Lundquist Institute
  • Torrance, United States
Recent publications
Objectives This study compares care-seeking behavior, care delivery, and outcomes for infants with suspected brief resolved unexplained events (BRUEs) who were treated by emergency medical services (EMS) and emergency department clinicians before and after the onset of the coronavirus disease 2019 (COVID-19) pandemic and stay-at-home mandates. Methods This multicenter, retrospective observational study uses prehospital and hospital data on EMS-treated infants (age ≤12 months) with a primary paramedic impression of BRUE. We evaluated interventions, management, and outcomes, including transports and admissions, before (April 2019 to February 2020) and after (April 2020 to February 2021) the start of the pandemic and stay-at-home mandates in March 2020. We also characterized longitudinal trends in transports and hospital admissions for BRUE infants between July 2017 and February 2021. Data were analyzed using descriptive statistics and interrupted time series modeling. Results There were no significant differences in demographic characteristics or infant presentations before and after the beginning of the pandemic and stay-at-home mandates. We noted an increase in transports during the before period, but transports plateaued in the after period. There was no significant difference in admissions between the before and after periods. Conclusions For EMS-treated infants with paramedic-suspected BRUE, presentations and hospital admissions were similar before and after the beginning of the COVID-19 pandemic and stay-at-home mandates. There was a longitudinal increase in EMS transports for infants with suspected BRUE before the COVID-19 pandemic and stay-at-home mandates, which then leveled off in the after period.
Objective Coronary artery calcium (CAC) scoring may be a useful tool for assessing cardiovascular disease in young adults, particularly in those with risk factors such as hypertension, dyslipidemia, or smoking. In this study, we aimed to address the risk factors for developing noncalcified plaque in young adults by assessing total plaque burden. Methods A single-center retrospective cohort study was conducted among 1026 consecutive patients aged 18–45 years who underwent CAC scoring and coronary computed tomography (CT) angiograms for clinical indications. CAC scores and total plaque scores (TPS) were calculated using standard scoring protocols. Multiple logistic regression analysis was conducted to identify independent risk factors of significant, noncalcified plaque in subjects where CAC = 0. Results This single-center retrospective cohort study included 1026 patients aged 18–45 years who underwent CAC scoring and coronary CT angiograms for clinical indications. The mean age of the population was 38.8 years old. Sixty-three patients had a CAC score of 0 and a TPS >0. Of the patients with noncalcified plaque burden, 15% had a stenosis >50%, and 10% had a stenosis >70%. The odds of a subject having noncalcified plaque presence and CAC absent were significantly associated with being Hispanic, having diabetes, and having hyperlipidemia. Conclusion In young adults aged 18–45 years old, we found diabetes, hyperlipidemia, and being of Hispanic origin to be significantly associated with noncalcified plaque burden.
Objective Investigate whether deaf or hard of hearing (D/HH) patients with COVID-19 exhibited different hospitalisation outcomes compared with hearing patients with COVID-19. Design Cohort study Setting Statewide Inpatient Databases for Florida, Maryland, New York and Washington, for the year 2020. Participants Records of patients aged 18–64 years with COVID-19 Primary outcomes and measures Differences in in-hospital death, 90-day readmission, length of stay, hospitalisation cost, hospitalisation cost per day, intensive care unit (ICU) or coronary care unit (CCU) utilisation and ventilation use were evaluated. Adjustment variables included patient basic characteristics, socioeconomic factors, and clinical factors. Results The analyses included 347 D/HH patients and 72 882 non-D/HH patients. Multivariable log-transformed linear regression models found an association of patients’ hearing loss status with longer length of stay (adjusted mean ratio (aMR) 1.15, 95% CI 1.04 to 1.27, p<0.01), higher hospitalisation cost (aMR 0.96, 95% CI 1.00 to 1.22, p=0.049) and lower hospitalisation cost per day (aMR 0.96, 95% CI 0.92 to 1.00, p=0.04). We did not detect any significant relationships with other outcomes. Conclusions Our findings suggest that higher hospitalisation costs were attributed to prolonged stays rather than costly interventions, such as ICU care. Communication barriers between healthcare providers and D/HH patients, coupled with providers’ cautious approach to discharging D/HH patients, may explain our findings.
