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This case report describes a man in his 50s with type 2 diabetes and hyperlipidemia who was admitted for rash and proximal muscle weakness, pain, and unintentional 15-pound weight loss associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy.
Stroke, Volume 56, Issue Suppl_1, Page ATP304-ATP304, February 1, 2025. Introduction:Stroke is a common complication of infective endocarditis (IE), affecting 16–25% of cases, and can be the initial or sole manifestation of the condition. This study aims to analyze annual mortality trends and demographic factors related to stroke in IE patients in the U.S. and Texas from 1999 to 2020, to guide public health initiatives and enhance prevention strategies.Methods:The data was analyzed from the CDC’s WONDER database from 1999 to 2020, focusing on stroke and IE-related mortality (ICD-10 Code I64.0 “Stroke”&Code I33.0 “IE”) in adults aged ≥65 years, annual percent changes (APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex, race/ethnicity, age) subgroups was calculated.Results:The AAMR for stroke-related mortality in IE cases reduced in the US from an adjusted rate (AR) 448.7 in 1999 to 171.6 in 2018 (APC: -8.09%; 95% CI: -9.00% to -6.81%) and then it increased to 183.5 in 2020 (APC: 3.07%; 95% CI: 1.22% to 4.69%). In Texas, AAMR for stroke-associated IE-related mortality overall decreased from AR 485.7 in 1999 to 176.2 in 2020 (APC: -5.23%; 95% CI: -5.50% to -4.96%). Males had higher consistently higher AAMRs than females (196.4 vs. 172). The AAMR in the US men decreased from 468.6 in 1999 to 176.7 in 2018(APC: -7.55%; 95% CI: -8.51% to -6.21%), then it increased to 196.4 in 2020(APC: 4.99%; 95% CI: 2.93% to 6.81%). The AAMR in the US women decreased from 431.5 in 1999 to 165.6 in 2018(APC: -8.25%; 95% CI: -9.15% to -6.97%) after which it increased to 172 in 2020(APC: 1.48%; 95% CI: -0.31% to 3.06 %). The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (278.7), followed by the NH White with an AAMR (179) and the NH American Indian or Alaska Native population with an AAMR (165.4). The low-risk populations were the Hispanic or Latino (143.6) and the NH Asian or Pacific Islander (135.2). AAMR also varied by region (overall AAMR: Midwest: 200.8; South: 193.9; Northeast: 166.2; West: 162.8) and non-metropolitan areas had higher AAMR (non-core areas: 233.4; micropolitan areas: 224.5) than metropolitan areas (large fringe metro areas: 170.5; large central metropolitan areas:160.4).Conclusions:The stroke-related mortality in infective endocarditis cases has overall risen in the United States than in Texas over the past two decades, specifically men and (NH) Black or AA, (NH) White and (NH) American Indian or Alaska Native are at high risk.
Stroke, Volume 56, Issue Suppl_1, Page ATP142-ATP142, February 1, 2025. Introduction:Coronary atherosclerotic disease (CAD) carries the highest risk of recurrent stroke, up to 15% annually, and individuals with coronary heart disease are twice as likely to have a stroke. This study aims to analyze annual mortality trends and sociodemographic factors related to stroke in CAD patients in the U.S. and Texas from 1999 to 2020, to inform public health policies.Methods:Using the CDC’s WONDER database from 1999 to 2020, focusing on stroke and CAD-related mortality(ICD-10 code I64.0 “Stroke”&Code I25.1 “Atherosclerotic heart disease ”) in adults aged ≥45 years, annual percent changes(APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex, race/ethnicity, age) subgroups were calculated.Results:The AAMR for stroke-related mortality in CAD cases reduced in the US from an adjusted rate(AR) 174.5 in 1999 to 105.2 in 2009(APC: 5.48%; 95% CI: -6.09% to -5.24%) after which it reduced further to 69.4 in 2018(APC: -7.87%; 95% CI: -8.77% to -6.53%) then it increased to 75.9 in 2020(APC: 4.38%; 95% CI: 2.63% to 5.88%). In Texas, AAMR for stroke-associated CAD-related mortality overall decreased from AR 189.7 in 1999 to 73.5 in 2020(APC: -4.96%; 95% CI: -5.27% to -4.66%). Males had higher consistently higher AAMRs than females (83 vs. 69.5). The AAMR in the US men decreased from 183.7 in 1999 to 72.9 in 2018(APC: -7.23%; 95% CI: -8.22% to -5.92%), then it increased to 83 in 2020(APC: 6.40%; 95% CI: 4.31% to 8.19%). The AAMR in the US women decreased from 166.3 in 1999 to 65.7 in 2018(APC: -7.89%; 95% CI: -8.79% to -6.63%) after which it increased to 69.5 in 2020(APC: 2.38%; 95% CI: 0.49% to 4.06 %). The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (122), followed by the NH American Indian or Alaska Native with an AAMR (76.8) and the NH White population with an AAMR (72.9). The low-risk populations were the Hispanic or Latino (58.8) and the NH Asian or Pacific Islander (54.2). AAMR also varied by region (overall AAMR: Midwest: 82.1; South:82; Northeast:67.1; West:66.4)&non-metropolitan areas had higher AAMR (non-core areas:98.5; micropolitan areas:94) than metropolitan areas (large fringe areas:69.3; large central metropolitan areas:66.7).Conclusions:The stroke-related mortality in CAD cases has overall risen in the US compared to Texas over the past two decades, specifically men and (NH) Black or AA, (NH) American Indian or Alaska Native and (NH) White are at high risk.
