Effectiveness of Two Models of Telerehabilitation in Improving Recovery from Subacute Upper Limb Disability after Stroke: Robotic vs. Non-Robotic.

BACKGROUND/OBJECTIVES: Finding innovative digital solutions is fundamental to ensure prompt and continuous care for patients with chronic neurological disorders, whose demand for rehabilitation also in home-based settings is steadily increasing. The aim is to verify the safety and the effectiveness of two telerehabilitation (TR) models in improving recovery from subacute upper limb (UL) disability after stroke, with and without a robotic device. METHODS: One hundred nineteen subjects with subacute post-stroke UL disability were assessed for eligibility. Of them, 30 patients were enrolled in the study and randomly assigned to either the Robotic Group (RG), undergoing a 20-session TR program, using a robotic device, or the Non-Robotic Group (NRG), undergoing a 20-session TR program without robotics. Clinical evaluations were measured at baseline (T0) and post-intervention (T1, 5 weeks after baseline), and included assessments of quality of life, motor skills, and clinical/functional status. The primary outcome measure was the World Health Organization Disability Assessment Schedule 2.0, evaluating the change in perceived disability. RESULTS: Statistical analysis shows that patients of both groups improved significantly over time in all domains analyzed (mean decrease from baseline in the WHODAS 2.0 of 6.09 ± 2.62% for the NRG, and of 0.76 ± 2.21% for the RG), with a greater improvement of patients in the NRG in motor (Fugl-Meyer Assessment Upper Extremity-motor function, Box and Block Test) and cognitive skills (Trail Making Test-A). CONCLUSIONS: This study highlights the potential of TR programs to transform stroke rehabilitation by enhancing accessibility and patient-centered care, promoting autonomy, improving adherence, and leading to better outcomes and quality of life for stroke survivors.

Assessment of Noninferiority Margins in Cardiovascular Medicine Trials.

Background: Noninferiority trials are increasingly common in cardiovascular medicine, but their reporting and interpretation are challenging, particularly when an absolute risk difference is used as noninferiority margin. Objectives: This study aimed to investigate the effect of using absolute rather than relative noninferiority margins in cardiovascular trials. Methods: We reviewed noninferiority trials presented at major cardiovascular conferences from 2015 to 2022 and published within the same period. Based on the actual versus anticipated event rates in the control group, we recalculated the absolute noninferiority margin and re-assessed the trial results. The primary outcome of interest was the proportion of trials with a different interpretation after recalculation. Additionally, we analyzed the conclusion statements of these trials to determine if cautionary notes for the interpretation of study results were included. Results: We analyzed a total of 768 trials, of which 88 had a noninferiority design and 66 used an absolute noninferiority margin. Of 48 comparisons from 45 trials qualifying for the analysis, 11 (22.9%) had divergent results after recalculation of the absolute noninferiority margin based on the observed rather than anticipated event rate. Ten trials originally claiming noninferiority, did not meet it after the margin recalculation. All of them did not include statements suggesting cautionary interpretation of the study results in the conclusion section. Compared with the other trials, these displayed a larger median difference between anticipated and recalculated noninferiority margins (44.7% [IQR: 38.6%-56.7%] vs 15.3% [IQR: -1.5% to 28.9%]; P < 0.001). Conclusions: Recalculating noninferiority margins based on actual event rates, rather than anticipated ones, led to different outcomes in approximately 1 out of 4 cardiovascular trials, with most divergent trials lacking cautionary interpretation. These findings emphasize the importance of using or supplementing the relative noninferiority margin, particularly in studies with significant deviations between observed and expected event rates. This underscores the critical need for enhanced methodological and reporting standards in noninferiority trials, especially those employing absolute margins.

Altered Brain Reactivity to Food Cues in Undergraduate Students with Disordered Eating Behaviors.

