Understanding the reasons for declining to participate in cancer genetics and genomic studies in the USA: a scoping review protocol

Introduction
Cancer is the second leading cause of death in the USA. Cancer genetics and genomic studies have improved our understanding of risk, onset and progression. However, disparities by race and ethnicity have resulted in a lack of representation for minorities in these studies, contributing to unequal reductions in the cancer burden across populations. Moreover, the reasons why some individuals decline to participate in cancer genetics and/or genomic studies across diverse populations remain unclear. This review will summarise the main reasons (concerns) associated with declining to participate in cancer genetics and/or genomic studies for individuals with a history of cancer living in the USA and Puerto Rico (PR), considering race and ethnicity.

Methods and analysis
We will follow the methodology presented by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews Statement extended to Scoping Reviews to guide manuscript generation. A standardised search strategy developed in collaboration with a health sciences librarian will be deployed in Medline (PubMed), Embase (Ovid) and Scopus from database inception till present. The search strategy consists of three concepts: (1) cancer; (2) genetics and genomic research; (3) declination to participate in research studies. Title and abstract screening, followed by full-text review, will be conducted by independent reviewers to determine study inclusion. Only the peer-reviewed literature in English, conducted in the USA and PR will be considered. Findings will be presented as a numerical summary, graphical presentation and narrative review of the literature.

Ethics and dissemination
Ethical review is not required for scoping reviews. This review aims to facilitate the development of targeted strategies to increase participation in cancer genetics and/or genomic studies across diverse populations. Results will be disseminated through a peer-reviewed publication and conference presentations. The protocol is registered in the Open Science Framework (www.osf.io).

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On Accelerated Aging

Approximately 500 000 individuals have survived childhood cancer in the US, and this number is growing each year. Unfortunately, these survivors carry a substantial burden of morbidity. The most prevalent severe or life-threatening chronic health conditions include endocrine disorders, subsequent neoplasms, and cardiovascular disease. These conditions are directly related to chemotherapy and/or radiation therapy used to treat the childhood cancer; examples include anthracycline-related cardiomyopathy, radiation-related breast and central nervous system subsequent neoplasms, and radiation-related coronary-artery disease and stroke. Radiation-related conditions are age- and dose-related, but generally develop within the radiation field. Chemotherapy-related conditions are also dose- and age-related but may affect multiple organs due to the systemic nature of the exposures. The conditions develop at varying intervals after the therapeutic exposures. Whereas chemotherapy-related complications can be seen as early as within 5 years of the exposure, radiation-associated complications are usually delayed and are typically diagnosed after 10 or more years from exposure. These conditions can cause premature death, resulting in a significant gap in life expectancy compared with the general population. The past decade has seen an increasing interest in a phenomenon called accelerated aging primarily from investigators leveraging the resources offered by the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime (SJLIFE) Cohorts.

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Association of hyperuricaemia and hyperglycaemia with risk of in-hospital mortality in acute aortic dissection: a multicentre cohort study in the Han Chinese population

Objective
The objective is to investigate the association of hyperuricaemia and hyperglycaemia with an increased risk of mortality in acute aortic dissection (AAD).

Design
Retrospective multicentre cohort study.

Setting
De-identified information of patients was collected from electronic medical records between 2010 and 2021 across five hospitals in China.

Participants
A total of 2603 AAD patients from 5337 patients who underwent arterial aortic computed tomographic angiography were selected after three rounds of screening.

Main outcome measure
All-cause in-hospital mortality.

Results
Of the 2603 patients, 20.3% were women, and the mean age was 54 years old. In-hospital mortality risk escalated linearly with increased levels of uric acid (P non-linearity=0.1699) and serum glucose (P non-linearity=0.2423). The per SD of increment in uric acid was associated with 40% (1.40, 1.22 to 1.60) in HR and 95% CI of AAD all-cause in-hospital mortality and 39% (1.39, 1.22 to 1.58) in serum glucose after full adjustment. Patients with a decrease in uric acid and/or serum glucose within the 7 days preceding admission showed significantly lower in-hospital mortality compared with those without a decrease. Notably, patients exhibiting both hyperuricaemia and serum glucose >180.2 mg/dL faced over double mortality risk (2.21, 1.58 to 3.10) compared with those with normal uric acid and normal serum glucose levels.

Conclusions
Hyperuricaemia and hyperglycaemia are significantly associated with an increased risk of mortality among AAD patients in the Han Chinese population. These findings suggest the importance of monitoring and managing uric acid and glucose levels in AAD patients to potentially improve outcomes.

