Publications by Year: 2026

Cardiovascular diseases, and most notably coronary artery disease (CAD), carry a large burden of mortality and morbidity, highlighting the need for better risk prediction and prevention. Several risk scoring tools for CAD have been developed to improve early detection, reduce the risk of acute cardiac events, and ensure adequate monitoring and follow-up of high-risk individuals. One that seized attention, especially with the groundbreaking advancements in disease's genetic buildup, was the polygenic risk score (PRS) for CAD. It was developed for potentially improving risk prediction at an early age, with individualized patient care. Our review aims to review the latest advances in this field of polygenic risk prediction, highlighting background information about PRS, current evidence supporting the utility of PRS for CAD, challenges associated with its implementation, and its complementary role with the coronary artery calcium score (CAC). Our review demonstrates that PRS could be a strong predictive indicator of CAD, especially when combined with other clinical factors. However, concerns remain regarding its applicability to genetically diverse populations, the ethical and psychological challenges, and practical feasibility. Lastly, PRS can augment and predict CAC in terms of risk discrimination and reclassification. In conclusion, PRS is a valuable tool that is upscaling with wider adoption. This requires a proper handling of its associated challenges to better shape the future of individualized care.

INTRODUCTION: The "Learning Health System" (LHS) relies on meaningful patient and public engagement to foster innovation in healthcare. However, effective methods for involving these stakeholders in LHS research are unclear. This scoping review examines the use of Human-Centered Design (HCD) to engage patients and the public in LHS research.

METHODS: Following Joanna Briggs Institute methodology and PRISMA-ScR guidelines, we searched MEDLINE, Cochrane Library, Embase, and Web of Science for LHS research studies using HCD to engage patients and the public. Data were categorized by: (1) Study Characteristics, (2) Participant Characteristics and Group Dynamics, (3) HCD Approach, Stages, and Methods, (4) Participant Satisfaction and Engagement, and (5) Focused Demographic Participation.

RESULTS: Among the included studies, participants in the HCD process included children and adults with conditions such as cancer, dementia, and stroke, often joined by their families and healthcare clinicians. Research spanned innovations in patient engagement, digital health, quality improvement, care delivery, environmental design, and clinical support tools. Participatory workshops were the most used HCD method. Group activities fostered creativity and diverse perspectives; individual activities offered deeper insights. A common challenge was limited engagement in later design stages, particularly prototyping. Studies involving harder-to-reach populations implemented extreme user design, creative design tools like photovoice and the 1-2-4-All technique, and community-based participatory research principles, all integrated into the HCD process.

CONCLUSIONS: Our review found HCD to be an effective method for engaging patients and the public in LHS research. It has been applied to engage individuals across a wide range of health conditions, age groups, and socioeconomic backgrounds, driving targeted innovations and system-level improvement. Its adaptability allows real-time adjustments in research pace and design, enabling iteration, strategy refinement, and inclusion of new populations as insights emerge. Blending discussion-based methods (e.g., interviews, workshops) with experiential approaches (e.g., role-playing, prototyping) boosts participant engagement and satisfaction. Future research should identify optimal group sizes, the most appropriate methods for each design stage, and the impact of integrating HCD with other research approaches.

AIMS: The long-term cardiovascular (CV) risks after percutaneous coronary intervention (PCI) in cancer patients are unclear. We assessed the risks of adverse events after PCI related to active or inactive cancer and the duration of dual antiplatelet therapy (DAPT).