Introduction Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized. Methods We used data from 44,047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium. We defined advanced disease as CAC ≥90th percentile for age, sex, and race, and compared risk factor profile of persons with advanced disease to those without CAC and those with CAC <90th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of premature advanced disease with all-cause, cardiovascular, and CHD mortality. Results Of 44,047 participants, 18,561 (42.2%) had CAC. Among those with CAC, 6,680 (36.0%) had CAC ≥90th percentile. Notably, 76.4% of those with CAC ≥90th percentile had multivessel CAC compared to 40.6% of those with CAC <90th percentile. After a mean follow-up of 12.5±3.6 years, the incidence per 1,000 person-years of all-cause (2.93 vs 1.85 vs 1.11), cardiovascular (1.11 vs 0.39 vs 0.21), and CHD mortality (0.65 vs 0.19 vs 0.08) was highest in the advanced disease group compared to CAC <90th percentile and the no CAC group. Persons with CAC ≥90th percentile had a higher multivariable-adjusted risk of all-cause (HR:2.17[1.83–2.57]), cardiovascular (SHR:3.89[2.78–5.44]), and CHD mortality (SHR:5.45[3.38–8.78]), compared to those without CAC. In the subgroup analysis, there was no difference in mortality between men and women with advanced CAC. Conclusions Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥ 90th percentile have the highest risk of early death and should be identified in future guidelines as a focus for aggressive clinical prevention.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists (GIP/GLP-1 RAs) are emerging as effective treatments for obesity and cardiometabolic disease. This study evaluated physician perceptions of the safety and efficacy of semaglutide and tirzepatide through a questionnaire administered to 165 attending physicians specializing in internal or family medicine, with 122 responses received. Physicians reported an average patient weight loss of 9.22%, significantly lower than the 14.9% and 18.5% reported in the STEP and SURMOUNT trials, respectively. Estimated side effect rates (32.62%) were markedly lower than trial-reported rates (89.7% and 80.5%), while estimated discontinuation rates (8.59%) exceeded trial data. Cardiovascular benefits were perceived by 48.4% of physicians in diabetic patients, consistent with random guessing, and by only 39.3% in nondiabetic patients, significantly below random guessing expectations. These results highlight discrepancies between physician perceptions and clinical evidence, suggesting gaps in understanding regarding these agents’ efficacy and safety profiles. Addressing these gaps could enhance physician knowledge, patient adherence, and clinical outcomes.
Background There is significant heterogeneity in cardiovascular disease (CVD) risk among patients with diabetes mellitus (DM). Objectives The purpose of this study was to develop risk scores for total CVD and its components from a contemporary pooled, observational cohort of U.S. adults with DM. Methods CVD-free adults with DM aged 40 to 79 years were pooled from 4 U.S. population-based cohorts (CARDIA [Coronary Artery Risk Development in Young Adults], Framingham Offspring, Jackson Heart Study, and the MESA (Multiethnic Study of Atherosclerosis) studied since 2000. Baseline DM-specific and non-DM–specific CVD risk factors were evaluated as predictors. We developed 10-year DM Risk Scores (DMRS) for total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), heart failure (HF) and stroke. Score performance was validated internally and externally. Results We included 2,174 adults with DM mean age 59.2 ± 10.5 years, 55.4% female and 47.5% Black followed up to 10 years. Age, sex, HbA1c, creatinine, systolic blood pressure, DM medication, and smoking were the most important predictors. The DMRS had good internal discrimination (c-statistics 0.72, 0.72, 0.72, 0.79 and 0.73 for CVD, ASCVD, CHD, HF, and stroke) and calibration (calibration slopes 0.93, 0.95, 0.93, 0.98, and 0.89 for CVD, ASCVD, CHD, HF, and stroke; Greenwood Nam-D’Agostino calibration tests were significant for CHD (P < 0.01) and CVD (P < 0.05) but not for ASCVD, HF, and stroke). From external validation in 2 other cohorts, the DMRS outperformed current risk scores. Conclusions Our U.S. pooled cohort DMRS for predicting CVD events demonstrated good predictive performance for assessing CVD risk in adults with DM.
