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Evaluating risk factors of embolism in patients with cardiac myxoma: A systematic review and meta-analysis.
No full textBACKGROUND: Cardiac myxomas (CM), the most common primary cardiac tumors, can cause embolism in about 40 % of cases, making it crucial to identify risk factors for guiding clinical decisions.
OBJECTIVES: In this meta-analysis, we studied the risk factors associated with embolism among patients with cardiac myxomas.
METHODS: A comprehensive search was conducted across PubMed, Embase, and Cochrane Library from their inception until May 2023. Statistical analyses were performed using Cochrane\u27s RevMan 5.4 software. For each risk factor, the pooled odds ratio or mean difference was calculated along with the corresponding 95 % confidence interval.
RESULTS: This meta-analysis incorporated 18 studies with 2601 patients, of whom 525 (20.1 %) experienced embolism. Significant risk factors included hypertension (p = 0.001), NYHA I/II (p = 0.03), irregular tumor surface (p \u3c 0.01), hyperlipidemia (p \u3c 0.01), coronary artery disease (p = 0.01), elevated mean platelet volume (p = 0.02), and high tumor mobility (p \u3c 0.01), while female gender (p = 0.03) was linked to reduced risk. Smoking, atrial fibrillation, tumor size, age, BMI, diabetes, LVEF, and LAD were not significantly associated with embolism (p \u3e 0.05).
CONCLUSION: This analysis is the first to highlight significant pooled outcomes for gender, hyperlipidemia, coronary artery disease, mean platelet volume, and tumor mobility. Patients with these risk factors may benefit from early evaluation and surgery to reduce embolism risk. Statistical analyses were performed using RevMan 5.4, with pooled odds ratios or mean differences calculated alongside 95 % confidence intervals
3-Year Outcomes of Mitral Valve-in-Valve Therapy Using Balloon-Expandable Transcatheter Valves in the United States
No full textBACKGROUND: Mitral valve-in-valve (MViV) is a safe and effective therapy for severe bioprosthetic mitral degeneration; however, longer-term outcomes are not well defined.
OBJECTIVES: This study aimed to evaluate 3-year outcomes following MViV.
METHODS: Outcomes of all-cause mortality, stroke, and reintervention were collected in patients undergoing transseptal MViV with the SAPIEN 3 valve family for failed surgical bioprostheses from June 2015 to March 2024 in the TVT (Transcatheter Valve Therapy) Registry, and Centers for Medicare and Medicaid Services data linkage was performed. Kaplan-Meier and Cox proportional hazards analysis was performed according to Society of Thoracic Surgeons (STS) score and procedure status.
RESULTS: A total of 5,971 patients (age 72.9 ± 11.4 years, 57.9% [n = 3457 of 5,971] female) underwent MViV. Low (\u3c 4), intermediate (4-8), and high (\u3e8) STS scores were present in 23.5% (n = 1,310 of 5,585), 35.1% (n = 1,960 of 5,585) and 41.5% (n = 2,315 of 5,585) of patients, respectively. Median follow-up duration was 377 days (Q1-Q3: 57-698 days). Mortality at 3 years was greatest in high STS score and nonelective procedures, while mortality was lowest in low STS score patients and elective procedures. Stroke rates at 3 years were comparable except between low and high STS groups. Mitral valve reintervention during 3 years of follow-up was uncommon in all groups.
CONCLUSIONS: Three-year survival after MViV is highest in low STS scores and elective procedures, whereas survival was significantly lower in high STS scores and nonelective procedures. These findings emphasize the importance of early identification and treatment of patients who may benefit from MViV. Reintervention rates at 3 years are low regardless of STS score
Comparative analysis of arch vessel revascularization techniques in proximal arch thoracic endovascular aortic repair
No full textOBJECTIVE: Endovascular stent grafting extending into the ascending aorta (zone 0) is increasingly used in the treatment of aortic arch disease. This study aims to evaluate the risk of stroke in patients undergoing zone 0 arch thoracic endovascular aortic repair (TEVAR) based on the technique used for head vessel revascularization.
