Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti-inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

During pathological pain, the actions of the endocannabinoid system, including the cannabinoid 2 receptor (CB2R), leads to effective anti-allodynia and modifies a variety of spinal microglial and astrocyte responses. Here, following spinal administration of the CB2R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen-activated protein kinase, interleukin-1β (IL-1β), the anti-inflammatory cytokine, interleukin-10 (IL-10) as well as degradative endocannabinoid enzymes, and markers for altered glial responses in neuropathic rats. In these studies, the dorsal horn of the spinal cord and dorsal root ganglia were examined. AM1241 produced profound anti-allodynia with corresponding immunoreactive levels of p38 mitogen-activated kinase, IL-1β, IL-10, the endocannabinoid enzyme monoacylglycerol lipase, and astrocyte activation markers that were similar to nonneuropathic controls. In contrast, spinal AM1241 did not suppress the increased microglial responses observed in neuropathic rats. The differences in fluorescent markers were determined within discrete anatomical regions by applying spectral analysis methods, which virtually eliminated nonspecific signal during the quantification of specific immunofluorescent intensity. These data reveal expression profiles that support the actions of intrathecal AM1241 control pathological pain through anti-inflammatory mechanisms by modulating critical glial factors, and additionally decrease expression levels of endocannabinoid degradative enzymes

Angioedema Secondary to Tenecteplase Use in a Patient with Acute Ischemic Stroke: A Case Report

Introduction: Angioedema, a swelling of the subcutaneous or submucosal layers of the skin or gastrointestinal tract, is a potential complication to thrombolytic therapy in the treatment of acute ischemic strokes. In these cases, angioedema develops due to increased levels of bradykinin as a result of the activation of the fibrinolytic pathway and contact activation system. Angioedema can involve the tongue, larynx, and vocal cords, leading to occlusion of the airway and death due to asphyxiation. It is vital for the emergency physician to know that this complication can occur to ensure appropriate monitoring for development of angioedema. Case Report: We report the case of a 65-year-old Black man who presented with signs of an acute ischemic stroke and was treated with tenecteplase. The patient’s stroke symptoms mostly resolved within 90 minutes; however, he developed swelling of his right upper lip consistent with angioedema. The patient was treated with steroids and antihistamines. He was closely monitored and did not require airway intervention. The angioedema was almost fully resolved by the following day. Conclusion: Angioedema is a known complication of thrombolytic therapy for acute ischemic stroke. Risk factors for alteplase-associated angioedema include use of angiotensin-converting enzyme inhibitors, female gender, diabetes, and infarcts of the insula and frontal cortex. As hospital systems switch from alteplase to tenecteplase for the treatment of acute ischemic strokes for reasons of cost and ease of administration, it is important to recognize that angioedema is also a potential complication of tenecteplase

Race differences in cardiac testing rates for patients with chest pain in a multisite cohort

BACKGROUND: Identifying and eliminating racial health care disparities is a public health priority. However, data evaluating race differences in emergency department (ED) chest pain care are limited. METHODS: We conducted a secondary analysis of the High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP) cohort, which prospectively enrolled adults with symptoms suggestive of acute coronary syndrome without ST-elevation from eight EDs in the United States from 2017 to 2018. Race was self-reported by patients and abstracted from health records. Rates of 30-day noninvasive testing (NIT), cardiac catheterization, revascularization, and adjudicated cardiac death or myocardial infarction (MI) were determined. Logistic regression was used to evaluate the association between race and 30-day outcomes with and without adjustment for potential confounders. RESULTS: Among 1454 participants, 42.3% (615/1454) were non-White. At 30 days NIT occurred in 31.4% (457/1454), cardiac catheterization in 13.5% (197/1454), revascularization in 6.0% (87/1454), and cardiac death or MI in 13.1% (190/1454). Among Whites versus non-Whites, NIT occurred in 33.8% (284/839) versus 28.1% (173/615; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.96) and catheterization in 15.9% (133/839) versus 10.4% (64/615; OR 0.62, 95% CI 0.45-0.84). After covariates were adjusted for, non-White race remained associated with decreased 30-day NIT (adjusted OR [aOR] 0.71, 95% CI 0.56-0.90) and cardiac catheterization (aOR 0.62, 95% CI 0.43-0.88). Revascularization occurred in 6.9% (58/839) of Whites versus 4.7% (29/615) of non-Whites (OR 0.67, 95% CI 0.42-1.04). Cardiac death or MI at 30 days occurred in 14.2% of Whites (119/839) versus 11.5% (71/615) of non-Whites (OR 0.79 95% CI 0.57-1.08). After adjustment there was still no association between race and 30-day revascularization (aOR 0.74, 95% CI 0.45-1.20) or cardiac death or MI (aOR 0.74, 95% CI 0.50-1.09). CONCLUSIONS: In this U.S. cohort, non-White patients were less likely to receive NIT and cardiac catheterization compared to Whites but had similar rates of revascularization and cardiac death or MI

