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FACE DROPS a Clinical Risk Assessment Tool for Differentiation of Acute Lyme Disease–Associated Facial Palsy From Bell Palsy
No full textBackground and Objectives Facial palsy is a common manifestation of Lyme disease, accounting for up to 5% of acute facial palsies in endemic regions. Lyme disease–associated facial palsy (LDFP) warrants prompt antibiotic therapy while corticosteroid therapy is indicated for Bell palsy. The role of adjuvant corticosteroids in the treatment of acute LDFP is unclear. Current limitations of diagnostic laboratory tests for Lyme disease render acute differentiation of LDFP and BP challenging in many cases. Methods We reviewed records from 285 patients with LDFP (N = 76) and BP (N = 209) referred to a specialized facial nerve center from 2005 to 2021 to determine clinical characteristics at time of presentation to medical care. We developed and internally validated a clinical risk assessment tool (“FACE DROPS”) based on pertinent differences between signs and symptoms of LDFP and BP at presentation. Results The risk assessment tool distinguishes LDFP from BP using 7 clinical criteria: fever (+8 to FACE DROPS score), aches (arthralgia/myalgia; +6), cephalalgia (headache; +3), exhaustion (unusual fatigue; +4), dermatomal or radicular pattern (transverse myelitis or radiculitis; +4), otalgia or postauricular pain (−1), and stiff neck (nuchal rigidity; +3). FACE DROPS scores ≤4 predicted BP with ≥93.5% accuracy while scores of ≥7 predicted LDFP with ≥96.0% accuracy. Discussion A novel risk assessment tool to distinguish LDFP from BP was developed. This tool may help guide the prescribing of antimicrobials for Lyme disease in the setting of acute facial palsy pending confirmatory laboratory evidence in the absence of an erythema migrans skin lesion
Cerebrovascular Health Among Sex- and Gender-Diverse People: A Narrative Review
No full textPurpose of ReviewSex and gender diversity includes people who are intersex, transgender, and nonbinary. Americans are identifying as sex and gender diverse (SGD) in increasing numbers. Although data are limited on the diagnosis and management of stroke in SGD communities, the current literature suggests that there may be unique health needs among these marginalized populations.Recent FindingsHealth disparities and community-specific stressors may influence the frequency of stroke and traditional cerebrovascular disease risk factors among SGD people. In addition, transgender and gender-diverse people have higher rates of atypical stroke risk factors, such as sexually transmitted infections and an increased mental health burden. The adverse effects of some gender-affirming therapies can increase the rates of stroke, particularly in transfeminine people who use long-term estrogen as part of their medical gender transition. Decisions to discontinue hormonal therapy after stroke should be weighed against the psychological risks of doing so. In addition, some commonly prescribed medications for stroke prevention could interact with gender-affirming hormone therapies. Neurologists should collaborate with primary care providers and endocrinologists to screen for and manage cerebrovascular disease risk factors for the primary and secondary prevention of stroke. Limited evidence suggests intersex people may be at higher risk of cerebrovascular disease, particularly those with congenital adrenal hyperplasia (CAH). People diagnosed with CAH have unique risk factors of stroke including treatment with stress-dose corticosteroids or polycythemia due to hyperandrogenism.SummaryCreating affirming environments and increasing knowledge of health care for SGD communities may lead to improved equitable treatment of SGD patients with stroke by increasing community trust in health providers and incorporating use of best practices in clinical care and research settings. Limited data exist on stroke clinical presentations and how stroke is experienced and treated among SGD people, particularly among those with multiple marginalized identities, those presenting with acute stroke, and those requiring secondary stroke prevention
Impact of Prior Antiplatelet Therapy on Safety and Efficacy of Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
