Cervicomedullary Compression in Achondroplasia: A Feared Complication and an Unforeseen Risk Factor of Posterior Circulation Stroke.

Achondroplasia is an autosomal dominant disorder with defect in the ossification of the cartilage of long bones. Many bony abnormalities constitute its clinical features, with craniovertebral junction (CVJ) anomalies being one of most common issues which need to be addressed at the earliest. CVJ anomalies in individuals may cause neurovascular compression, which may warrant an early surgery to prevent catastrophic complications. Posterior circulation strokes secondary to CVJ anomalies are well known. We hereby present an unusual case of posterior circulation stroke in an achondroplastic dwarf who presented to our tertiary care centre. Prospective case study. The present case adds to the existing literature about one of the preventable causes of fatal posterior circulation strokes in the young. A high index of suspicion for neurovascular compression at the foramen magnum and early initiation of treatment in achondroplastic young individuals may have gratifying results.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

BACKGROUND AND OBJECTIVES: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. METHODS: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. RESULTS: Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. DISCUSSION: Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Cost-effectiveness of left atrial appendage occlusion during cardiac surgery in France: An economic evaluation based on the LAAOS III study.

OBJECTIVES: Left atrial appendage occlusion during cardiac surgery is a therapeutic option for stroke prevention in patients with atrial fibrillation. The effectiveness and safety of left atrial appendage occlusion have been evaluated in several studies, including the LAAOS-III trial. While these studies have demonstrated efficacy and safety, the long-term economic impact of this surgical technique has not yet been assessed. Here, we aimed to evaluate the cost-effectiveness and cost-utility of left atrial appendage occlusion during cardiac surgery over a long-term time horizon. METHODS: Our study was based on a model representing an hypothetical cohort with the same characteristics as LAAOS-III trial patients. We modelled the incidence of ischemic strokes and systemic embolisms in each intervention arm: "occlusion" and "no-occlusion," using a one-month cycle length with a 20-year time horizon. Regarding occlusion devices, sutures, staples, or an approved surgical occlusion device (AtriClip™-AtriCure, Ohio, USA) could be used. RESULTS: Our model generated an average cost savings of 607 euros per patient and an incremental gain of 0.062 quality-adjusted life years (QALYs), resulting an incremental cost-utility ratio (ICUR) of €-9,775/QALY. The scenario analysis in which occlusion was systematically performed using the AtriClip™ device generated an ICUR of €3,952/QALY gained. CONCLUSIONS: In the base-case analysis, the strategy proved to be more effective and less costly, confirming left atrial appendage occlusion during cardiac surgery as an economically dominant strategy. The scenario analysis also appeared cost-effective, although it did not result in cost savings. This study provides a new perspective on the assessment of the cost-effectiveness of these techniques.

Atrial fibrillation increases thrombogenicity of LVAD therapy.

BACKGROUND: This study investigates the hypothesis that presence of atrial fibrillation (AF) in LVAD patients increases thrombogenicity in the left ventricle (LV) and exacerbates stroke risk. METHODS: Using an anatomical LV model implanted with an LVAD inflow cannula, we analyze thrombogenic risk and blood flow patterns in either AF or sinus rhythm (SR) using unsteady computational fluid dynamics (CFD). To analyze platelet activation and thrombogenesis in the LV, hundreds of thousands of platelets are individually tracked to quantify platelet residence time (RT) and shear stress accumulation history (SH). RESULTS: The irregular and chaotic mitral inflow associated with AF results in markedly different intraventricular flow patterns, with profoundly negative impact on blood flow-induced stimuli experienced by platelets as they traverse the LV. Twice as many platelets accumulated very high SH in the LVAD + AF case, resulting in a 36% increase in thrombogenic potential score, relative to the LVAD + SR case. CONCLUSIONS: This supports the hypothesis that AF results in unfavorable blood flow patterns in the LV adding to an increased stroke risk for LVAD + AF patients. Quantification of thrombogenic risk associated with AF for LVAD patients may help guide clinical decision-making on interventions to mitigate the increased risk of thromboembolic events.

Early-life tobacco smoke exposure and stroke risk: a prospective study of 341,783 and 352,737 UK Biobank participants.

INTRODUCTION: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging. CONCLUSION: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

The left atrial appendage closure by surgery 2 trial: statistical analysis plan for a randomized multicenter trial exploring if the closure of the left atrial appendage during open-heart surgery reduces stroke irrespective of patients' stroke risk and preoperative atrial fibrillation status.