Sex and race differences in the performance of the European Society of Cardiology 0/1‐h algorithm with high‐sensitivity troponin T

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs <99% in each subgroup suggest the hs-cTnT ESC 0/1-h algorithm may not be safe for use in US EDs. Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436)

Derivation and validation of a high sensitivity troponin-T HEART pathway

BACKGROUND: The HEART Pathway is widely used for chest pain risk stratification but has yet to be optimized for high sensitivity troponin T (hs-cTnT) assays. METHODS: We conducted a secondary analysis of STOP-CP, a prospective cohort study enrolling adult ED patients with symptoms suggestive of acute coronary syndrome at 8 sites in the United States (US). Patients had a 0- and 1-hour hs-cTnT measured and a HEAR score completed. A derivation set consisting of 729 randomly selected participants was used to derive a hs-cTnT HEART Pathway with rule-out, observation, and rule-in groups for 30-day cardiac death or myocardial infarction (MI). Optimal baseline and 1-hour troponin cutoffs were selected using generalized cross validation to achieve a negative predictive value (NPV) \u3e99% for rule out and positive predictive value (PPV) \u3e60% or maximum Youden index for rule-in. Optimal 0-1-hour delta values were derived using generalized cross validation to maximize the NPV for the rule-out group and PPV for the rule-in group. The hs-cTnT HEART Pathway performance was validated in the remaining cohort (n = 723). RESULTS: Among the 1452 patients, 30-day cardiac death or MI occurred in 12.7% (184/1452). Within the derivation cohort the optimal hs-cTnT HEART Pathway classified 36.5% (266/729) into the rule-out group, yielding a NPV of 99.2% (95% CI: 98.2-100) for 30-day cardiac death or MI. The rule-in group included 15.4% (112/729) with a PPV of 55.4% (95% CI: 46.2-64.6). In the validation cohort, the hs-cTnT HEART Pathway ruled-out 37.6% (272/723), of which 2 had 30-day cardiac death or MI, yielding a NPV of 99.3% (95% CI: 98.3-100). The rule-in group included 14.5% (105/723), yielding a PPV of 57.1% (95% CI: 47.7-66.6). CONCLUSIONS: A novel hs-cTnT HEART Pathway with serial 0- and 1-hour hs-cTnT measures has high NPV and moderate PPV for 30-day cardiac death or MI

Diagnostic Performance of High Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite United States Cohort

Background: European data support the use of low high-sensitivity troponin (hs-cTn) measurements or a 0/1-hour (0/1-h) algorithm for myocardial infarction (MI) or to exclude major adverse cardiac events (MACE) among Emergency Department (ED) patients with possible acute coronary syndrome (ACS). However, modest US data exist to validate these strategies. This study evaluated the diagnostic performance of an initial hs-cTnT measure below the limit of quantification (LOQ: 6 ng/L), a 0/1-h algorithm, and their combination with HEART scores for excluding MACE in a multisite US cohort. Methods: A prospective cohort study was conducted at 8 US sites, enrolling adult ED patients with symptoms suggestive of ACS and without ST-elevation on electrocardiogram. Baseline and 1-hour blood samples were collected and hs-cTnT (Roche, Basel Switzerland) measured. Treating providers blinded to hs-cTnT results prospectively calculated HEART scores. MACE (cardiac death, MI, and coronary revascularization) at 30-days was adjudicated. The proportion of patients with initial hs-cTnT measures Results: Among 1,462 participants with initial hs-cTnT measures, 46.4% (678/1,462) were women and 37.1% (542/1,462) were African American with a mean age of 57.6 (SD±12.9) years. MACE at 30-days occurred in 14.4% (210/1,462). Initial hs-cTnT measures Conclusions: In a prospective multisite US cohort, an initial hs-cTnT 99% for 30-day MACE when used alone or with a HEART score

Performance of the European Society of Cardiology 0/1-Hour Algorithm With High-Sensitivity Cardiac Troponin T Among Patients With Known Coronary Artery Disease

