients at eight level 1 trauma centers in the USA. Each hospital will contribute pre-implementation (control) and post-implementation (intervention) data. All sites will begin in the control phase with usual care. When sites reach their randomly assigned time to transition, there will be a one-month training period, which does not contribute to data collection. Following the 1-month training period, the site will remain in the intervention phase for the duration of the trial. MAIN OUTCOME MEASURES: The primary outcome will be supplemental oxygen-free days, defined as the number of days alive and not on supplemental oxygen. Secondary outcomes include in-hospital mortality to day 90, hospital-free days to day 90, ventilator-free days (VFD) to day 28, time to room air, Glasgow Outcome Score (GOS), and duration of time receiving supplemental oxygen. DISCUSSION: SAVE-O2 will determine if a multimodal intervention to improve compliance with targeted normoxia will safely reduce the need for concentrated oxygen for critically injured trauma patients. These data will inform military stakeholders regarding oxygen requirements for critically injured warfighters, while reducing logistical burden in prolonged combat casualty care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04534959 . Registered September 1, 2020.

Association Between Hyperoxia, Supplemental Oxygen, and Mortality in Critically Injured Patients.

OBJECTIVES: Hyperoxia is common among critically ill patients and may increase morbidity and mortality. However, limited evidence exists for critically injured patients. The objective of this study was to determine the association between hyperoxia and in-hospital mortality in adult trauma patients requiring ICU admission. DESIGN SETTING AND PARTICIPANTS: This multicenter, retrospective cohort study was conducted at two level I trauma centers and one level II trauma center in CO between October 2015 and June 2018. All adult trauma patients requiring ICU admission within 24 hours of emergency department arrival were eligible. The primary exposure was oxygenation during the first 7 days of hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days and ventilator-free days. We included 3,464 critically injured patients with a mean age of 52.6 years. Sixty-five percent were male, and 66% had blunt trauma mechanism of injury. The primary outcome of in-hospital mortality occurred in 264 patients (7.6%). Of 226,057 patient-hours, 46% were spent in hyperoxia (oxygen saturation > 96%) and 52% in normoxia (oxygen saturation 90-96%). During periods of hyperoxia, the adjusted risk for mortality was higher with greater oxygen administration. At oxygen saturation of 100%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 6.4 (3.5-11.8), 5.4 (3.4-8.6), 2.7 (1.7-4.1), and 1.5 (1.1-2.2), respectively. At oxygen saturation of 98%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 7.7 (4.3-13.5), 6.3 (4.1-9.7), 3.2 (2.2-4.8), and 1.9 (1.4-2.7), respectively. CONCLUSIONS: During hyperoxia, higher oxygen administration was independently associated with a greater risk of mortality among critically injured patients. Level of evidence: Cohort study, level III.

A quasiexperimental study of targeted normoxia in critically ill trauma patients.

BACKGROUND: Avoidance of hypoxia and hyperoxia may reduce morbidity and mortality in critically ill civilian and military trauma patients. The objective of this study was to determine if a multimodal quality improvement intervention increases adherence to a consensus-based, targeted normoxia strategy. We hypothesized that this intervention would safely improve compliance with targeted normoxia. METHODS: This is a pre/postquasiexperimental pilot study to improve adherence to normoxia, defined as a pulse oximetry (SpO2) of 90% to 96% or an arterial partial pressure oxygen (PaO2) of 60 to 100 mm Hg. We used a multimodal informatics and educational intervention guiding clinicians to safely titrate supplemental oxygen to normoxia based on SpO2 monitoring in critically ill trauma patients admitted to the surgical-trauma or neurosurgical intensive care unit within 24 hours of emergency department arrival. The primary outcome was effectiveness in delivering targeted normoxia (i.e., an increase in the probability of being in the targeted normoxia range and/or a reduction in the probability of being on a higher fraction-inspired oxygen concentration [FiO2]). RESULTS: Analysis included 371 preintervention subjects and 201 postintervention subjects. Preintervention and postintervention subjects were of similar age, race/ethnicity, and sex and had similar comorbidities and Acute Physiologic and Chronic Health Evaluation II scores. Overall, the adjusted probability of being hyperoxic while on supplemental oxygen was reduced during the postintervention period (adjusted odds ratio, 0.74; 95% confidence interval, 0.57-0.97). There was a higher probability of being on room air (FiO2, 0.21) in the postintervention period (adjusted odds ratio, 1.38; 95% confidence interval, 0.83-2.30). In addition, there was a decreased amount of patient time spent on higher levels of FiO2 (FiO2, >40%) without a concomitant increase in hypoxia. CONCLUSION: A multimodal intervention targeting normoxia in critically ill trauma patients increased normoxia and lowered the use of supplemental oxygen. A large clinical trial is needed to validate the impact of this protocol on patient-centered clinical outcomes. LEVEL OF EVIDENCE: Therapeutic/care management, level II.