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Association Between Dietary Fiber Intake and Stroke Among US Adults: From NHANES and Mendelian Randomization Analysis

Stroke, Ahead of Print. BACKGROUND:There is debate on the link between dietary fiber intake and stroke risk. The purpose of this study was to look at how it impacts dietary fiber intake and stroke risk, as well as mortality among stroke survivors. Two-sample Mendelian randomization was also used to investigate the causal relationship.METHODS:This research examined information from 1453 patients with stroke participating in the National Health and Nutrition Examination Survey from 1999 to 2018. To assess the incidence of stroke, we conducted a survey-weighted multivariate logistic regression analysis and subgroup analysis. To evaluate the mortality associated with stroke, we used Kaplan-Meier survival analysis combined with survey-weighted Cox regression models. Using 2-sample Mendelian randomization and inverse-variance weighted method, we established a causal relationship between dietary fiber intake and stroke. The article was organized according to Strengthening the Reporting of Observational Studies in Epidemiology and Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines.RESULTS:In the fully adjusted model, dietary fiber intake was negatively associated with stroke (odds ratio, 0.98 [95% CI, 0.97–0.99];P

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Time Window and Watch-and-Wait: Stroke

Stroke, Volume 56, Issue 5, Page 1349-1350, May 1, 2025. According to Global Stroke Fact Sheet 2022, stroke is the second leading cause of death and a major cause of disability. Stroke treatment and care need immediate attention and fill the large existing gaps. This article focuses on the gaps in stroke prevention, management, and care. The author has highlighted 2 main facts, time window and watch-and-wait, which play a critical role in the management of patients upon stroke onset.

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Endoscopic variceal ligation combined with carvedilol versus endoscopic variceal ligation combined with propranolol for the treatment of oesophageal variceal bleeding in cirrhosis: study protocol for a multicentre, randomised controlled trial

Introduction
Liver cirrhosis and its severe complication, oesophageal variceal bleeding (EVB), pose significant health risks. Standard treatment for EVB combines non-selective beta-blockers (NSBB) with endoscopic variceal ligation (EVL). Carvedilol, an NSBB with additional benefits, is preferred for compensated cirrhosis. However, no randomised controlled trial (RCT) has compared carvedilol with propranolol, a conventional NSBB, in combination with EVL for secondary prophylaxis. This study aims to compare the effectiveness and safety of these treatments in preventing variceal rebleeding or death in patients with cirrhosis and EVB.

Methods and analysis
This multicentre, RCT is scheduled to begin in December 2024, with recruitment and follow-up continuing until December 2026. Eligible participants are patients with liver cirrhosis and EVB. Participants are randomly assigned in a 1:1 ratio to receive EVL combined with either carvedilol or propranolol. The primary endpoint is the incidence of variceal rebleeding or all-cause death. Secondary endpoints include all-cause death, liver-related death, each of the complications of portal hypertension (overt ascites, overt hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis), hepatocellular carcinoma, changes in liver function (assessed by Child-Pugh and Model for End-Stage Liver Disease scores), changes in liver stiffness, changes in spleen stiffness, and adverse events. Subgroup and sensitivity analyses will be conducted to evaluate the consistency and robustness of the treatment effects. A total sample size of 524 patients (262 per group) is required to detect a significant difference between the treatment arms.

Ethics and dissemination
The study protocol has been approved by the ethics committee of the First Hospital of China Medical University (No. 2024-656-2). The study will follow the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this trial will be disseminated through peer-reviewed publications, conference presentations and healthcare professionals to guide future clinical practice.

Trial registration number
Chinese Clinical Trial Registry (Registration number: ChiCTR2400089692).

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Stepwise Anatomical Approach to Ablation of Intramural Outflow Tract Ventricular Arrhythmias Guided by Septal Coronary Venous Mapping

Circulation, Ahead of Print. Background: Intramural site of origin is a major cause of ablation failure of ventricular arrhythmias and the optimal strategy is unclear. This study investigated the efficacy of a stepwise ablation approach for intramural outflow tract (OT) premature ventricular complexes (PVCs) guided by mapping of the septal coronary venous system.Methods: Consecutive patients with OT PVCs were included in which an intramural origin was confirmed by demonstration of earliest activation in a septal coronary vein. Radiofrequency ablation was performed from the closest endocardial site in the left (LVOT) and/or right ventricular OT (RVOT) independent of the local activation time. If there was no suppression by endocardial ablation, retrograde transvenous ethanol infusion with a single or double balloon technique was performed, targeting the earliest septal coronary vein. If venous anatomy was not suitable for ethanol ablation or if this failed, bipolar ablation was performed.Results: Sixty patients (age 61±12 years, 78% male) were included. The mean QRS duration of the PVC was 150.8±17.6 ms with a maximum deflection index of 0.51±0.11, and the most common ECG pattern was a left bundle branch block with inferior axis and V3 transition (63%) followed by a right bundle branch block with inferior axis and no transition (27%). Earliest ventricular activation (28.6±11.2 ms pre-QRS) was recorded in the left ventricular annular vein in 15 cases and a septal perforator vein in 45 cases. Acute PVC suppression at the end of the procedure was achieved in all cases. In 87% of cases (n=52), endocardial ablation from the endocardial LVOT, RVOT or both was successful in eliminating the PVC. In the remaining 8 patients, the PVC was eliminated with ethanol infusion (n=7) and bipolar ablation (n=1). Complications included one case of pericardial effusion related to venous mapping. During follow-up (17±24 months), the PVC burden was reduced from 28±12% to 2.3±4.7% and long-term success (≥80% burden reduction) was 88%.Conclusions: Most intramural OT PVCs can be successfully eliminated with endocardial ablation adjacent to the earliest intramural activation site. A high success rate is achieved when following a stepwise approach, with bailout ablation strategies required in a minority of cases.