Purpose of Review Inflammation has been commonly known for the past decade as a part of the pathophysiology of atherosclerosis, along with lipid accumulation. However, some patients with optimized lipid-lowering therapy still have elevated inflammatory biomarkers. Anti-inflammation therapies were developed to eradicate this residual risk. We summarized the primary inflammatory pathway and recent clinical trials in anti-inflammation therapies. Recent Findings Colchicine Cardiovascular Outcomes Trial (COLCOT) and LoDoCo2 (Colchicine Reduces Risk of Major Cardiovascular Events in Chronic Coronary Disease) found that low-dose colchicine significantly reduced cardiovascular death, myocardial infarction (MI), ischemic stroke and coronary revascularization in patients with recent MI within 30 days and chronic coronary disease respectively. The US Food and Drug Administration approved low-dose colchicine in 2023 for patients with established atherosclerotic cardiovascular disease (ASCVD). However, its use was limited for chronic kidney disease (CKD) patients. Reduction in Inflammation in Patients with Advanced Chronic Renal Disease Utilizing Antibody Mediated Interleukin-6 Inhibition (RESCUE) was conducted using Ziltivekimab, an IL-6 ligand monoclonal antibody and found that it significantly reduced high-sensitivity C-reactive protein, an inflammatory surrogate marker. There is an ongoing phase-3 clinical trial, Ziltivekimab Versus Placebo Cardiovascular Outcomes in Participants with Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease, and Systemic Inflammation trial (ZEUS), which will be essential for further anti-inflammation therapy for patients with CKD. Summary Numerous clinical trials have investigated anti-inflammation therapies. Colchicine is by far the only one that has the potential to be widely used due to its cost-effectiveness. Further research is needed on other novel anti-inflammation therapies and their real-world implementation.
Public health emergencies, including climate-related and manmade disasters such as active shooter incidents, occur regularly in the United States. A comprehensive approach is needed to ensure that children’s mental health needs are adequately addressed following disasters. This article summarizes the latest evidence on how health systems can effectively address children’s unique developmental, social, emotional, and behavioral needs in the context of disasters. To do so requires the integration of mental health considerations throughout all disaster phases, including preparedness, response, and recovery. We discuss the role of traditional emergency response systems and emerging models for responding to mental health crises. These include the national children’s disaster mental health concept of operations and specific resources such as crisis lines, mobile crisis units, and telemental health. To achieve a broader reach in addressing children’s mental health needs during disasters, health systems can foster a “pediatric disaster system of care” by partnering with community touch points such as schools, faith-based organizations, public health, and law enforcement. Unique considerations during disasters are required to maintain access to care for children with preexisting behavioral health conditions. During disasters, attention is needed to promote equitable identification of mental health needs and linkage to services, particularly for minoritized groups and children living in rural, frontier, and high-poverty areas. Strategies to address children’s mental health needs during disasters include the provision of psychological first aid, screening for and triaging mental health needs, and stepped care approaches that progressively allocate higher-intensity evidence-based treatments to children with greater and enduring needs.
