bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized MRD Assessment in Perisurgical ctDNA for Prognostic Prediction in Hepatocellular Carcinoma
Authors: Hu Jie , Tang Haoran , Jia Can-Can , Zhang Xiang-Yu , Xu Ying , Tan Jin-Peng , Fan Jia , Jia Shidong , Zhou Jian 
Published: November 2024

Abstract

Purpose:
Detecting residual disease is a critical clinical requirement in the perisurgical management of patients with resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions exhibiting limited sensitivity and failed to meet the minimal residual disease (MRD) testing threshold. We introduce a next-generation sequencing–based assay, informed by baseline samples, facilitating MRD detection in hepatectomized patients with HCC and offering prognostic predictions.

Experimental Design:
This study involved 88 patients with HCC who underwent surgical resections from January 2016 to May 2016 in Zhongshan Hospital, Fudan University. Tumor and normal tissue samples were collected during surgery, whereas plasma samples were obtained both before surgery and up to 7 days after surgery. Using a next-generation sequencing–based personalized ctDNA assay, we analyzed the MRD in both presurgical and postsurgical blood samples and its correlation with prognosis.

Results:
With a median follow-up period of 80.7 months, our findings demonstrated significant correlations between presurgical ctDNA tumor fractions, postsurgical plasma MRD status, and both recurrence-free survival and overall survival. Postsurgical MRD status emerged as the most significant risk factor for cancer recurrence (HR = 2.162; 95% confidence interval, 1.09–4.30; P = 0.027) compared with other clinical characteristics in multivariate Cox regression analysis. Notably, MRD status showed potential as a prognostic indicator among clinically low-recurrent-risk patients, such as those with Barcelona Clinic Liver Cancer stages 0 to A or China Liver Cancer Staging stages I to II.

Conclusions:
Evaluating personalized MRD provided crucial prognostic insights into recurrence-free survival and overall survival. It efficiently identified patients at high risk of recurrence, even among those initially perceived as low-risk cases.
Inflammatory Stress Determines the Need for Chemotherapy in Patients with HER2-Positive Esophagogastric Adenocarcinoma Receiving Targeted Therapy and Immunotherapy
Authors: Tintelnot Joseph , Paschold Lisa , Goekkurt Eray , Schultheiss Christoph , Matschl Urte , Santos Cruz Mariana , Bauer Marcus , Wickenhauser Claudia , Thuss-Patience Peter , Lorenzen Sylvie , Ettrich Thomas J. , Riera-Knorrenschild Jorge , Jacobasch Lutz , Kretzschmar Albrecht , Kubicka Stefan , Al-Batran Salah-Eddin , Reinacher-Schick Anke , Pink Daniel , Bokemeyer Carsten , Sinn Marianne , Lindig Udo , Hinke Axel , Hegewisch-Becker Susanna , Stein Alexander , Binder Mascha 
Published: November 2024

Abstract
Anti–PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma, but long-term survival remains limited. In this study, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti–PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison with a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti–CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% confidence interval, 41%–71%) in the Ipi arm and 70% OS (95% confidence interval, 54%–82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analyses demonstrated elevated levels of normetanephrine, cortisol, and IL6 in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil to lymphocyte ratio that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low neutrophil to lymphocyte ratio characterized patients benefiting from immunotherapy and targeted therapy without the need for additional chemotherapy. These data suggest that patient selection based on inflammatory stress–driven immune changes could help customize first-line treatment in patients with advanced HER2-positive esophagogastric adenocarcinoma to potentially improve long-term survival.
Social Determinants of Health and Disparities in Guideline-Directed Medical Therapy Optimization for Heart Failure
Authors: Jacobs Joshua A. , Ayodele Iyanuoluwa , Bress Adam P. , Sterling Madeline R. , Pandey Ambarish , Derington Catherine G. , Zheutlin Alexander R. , Shah Kevin S. , Greene Stephen J. , Alhanti Brooke , Blanco Rosalia , Fonarow Gregg C. 
Published: November 2024

BACKGROUND:
Fewer than 20% of eligible patients with heart failure with reduced ejection fraction receive all 4 pillars of guideline-directed medical therapy. Understanding disparities by race, ethnicity, sex, and adverse social determinants of health is necessary to equitably optimize quadruple therapy.