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Mean arterial pressure after out-of-hospital cardiac arrest (METAPHORE): study protocol for a multicentre controlled trial with blinded primary outcome assessor

Introduction
Out-of-hospital cardiac arrest is a public health concern with a high mortality rate. Hypoxic ischaemic brain injury is the primary cause of death in patients admitted to the intensive care unit (ICU) after return of spontaneous circulation (ROSC). Several systemic factors, such as hypotension, can exacerbate brain injuries. International guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg. Several observational studies suggest that a higher MAP may be associated with better outcomes, but no randomised trials have shown an effect of higher MAP. The ongoing METAPHORE (mean arterial pressure after out-of-hospital cardiac arrest) trial aims to compare a standard MAP threshold (MAP ≥65 mm Hg) with a high MAP threshold (MAP ≥90 mm Hg) to evaluate whether implementing a higher MAP threshold can improve neurological outcomes in patients admitted to ICU after cardiac arrest.

Methods and analysis
METAPHORE is a randomised, controlled, multicentre, open-label trial with a blinded primary outcome assessor, comparing two parallel groups of patients 18 years of age or older, receiving invasive mechanical ventilation for coma defined by a Glasgow Coma Score ≤8/15 after out-of-hospital cardiac arrest and sustained ROSC. Eligible patients are randomly assigned in a 1:1 ratio to either a MAP target threshold of 65 mm Hg or higher throughout the ICU stay (control group) or a MAP target threshold of 90 mm Hg or higher during the first 24 hours after randomisation, followed by 65 mm Hg or higher for the remainder of the ICU stay (intervention group). Both groups receive the same general care concerning post-cardiac arrest syndrome management according to international guidelines. The primary endpoint is the proportion of patients with a favourable neurological outcome as defined by a modified Rankin scale (mRS) of 0 to 3 measured on day 180 after inclusion by a psychologist blinded to the allocation of the intervention. Secondary outcomes are the proportion of patients alive at ICU and hospital discharge, at day 28 and day 180; proportion of patients alive at ICU discharge with a mRS of 0 to 3; the EuroQOL-5D-5L at day 180; the Clinical Frailty Scale at day 180; the number of ICU-free days, ventilator-free days, catecholamine-free days and renal replacement therapy-free days at day 28; the proportion of patients with acute kidney injury stage 3 and need for renal replacement therapy within ICU stay and proportion of patients with persistent need for renal replacement therapy at ICU discharge; and safety outcomes (cardiovascular, neurological, cutaneous, digestive and haemorrhagic complications within 7 days after inclusion). Subgroup analyses are planned according to initial cardiac arrest rhythm (shockable or non-shockable), chronic hypertension and Cardiac Arrest Hospital Prognosis score. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in October 2024 in 27 French ICUs, and a sample of 1380 patients is expected by October 2027.

Ethics and dissemination
The study received approval from the national ethics review board on 8 February 2024 (Comité de Protection des Personnes Sud-Est V – 2023-A00257-38). Patients are included after informed consent has been obtained either from a proxy or through an emergency procedure. Results will be submitted for publication in peer-reviewed journals.

Trial registration number
ClinicalTrials.gov: NCT05486884.