PURPOSE: A growing body of evidence has shown that electroencephalography (EEG) is an interesting method of assessing the underlying brain physiology associated with disordered eating. Using EEG, we sought to evaluate brain reactivity to hyper-palatable food cues in undergraduate students with disordered eating behavior (DEB). METHODS: After assessing the eating behaviors of twenty-six undergraduate students using the Eating Attitudes Test (EAT-26), electroencephalographic signals were recorded while the participants were presented with pictures of hyper-palatable food. The current study used a temporospatial principal component analysis (PCA) approach to identify event-related potential (ERP) responses that differed between DEB and non-DEB individuals. RESULTS: A temporospatial PCA applied to the ERPs identified a positivity with a maximum amplitude at 347 ms at the occipital-temporal electrodes in response to pictures of hyper-palatable food. This positivity was correlated with the EAT-26 scores. Participants with DEB showed reduced positivities in this component compared with those without DEB. CONCLUSION: Our findings may reflect greater motivated attention toward hyper-palatable food cues in undergraduate students with DEB. These results are an important step toward obtaining a more refined understanding of specific abnormalities related to reactivity to food cues in this population.

DDS-SIRC Cooperative Conferences Feel the Burn: RFA for Chronic Radiation Proctitis.

Chronic radiation proctitis, although relatively rare, can be the source of severe comorbidity in patients who had undergone prior radiotherapy for pelvic malignancy. Although current treatments for radiation proctitis include argon plasma coagulation, heater probe, bipolar neodymium/yttrium aluminum garnet (Nd: YAG) lasers, these interventions are often burdened by the frequent occurrence of rectal ulcerations and stenosis. Since radiofrequency ablation (RFA) is frequently used to ablate esophageal malignancy and pre-malignancy, we report the efficacy of RFA using through the scope system in two patients with rectal bleeding due to radiation proctitis. In both cases, the procedure was well-tolerated with hemostasis achieved after 1 or 2 sessions of RFA. Mucosal re-epithelialization was observed in areas of previous bleeding with no stenosis or ulceration observed at follow-up.

Influence of different palatal morphologies on the accuracy of intraoral scanning of the edentulous maxilla: A three-dimensional analysis.

PURPOSE: This study investigated the influence of different palatal morphologies on the accuracy of intraoral scanning (TRIOS 4) of edentulous maxillae. METHODS: Six typodonts were fabricated for different palatal morphologies with flat (F), medium (M), and deep (D) palates, with palatal wrinkles (W), or smooth palates (S), resulting in six groups: WF, WM, WD and SF, SM, SD. Ten scans were performed for each group; standard tessellation language files obtained were imported into a software to measure trueness and precision in micrometer. Trueness was calculated as the mean of the standard deviation values obtained by superimposing each scan onto the reference scan. Precision was achieved by overlapping each scan with that with the best trueness in the group. Descriptive and post-hoc analyses were conducted. RESULTS: The mean values for trueness were as follows: WM=48.7±4.7, WD=161.7±18.4, WF=85.9±16, SM=48.1±2.4, SD=349.9±8.8, and SF=349.1±25.5. The precision values were as follows: WM=46.7±7.3, WD=46.9±9, WF=48.9±6.7, SM=46±2.7, SD=105.9±17.4, SF=72.6±10.8. Significant differences were observed for trueness between SM and SD (P < 0.001), SM and SF (P < 0.001), and WF and SF (P = 0.003); whereas for precision, significant differences were reported between WD and SD (P = 0.015). Regarding trueness and precision, no difference was found between WM and SM (P = 1.0). CONCLUSIONS: Medium palatal depth showed the best accuracy. The mean accuracy values were within the clinical acceptability thresholds for all palatal morphologies. The presence of rugae improved the precision of deeper palates and the trueness of flat palates. No differences were observed in the medium palates with or without rugae.

Epidemiology and Clinical impact of single and multi-viral respiratory infections in post-pandemic era.

