Clinical application and feasibility of capsule endoscopy in children at a medical center in central Taiwan.

BACKGROUND PURPOSE: Capsule endoscopy (CE) is a noninvasive examination for excellent visualization of small bowel mucosal lesions. We aimed to evaluate the clinical efficacy and safety of CE in pediatric patients. METHODS: From April 2014 to December 2022, CE procedures performed in children younger than 18 years of age at Taichung Veteran General Hospital were analyzed retrospectively. RESULTS: Among 136 procedures, the completion rate was 95.6% (n = 130), with a median age of 14 years old. Suspicion or evaluation of inflammatory bowel diseases (IBD) (41%) was the most common indication for CE. Other common indications of CE were chronic unexplained abdominal pain (35%) and obscure gastrointestinal bleeding or iron deficiency anemia (21%). No procedure-related complications occurred. The diagnosis of those patients with incomplete study were CD with small bowel stricture, graft-versus-host disease and duodenal ulcers. A total of 86 CE procedures showed positive findings, and the overall diagnostic yield rate was 63.2%. Small bowel ulcers (65.12%) were the most common findings. Overall, 26.5% of CE examinations resulted in a new diagnosis and 44.9% of CE exams led to a change in therapy. For patients with IBD, CE findings resulted in an even higher therapeutic change rate of 48.1%. CONCLUSIONS: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for IBD. Incomplete study could be an indicator of positive finding and can potentially be a guide to identify the site of possible strictures.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Enhanced versus standard hydration in acute ischaemic stroke: REVIVE - a randomised clinical trial.

RATIONALE: Early neurological deterioration (END) within 72 hours of stroke onset is associated with poor prognosis. Optimising hydration might reduce the risk of END. AIMS: To determine in acute ischaemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as whether it increased the incidence of early neurological improvement (secondary), at 72 hours after admissionSample Size Estimate: 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicentre, parallel-group, randomised controlled trial conducted at 4 hospitals from April 2014 to July 2020, with data analysed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischaemic stroke patients with measurable neurological deficits of onset within 12 hours of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ≥15 at point of admission were enrolled and randomised to 0.9% sodium chloride infusions of varying rates - enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 hours) versus standard hydration (60 mL/hour for 8 hours), followed by maintenance infusion of 40-80 mL/hour for the subsequent 64 hours. The primary outcome measure was the incidence of major early neurological deterioration at 72 hours after admission, defined as an increase in National Institutes of Health Stroke Scale of ≥4 points from baseline. RESULTS: 487 participants were randomised (median age 67 years; 287 females). At 72 hours: 7 (2.9%) in the enhanced-hydration arm and 5(2.0%) in the standard-hydration developed major early neurological deterioration (p=0.54). The incidence of minor early neurological deterioration and early neurological improvement did not differ between treatment arms. CONCLUSIONS AND RELEVANCE: Enhanced hydration ratio did not reduce END or improve short term outcomes in acute ischaemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).

Exploring the relationship between lesion morphology and pathogenesis in acute small subcortical infarction.

Introduction Acute small subcortical infarctions (SSIs) result from occlusions of small penetrating arteries, and the underlying pathological factors can have different clinical implications. The objective of this study was to assess the clinical relevance of acute SSIs based on their sizes and morphologies. Methods This retrospective case-control study analyzed clinical and imaging data of stroke patients with acute SSIs in penetrating artery territories who underwent MRI within 5 days of stroke onset, registered between 2016 and 2020. We categorized these patients into three groups based on size and morphology: diameter < 20mm, diameter ≧ 20mm, and separated lesions. We then evaluated their clinical characteristics and outcomes. Results We analyzed 726 stroke patients with SSIs, among whom 573 had a diameter <20mm, 99 had a diameter ≥20mm, and 54 had separated lesions. The patients had a median age of 70 years and a median National Institutes of Health Stroke Scale (NIHSS) score of 4 on arrival. Patients who experienced early neurological deterioration (END) had a significantly lower chance of good functional outcomes (27.3% vs. 64.4%, p<0.001). Patients with a diameter ≧20mm had the most severe NIHSS on arrival and at day 3, the highest rate of END, and the lowest rate of good outcome at 3 months. The incidence of cardioembolism did not differ between patients with diameters of ≥20mm and <20mm. However, multiple logistic regression analysis revealed that separated lesions were more likely to be associated with cardioembolic stroke (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 2.0-28.5) and parent artery stenosis >50% (aOR, 3.8; 95% CI, 2.1-7.0) than a diameter of <20mm. Moreover, SSIs with a diameter of ≥20mm was found to be associated with an increased risk of END compared to that with a diameter of <20mm (aOR, 2.9; 95% CI, 1.7-5.2). Conclusion Our study suggests that the sizes and morphologies of acute SSIs may indicate different underlying pathologies and be linked to diverse clinical outcomes. Our findings also challenge the current imaging criteria for embolic stroke of undetermined source, as we did not find a link between large subcortical infarction and cardioembolic stroke.