METHODS: Patients undergoing zone 0 arch TEVAR covering all the aortic arch vessels were identified in the Vascular Quality Initiative between 2014 and 2023. Patients treated for aortic rupture or trauma were excluded. Head vessel revascularization techniques were classified into three groups: open revascularization (OR), endovascular revascularization (ER), and hybrid revascularization (HR). Multivariate logistic regression analysis was used to evaluate the association of head vessel revascularization technique with the primary outcomes of perioperative mortality and stroke.
RESULTS: A total of 409 patients underwent zone 0 arch TEVAR covering all the aortic arch vessels, of which 50% (207/409) underwent OR, 20% (80/409) underwent ER, and 30% (122/409) underwent HR of the head vessels. The in-hospital mortality and stroke rates were 9% and 12%, respectively. Survival at 30 days, 1 year, and 2 years were 88%, 79%, and 74%, respectively. Patients undergoing ER of the head vessels had significantly higher stroke compared with those undergoing OR and HR (OR 11%, ER 21%, HR 8%; P = .02). ER was associated with a two-fold higher risk of perioperative stroke compared with OR (odds ratio, 2.16; 95% confidence interval, 1.08-4.30; P = .03), whereas no difference in perioperative stroke was observed between OR and HR (P = .40). Although OR and HR of the head vessels had a significantly lower rate of perioperative stroke compared with ER in 2017-2020 (OR 10% vs ER 30% vs HR 10%, P = .02), this difference diminished over time with no significant difference observed in the most recent interval (2021-2023) studied (OR 9% vs ER 12% vs HR 8%; P = .76). Trends revealed an increase in the use of HR (from 4% in 2014 to 57% in 2023) alongside a significant decrease in ER (from 39% in 2020 to 14% in 2023).
CONCLUSIONS: Stroke remains a significant concern during zone 0 arch TEVAR. Total endovascular repair of the aortic arch is associated with a greater than two-fold higher risk of stroke compared with OR and HR of the head vessels. However, advances in ER techniques and increased use of hybrid strategies highlight an ongoing evolution toward safer and less invasive approaches resulting in a decrease in perioperative stroke rates over time
Inflammatory Pathways in Residual Asthma Exacerbations Among Mepolizumab-Treated Urban Children: A Secondary Analysis of a Randomized Clinical Trial
No full textIMPORTANCE: While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined.
OBJECTIVE: To identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab vs placebo.
DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (MUPPITS-2) double-blind, placebo-controlled, parallel-group, randomized clinical trial comparing treatment with mepolizumab vs placebo among children with exacerbation-prone asthma in low-income urban centers in 9 US cities. Data analysis was performed from September 2022 to April 2025.
INTERVENTION: Participants were randomized to receive either mepolizumab (aged 6-11 years: 40 mg; aged 12-17 years: 100 mg) or matching placebo by subcutaneous injection once every 4 weeks for 52 weeks.
MAIN OUTCOMES AND MEASURES: The primary measurement was a transcriptomic modular analysis by RNA sequencing of nasal samples obtained during acute respiratory illnesses. Associations among upper airway transcriptional signatures, the clinical outcome of respiratory illnesses, and pulmonary functions were investigated.
RESULTS: Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants (median [IQR] age, 10.0 [9.0-13.0] years; 48 [44%] female) were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module associated with T2 inflammation (log2 fold change [FC] estimate, -0.60; false discovery rate [FDR] \u3c .05) but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo (log2 FC estimates, 0.22-0.85; FDR \u3c .05). Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to nonexacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus, while macrophage pathways contributed specifically to viral exacerbations. Three distinct, semiorthogonal inflammatory axes were shown to underlie the majority of the heterogeneity among exacerbations in the 2 groups.