Acute respiratory tract infections (ARI) are common diseases in children and adults and could cause severe infections in high-risk patients, like the immunocompromised and elderly, and are the leading cause of morbidity, hospitalization and mortality. This study aimed to explore the prevalence of respiratory viruses and the clinical impact of single- and multi-infection among hospitalized patients in various age groups. 3578 nasopharyngeal swabs (NPS) were analyzed for pathogen detection of acute respiratory tract infections. 930 out of 3578 NPS were diagnosed positive for at least one respiratory virus. The distribution of viral infections, prevalence and pathogen, differed significantly among age groups. Most RTI are observed in the age group over 65 years (50.6%) with a high SARS-CoV2 prevalence, following by group <5 years (25.6%), where the most frequently detected viruses were RSV, Rhinovirus, FluA-H3, MPV, and AdV. The co-infection rate also varies according to age and, in some cases, especially in older adults, could have severe clinical impact. This study emphasizes that it is important to know and analyze, in all age groups of hospitalized patients, the epidemiology of respiratory viruses, the prevalence of coinfections, and the clinical impact of various pathogens. Furthermore, in a clinical setting, the rapid diagnosis of respiratory infections by means of molecular tests is crucial not only to avoid hospital outbreaks, but also to allow early and optimal treatment to reduce morbidity and mortality.

Exploring the impact of cardiologists expertise on publication metrics.

BACKGROUND: In the field of academic cardiology, the assessment of an author's scholarly impact and professional progression heavily relies on publications and citations. This study investigates whether specific cardiology expertise correlates with accelerated professional growth. METHODS: Using data from the 2023 European Society of Cardiology congress, 948 faculty attendees with an h-index of 30 or higher were analyzed. Expertises were categorized into six groups, and their association with publications and citations peaks was explored. RESULTS: Interventional cardiologists exhibited the highest annual publication peak, followed by imaging and electrophysiology experts. However, no significant differences were observed in citation peaks among expertise groups. While imaging experts initially appeared to reach citation peaks faster, this effect diminished after statistical adjustments. Additionally, holding multiple expertise areas prolonged the time to reach publication and citation peaks by approximately six years. CONCLUSION: This study underscores the influence of expertise in interventional cardiology on publication peaks but suggests that citation peaks and career progression velocity remain unaffected by expertise type. Furthermore, it highlights that holding multiple areas of expertise slowers the attainment of career peak for scholarly authors.

Percutaneous interventions for pulmonary embolism.

Pulmonary embolism (PE) ranks as a leading cause of in-hospital mortality and the third most common cause of cardiovascular death. The spectrum of PE manifestations varies widely, making it difficult to determine the best treatment approach for specific patients. Conventional treatment options include anticoagulation, thrombolysis, or surgery, but emerging percutaneous interventional procedures are being investigated for their potential benefits in heterogeneous PE populations. These novel interventional techniques encompass catheter-directed thrombolysis, mechanical thrombectomy, and hybrid approaches combining different mechanisms. Furthermore, inferior vena cava filters are also available as an option for PE prevention. Such interventions may offer faster improvements in right ventricular function, as well as in pulmonary and systemic haemodynamics, in individual patients. Moreover, percutaneous treatment may be a valid alternative to traditional therapies in high bleeding risk patients and could potentially reduce the burden of mortality related to major bleeds, such as that of haemorrhagic strokes. Nevertheless, the safety and efficacy of these techniques compared to conservative therapies have not been conclusively established. This review offers a comprehensive evaluation of the current evidence for percutaneous interventions in PE and provides guidance for selecting appropriate patients and treatments. It serves as a valuable resource for future researchers and clinicians seeking to advance this field. Additionally, we explore future perspectives, proposing "percutaneous primary pulmonary intervention" as a potential paradigm shift in the field.

Antithrombotic strategies for preventing graft failure in coronary artery bypass graft.