METHODS:
Utilizing the American Heart Association’s Get With The Guidelines-Heart Failure registry, we examined associations between race and ethnicity, sex, and adverse social determinants of health (insurance type and documented social need [any barrier to accessing health care]) with quadruple therapy optimization (QTO) in patients with heart failure with reduced ejection fraction hospitalized between July 1, 2021, and September 30, 2023, with complete medication data at discharge. We calculated adjusted mean differences (AMDs) in the discharge QTO score (range, 0%–100%) reflecting the proportion of eligible use of renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors and compared across demographic and adverse social determinants of health groups.

RESULTS:
Among 82 637 patients (median age, 66 years; 32.5% female; 57.0% non-Hispanic White; 76.4% prior heart failure with reduced ejection fraction), the overall mean QTO score was 56.2% (SD, 25.5). After adjustment, compared with non-Hispanic White individuals, Black (AMD, 2.56 percentage points [95% CI, 2.16–2.96]) and Hispanic individuals (AMD, 0.71 percentage points [95% CI, 0.11–1.31]) had higher QTO scores. Females had higher QTO scores than males (AMD, 1.94 percentage points [95% CI, 1.58–2.31]). Patients with no insurance (AMD, −4.90 percentage points [−5.62 to −4.17]), Medicaid (AMD, −0.45 percentage points [−0.89 to −0.01]), and Medicare (AMD, −1.64 percentage points [−2.10 to −1.18]) had lower QTO scores versus private insurance. Those with an identified social need (n=24 651) had lower QTO scores than those without (AMD, −3.40 percentage points [95% CI, −4.10 to −2.71]).

CONCLUSIONS:
Disparities in QTO were most evident for patients with no insurance, Medicaid, Medicare, or potentially an identified social need. Future efforts should focus on reducing gaps to improve equitable guideline-directed medical therapy use.
Comprehensive Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy From Other Cardiomyopathies With Left Ventricular Hypertrophy
Authors: Akita Keitaro , Maurer Mathew S. , Tower-Rader Albree , Fifer Michael A. , Shimada Yuichi J. 
Published: November 2024

BACKGROUND:
Distinguishing hypertrophic cardiomyopathy (HCM) from other cardiomyopathies with left ventricular hypertrophy (LVH), such as hypertensive LVH, transthyretin amyloid cardiomyopathy, and aortic stenosis, is sometimes challenging. Using plasma proteomics profiling, we aimed to identify circulating biomarkers and dysregulated signaling pathways specific to HCM.

METHODS:

In this multicenter case-control study, plasma proteomics profiling was performed in cases with HCM and controls with hypertensive LVH, transthyretin amyloid cardiomyopathy, and aortic stenosis. Two-thirds of patients enrolled earlier in each disease group were defined as the training set and the remaining one-third as the test set. Protein concentrations in HCM were compared with those in hypertensive LVH (comparison 1), transthyretin amyloid cardiomyopathy (comparison 2), and aortic stenosis (comparison 3). Candidate proteins that meet the following 2 criteria were selected: (1) higher abundance in HCM throughout all 3 comparisons or lower abundance in HCM throughout all 3 comparisons with univariable
P
<0.05 and |log
2
(fold change)| >0.5 in both the training and test sets and (2) independently associated with HCM with multivariable
P
<0.05 after adjusting for clinical parameters significantly different between HCM and controls. Using the selected candidate proteins, a logistic regression model to distinguish HCM from controls was developed in the training set and applied to the test set. Finally, pathway analysis was performed in each comparison using proteins with different abundance.