CONCLUSIONS AND RELEVANCE: The study\u27s findings implicate multiple alternative inflammatory pathways associated with the epithelium and macrophages, as well as mucus hypersecretion, as mechanisms of residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes can independently contribute to asthma exacerbations.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03292588
Aggressive Progression of High Programmed Death-Ligand 1 (PD-L1) Non-small Cell Lung Cancer Presenting as Life-Threatening Esophageal Obstruction: A Case of Food Impaction Secondary to Subcarinal Lymph Node Compression
No full textDysphagia secondary to esophageal obstruction is a rare but clinically relevant presentation in the setting of non-small cell lung cancer (NSCLC). While pembrolizumab demonstrates efficacy in metastatic NSCLC with high programmed death-ligand 1 (PD-L1), diagnostic challenges in distinguishing pseudoprogression from true progression and paradoxical disease progression pose a clinical challenge, highlighting complexities inherent in immune checkpoint inhibitor resistance mechanisms. We present the case of an 82-year-old Caucasian woman with a diagnosis of stage IV NSCLC with extremely high PD-L1 expression who developed accelerated disease progression on pembrolizumab monotherapy. Following 11 cycles of immunotherapy, the patient developed life-threatening esophageal obstruction due to a massively enlarged subcarinal lymph node, causing significant extrinsic compression. This resulted in food impaction necessitating urgent endoscopic management, followed by aspiration pneumonia requiring medical intensive care unit admission. Endoscopic evaluation revealed a critically narrowed esophageal lumen with ulcerated and necrotic mucosa. To facilitate nutritional support and airway protection, a gastrostomy tube was inserted. This case highlights several key clinical points: mediastinal lymphadenopathy can result in life-threatening esophageal compression requiring immediate intervention; high PD-L1 expression level is no guarantee of immunotherapy efficacy and may paradoxically be associated with aggressive disease progression; tissue sampling is imperative to differentiate between true progression versus pseudoprogression; and gastrostomy tube insertion is a vital palliative intervention for malignant esophageal obstruction secondary to extrinsic compression
Targeting Triglycerides: The Rise of Apolipoprotein C3 and Angiopoietin-Like Protein 3 Inhibitors
No full textHypertriglyceridemia has been proposed as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Triglycerides (TG) are viewed as a marker for remnant cholesterol in triglyceride-rich lipoproteins, as this remnant cholesterol has been identified as a causal risk factor for ASCVD. The limited number of effective treatments for elevated TG has fueled the search for novel pharmacotherapy options, and multiple medication classes are being explored. Apolipoprotein C3 (APOC3) and angiopoietin-like protein 3 (ANGPTL3) are among the most promising targets. Several novel agents utilizing these pathways, including olezarsen, plozasiran, and zodasiran, are currently under development for the management of elevated TG, with olezarsen approved in 2024 for the management of familial chylomicronemia syndrome. This comprehensive review provides updated insights into the development of novel hypertriglyceridemia treatments
Considerations in the development of learning health networks for mood disorders
No full textBACKGROUND: Learning Health Networks (LHNs), such as the one described in Savitz et al. (in press), involve employing a network of treatment centers to produce standardized data from routine clinical practice, produce knowledge from that data, and systematically use that knowledge to inform care. To date, there are limited examples of LHNs in psychiatry. It is essential to establish robust dialogue around best practices for building LHNs to advance precision medicine in psychiatry.
METHODS: A task group consensus on key elements of LHNs as applied to mood disorders was convened. Task group members reviewed current literature and ongoing LHN network efforts and evaluated opportunities and gaps within psychiatry broadly, and mood disorders specifically.
RESULTS: Task group members noted four key considerations for building LHNs for mood disorders. First, obtain qualitative and quantitative stakeholder input at every stage of development, specifically input from patients and patients\u27 families, clinicians and health system leadership. Second, collect data on objective measures of functioning, such as neuropsychological testing, quality of life indicators, and blood-based markers of health, alongside more standard measures such as symptom severity. Third, carefully consider the details of how new evidence-based practices will be identified and implemented. Fourth, identify a plan for sustainability.
LIMITATIONS: Literature was reviewed and discussed among expert task group members, but this was not a systematic review.
CONCLUSIONS: With stakeholder input, data on functioning as well as symptom severity, thoughtful implementation strategies, and an eye to sustainability, LHNs represent an important opportunity for advancement in the treatment of mood disorders
Pre-trauma insomnia and posttraumatic alcohol and cannabis use in the AURORA observational cohort study of trauma survivors
No full textBACKGROUND AND AIMS: Insomnia symptoms are a potential risk factor for alcohol and cannabis use, particularly in trauma-exposed populations. The initial weeks and months after trauma are a period of risk for problematic substance use, however prior research has not examined whether insomnia symptoms predict alcohol or cannabis use after trauma.