Coronary artery bypass graft (CABG) procedures face challenges related to graft failure, driven by factors such as acute thrombosis, neointimal hyperplasia, and atherosclerotic plaque formation. Despite extensive efforts over four decades, the optimal antithrombotic strategy to prevent graft occlusion while minimizing bleeding risks remains uncertain, relying heavily on expert opinions rather than definitive guidelines. To address this uncertainty, we conducted a review of randomized clinical trials and meta-analyses of antithrombotic therapy for patients with CABG. These studies examined various antithrombotic regimens in CABG such as single antiplatelet therapy (aspirin or P2Y12 inhibitors), dual antiplatelet therapy, and anticoagulation therapy. We evaluated outcomes including the patency of grafts, major adverse cardiovascular events, and bleeding complications and also explored future perspectives to enhance long-term outcomes for CABG patients. Early studies established aspirin as a key component of antithrombotic pharmacotherapy after CABG. Subsequent randomized controlled trials focused on adding a P2Y12 inhibitor (such as clopidogrel, ticagrelor, or prasugrel) to aspirin, yielding mixed results. This article aims to inform clinical decision-making and guide the selection of antithrombotic strategies after CABG.

Trueness and precision of an intraoral scanner on abutments with subgingival vertical margins: An in vitro study.

OBJECTIVES: This study aimed to evaluate the accuracy of an intraoral scanner (IOS - Medit i700) on tooth abutments with vertical preparations at 2 depths below the free gingival margin, and to determine if the IOS can reproduce the area beyond the finish surface of the tested preparation geometry. METHODS: Two abutments for a maxillary first molar were designed by means of CAD software, with vertical preparations set at 1 and 2 mm below the gingiva. These abutments were subsequently printed in resin and placed on a reference model. The reference files consisted of scans made using a metrological machine on these abutments. Ten scans were made with the tested IOS on each sample, resulting in two study groups. The scans from the experimental groups were labeled "V-1″ for vertical preparation at 1 mm below the gingival margin and "V-2″ for 2 mm below. The analysis of these scans was performed using Geomagic Control X (3D SYSTEMS) to assess their trueness and precision in µm. Descriptive statistics with a 95 % confidence interval were employed, alongside independent sample tests, to ascertain any differences between the groups (α=0.05). RESULTS: Statistically significant differences were not found both for trueness (p=.104) and precision (p=.409), between the tested geometries. The mean values for trueness were V-1 = 37.5[31.4-43.6]; V-2 = 32.6[30.6-34.6]. About the precision, the mean values were V-1 = 20.5[8.4-32.5]; V-2 = 18.4[8.2-28.5]. In both the study groups, it was possible to detect the surface beyond the finish area. CONCLUSIONS: Within the limitations of this study, vertical preparation design allows for registration of the tooth anatomy beyond the finish area with IOS. Moreover, the mean accuracy values were clinically acceptable at both 1 and 2 mm below the gingival margin.