RESULTS:
Overall, 4979 proteins in 1415 patients (HCM, n=879; hypertensive LVH, n=331; transthyretin amyloid cardiomyopathy, n=169; aortic stenosis, n=36) were analyzed. Of those, 5 proteins were selected as candidate proteins. The logistic regression model with these 5 proteins had an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.82–0.89) in the test set. The MAPK (mitogen-activated protein kinase) and HIF-1 (hypoxia-inducible factor 1) pathways were dysregulated in HCM throughout the 3 comparisons.

CONCLUSIONS:
This study identified circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from confounders and revealed signaling pathways associated with HCM.
Mavacamten: Real-World Experience From 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program
Authors: Desai Milind Y. , Seto Dewey , Cheung Michael , Afsari Sonia , Patel Niki , Bastien Arnaud , Lockman Jeffrey , Coiro Michele , Martinez Matthew W. 
Published: November 2024

BACKGROUND:
Mavacamten is the only cardiac myosin inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with symptomatic New York Heart Association class II–III obstructive hypertrophic cardiomyopathy. Under the Risk Evaluation and Mitigation Strategy program for mavacamten, patients are required to be monitored for the development of systolic heart failure and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten Risk Evaluation and Mitigation Strategy database (April 28, 2022 to February 27, 2024).

METHODS:
Data on health care providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions before each dispense were collected.

RESULTS:
Of the 6299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were aged >60 years. Of the 5573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50%, and 71 (1.3%) experienced heart failure requiring hospitalization. On the 29 111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%), and heart failure requiring hospitalization was reported on 86 (0.3%). Of the 1929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50%, and 4 (0.2%) experienced LVEF <50% and heart failure requiring hospitalization but later resumed treatment. Of the 3228 patients initiated on 5 mg/d mavacamten and were treated for at least 6 months, 2391 (74.1%) remained at 5 or 10 mg/d. At 3 and 6 months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva left ventricular outflow tract gradient <30 mm Hg.

CONCLUSIONS:
We describe the feasibility and experience of the first 22 months of the Risk Evaluation and Mitigation Strategy program for prescribing mavacamten in >6000 patients with symptomatic obstructive hypertrophic cardiomyopathy. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with heart failure requiring hospitalization.
Associations of Circulating Platelet Endothelial Cell Adhesion Molecule‐1 Levels With Progression of Cerebral Small‐Vessel Disease, Cognitive Decline, and Incident Dementia
Authors: Sim Ming Ann , Tan Eugene S. J. , Chan Siew Pang , Cai Yuan , Chai Yuek Ling , Chong Joyce Ruifen , Chong Eddie Jun Yi , Robert Caroline , Venketasubramanian Narayanaswamy , Tan Boon Yeow , Lai Mitchell K. P. , Hilal Saima , Chen Christopher L. H. 
Published: November 2024

Background
The association between platelet endothelial cell adhesion molecule‐1 (PECAM‐1) with cerebral small‐vessel disease and cognition in dementia‐free subjects remains uninvestigated.

Methods and Results

A prospective cohort of dementia‐free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice‐yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM‐1 levels with cerebral small‐vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function
Z
scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM‐1 levels were 0.790 (interquartile range, 0.645–0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM‐1 tertile had greater cross‐sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67–9.01];
P
=0.023), age‐related white matter change scores (β=1.39 [95% CI, 0.12–2.67];
P
=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19–5.62];
P
=0.016). Of the 204 participants with follow‐up data (median, 60.0 [interquartile range, 60.0–60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM‐1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35–15.13];
P
=0.024; second tertile: AHR, 3.28 [95% CI, 1.02–10.60];
P
=0.047). The lowest PECAM‐1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06–8.24];
P
=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05–4.65];
P
=0.036), and decline in executive function (β=−0.45 [95% CI, −0.76 to −0.14];
P
=0.004), and Montreal Cognitive Assessment (β=−1.32 [95% CI, −2.30 to −0.35];
P
=0.008) scores.