No full textBackground: Intravenous thrombolysis (IVT), utilizing the clot-dissolving medications alteplase (rt-PA) or tenecteplase (TNK), is the cornerstone in acute ischemic stroke (AIS) emergency intervention. However, the impact of prior antiplatelet therapy (APT) on post-IVT outcomes when utilizing alteplase remains controversial. We conducted a systematic review and meta-analysis to evaluate the effect of prior APT on the outcomes after using alteplase in AIS patients. Methods: We conducted a systematic review and meta-analysis synthesizing studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through June 30, 2024. We used the R language V. 4.3. to pool dichotomous data using odds ratio (OR) with a 95% confidence interval (CI). PROSPERO ID: CRD42024495393. Results: Thirty studies were included in our analysis, with 436,232 patients. Prior APT was significantly associated with increased odds of symptomatic intracranial hemorrhage (sICH) (OR, 1.78; 95%CI [1.48, 2.13]; P \u3c 0.01), any ICH (OR, 1.44; 95%CI [1.16, 1.78]; P \u3c 0.01), mortality (OR, 1.39; 95%CI [1.23, 1.58]; P \u3c 0.01), and poor functional outcomes (modified Rankin Scale score of 3–6 [mRS 3–6]) (OR, 1.81; 95%CI [1.03, 3.19]; P = 0.04). Additionally, prior APT significantly reduced the odds of good functional outcome [mRS 0–2] (OR, 0.85; 95%CI [0.74, 0.97]; P = 0.02). Conclusion: Prior APT increased hemorrhagic complications, mortality, and poor functional outcome, while reducing the odds of good functional outcome after IV alteplase. Future research should focus on identifying adjunctive agents that may decrease hemorrhagic complications and investigate the impact of various APT regimens and alternative thrombolytics beyond alteplase in this specific population
Combinatorial Immunotherapy With Anti-ROR1 CAR NK Cells and an IL-21 Secreting Oncolytic Virus Against Neuroblastoma
No full textChildren with recurrent/metastatic neuroblastoma (NB) have a dismal survival (\u3c25%). Novel therapies are desperately needed. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed on NB. C021 is a selective oncolytic herpes simplex virus modified to overexpress human interleukin-21 (hIL-21), a cytokine that enhances natural killer (NK) cell cytotoxicity. In the current study, we successfully engineered ex-vivo-expanded NK cells to express a chimeric antigen receptor (CAR) against ROR1 using mRNA electroporation and investigated the efficacy of anti-ROR1-CAR-NK cells combined with C021 in targeting ROR1+ NB. We found that C021-infected NB cells secreted hIL-21 in vitro and in vivo. Compared to the non-cytokine-secreting parental virus C134, C021 significantly enhanced the in vitro cytotoxicity (p \u3c 0.05) of anti-ROR1-CAR-NK cells with increased interferon (IFN)-γ (p \u3c 0.05), granzyme B (p \u3c 0.05), and perforin (p \u3c 0.05) secretion against NB cells. Furthermore, the combination of C021 and anti-ROR1-CAR-NK cells significantly extended the survival of human NB xenografted NSG mice compared to controls (mock NK, ROR1-CAR-NK, C134, C021, C134+ROR1-CAR-NK, and C021+mock NK). Our results suggest that cytokine-secreting oncolytic virus in combination with CAR-NK cells is a novel, effective immunotherapeutic approach for high-risk NB
Advances of the Exposome at Individual Levels and Prevention in Atopic Dermatitis
No full textAtopic dermatitis (AD), or eczema, is an inflammatory skin disease related to environmental factors. As a heterogeneous disease, it presents with complex phenotypes and endotypes. A variety of intrinsic and extrinsic factors can promote the development of AD. While there has been extensive discussion on environmental exposure at the population and community levels, discourse on exposome at individual levels in AD remains insufficient. For example, allergens, microorganisms, parasites, dietary factors, and psychological factors such as stress and anxiety play important roles in AD development. Microorganisms, in particular, exhibit altered composition and diversity on the skin of AD patients, influencing skin barrier integrity and immune responses. The impact of certain microorganisms, such as fungi and viruses, on AD has garnered increasing attention because of their important role in maintaining skin homeostasis. Dietary factors, including sugar intake and histamine-rich foods, may modulate AD risk and severity, although findings are controversial. Allergens, particularly house dust mite allergens, and aeroallergens, exacerbate AD symptoms by promoting inflammation and barrier dysfunction. Since AD is often the first step in the atopic march, its primary prevention measures are crucial. Some preventive measures involving microorganisms, diet, and moisturizers remain controversial. Effective preventive strategies necessitate a clear understanding of the complex mechanisms of AD, especially host–microbe–environment interactions. This review summarizes recent advances in understanding various risk and protective factors, as well as primary prevention measures for AD