DESIGN: Using a large-scale, multi-site, prospective study of trauma survivors presenting to emergency departments (EDs), the current study tested direct and indirect associations between pre-trauma insomnia symptoms, two-week posttraumatic stress disorder (PTSD) symptoms, and eight-week post-trauma heavy alcohol and cannabis use and binge drinking.
SETTING: Participants were recruited from 23 EDs in the United States and followed up using remote assessments.
PARTICIPANTS/CASES: Participants were from the AURORA study (n = 2449). A slight majority were women (63.8 %) and were an average of 37 years old. Participants were racially and ethnically diverse (50.5 % Black, 11.2 % Hispanic).
MEASUREMENTS: Participants completed self-report measures during their ED visit, and two- and eight-weeks post-trauma.
FINDINGS: Pre-trauma insomnia symptoms significantly predicted eight-week post-trauma heavy alcohol and cannabis use, as well as binge drinking. Associations persisted after covarying for pre-trauma substance use, demographic variables, and trauma severity at the time of emergency care. Further, the association between pre-trauma insomnia symptoms and heavy alcohol and cannabis use at eight-weeks post-trauma was significantly mediated by two-week PTSD symptoms.
CONCLUSIONS: Insomnia symptoms may be an important malleable risk factor for heavy alcohol and cannabis use and binge drinking after trauma. Further research is needed to explore the effectiveness of insomnia interventions to mitigate post-trauma substance use and to better understand the complex relationships between sleep, trauma, PTSD, and substance use
Transient Proteinuria Induced by High-Dose Rosuvastatin
No full textBackground/Objective: This case describes a 70-year-old woman who developed transient proteinuria after starting high-dose rosuvastatin following a non-ST elevation myocardial infarction. The objective of this report is to describe the development of proteinuria in a patient after high-dose rosuvastatin therapy and discuss the subsequent resolution with a medication switch.
Case Report: A 70-year-old woman with a history of type 2 diabetes, primary hypertension, hypothyroidism, and hyperlipidemia, developed proteinuria after receiving high-dose rosuvastatin following an episode of non-ST elevation myocardial infarction. Prior to therapy, her low-density lipoprotein cholesterol was 123 mg/dL, coronary calcium score was 270, and urine albumin-to-creatinine ratios were 7.6 mg/g and 6.7 mg/g (normal albumin-to-creatinine ratio \u3c 30 mg/g). After 3 months of rosuvastatin therapy, proteinuria (albumin-to-creatinine ratio of 344.1) and muscle cramps developed, though her renal function remained stable (glomerular filtration rate \u3e70 mL/min/1.73 m2). After discontinuing rosuvastatin and switching to atorvastatin (20 mg/d) and ezetimibe (10 mg/d), proteinuria resolved, and low-density lipoprotein cholesterol was maintained at 45 mg/dL.
Discussion: Statin-induced proteinuria is a dose-dependent and typically reversible condition, more likely to occur with higher statin doses, such as rosuvastatin. Although proteinuria is generally transient, careful monitoring and dose adjustments are critical to optimizing statin therapy and patient adherence.
Conclusion: This case highlights the importance of individualized statin therapy, emphasizing monitoring for dose-dependent side effects such as proteinuria
Five Data-Informed Principles for Advancing Inclusive Research in Clinical Trials: A Pharma Perspective
No full textAdvancing inclusive research (AIR) in clinical trials requires frameworks and metrics for assessing real-world data and measuring population science. Because different factors drive health inequities and variables in measuring population science, relying on one metric for measuring progress may have limitations. Five principles (5Ps) are proposed for AIR globally that form the basis for a data-informed framework to measure and systematically define inclusive research to ensure rigor and benchmarking within organizations and across the broader sector. The first principle addresses biological, genetic, and population science considerations and their responsible use as data elements. The second principle pertains to using data to inform global region, country, and site placement, which includes geographical proportionality in trial enrollment, enabled access and commercialization strategies, and representative real-world demographic representation. The third principle is developing a data-informed and user-informed approach to end-to-end inclusive trial design. The fourth principle integrates patient-reported data collection standards and initiatives supporting complete and consistent clinical trial collection. The fifth principle enables trial access by demonstrating trustworthiness, improving patient navigation, and providing assistance programs. These 5Ps can be used as an end-to-end measurable framework using reference metrics, reproducible data, and methodologies for AIR in clinical development.Infographic available for this article