Association Between Chronic Inflammatory Diseases and Stroke-Associated Pneumonia - An Epidemiological Study.

BACKGROUND: Pneumonia, the most common post-acute ischemic stroke (AIS) infection, accounts for up to 30% of deaths after a stroke. Multiple chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, are associated with increased risk of stroke and stroke morbidity. This study assessed the relationship between chronic inflammatory diseases and stroke-associated pneumonia (SAP). METHODS: Using data from the 2015-2017 National Inpatient Sample, we classified hospital discharges with a diagnosis of AIS as having ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, other chronic inflammatory diseases, multiple chronic inflammatory diseases, or none. With multivariable logistic regression, we assessed for associations between chronic inflammatory disease and in-hospital SAP or death. RESULTS: Among AIS discharges, there was a decreased risk of SAP among those with psoriasis or other chronic inflammatory diseases (adjusted odds ratio (aOR) 0.70, 95%CI 0.63-0.99; aOR 0.64, 95%CI, 0.46-0.89, respectively), compared to those without psoriasis and without other chronic inflammatory disease, respectively. Rheumatoid arthritis, psoriasis, and other chronic inflammatory diseases were associated with reduced in-hospital mortality (aOR 0.89, 95%CI 0.78-1.00; aOR 0.77, 95%CI 0.59-1.00; aOR 0.69, 95%CI 0.50-0.94, respectively). CONCLUSIONS: The risk of SAP and in-hospital mortality varies by chronic inflammatory disease - psoriasis and other chronic inflammatory diseases are associate with reduced rates of SAP, whereas rheumatoid arthritis, psoriasis and other chronic inflammatory disease were associated with reduced in-hospital mortality. Further investigations are needed to determine a relationship between the potential role of immunomodulation and the reduction in SAP and mortality in chronic inflammatory diseases.

Retrospective analysis of the hemodynamic consequences of prehospital supplemental oxygen in acute stroke.

OBJECTIVE: Hyperoxia, the delivery of high levels of supplemental oxygen (sO2) despite normoxia, may increase cerebral oxygenation to penumbral tissue and improve stroke outcomes. However, it may also alter peripheral hemodynamic profiles with potential negative effects on cerebral blood flow (CBF). This study examines the hemodynamic consequences of prehospital sO2 in stroke. METHODS: A retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017 was conducted using demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records. Outcomes were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariable linear regression were used to determine if sO2 was associated with differences in peripheral hemodynamic profiles. RESULTS: All subjects had similar initial EMS vitals except for oxygen saturation. However, both univariate and multivariable analysis revealed that hyperoxia subjects had slightly lower average ED mean arterial pressures (MAP) compared to normoxia (Cohen's d = 0.313). CONCLUSIONS: Prehospital-initiated hyperoxia for acute stroke is associated with a small, but significant decrease in average ED MAP, without changes in heart rate, compared to normoxia. While limited by the inability to link changes in peripheral hemodynamical profiles directly to changes in CBF, this study suggests that hyperoxia may result in a relative hypotension. Further studies are needed to determine if this small change in peripheral vascular resistance translates into a clinically significant reduced CBF.

Prehospital supplemental oxygen for acute stroke - A retrospective analysis.

OBJECTIVE: Brief early administration of supplemental oxygen (sO2) to create hyperoxia may increase oxygenation to penumbral tissue and improve stroke outcomes. Hyperoxia may also result in respiratory compromise and vasoconstriction leading to worse outcomes. This study examines the effects of prehospital sO2 in stroke. METHODS: This is a retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017. Demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariate logistic regression were used to determine if sO2 status was associated with neurological outcomes or respiratory complications. RESULTS: 1352 eligible patients were identified. 62.7% (n = 848) did not receive sO2 ("controls"), 10.7% (n = 144) received sO2 due to hypoxia ("hypoxia"), and 26.6% (n = 360) received sO2 despite normoxia ("hyperoxia"). The groups represented a continuum from more severe deficits (hypoxia) to less severe deficits (controls): mean prehospital GCS (hypoxia -12, hyperoxia - 2, controls - 14 p ≤ 0.001), mean initial NIHSS (hypoxia - 15, hyperoxia - 13, controls - 8 p < 0.001). After controlling for potential confounders, all groups had similar rates of respiratory complications and favorable neurological outcomes. CONCLUSIONS: Hyperoxic subjects had no significant increase in respiratory complications, nor did they differ in neurologic outcomes at discharge when controlling for confounders. While limited by the retrospective nature, this suggests brief, early sO2 for stroke may be safe to evaluate prospectively.

Dexamethasone-Related Perineal Burning in the Prehospital Setting: A Case Series.

Dexamethasone is frequently used in the treatment of allergic reactions and airway inflammation because of its potent anti-inflammatory effects and long duration of action. As prehospital use becomes more common, it is important for providers to be aware of unique and potentially distressing associated adverse effects. We report eight cases of intravenous dexamethasone administration associated with perineal or diffuse burning sensation in female patients.