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Diagnostic Accuracy of Finger-Like Projections and Subarachnoid Hemorrhage for Cerebral Amyloid Angiopathy: Pathological Validation From Lobar Hematoma Evacuation or Brain Biopsy

Stroke, Ahead of Print. BACKGROUND:Diagnosing cerebral amyloid angiopathy (CAA) after spontaneous lobar intracerebral hemorrhage has significant clinical implications. A previous postmortem study found that the presence of both subarachnoid hemorrhage (SAH) and hematoma finger-like projections (FLP) on acute-stage computed tomography strongly rules in CAA. In the present study, we assessed the diagnostic value of these imaging markers against histopathologic diagnosis in less severe presentations.METHODS:This retrospective (2002–2022) multicenter study included patients aged ≥45 years with lobar intracerebral hemorrhage of unknown cause, for whom acute-stage computed tomography or magnetic resonance imaging and neuropathological samples from hematoma evacuation or biopsy were available. Centralized consensus reading (2 raters) of imaging and neuropathological data (including Aβ immunohistochemistry) were performed. Analysis was restricted to samples containing at least 10 vessels. The diagnostic performance was evaluated against the neuropathological reference, that is, CAA/no CAA.RESULTS:We analyzed data from 66 patients (age, 65±9 years; men, 33%; hematoma volume, 45±26 mL; death within 1 year, 14%) from 6 French centers. Neuropathological material included samples from hematoma evacuation (n=48) and biopsy (n=18). CAA was present in 38 patients (58%), and FLP and SAH were observed in 29 (44%) and 50 (76%) patients, respectively. FLP had a sensitivity of 0.58 (95% CI, 0.41–0.74) and a specificity of 0.74 (95% CI, 0.54–0.89) for the diagnosis of CAA. SAH demonstrated a high sensitivity of 0.92 (95% CI, 0.78–0.98; negative predictive value=0.80 [0.52–0.96]) but moderate specificity of 0.43 (95% CI, 0.24–0.63). The combined presence of FLP and SAH had a specificity of 0.54 (95% CI, 0.37–0.71) and a sensitivity of 0.79 (95% CI, 0.59–0.92).CONCLUSIONS:This study is the first to evaluate the diagnostic performance of FLP and SAH with histopathologic reference in nonautopsied patients. The results suggest these markers have lower diagnostic performance than previously reported in severe hematomas leading to early death. However, the high sensitivity of SAH suggests its potential clinical utility in ruling out CAA when absent.

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Association of the Timing and Type of Acute Symptomatic Seizures With Poststroke Epilepsy and Mortality

Stroke, Ahead of Print. BACKGROUND:Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear.METHODS:This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024. The study included 4552 adults (2005 female; median age, 73 years) with ischemic stroke and no seizure history. Seizures were classified using International League Against Epilepsy definitions. We examined ASyS occurring within seven days after stroke. The main outcomes were all-cause mortality and epilepsy. Validation of the updated SeLECT score (SeLECT-ASyS) was performed in 3 independent cohorts (Switzerland, Argentina, and Japan) collected between 2012 and 2024, including 74 adults with ASyS.RESULTS:The 10-year risk of poststroke epilepsy ranged from 41% to 94%, and mortality from 36% to 100%, depending on ASyS type and timing. ASyS on stroke onset day had a higher epilepsy risk (adjusted hazard ratio [aHR], 2.3 [95% CI, 1.3–4.0];P=0.003) compared with later ASyS. Status epilepticus had the highest epilepsy risk (aHR, 9.6 [95% CI, 3.5–26.7];P

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Estimating the clinical and healthcare burden of metabolic dysfunction-associated steatohepatitis in England: a retrospective cohort study using routinely collected healthcare data from 2011 to 2020

Objective
To characterise patients with metabolic dysfunction-associated steatohepatitis (MASH) in England and to estimate its associated healthcare resource use (HCRU) and costs, both overall and by progression status and comorbidities.

Design
This was a retrospective observational study of adults with a MASH-coded primary and/or secondary care recorded diagnosis in England (2011–2020). The analysis used data from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and death registrations. Annualised all-cause and MASH-related (ie, coded as MASH, end-stage liver disease or major adverse cardiovascular event) HCRU and costs were calculated for patients with incident MASH. Subgroup analyses were conducted for patients with type 2 diabetes, overweight/obesity, cardiovascular disease or progression to cirrhosis. Comparative cost analysis was conducted between those with progressed MASH and those who did not progress.

Results
A total of 2696 patients were included (mean follow-up: 4 years). Incidence of MASH was estimated at 4.7 per 100 000 person-years overall and increased among patients with key comorbidities. Patients who had type 2 diabetes had greater HCRU and costs than those who did not (eg, mean 1.8 vs 1.0 all-cause inpatient admissions and £2227 vs £1151 all-cause inpatient costs per-patient per-year). Some patients with MASH progressed to compensated (8.6%) or decompensated cirrhosis (6.5%) during the study. HCRU and costs were substantially higher among patients who progressed than among those who did not (eg, mean 2.4 vs 1.1 all-cause inpatient admissions and £3620 vs £1290 all-cause inpatient costs per-patient per-year).

Conclusion
HCRU and costs associated with MASH are higher among patients who have cardiometabolic comorbidities or who progress to advanced disease stages. Therefore, efforts to detect cases early and prevent disease progression could reduce healthcare burden.

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