Conclusions
In dementia‐free subjects, lower circulating PECAM‐1 levels are associated with greater cerebral small‐vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.
Burden of Hyperlipidemia, Cardiovascular Mortality, and COVID‐19: A Retrospective‐Cohort Analysis of US Data
Authors: Pham Hoang Nhat , Ibrahim Ramzi , Sainbayar Enkhtsogt , Olson April , Singh Amitoj , Khanji Mohammed Y. , Lee Justin , Somers Virend K. , Wenger Christopher , Chahal C. Anwar A. , Mamas Mamas A. 
Published: November 2024

Background
Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but there are limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact.

Methods and Results

Mortality data were obtained from the Centers for Disease Control and Prevention repository between 1999 and 2020 among patients ≥15 years old, using
International Classification of Diseases, Tenth Revision
(
ICD‐10
) codes for hyperlipidemia (E78.0–E78.5) and CVD (I00–I99). Age‐adjusted mortality rates (AAMRs) per 1 000 000 population were standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change from 1999 to 2019 was used to project 2020 AAMRs, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483 155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMRs rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause, whereas hypertension had the highest mortality increase (average annual percentage change +10.23%). Mortality rates were higher in men (AAMR 104.87) and non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years old (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35 to 75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups.

Conclusions
Hyperlipidemia‐related CVD mortality has risen over the past 2 decades, further heightened by the COVID‐19 pandemic, with higher impact on men, Black Americans, the older population, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.
Impact of Environmental Noise and Sleep Health on Pediatric Hypertension Incidence: ABCD Study
Authors: De Moraes Augusto César F. , Ma Martin Y. , Nascimento‐Ferreira Marcus V. , Hunt Ethan H. , Hoelscher Deanna M. 
Published: November 2024

Background
Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored.

Methods and Results
We analyzed data from 3320 participants of the ABCD (Adolescent Brain Cognitive Development) study, recruited across 21 US cities and monitored from 2018 to 2020 through 2020 to 2022. Participants with complete data on Fitbit‐tracked sleep, blood pressure, height, neighborhood noise, and covariates (biological sex, race and ethnicity, pubertal stage, waist circumference) were included. Hypertension was defined as average blood pressure ≥95th percentile for age, sex, and height. Sleep health was categorized on the basis of daily duration: healthy (9–12 hours), moderately healthy (±1 hour from optimal), and low (≥1 hour deviation). Noise exposure was measured as median nighttime anthropogenic noise levels by zip code. The incidence of hypertension increased from 1.7% (95% CI, 1.4–2.1) in 2018 to 2020 to 2.9% (95% CI, 2.4–3.6) in 2020 to 2022. Adolescents with healthier sleep had a lower risk of developing hypertension (relative risk, 0.63 [95% CI, 0.25–0.82]), while no significant effects were found for neighborhood noise alone or in combination with sleep health.

Conclusions
Adequate sleep significantly reduces the risk of hypertension in adolescents, independent of environmental noise exposure. These findings underscore the importance of promoting good sleep hygiene among youth to mitigate hypertension risk.
Racial and Ethnic and Sex Disparities in the Outcomes and Treatment of In‐Hospital Cardiac Arrest: A Nationwide Analysis From the United States
Authors: Mohamoud Abdilahi , Abdallah Nadhem , Ismayl Mahmoud , Linzer Mark , Karim Rehan M. , Wardhere Abdirahman , Johnson Dawn , Goldsweig Andrew 
Published: November 2024

Background
In‐hospital cardiac arrest (IHCA) is associated with significant morbidity and mortality. The relationships between race and ethnicity and sex on outcomes and treatment patterns among patients with IHCA remain poorly understood.