Stroke, Volume 56, Issue Suppl_1, Page A55-A55, February 1, 2025. Introduction:Approved thrombolytic agents are currently only recommended for acute ischemic stroke (AIS) within 4.5 hours from the last known well (LKW). Hence, there remains an unmet need in the treatment of AIS for safer and more effective thrombolytics, which can also be administered to a broader population with an extended treatment window. JX10 is a novel thrombolytic that works by inducing conformational changes in plasminogen to increase downstream fibrin affinity and promote physiological fibrinolysis instead of direct plasminogen activation like that of tissue plasminogen activators (t-PA). JX10 also exerts anti-inflammatory activity through inhibition of soluble epoxide hydrolase, which may suppress hemorrhagic changes associated with cerebral infarction. In a randomized, double-blind, placebo-controlled, dose-escalation phase 2a study conducted in Japan, JX10 increased vessel recanalization and improved neurologic outcomes. This subgroup analysis evaluated the safety and efficacy of JX10 in participants who presented with acute lacunar infarct.Methods:JX10 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for tissue plasminogen activator or thrombectomy within 12 h of LKW. Safety and Efficacy outcomes were assessed at 90 days.Results:Among the 90 patients enrolled in the trial, a total of 25 patients with acute lacunar infarct were dosed (JX10 1 mg/kg group: 1 subject; 3 mg/kg group: 3 subjects; 6 mg/kg group: 7 subjects; and placebo group: 14 subjects). In the JX10 1, 3, 6 mg/kg, pooled groups, and the placebo group, the rates of mRS 0–1 were 0 subject out of 1 (0.0%), 1 subject out of 3 (33.3%), 3 subjects out of 7 (42.9%), 4 subjects out of 11 (36.4%), and 1 subject out of 14 (7.1%), respectively, and those of mRS 0–2 were 0 subjects out of 1 (0.0%), 3 subjects out of 3 (100.0%), 4 subject out of 7 (57.1%), 7 subjects out of 11 (63.6%), and 2 subjects out of 14 (14.3%), respectively. Despite small numbers, patients with acute lacunar infarct who were treated with JX10 showed trend of improved neurologic function at 90 days, as measured by mRS. Symptomatic intracranial hemorrhage was not observed in any JX10 treated patients.Conclusions:JX10 improved functional outcome in patients who presented with lacunar infarct, as measured by mRS at day 90 vs placebo. Findings support further testing of JX10 in larger and broader patient populations.
Stroke, Volume 56, Issue Suppl_1, Page AWP331-AWP331, February 1, 2025. Introduction:Stroke is the second leading cause of death worldwide,around 50,000 U.S. residents with valvular heart disease experiencing a stroke annually. This study examines trends in stroke-related mortality due to mitral valve disorders (MVD) in the U.S. from 1999 to 2020, with a focus on demographic factors and racial disparities. The goal is to inform public health strategies and improve prevention and treatment efforts.Methods:We analyzed death certificate data from the CDC’s WONDER database from 1999 to 2020, focusing on stroke and MVD-related mortality (ICD-10 code I64.0 “Stroke” and Code I34.0 “MVD”) in adults aged ≥25 years. Using joint point regression analysis, we calculated annual percent changes (APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex,race/ethnicity,age) subgroups.Results:The AAMR for stroke due to MVD-related mortality decreased in the US from an adjusted rate (AR) 98.6 in 1999 to 92.9 in 2001 (APC: -2.64%; 95% CI: -4.18% to -1.35%),after which it decreased to 59.6 in 2009 (APC: -5.47%; 95% CI: -6.20% to -5.19%) then it further reduced to 50.1 in 2015 (APC: -2.84%; 95% CI: -3.27% to -1.78%).The AAMR decreased in 2018 to 40.2 (APC: -7.28%; 95% CI: -8.08% to -6.22%) after which it increased to 43.9 in 2020 (APC: 4.15%; 95% CI: 2.56% to 5.59%). Males had higher consistently higher AAMRs than females (47.8 vs. 40.3).The AAMR in the US men decreased from 103.6 in 1999 to 51.5 in 2015 (APC: -2.62%; 95% CI: -3.04% to -1.49%) after which it decreased further to 42.2 in 2018 (APC: -6.75%; 95% CI: -7.72% to -5.48%)&then it increased to 47.8 in 2020 (APC: 6.11%; 95% CI: 4.10% to 7.85%).The AAMR in the US women decreased from 94.1 in 1999 to 48.3 in 2015 (APC: -3.05%; 95% CI: -3.51% to -1.75%) after which it decreased further to 38.2 in 2018 (APC: -7.57%; 95% CI: -8.81% to -6.18%) and then it increased to 40.3 in 2020 (APC: 2.32%; 95% CI: -0.26% to 4.49%).The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (69.2), followed by the NH American Indian or Alaska Native with an AAMR (44.2) and the NH White population with an AAMR (42.4).The low-risk populations were the Hispanic or Latino (33.6) and the NH Asian or Pacific Islander(31).Conclusions:The mortality rates from stroke due to MVD have overall increased in the United States over the past two decades, specifically men&(NH) Black or AA, NH American Indian or Alaska Native, and (NH) White are at high risk.