Nicotinic acetylcholine receptors (nAChRs) are ubiquitous neurotransmitter receptors predominantly located at the cell-surface of neurons and muscle cells. Their dynamics affect synaptogenesis at neurodevelopmental stages and the efficacy of synaptic transmission in the adult synapse. Here we exploit the enhanced capabilities of superresolution fluorescence MINFLUX microscopy to track for minute-long periods with nanometric precision and sub-millisecond time resolution the 2D translational dynamics of the bungarotoxin-labelled adult muscle-type nAChR in tandem with a fluorescent cholesterol analogue. To this end, we implemented a multiplexing procedure in continuous MINFLUX microscopy that enabled the simultaneous excitation of the two molecules using a single wavelength, followed by discrimination of their emissions via differential ratiometric recording. Single-molecule trajectories displayed a heterogeneous spectrum of diffusive behaviours (subdiffusive, Brownian and superdiffusive), with a predominance of the subdiffusive component, which became less pronounced upon cholesterol depletion. nAChRs spent most of their lifetime in confined areas of characteristic size (~ 0.005 µm ² ) lasting for ~ 100 ms. Further, MINFLUX captured regions where nAChR and fluorescent cholesterol moved jointly, both in confinement sojourns and along the free Brownian walks, which strongly indicated mutual interactions between the receptor macromolecule and the neutral lipid. To the best of our knowledge, this study constitutes the first series of experiments showing the diffusion dynamics of a transmembrane protein -a functionally important neurotransmitter receptor- together with a key membrane lipid in the native plasma membrane of a live cell at such high detail, thanks to the MINFLUX-based recordings.
Cardiovascular disease remains the leading cause of death in the United States and globally. Significant advances have been made throughout the history of cardiology and the treatment of this disease; however, these efforts have not halted the alarming statistics. Emerging approaches, such as artificial intelligence applied to cardiac imaging, genetic testing, and genetic silencing, may offer essential additional steps in treating the disease. Moreover, new pathways of the disease are being identified, which differ from traditional risk factors and offer a fresh, innovative approach. This paper focuses on a novel strategy that includes identifying and treating multiple pathways of the disease using both new and traditional interventions. These interventions include plaque-directed therapy rather than surrogate therapy, with the potential to mitigate consequences and possibly eradicate the disease through personalized, multi-approach treatments similar to those used in cancer treatment.
BACKGROUND The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography. METHODS Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index. RESULTS Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity. CONCLUSIONS Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.
Objective Excess cholesterol loading on arterial macrophages is linked to foam cell formation, atherosclerosis and cardiovascular risk in rheumatoid arthritis (RA). However, the effect of changes in cholesterol loading on coronary plaque trajectory and the impact of RA therapies on this relationship are unknown. We investigated the association between variations in cholesterol loading capacity (CLC) over time and atherosclerosis progression. Methods In a prospective observational cohort study, coronary CT angiography evaluated atherosclerosis (non-calcified, partially calcified or fully calcified plaques and coronary artery calcium (CAC) score) in 100 patients with RA without cardiovascular disease at baseline and 6.9±0.4 years later. The presence of ≥5 plaques and lesions rendering >50% stenosis was considered an extensive and obstructive disease, respectively. Serum CLC was measured on human THP-1 monocyte-derived macrophages with a fluorometric assay. Results Mean CLC change (follow-up CLC−baseline CLC) was 1.54 (SD 3.69) μg cholesterol/mg protein. In models adjusting for atherosclerotic cardiovascular disease risk score, baseline plaque and other relevant covariates, CLC change (per SD unit increase) is associated with a higher likelihood of progression of non-calcified (OR 2.55, 95% CI 1.22 to 5.35), fully calcified plaque (OR 3.10, 95% CI 1.67 to 5.76), CAC (OR 1.80, 95% CI 1.18 to 2.74) and new extensive or obstructive disease (OR 2.43, 95% CI 1.11 to 5.34). Exposure to prednisone unfavourably influenced, while biologics and statins favourably affected the relationship between CLC change and atherosclerosis progression (all p-for-interactions ≤0.048). Conclusion CLC change is associated with atherosclerosis progression in a dose-dependent manner, including lipid-rich non-calcified plaques and extensive or obstructive disease that yield the greatest cardiovascular risk.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
210 members
Juanita K Jellyman
  • Department of OBGYN
Rachelle Bross
  • Clinical and Translational Research Center
Janos Porszasz
  • Department of Medicine
Information
Address
Torrance, United States