Recommendations for Aligned Nomenclature of Peripheral Nervous System Disorders Across Rheumatology and Neurology
No full textFlowtriever System for Pulmonary Embolism a Review of Clinical Evidence
No full textPulmonary embolism (PE) is a significant cause of cardiovascular mortality, and its incidence has been increasing due to the growing aging population. Systemic or catheter-directed thrombolytic treatment for PE has an increased risk of bleeding that may offset the benefit in some patients. Mechanical thrombectomy devices such as the FlowTriever System are designed to resolve vascular occlusion and correct ventilation-perfusion mismatch without the need for thrombolytic drugs. This review covers the FlowTriever system, clinical data from the FlowTriever Pulmonary Embolectomy Clinical Study, FlowTriever for Acute Massive Pulmonary Embolism, and FlowTriever All-comer Registry for Patient Safety and Hemodynamics trials, and real-world experiences, demonstrating its safety and effectiveness in treating intermediate-risk and high-risk PE. Additionally, we explore off-label uses of the FlowTriever System for various large vessel thromboses
Correction To: Efficacy of Xanomeline and Trospium Chloride in Schizophrenia: Pooled Results From Three 5-Week, Randomized, Double-Blind, Placebo-Controlled, EMERGENT Trials (Schizophrenia, (2024), 10, 1, (102), 10.1038/S41537-024-00525-6)
No full textCorrection to: Schizophreniahttps://doi.org/10.1038/s41537-024-00525-6, published online 02 November 2024 In the original version of this article, in Table 2, the difference for the PANSS total score was incorrect and should have been −9.9. In the methods section under “Statistical methods,” the text should have read: “participants who received ≥1 dose of study medication and had a baseline and at…”. Additionally, the text should have read: “..treatment groups and visit, baseline PANSS total score, age, sex, and trial…”. In the results section under “Efficacy,” the PANSS positive subscale data should have been formatted as “PANSS positive subscale score (95% CI –4.1, –2.4; p \u3c 0.0001;…)”. This has been corrected in the original article
The Etiology of Ige-Mediated Food Allergy: Potential Therapeutics and Challenges
No full textImmunoglobulin E (IgE)-mediated food allergy has been dramatically increasing in incidence over the last few decades. The combinations of both genetic and environmental factors that affect the microbiome and immune system have demonstrated significant roles in its pathogenesis. The morbidity, and at times mortality, that occurs as the result of this specific, reproducible, but impaired immune response is due to the nature of the shift from a regulatory T (Treg) cellular response to a T helper 2 (Th2) cellular response. This imbalance caused by food allergens results in an interleukin (IL)-4 and IL-13 dominant environment that drives B cell activation and differentiation into IgE-producing plasma cells. The resulting symptoms can range from mild to more severe anaphylaxis, and even death. Current therapeutic strategies involve avoidance and broad symptom management upon accidental exposure; however, no definitive cure exists. This narrative review highlights how the elucidation of the pathogenesis of IgE-mediated food allergy resulted in the development of therapeutics that are more specific to these individual receptors and molecules which have been relatively successful in mitigating this potentially life-threatening allergic response. However, potential adverse effects and re-sensitization following the conclusion of treatment has urged the need for improved therapeutic methods. Therefore, given the understanding of their mechanism of action and the overlap with the mechanism of IgE-mediated food allergies, probiotics and small molecule natural compounds may provide novel therapeutic and preventative strategies. This is compelling, as they have demonstrated success in clinical trials and may provide hope to improve quality of life in allergy patients