Stroke, Volume 56, Issue Suppl_1, Page ATP214-ATP214, February 1, 2025. Background:Amyloid-related Imaging Abnormalities (ARIA) are adverse effects that occur during amyloid beta monoclonal antibody treatment for Alzheimer’s disease, including edema-type ARIA and hemorrhage-type ARIA. Few retrospective analysis have compared ARIA-H incidence among individual monoclonal antibodies, and a comprehensive comparison is currently lacking. After the approval of these antibodies, research has mainly focused on dosing frequency and drug dosage, leaving it unclear whether ARIA-H is associated with the specific characteristics of different monoclonal antibodies.Methods:1. For monoclonal antibodies targeting Aβ clearance, we selected seven: Aducanumab, Bapineuzumab, Crenezumab, Donanemab, Gantenerumab, Lecanemab, and Solanezumab. Our data is derived from systematic reviews and meta-analyses of Phase III clinical trials for these seven monoclonal antibodies. Data from Jeremic D et al. include six monoclonal antibodies (mAbs), while data from Qiao Y et al. include four mAbs. 2. For the evaluation variables, we selected the following factors: the form of monoclonal antibody binding to Aβ protein, binding affinity, binding epitope, Fc subtype of the monoclonal antibody, and the Aβ clearance rate. ARIA-H occurrence was used as a categorical variable for differential analysis. The odds ratio (OR) was utilized for data assessment, with an OR not equal to 1 and a 95% confidence interval excluding 1 used as the criterion for statistical significance. 3. We standardized the data for the seven monoclonal antibodies (mAbs). We compared the ARIA-H occurrence rates for the mAbs, taking into account other dimensional variables.Results:The risk of ARIA-H, from highest to lowest, is as follows: Donanemab, Aducanumab, Bapineuzumab, Lecanemab, Gantenerumab, Crenezumab, Solanezumab. Besides, ARIA-H is associated with the characteristics of mAb. (1)More mature Aβ clearance is associated with a higher risk of ARIA-H.(2)Lower clearance of Aβ oligomers is associated with a higher risk of ARIA-H.(3)Aβ clearance closer to the N-terminus is associated with a higher risk of ARIA-H.(4)mAb with an IgG4 structure are more likely to cause ARIA-H than those with an IgG1 structure.(5)Faster achievement of Aβ clearance thresholds is associated with a higher risk of ARIA-H.Conclusion:This research enhances our understanding of ARIA-H and may guide future monoclonal antibody drug development, which may improve the cognition and overall prognosis of Alzheimer’s disease patients.
Stroke, Volume 56, Issue Suppl_1, Page ATP273-ATP273, February 1, 2025. Introduction:Patients suffering from transient ischemic attack (TIA) are at high risk of ischemic stroke (IS). This study describes clinical characteristics and outcomes in patients with a first non-cardioembolic TIA.Methods:Using two US administrative claims databases (MarketScan and Optum’s de-identified Clinformatics® Data Mart Database [CDM]) converted to the Observational Medical Outcomes Partnership (OMOP) common data model, we conducted an observational, retrospective cohort study of adults with a first diagnosis of non-cardioembolic TIA between 2012 and 2022. Demographic and clinical characteristics were described at baseline, and incidence rates of IS, intracranial bleeding, and bleeding leading to hospitalization with sensitivity analyses at different time points were calculated.Results:Overall, 203,757 patients were included in the study, 97,481 from MarketScan, 106,276 from CDM. Mean age was 62 years in MarketScan and 72 years in CDM. Patients were mostly women (57.6% in MarketScan, 59.3% in CDM). At baseline, prevalence of comorbidities was high (hypertension 66% and 84%, hyperlipidemia 53% and 75%, coronary artery disease 18% and 31%, diabetes 25% and 38% in MarketScan and CDM, respectively). Median follow-up time was 569 days in MarketScan and 716 days in CDM. At 1 year follow-up, incidence rates per 100 person-years of IS, intracranial bleeding, and bleeding leading to hospitalization were 10.9, 0.9, and 4.2, respectively, in MarketScan and 20.2, 1.6, and 7.6 respectively, in CDM. Sensitivity analyses showed that most IS events occurred within 7 days of the index event. Additional event rates and sensitivity analyses are shown in Table 1.Conclusion:Results from two US claims databases show that the annual risk of IS is higher than expected following a first TIA diagnosis, especially when including the first 7 days in the ascertainment. Implementation of guideline directed antiplatelet therapies, or new antithrombotic strategies, is needed.