Methods and Results
We conducted a retrospective study using the National (Nationwide) Inpatient Sample (NIS) database from 2016 to 2020 to identify adult patients with IHCA and examine the associations between in‐hospital outcomes and race and ethnicity (White, Black, Hispanic) and sex. The primary outcome was in‐hospital mortality. Secondary outcomes included rates of in‐hospital procedures. Multivariable logistic regression analysis was used to adjust for potential confounders. Among 207 770 patients with IHCA, 26.6% had ventricular tachycardia/ventricular fibrillation and 73.4% had pulseless electrical activity/asystole. For ventricular tachycardia/ventricular fibrillation arrest, Black men (adjusted odds ratio [aOR], 1.42 [95% CI, 1.21–1.66]), Black women (aOR, 1.25 [95% CI, 1.05–1.50]), and Hispanic women (aOR, 1.30 [95% CI, 1.01–1.66]) had higher odds of mortality compared with White men (corresponding adjusted risk ratios [aRRs], 1.10 [CI, 1.06–1.14], 1.06 [95% CI, 1.02–1.11], and 1.08 [95% CI, 1.01–1.14], respectively). In the pulseless electrical activity/asystole arrest subgroup, Black men (aOR, 1.25 [95% CI, 1.11–1.39]) and Hispanic men (aOR, 1.22 [95% CI, 1.07–1.40]) had higher odds of mortality (corresponding aRRs, 1.04 [95% CI, 1.02–1.06] and 1.04 [95% CI, 1.01–1.06], respectively). Black patients with IHCA were less likely to receive percutaneous coronary intervention, coronary artery bypass grafting, and mechanical circulatory support compared with White men.

Conclusions
Significant racial and ethnic and sex disparities exist in outcomes and treatment patterns among patients with IHCA. Targeted efforts and further studies are needed to better understand and address these disparities and improve outcomes.
Diastolic Dysfunction and the Risk of Stroke and Major Bleeding
Authors: Kundrick John , Saba Karina I. , Naniwadekar Aditi , Singla Virginia , Mulukutla Suresh , Thoma Floyd , Bhonsale Aditya , Kancharla Krishna , Voigt Andrew , Shalaby Alaa A. , Estes III N.A. Mark , Jain Sandeep , Saba Samir 
Published: November 2024

BACKGROUND:
Left ventricular diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident stroke and transient ischemic attack (TIA) and with bleeding events is not known. We performed this observational cohort analysis to examine the impact of DD on the risk of stroke/TIA and major bleeding.

METHODS:

Patients who underwent at least 1 cardiac echocardiogram and were followed for at least 3 months were included in this study. Patients with a prior history of stroke, TIA, or major bleeding, as determined by
International Classifications of Diseases
codes, were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups based on the most severe DD assessment. Patients in whom the presence of DD could not be determined were excluded. The final study cohort was followed to the end point of hospital admission for stroke/TIA and major bleeding, and independent predictors of these events were evaluated using the multivariable Cox proportional hazards method.

RESULTS:

The final study cohort (age, 56±18 years; 56% women) had 96 702 patients with no DD and 18 164, 5881, and 1340 patients with DD grades I, II, and III, respectively. Over a median follow-up of 3.4 years, 2938 (2.4%) patients were hospitalized for stroke/TIA and 5567 (4.6%) for major bleeding. After adjusting for age, the CHA
2
DS
2
-VASc score, chronic kidney disease, use of antiplatelet agents, use of anticoagulation agents, the year of echocardiographic testing, household income, and history of atrial fibrillation, DD remained a strong predictor of incident stroke/TIA (hazard ratio, 1.22 per grade increase in DD [95% CI, 1.16–1.29];
P
<0.001) and major bleeding (hazard ratio, 1.20 per grade increase in DD [95% CI, 1.16–1.25];
P
<0.001).

CONCLUSIONS:
DD is independently associated with a higher risk of cerebrovascular accidents and major bleeding. DD should be considered when counseling patients regarding their risk profile and management options.