IMPORTANCE: The European Society of Cardiology (ESC) 0/1-hour algorithm is a validated high-sensitivity cardiac troponin (hs-cTn) protocol for emergency department patients with possible acute coronary syndrome. However, limited data exist regarding its performance in patients with known coronary artery disease (CAD; prior myocardial infarction [MI], coronary revascularization, or ≥70% coronary stenosis). OBJECTIVE: To evaluate and compare the diagnostic performance of the ESC 0/1-hour algorithm for 30-day cardiac death or MI among patients with and without known CAD and determine if the algorithm could achieve the negative predictive value rule-out threshold of 99% or higher. DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned subgroup analysis of the STOP-CP prospective multisite cohort study, which was conducted from January 25, 2017, through September 6, 2018, at 8 emergency departments in the US. Patients 21 years or older with symptoms suggestive of acute coronary syndrome without ST-segment elevation on initial electrocardiogram were included. Analysis took place between February and December 2022. INTERVENTIONS/EXPOSURES: Participants with 0- and 1-hour high-sensitivity cardiac troponin T (hs-cTnT) measures were stratified into rule-out, observation, and rule-in zones using the ESC 0/1-hour hs-cTnT algorithm. MAIN OUTCOMES AND MEASURES: Cardiac death or MI at 30 days determined by expert adjudicators. RESULTS: During the study period, 1430 patients were accrued. In the cohort, 775 individuals (54.2%) were male, 826 (57.8%) were White, and the mean (SD) age was 57.6 (12.8) years. At 30 days, cardiac death or MI occurred in 183 participants (12.8%). Known CAD was present in 449 (31.4%). Among patients with known CAD, the ESC 0/1-hour algorithm classified 178 of 449 (39.6%) into the rule-out zone compared with 648 of 981 (66.1%) without CAD (P \u3c .001). Among rule-out zone patients, 30-day cardiac death or MI occurred in 6 of 178 patients (3.4%) with known CAD and 7 of 648 (1.1%) without CAD (P \u3c .001). The negative predictive value for 30-day cardiac death or MI was 96.6% (95% CI, 92.8-98.8) among patients with known CAD and 98.9% (95% CI, 97.8-99.6) in patients without known CAD (P = .04). CONCLUSIONS AND RELEVANCE: Among patients with known CAD, the ESC 0/1-hour hs-cTnT algorithm was unable to safely exclude 30-day cardiac death or MI. This suggests that clinicians should be cautious if using the algorithm in patients with known CAD. The negative predictive value was significantly higher in patients without a history of CAD but remained less than 99%

The Rapid Evaluation of COVID-19 Vaccination in Emergency Departments for Underserved Patients Study.

Study objectiveEmergency departments (EDs) often serve vulnerable populations who may lack primary care and have suffered disproportionate COVID-19 pandemic effects. Comparing patients having and lacking a regular source of medical care and other ED patient characteristics, we assessed COVID-19 vaccine hesitancy, reasons for not wanting the vaccine, perceived access to vaccine sites, and willingness to get the vaccine as part of ED care.MethodsThis was a cross-sectional survey conducted from December 10, 2020, to March 7, 2021, at 15 safety net US EDs. Primary outcomes were COVID-19 vaccine hesitancy, reasons for vaccine hesitancy, and sites (including EDs) for potential COVID-19 vaccine receipt.ResultsOf 2,575 patients approached, 2,301 (89.4%) participated. Of the 18.4% of respondents who lacked a regular source of medical care, 65% used the ED as their usual source of health care. The overall rate of vaccine hesitancy was 39%; the range among the 15 sites was 28% to 58%. Respondents who lacked a regular source of medical care were more commonly vaccine hesitant than those who had a regular source of medical care (47% versus 38%, 9% difference, 95% confidence interval 4% to 14%). Other characteristics associated with greater vaccine hesitancy were younger age, female sex, Black race, Latinx ethnicity, and not having received an influenza vaccine in the past 5 years. Of the 61% who would accept a COVID-19 vaccine, 21% stated that they lacked a primary physician or clinic at which to receive it; the vast majority (95%) of these respondents would accept the COVID-19 vaccine as part of their care in the ED.ConclusionED patients who lack a regular source of medical care are particularly hesitant regarding COVID-19 vaccination. Most COVID-19 vaccine acceptors would accept it as part of their care in the ED. EDs may play pivotal roles in COVID-19 vaccine messaging and delivery to highly vulnerable populations