Stroke, Volume 56, Issue Suppl_1, Page ATP228-ATP228, February 1, 2025. Introduction:Cerebrovascular and cardiovascular diseases are major causes of global mortality, with significant impact in India. Clopidogrel, an antiplatelet prodrug, requires activation by CYP enzymes to inhibit platelet activation. Clopidogrel resistance, affecting 4-30% of patients, is often due to CYP2C19 gene variations, among other factors. This study explores genetic variants associated with clopidogrel resistance to improve personalized therapy for thrombotic conditions.Objective:To evaluate the relationship between CYP2C19 polymorphisms and recurrent thrombotic events in patients treated with clopidogrel for coronary artery disease and stroke.Methods:An ambispective observational study at a tertiary hospital over six months included 114 adults on clopidogrel for various ischemic conditions. Exclusion criteria were pregnancy, lactation, intracerebral hemorrhage, atrial fibrillation, left ventricular clot, and cardioembolic stroke. Data were collected from medical records. CYP2C192 and CYP2C193 polymorphisms were analyzed using PCR and gel electrophoresis. Statistical analysis was conducted with chi-square tests in IBM SPSS version 20.0 (p
Stroke, Volume 56, Issue Suppl_1, Page ATP281-ATP281, February 1, 2025. Introduction:We assess the risk of stroke in individuals with and without a migraine diagnosis, adjusting for demographic variables and stroke risk factors using participant information from the All of Us database.Method:Diagnoses of migraine, stroke and comorbidities were identified using ICD9 and ICD10 codes. A multivariable logistic regression analysis was performed to assess the association between migraine and risk of stroke adjusting for comorbidities including hypertension, atrial fibrillation, hyperlipidemia, diabetes, tobacco use, depression and demographics (age, sex at birth, race and ethnicity). To compare the prevalence of stroke between individuals with and without migraine, odds ratios using a 95% confidence interval (CI) were calculated.Results:Within theAll of Usdatabase, 31,444 individuals received a migraine diagnosis (female=25,374/81%, male=5,391/17%, other=679/2%; mean (std) age=54.9 (15.6)) and 379,283 did not have a migraine diagnosis (female=222,104/59%, male=149,182/39%, other=7,997/2%; mean (SD) age=55.9 (17.2)), see Figure 1 for detailed demographics.The migraine cohort had a greater proportion of women (81% vs 59%, p
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Esperti, ‘da depressione ad Alzheimer si studiano nuovi usi”
Objectives
This study aims to report the trends in the certification of both sight impairment (SI) and severe sight impairment (SSI) in England and Wales during the period of 2010 to 2020, prior to the COVID-19 pandemic. The focus is on diabetic retinopathy/maculopathy as the key causative factor.
Design
Retrospective database analysis.
Setting
England and Wales.
Participants
Individuals certified as SI or SSI.
Outcome measures
Trends in certification of vision impairment in England and Wales due to any cause, with specific attention to diabetic retinopathy.
Methods
Certifications of vision impairment made by ophthalmologists in England and Wales were recorded and copies were sent to Moorfields Eye Hospital for epidemiological analysis. All certificates completed in England and Wales over an 11-year period, from April 2009 to March 2020, were queried and analysed on an annual basis. This analysis included all causes, and where both the main cause was diabetic eye disease or where diabetic eye disease was a contributory cause among multiple pathologies. Poisson regression was employed to analyse changes in trends over time for certifications of vision impairment.
Results
In England, from 2010 to 2020, there was a small but significant reduction (p
Rallenta la ricerca sui farmaci in Italia che con le sperimentazioni cliniche – passate nel 2023 a 611 dalle 663 dell’anno prima (-7,8%) – muove ogni anno 700-800 milioni di…
Nistico’, sistema italiano tiene ma -7,8% trial,1 su 3 oncologico
Background
Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.
Objective
We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.
Design
Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.
Results
Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.
Conclusion
Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.
Fujifilm Diosynth Biotechnologies costruirà i nuovi impianti nel sito danese di Hillerød in grado di produrre una maxi coltura di cellule per le terapie