METHODS AND RESULTS: This is a retrospective cohort of all patients having PCI with second-generation drug-eluting stents in the national Veterans Affairs Healthcare System between 2008 and 2016. We compared patients with active cancer (cancer and chemotherapy/radiotherapy), inactive cancer (cancer without chemotherapy/radiotherapy), or no cancer using Cox proportional hazards regression models adjusted by the propensity for cancer. Models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for myocardial infarction (MI), major bleeding, and death and the relationship to duration of DAPT after PCI. Of 40 677 patients, 791 (2%) had active cancer, 7633 (19%) had inactive cancer, and 32 253 (79%) had no cancer. Over a mean 5.4 (SD 2.8) years, the risks of MI and major bleeding were higher in patients with active cancer (MI: HR = 1.18, 95% CI = 1.00, 1.40; major bleed: HR = 1.73, 95% CI = 1.43, 2.10) and inactive cancer (MI: HR = 1.13 95% CI = 1.07, 1.20; major bleed: HR = 1.30, 95% CI = 1.21, 1.41). Discontinuing DAPT more than 9 months after PCI associated with lower risks of MI (active cancer: HR = 0.91, 95% CI = 0.70, 1.19; inactive cancer: HR = 0.78, 95% CI = 0.70, 0.88) and major bleeding (active cancer: HR = 0.68, 95% CI = 0.49, 0.97; inactive cancer: HR = 0.87, 95% CI = 0.76, 0.99).

CONCLUSION: Patients with cancer have higher risks of ischaemic and bleeding outcomes after PCI. However, we found no evidence that DAPT duration should differ from current guidelines in patients with cancer after PCI.

PURPOSE: Resilience is crucial in mitigating the risk of stress-related health issues. Although many people can adapt to adverse stress or trauma, stress exposure can increase the risk of health issues, including obesity, cardiovascular disease, and digestive illnesses. Some individuals may even develop debilitating conditions, such as post-traumatic stress disorder (PTSD). People with PTSD often struggle to adapt, sometimes turning to alcohol to cope, which can lead to alcohol use disorder (AUD), characterized by excessive alcohol-seeking and dependence. Understanding the biological underpinnings of resilience, therefore, is a key to preventing both PTSD and AUD. Recent research has uncovered the neurobiological traits that protect against the development of stress-induced alcohol dependence. Studies have shown that proactive coping and a lack of stress-related symptoms are associated with resilience. Preclinical studies, especially in rodents, have provided deeper insights into how stress impacts alcohol-seeking behaviors. Research has shown that resilience involves adaptive changes at the molecular, cellular, neural circuit, and systems levels. This review aims to integrate this research to better understand what makes people vulnerable to stress and alcohol consumption, highlighting aspects frequently overlooked in clinical models.

SEARCH METHODS: This review employed systematic search strategies to achieve a comprehensive and structured assessment of the existing body of literature using the academic databases PubMed, Google Scholar, and Web of Science. Targeted keywords included "stress," "PTSD," "trauma," "alcohol," "AUD," "resilience," "vulnerability," "susceptibility," "sex difference," and "animal models"; Boolean operators (AND, OR, NOT) were used to refine the results. Exclusion criteria included research published before 1990, research that was not peer reviewed, and publications in languages other than English. Additional studies were identified by reviewing the references cited in key articles as well as by identifying subsequent studies that referenced these pivotal works. The search was carried out from April to June 2025 focusing on, but not limited to, experiments involving rodent models.

SEARCH RESULTS: The search yielded a total of 347 articles. After screening, 283 articles were removed, either because they met the predefined exclusion criteria or because they were duplicates. This process resulted in 64 articles, forming the core of this comprehensive review.

DISCUSSION AND CONCLUSIONS: This review summarizes an overview of recent progress in studies of PTSD and AUD, primarily focusing on the effect of resilience on post-stress alcohol intake in animal models. The findings highlight several biomarkers that may help identify individuals at risk for PTSD, AUD, or their co-occurrence, acknowledging that no single identifier can predict post-trauma outcomes. The identification of these markers is an ongoing process, yet it will be crucial for early diagnosis and risk assessment moving forward.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in malignancy. Low-molecular-weight heparins and direct oral anticoagulants have replaced vitamin K antagonists (VKAs) as the standard of care for cancer-associated VTE. Nonetheless, clinical trials have not established a survival benefit of these agents compared with VKA.