Coronary Angiography, Intravascular Ultrasound, and Optical Coherence Tomography for Guiding of Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)- and optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)-guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results. METHODS: Major electronic databases were searched to identify eligible trials evaluating at least 2 PCI guidance strategies among ICA, IVUS, and OCT. The 2 coprimary outcomes were target lesion revascularization and myocardial infarction. The secondary outcomes included ischemia-driven target lesion revascularization, target vessel myocardial infarction, death, cardiac death, target vessel revascularization, stent thrombosis, and major adverse cardiac events. Frequentist random-effects network meta-analyses were conducted. The results were replicated by Bayesian random-effects models. Pairwise meta-analyses of the direct components, multiple sensitivity analyses, and pairwise meta-analyses IVI versus ICA were supplemented. RESULTS: The results from 24 randomized trials (15 489 patients: IVUS versus ICA, 46.4%, 7189 patients; OCT versus ICA, 32.1%, 4976 patients; OCT versus IVUS, 21.4%, 3324 patients) were included in the network meta-analyses. IVUS was associated with reduced target lesion revascularization compared with ICA (odds ratio [OR], 0.69 [95% CI, 0.54-0.87]), whereas no significant differences were observed between OCT and ICA (OR, 0.83 [95% CI, 0.63-1.09]) and OCT and IVUS (OR, 1.21 [95% CI, 0.88-1.66]). Myocardial infarction did not significantly differ between guidance strategies (IVUS versus ICA: OR, 0.91 [95% CI, 0.70-1.19]; OCT versus ICA: OR, 0.87 [95% CI, 0.68-1.11]; OCT versus IVUS: OR, 0.96 [95% CI, 0.69-1.33]). These results were consistent with the secondary outcomes of ischemia-driven target lesion revascularization, target vessel myocardial infarction, and target vessel revascularization, and sensitivity analyses generally did not reveal inconsistency. OCT was associated with a significant reduction of stent thrombosis compared with ICA (OR, 0.49 [95% CI, 0.26-0.92]) but only in the frequentist analysis. Similarly, the results in terms of survival between IVUS or OCT and ICA were uncertain across analyses. A total of 25 randomized trials (17 128 patients) were included in the pairwise meta-analyses IVI versus ICA where IVI guidance was associated with reduced target lesion revascularization, cardiac death, and stent thrombosis. CONCLUSIONS: IVI-guided PCI was associated with a reduction in ischemia-driven target lesion revascularization compared with ICA-guided PCI, with the difference most evident for IVUS. In contrast, no significant differences in myocardial infarction were observed between guidance strategies.

Spontaneous pneumomediastinum associated with subcutaneous emphysema, pneumopericardium and pneumothorax: a rare association complicating measles.

A unique case of severe measles complicated by multiple features of gas accumulation is described, on the ground of the available literature evidences. Complications from measles have been reported in every organ system and they may vary by age and underlying conditions. Pneumomediastinum is usually associated with subcutaneous emphysema and pneumopericardium, but rarely associated with pneumothorax. We report extremely rare simultaneous occurrence of self-limiting pneumomediastinum, pneumopericardium, subcutaneous neck and chest region emphysema, and pneumothorax, in a 19-year-old girl with measles. A review of the literature has documented only one previous report of spontaneous pneumomediastinum, subcutaneous emphysema and pneumothorax in the course of measles, and no previous cases reported the association of pneumomediastinum, subcutaneous emphysema, pneumopericardium and pneumothorax complicating measles.

Pharmacological and clinical appraisal of factor XI inhibitor drugs.

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study.

INTRODUCTION AND OBJECTIVES: Randomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. METHODS: In this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. RESULTS: Of 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). CONCLUSIONS: Randomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

PCSK9 inhibitors: current status and emerging frontiers in lipid control.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels. AREAS COVERED: The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed. EXPERT OPINION: Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research.

Extremely severe thrombocytopenia in both immunocompetent and immunocompromised hosts as a consequence of cytomegalovirus infection.

Two recent cases of extremely severe thrombocytopenic purpura related to a concomitant cytomegalovirus infection, either associated or not with an underlying immunosuppression, draw our attention on this intriguing pathologic association, on the ground of an updated literature review.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

Antithrombotic Therapy for Primary and Secondary Prevention of Ischemic Stroke: JACC State-of-the-Art Review.

Stroke is a devastating condition with significant morbidity and mortality worldwide. Antithrombotic therapy plays a crucial role in both primary and secondary prevention of stroke events. Single or dual antiplatelet therapy is generally preferred in cases of large-artery atherosclerosis and small-vessel disease, whereas anticoagulation is recommended in conditions of blood stasis or hypercoagulable states that mostly result in red thrombi. However, the benefit of antithrombotic therapies must be weighed against the increased risk of bleeding, which can pose significant challenges in the pharmacological management of this condition. This review provides a comprehensive summary of the currently available evidence on antithrombotic therapy for ischemic stroke and outlines an updated therapeutic algorithm to support physicians in tailoring the strategy to the individual patient and the underlying mechanism of stroke.