First-Time Seizure Patients have High Rate of Abnormalities on Emergency Department Performed Brain Computed Tomography: A Prospective Study.

BACKGROUND: First-time seizures comprise 15% to 35% of all seizure-related complaints in the emergency department (ED). Emergent neuroimaging of first-time seizure patients is recommended by both the American Academy of Neurology and American College of Emergency Physicians. However, most of these studies are over 10 years old and included both adults and children. OBJECTIVES: The goal of this investigation is to determine the rate of abnormal neuroimaging in adults with first-time seizures presenting to the ED during the current era. METHODS: This was a prospective observational study of patients presenting to three urban EDs with a chief complaint of seizure over 18 months. Abnormal neuroimaging findings were defined a priori and were dichotomized into acute and subacute/chronic categories. RESULTS: Of the 2505 patients who presented with a seizure, 242 patients (9.7%) presented with a first-time seizure. The most common etiologies for first-time seizures were drug intoxication and drug withdrawal. Of those 242 patients, 29 (11.9%) patients had abnormal findings on brain computed tomography (CT). Brain CT demonstrated an acute finding in 13 (45%) patients and a subacute/chronic finding in 16 (55%) patients. The most common abnormality overall and the most common chronic finding was ischemic changes. The most common acute findings were traumatic intracranial hemorrhage and intracranial metastases. CONCLUSIONS: This study demonstrated that 11.9% of first-time seizure patients presenting to the ED had abnormal findings on neuroimaging. Our findings support current recommendations to obtain emergent neuroimaging for adult patients with first-time seizures.

Acute Epiglottitis Secondary to the Severe Acute Respiratory Syndrome Coronavirus 2: A Case Report.

INTRODUCTION: Acute epiglottis is a rapidly progressive, potentially life-threatening infection causing inflammation of the epiglottis and adjacent supraglottic structures.- Since the introduction of the Haemophilus influenzae vaccine, the incidence of pediatric cases has decreased dramatically while adult instances have increased. Likewise, the etiology has changed considerably with the increasing prevalence of other causative bacterial and viral pathogens. CASE REPORT: We present a novel case of acute epiglottis secondary to infection with the severe acute respiratory syndrome coronavirus 2. This case report highlights the changing landscape of epiglottitis and the importance of airway assessment. CONCLUSION: Present-day epiglottitis differs greatly from our traditional understanding. Numerous etiologies beyond Haemophilus influenzae now afflict adults predominately. As a clinically significant, novel complication of coronavirus disease 2019, acute epiglottitis is a life-threatening airway emergency. Emergency physicians must maintain a high index of suspicion, especially given the evolving clinical landscape. Early airway assessment with nasopharyngolaryngoscopic is critical.

The LIMIT-NI clinical decision instrument reduces neuroimaging compared to unstructured clinician judgement in recurrent seizure patients.

OBJECTIVE: The LIMIT clinical decision instrument (CDI) was published in 2021 to safely reduce neuroimaging in patients with recurrent seizures. The LIMIT CDI had a sensitivity of 90%, negative predictive value of >99.9%, and reduced neuroimaging by 13.3%. However, the design of the original LIMIT CDI made it cumbersome to use. The goal of this study was to validate the streamlined LIMIT-NeuroImaging (LIMIT-NI) CDI and compare its performance to the original LIMIT CDI. METHODS: This was an observational study of patients presenting to three emergency departments with recurrent seizures. The LIMIT-NI CDI was applied to all patients. We calculated the test characteristics of the LIMIT-NI CDI and compared it to unstructured clinical judgement. RESULTS: 3401 patients were screened, and 2125 patients were included in the final analysis. 16 patients (0.75%) had positive CTs; Both the LIMIT-NI CDI and clinician judgement identified all 16 patients with a sensitivity of 100.0% and a negative predictive value of 100.0%. Using unstructured clinical judgement, emergency providers ordered 835 brain CTs, while only 499 brain CTs would have been ordered using the CDI, a reduction of 15.8% (relative reduction 40.2%). CONCLUSION: The LIMIT-NI CDI demonstrated greater ease of application and improved test characteristics compared to the original LIMIT CDI. Compared to unstructured clinician judgement, the LIMIT-NI CDI reduced neuroimaging by 15.8% (relative reduction 40.2%) in recurrent seizure patients. The LIMIT-NI CDI can be used by physicians along with clinical judgement to reduce neuroimaging in the recurrent seizure patient.

The LIMIT clinical decision instrument reduces neuroimaging compared to unstructured clinician judgement in recurrent seizures.

INTRODUCTION: Given the many causes of seizures, emergency physicians often utilize brain computed tomography (CT) to evaluate for intracranial pathology. Previously, we have validated the LIMIT (Let's Image Malignancy, Intracranial Hemorrhage, and Trauma) clinical decision instrument (CDI) study to determine which patients with recurrent seizures require emergent neuroimaging. The LIMIT CDI had a negative predictive value (NPV) of 99.9%. Here, we seek to compare the LIMIT CDI to unstructured physician judgement. METHODS: This was an observational study of patients who presented with a complaint of seizure. A research assistant reviewed the electronic medical record (EMR) for each patient and applied the LIMIT CDI. Brain CT was used as a proxy for physician judgement. If no brain CT was ordered and the patient was discharged from the emergency department (ED), the EMR was searched to determine whether patient had any medical visits within one year of the index visit. If the patient had no new neurological findings on follow up or abnormalities on follow up neuroimaging, this was considered a patient who did not require a brain CT in the ED. Patients who did not have a CT on their ED visit and had no follow up visits were excluded. RESULTS: 1739 patients were screened and 1108 patients were in the final analysis. 24 patients who did not have a brain CT and no follow up visits were excluded. 10 patients (0.9%) had positive CTs. 9/10 of the patients were identified by the CDI resulting in a sensitivity of 90%, specificity of 81.1% and a negative predictive value (NPV) of 99.9%, and a negative likelihood ratio (LR) of 0.12. Clinician judgement identified all 10 patients with a positive brain CT for a sensitivity of 100%, specificity of 67.8%, and a NPV and negative LR of 100% and 0, respectively. Using unstructured clinical judgement, EPs ordered 364 brain CTs while only 217 brain CTs would have been ordered using the CDI, a reduction of 13.3%. DISCUSSION: When compared to unstructured physician judgement, the LIMIT CDI would have reduced brain CT usage by more than 13%. Although the LIMIT CDI needs to be validated in a larger set of patients, it performed better than unstructured physician judgement for evaluating need for emergent neuroimaging after recurrent seizures.

Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation.

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.