OBJECTIVES: We conducted a systematic review and meta-analysis to compare survival in cancer patients receiving VKA vs other anticoagulants.

METHODS: We searched Embase, Web of Science, PubMed, ClinicalTrials.gov, and Cochrane from inception until April 10, 2025, focusing on the use of VKA and non-VKA in cancer patients. Primary outcome was mortality and secondary outcomes included thromboembolism and bleeding.

RESULTS: Of 11,198 studies screened, 14 studies (70,025 patients) were included. VKA were associated with lower mortality than non-VKA in observational studies (odds ratio [OR], 0.84; 95% CI, 0.78-0.91; I 2 = 81%; n = 6 studies) but not in randomized controlled trials (OR, 0.99; 95% CI, 0.86-1.13; I 2 = 0%; n = 8 studies). In subgroup analysis, follow-up period of >6 months (OR, 0.85; 95% CI, 0.79-0.92; I 2 = 75%), solid malignancies (OR, 0.81; 95% CI, 0.75-0.88; I 2 = 78%), and indication of VTE only (OR, 0.89; 95% CI, 0.83-0.96; I 2 = 42%) demonstrated improved survival with VKA.

CONCLUSION: The use of VKA was associated with lower mortality than non-VKA anticoagulation in patients with cancer in observational studies but not in randomized trials. The analysis was limited by high heterogeneity, which must be considered when interpreting results.

The Mycoses Study Group Education and Research Consortium (MSGERC)-a group comprising clinicians, researchers, patients, and industry partners-meets every 2 years to review the most significant challenges facing the clinical mycology community and plan research, education, and advocacy strategies to prevent fungal infections and improve outcomes. Key themes of the 2024 biennial meeting included emergence of antifungal resistance, the effects of climate change on incidence of IFI, recent healthcare-and community-associated outbreaks and their management, and the potential benefits of novel approaches, such as innovative study designs, host-directed diagnostics and therapies, and artificial intelligence in clinical and academic mycology.

INTRODUCTION: Despite increasing recognition of pediatric acute-onset neuropsychiatric syndrome (PANS), its neuropsychological underpinnings remain limited, particularly in relation to obsessive-compulsive disorder (OCD) symptoms. PANS manifests abruptly with severe OCD and/or eating restrictions alongside concurrent neuropsychiatric symptoms, causing distress and functional impairment. This study aimed to examine the relationship between neurocognitive performance and OCD symptom severity in children and adolescents with PANS.

METHOD: Twelve children and adolescents with PANS were assessed on a total of 39 occasions using a novel touchscreen-based button-choice reaction time task. The task was designed to capture subtle aspects of attentional focus, motor precision, and response speed. Analyses examined associations between OCD symptom severity, assessed for each testing session, and performance measures.

RESULTS: Greater OCD symptom severity was associated with heightened attentiveness (noticing the lit-up button) and more centered touch positioning, but not with faster reaction times. A significant interaction was observed, whereby increased attentiveness and precision in touch placement were linked to longer reaction times, suggesting a trade-off between speed and perfectionistic response strategies.

CONCLUSIONS: Overall, while OCD symptom severity was not directly associated with reaction time, it significantly shaped response monitoring and touch positioning. These findings indicate a neurocognitive profile in PANS characterized by heightened self-monitoring and meticulousness, potentially reflecting mechanisms underlying OCD symptomatology. Our findings highlight the complex interplay between neurocognitive performance and OCD symptom severity in PANS, as revealed through digital assessment, contributing to a deeper understanding of the condition.

Diffuse axonal injury (DAI) is caused by acceleration-deceleration forces during trauma that shear white matter tracts. Susceptibility-weighted MRI (SWI) identifies microbleeds that are considered the radiologic hallmark of DAI and are used in clinical prognostication. However, this assumption is limited by a lack of systematic radiologic-pathologic correlation studies. Here, we performed ex vivo SWI on three brains from patients who died after severe TBI and assessed axonal injury around SWI microbleeds using immunohistochemistry to the amyloid-beta precursor protein. Axonal injury was present in 64% of microbleeds, indicating a heterogeneous injury response in the white matter.