An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration.

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31-22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.

Association between initial in-hospital heart rate and glycemic control in patients with acute ischemic stroke and diabetes mellitus.

BACKGROUND: A high resting heart rate (HR) has been associated with an increased risk of diabetes mellitus. This study explored the association between initial in-hospital HR and glycemic control in patients with acute ischemic stroke (AIS) and diabetes mellitus. METHODS: We analyzed data from 4,715 patients with AIS and type 2 diabetes mellitus enrolled in the Chang Gung Research Database between January 2010 and September 2018. The study outcome was unfavorable glycemic control, defined as glycated hemoglobin (HbA1c) ≥ 7%. In statistical analyses, the mean initial in-hospital HR was used as both a continuous and categorical variable. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression analysis. The associations between the HR subgroups and HbA1c levels were analyzed using a generalized linear model. RESULTS: Compared with the reference group (HR < 60 bpm), the adjusted ORs for unfavorable glycemic control were 1.093 (95% CI 0.786-1.519) for an HR of 60-69 bpm, 1.370 (95% CI 0.991-1.892) for an HR of 70-79 bpm, and 1.608 (95% CI 1.145-2.257) for an HR of ≥ 80 bpm. Even after adjusting for possible confounders, the HbA1c levels after admission and discharge among diabetic stroke patients increased significantly in the subgroups with higher HRs (p < 0.001). CONCLUSIONS: High initial in-hospital HR is associated with unfavorable glycemic control in patients with AIS and diabetes mellitus, particularly in those with an HR of ≥ 80 bpm, compared with those with an HR of < 60 bpm.

Development and Validation of a Novel Score for Predicting Long-Term Mortality after an Acute Ischemic Stroke.

BACKGROUND: Long-term mortality prediction can guide feasible discharge care plans and coordinate appropriate rehabilitation services. We aimed to develop and validate a prediction model to identify patients at risk of mortality after acute ischemic stroke (AIS). METHODS: The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular death. This study included 21,463 patients with AIS. Three risk prediction models were developed and evaluated: a penalized Cox model, a random survival forest model, and a DeepSurv model. A simplified risk scoring system, called the C-HAND (history of Cancer before admission, Heart rate, Age, eNIHSS, and Dyslipidemia) score, was created based on regression coefficients in the multivariate Cox model for both study outcomes. RESULTS: All experimental models achieved a concordance index of 0.8, with no significant difference in predicting poststroke long-term mortality. The C-HAND score exhibited reasonable discriminative ability for both study outcomes, with concordance indices of 0.775 and 0.798. CONCLUSIONS: Reliable prediction models for long-term poststroke mortality were developed using information routinely available to clinicians during hospitalization.

Initial In-Hospital Visit-to-Visit Heart Rate Variability Is Associated with Higher Risk of Atrial Fibrillation in Patients with Acute Ischemic Stroke.

BACKGROUND: To evaluate the association between the visit-to-visit heart rate variability and the risk of atrial fibrillation (AF) in acute ischemic stroke (AIS). METHODS: We analyzed the data of 8179 patients with AIS. Patients without AF on 12-lead electrocardiography underwent further 24 h Holter monitoring. They were categorized into four subgroups according to the visit-to-visit heart rate variability expressed as the coefficient of variation in heart rate (HR-CV). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the HR-CV < 0.08 subgroup as a reference. RESULTS: The adjusted OR of paroxysmal AF was 1.866 (95% CI = 1.205-2.889) for the HR-CV ≥ 0.08 and <0.10 subgroup, 1.889 (95% CI = 1.174-3.038) for the HR-CV ≥ 0.10 and <0.12 subgroup, and 5.564 (95% CI = 3.847-8.047) for the HR-CV ≥ 0.12 subgroup. The adjusted OR of persistent AF was 2.425 (95% CI = 1.921-3.062) for the HR-CV ≥ 0.08 and <0.10 subgroup, 4.312 (95% CI = 3.415-5.446) for the HR-CV ≥ 0.10 and <0.12 subgroup, and 5.651 (95% CI = 4.586-6.964) for the HR-CV ≥ 0.12 subgroup. CONCLUSIONS: HR-CV can facilitate the identification of patients with AIS at a high risk of paroxysmal AF.