BACKGROUND: Surgical left atrial appendage (LAA) closure concomitant to open-heart surgery prevents thromboembolism in high-risk patients. Nevertheless, high-level evidence does not exist for LAA closure performed in patients with any CHA2DS2-VASc score and preoperative atrial fibrillation or flutter (AF) status-the current trial attempts to provide such evidence. METHODS: The study is designed as a randomized, open-label, blinded outcome assessor, multicenter trial of adult patients undergoing first-time elective open-heart surgery. Patients with and without AF and any CHA2DS2-VASc score will be enrolled. The primary exclusion criteria are planned LAA closure, planned AF ablation, or ongoing endocarditis. Before randomization, a three-step stratification process will sort patients by site, surgery type, and preoperative or expected oral anticoagulation treatment. Patients will undergo balanced randomization (1:1) to LAA closure on top of the planned cardiac surgery or standard care. Block sizes vary from 8 to 16. Neurologists blinded to randomization will adjudicate the primary outcome of stroke, including transient ischemic attack (TIA). The secondary outcomes include a composite outcome of stroke, including TIA, and silent cerebral infarcts, an outcome of ischemic stroke, including TIA, and a composite outcome of stroke and all-cause mortality. LAA closure is expected to provide a 60% relative risk reduction. In total, 1500 patients will be randomized and followed for 2 years. DISCUSSION: The trial is expected to help form future guidelines within surgical LAA closure. This statistical analysis plan ensures transparency of analyses and limits potential reporting biases. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03724318. Registered 26 October 2018, https://clinicaltrials.gov/study/NCT03724318 . PROTOCOL VERSION: https://doi.org/10.1016/j.ahj.2023.06.003 .

[Stroke and stroke prevention in cardiac and thoracic aortic surgery]. / Ictus e prevenzione dell'ictus in cardiochirurgia e in chirurgia dell'aorta toracica.

Perioperative stroke and neurological injuries in general are complications that can occur during and after cardiac surgery, particularly in aortic surgery that involves the aortic arch. The overall incidence of early and delayed stroke is about 1% according to recent meta-analyses. This incidence depends on interindividual risk factor profile and type of surgery. In order to reduce cerebrovascular complications during cardiac surgery, a number of preventative measures can be taken, including the evaluation of atherosclerotic plaques, the site of cannulation and neuroprotection strategies. During aortic arch surgery, main strategies for cerebral protection are represented by deep hypothermic circulatory arrest, retrograde and antegrade cerebral perfusion.

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Prediction of aneurysmal subarachnoid hemorrhage in comparison with other stroke types using routine care data.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

Interactions between antiepileptic drugs and direct oral anticoagulants for primary and secondary stroke prevention.

INTRODUCTION: Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023. AREAS COVERED: Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC. EXPERT OPINION: Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to in vitro and in vivo findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.

New Horizons in Emergency Department Management of Pediatric Sickle Cell Disease.

ABSTRACT: Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.

Prevalence of major adverse cardiovascular events among Saudi patients with systemic lupus erythematosus compared with the general population: updates from the national SLE and PURE cohorts.

OBJECTIVE: This study examined the prevalence of major adverse cardiovascular events (MACE) among Saudi patients with SLE and the general population and considered factors associated with such outcomes were taken into consideration. METHODS: This is a cohort study evaluating the period prevalence of MACE from 2020 to 2023. The study used two datasets, namely the Saudi national prospective cohort for SLE patients and the Prospective Urban-Rural Epidemiology Study Saudi subcohort (PURE-Saudi) for the general population. Participants in both studies were monitored using a standardised protocol. MACE was defined as myocardial infarction (MI), stroke or angina. The analysis was adjusted for demographics, traditional cardiovascular risk factors and SLE diagnosis through logistic regression models. RESULTS: The PURE and national SLE cohorts comprised 488 and 746 patients, respectively. Patients with SLE from the SLE cohort were younger (40.7±12.5 vs 49.5±8.6 years) and predominantly female (90.6% vs 41.6%). The prevalence of traditional risk factors was greater in the PURE cohort compared with the SLE cohort. These factors included dyslipidaemia (28.9% vs 49.4%), obesity (63% vs 85%) and diabetes (7.8% vs 27.2%), but not hypertension (19.3% vs 18.8%). MACE (defined as MI or stroke or venous thromboembolism or heart failure) occurred more frequently in patients with SLE (4.3% vs 1.6%, p=0.004). Older age and lupus diagnosis were independently associated with MACE after adjusting for conventional risk factors. The odds of MACE were significantly related to age and lupus diagnosis (p=0.00 and p=0.00, respectively), but not cardiovascular disease (CVD) risk factors (p=0.83). CONCLUSION: Patients with SLE have a significantly higher risk of developing MACE than the general population. This risk is not well explained by traditional risk factors, which may explain the failure of CVD risk scores to stratify patients with SLE adequately. Further studies are needed to understand CVD risk's pathogenesis in SLE and mitigate it.