INTRODUCTION: In a prospective cohort from the Tampa Bay region (2016-2020), patients with autoimmune cytopenia (AIC) were evaluated to identify cellular and serum biomarkers that distinguish those with underlying inborn errors of immunity (IEI).

METHODS: Clinical phenotype and genetic causes of IEI were assessed using targeted panel-based sequencing. Unique lymphocyte subsets, including activated naïve and transitional B cells, CD19hiCD21lo B cells, follicular helper T (TFH) cells, regulatory T (Treg) cells, and TCRαβ+CD4-CD8- double-negative T cells (DNTαβ), were assessed by flow cytometry. Serum levels of lipopolysaccharide (LPS), B-cell activating factor (BAFF), and soluble IL-2 receptor (sIL2R) were quantified by ELISA.

RESULTS: Among 104 AIC patients, 53 (51%) showed evidence of IEI, including 27 (26%) with monogenic disorders-most commonly partial DiGeorge syndrome (pDGS), followed by variants in NFKB1, CTLA4, and FAS. The prevalence of IEI was highest in autoimmune hemolytic anemia (AIHA) (62.5%) and Evans syndrome (61.5%). Low levels of IgG, IgA, and IgM, as well as reduced percentages of naïve CD4+ and CD8+ T cells, were significantly associated with increased odds of IEI. In AIC-IEI patients, transitional B cells, CD19hiCD21lo B cells, and TFH cells were expanded, accompanied by elevated serum levels of BAFF and sIL2R.

CONCLUSIONS: Quantitative immunoglobulin levels and naïve T cells remain valuable indicators of IEI in AIC. Our findings highlight the diagnostic value of emerging cellular and serum biomarkers in identifying IEI, including dysregulation of early B-cell subsets (transitional B cells and CD19hiCD21lo B cells), expansion of TFH cells, and elevated levels of BAFF and sIL2R.

PURPOSE: The aim of this study was to compare imaging use on pediatric outpatients at children's hospitals (CHs) versus non-children's hospitals (NCHs) to identify differences across modalities that differ in ionizing radiation exposure.

METHODS: CMS Medicaid Research Identifiable Files were used to identify all year 2019 pediatric (ages 0-17 years) outpatient claims from hospital outpatient facilities (HOFs) and emergency departments (EDs). CMS data from 2018 were used to calculate the pediatric comorbidity index (PCI) for risk adjustment. Primary outcomes were CT, MR, ultrasound, or radiography (XR) use at each visit, comparing frequencies between CHs and NCHs. Additional covariates included age group (0, 1-2, 3-5, 6-11, and 12-17 years), PCI (0, 1 or 2, 3-6, 7), and place of service (HOF vs ED).

RESULTS: A total of 5,474,082 claims meeting the selection criteria were identified. More than half of visits (53%) were to CHs, and 15% were to EDs. CH encounters were more likely (vs NCH encounters) to be among patients aged 0 to 5 years versus >5 years (41.2% vs 38.7%, P < .01), those with PCI > 2 (32.3% vs 22.9%, P < .01), and those seen at HOFs (87.8% vs 81.9%, P < .01). The most commonly used modalities were XR (9.5%) and ultrasound (2.1%). Use of XR (11.8% vs 7.5%, P < .01) and CT (1.0% vs 0.5%, P < .01) was more frequent at NCHS. Use of ultrasound (2.5% vs 1.7%, P < .01) and MR (0.9% vs 0.5%, P < .01) was more frequent at CHs.

CONCLUSIONS: This study reveals that imaging modalities that expose children to ionizing radiation are used more frequently at NCHs than at CHs. The clinical implications of these variations warrant further investigation.