Evaluation of clinical relevance and underlying pathology for hemodynamic compromise in acute small subcortical infarction using MRI-based neuroimaging markers.

BACKGROUND: Hemodynamic compromise has been observed in patients with acute small subcortical infarction (SSI), and it may play a critical role in the development of early neurological deterioration (END). This study aimed to evaluate the clinical relevance and underlying pathology of hemodynamic compromise in SSI using MRI-based neuroimaging markers. METHODS: We retrospectively analyzed data and imaging of previous prospective studies. Patients with acute SSI in penetrating artery territories were recruited, all of whom underwent perfusion MRI within 24 h of stroke onset. We examined the relationships among perfusion defects and neuroimaging markers of small vessel disease, including white matter hyperintensities, cerebral microbleeds, enlarged perivascular spaces (EPVSs) and lacunes. RESULTS: One hundred and seven patients were recruited, of whom 21 (19.6%) had END and 55 (51.4%) had visible perfusion defects. Patients with perfusion defects were associated with a higher rate of END (34.5% vs. 3.8%; p < 0.001), higher initial National Institutes of Health Stroke Scale scores (5.4 vs. 3.4, p < 0.001), higher rate of branch atheromatous disease (61.8% vs. 34.6%, p = 0.005) and higher rate of poor outcome at 3 months (40.0% vs. 5.4%; p = 0.005). In multiple logistic regression, perfusion defects were significantly associated with basal ganglia EPVS scores (adjusted odds ratio [aOR]: 3.93; 95% confidence interval [CI]: 1.76-8.77; p = 0.001) and branch atheromatous disease (aOR: 2.64; 95% CI: 1.06-6.60; p = 0.037). CONCLUSION: Hemodynamic compromise in acute SSI was highly related to the development of END, basal ganglia EPVS and branch atheromatous disease, suggesting the correlation with underlying pathologies of hypertensive arteriopathy and atherosclerosis.

Human thirst behavior requires transformation of sensory inputs by intrinsic brain networks.

BACKGROUND: To survive and thrive, many animals, including humans, have evolved goal-directed behaviors that can respond to specific physiological needs. An example is thirst, where the physiological need to maintain water balance drives the behavioral basic instinct to drink. Determining the neural basis of such behaviors, including thirst response, can provide insights into the way brain-wide systems transform sensory inputs into behavioral outputs. However, the neural basis underlying this spontaneous behavior remains unclear. Here, we provide a model of the neural basis of human thirst behavior. RESULTS: We used fMRI, coupled with functional connectivity analysis and serial-multiple mediation analysis, we found that the physiological need for water is first detected by the median preoptic nucleus (MnPO), which then regulates the intention of drinking via serial large-scale spontaneous thought-related intrinsic network interactions that include the default mode network, salience network, and frontal-parietal control network. CONCLUSIONS: Our study demonstrates that the transformation in humans of sensory inputs for a single physiological need, such as to maintain water balance, requires large-scale intrinsic brain networks to transform this input into a spontaneous human behavioral response.

Identification of magnetic resonance imaging features for the prediction of unrecognized atrial fibrillation in acute ischemic stroke.

Background and purpose: The early identification of cardioembolic stroke is critical for the early initiation of anticoagulant treatment. However, it can be challenging to identify the major cardiac source, particularly since the predominant source, paroxysmal atrial fibrillation (AF), may not be present at the time of stroke. In this study, we aimed to evaluate imaging predictors for unrecognized AF in patients with acute ischemic stroke. Methods: We performed a cross-sectional analysis of data and magnetic resonance imaging (MRI) scans from two prospective cohorts of patients who underwent serial 12-lead electrocardiography and 24-h Holter monitoring to detect unrecognized AF. The imaging patterns in diffusion-weighted imaging and imaging characteristics were assessed and classified. A logistic regression model was used to identify predictive factors for newly detected AF in patients with acute ischemic stroke. Results: A total of 734 patients were recruited for analysis, with a median age of 72 (interquartile range: 65-79) years and a median National Institutes of Health Stroke Scale score of 4 (interquartile range: 2-6). Of these patients, 64 (8.7%) had newly detected AF during the follow-up period. Stepwise multivariate logistic regression revealed that age ≥75 years [adjusted odds ratio (aOR) 5.66, 95% confidence interval (CI) 2.98-10.75], receiving recombinant tissue plasminogen activator treatment (aOR 4.36, 95% CI 1.65-11.54), congestive heart failure (aOR 6.73, 95% CI 1.85-24.48), early hemorrhage in MRI (aOR 3.62, 95% CI 1.52-8.61), single cortical infarct (aOR 6.49, 95% CI 2.35-17.92), and territorial infarcts (aOR 3.54, 95% CI 1.06-11.75) were associated with newly detected AF. The C-statistic of the prediction model for newly detected AF was 0.764. Conclusion: Initial MRI at the time of stroke may be useful to predict which patients have cardioembolic stroke caused by unrecognized AF. Further studies are warranted to verify these findings and their application to high-risk patients.

Development and Validation of a Novel Score for Predicting Paroxysmal Atrial Fibrillation in Acute Ischemic Stroke.

Atrial fibrillation (AF)-whether paroxysmal or sustained-increases the risk of stroke. We developed and validated a risk score for identifying patients at risk of paroxysmal atrial fibrillation (pAF) after acute ischemic stroke (AIS). A total of 6033 patients with AIS who received 24 h Holter monitoring were identified in the Chang Gung Research Database. Among the identified patients, 5290 with pAF and without AF were included in the multivariable logistic regression analysis to develop the pAF prediction model. The ABCD-SD score (Age, Systolic Blood pressure, Coronary artery disease, Dyslipidemia, and Standard Deviation of heart rate) comprises age (+2 points for every 10 years), systolic blood pressure (-1 point for every 20 mmHg), coronary artery disease (+2 points), dyslipidemia (-2 points), and standard deviation of heart rate (+2 points for every 3 beats per minute). Overall, 5.2% (274/5290) of patients had pAF. The pAF risk ranged from 0.8% (ABCD-SD score ≤ 7) to 18.3% (ABCD-SD score ≥ 15). The model achieved an area under the receiver operating characteristic curve (AUROCC) of 0.767 in the model development group. The ABCD-SD score could aid clinicians in identifying patients with AIS at risk of pAF for advanced cardiac monitoring.

PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging.

INTRODUCTION: Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis. METHODS AND ANALYSIS: In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT05001984; Pre-results.

Initial in-hospital heart rate is associated with long-term survival in patients with acute ischemic stroke.

AIMS: Increased heart rate has been associated with stroke risk and outcomes. The purpose of this study was to explore the long-term prognostic value of initial in-hospital heart rate in patients with acute ischemic stroke (AIS). METHODS: We analyzed data from 21,655 patients with AIS enrolled (January 2010-September 2018) in the Chang Gung Research Database. Mean initial in-hospital heart rates were averaged and categorized into 10-beat-per-minute (bpm) increments. The primary and secondary outcomes were all-cause mortality and cardiovascular death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable adjusted Cox proportional hazard models, using the heart rate < 60 bpm subgroup as the reference. RESULTS: The adjusted HRs for all-cause mortality were 1.23 (95% CI 1.08-1.41) for heart rate 60-69 bpm, 1.74 (95% CI 1.53-1.97) for heart rate 70-79 bpm, 2.16 (95% CI 1.89-2.46) for heart rate 80-89 bpm, and 2.83 (95% CI 2.46-3.25) for heart rate ≥ 90 bpm compared with the reference group. Likewise, heart rate ≥ 60 bpm was also associated with an increased risk of cardiovascular death (adjusted HR 1.18 [95% CI 0.95-1.46] for heart rate 60-69 bpm, 1.57 [95% CI 1.28-1.93] for heart rate 70-79 bpm, 1.98 [95% CI 1.60-2.45] for heart rate 80-89 bpm, and 2.36 [95% CI 1.89-2.95] for heart rate ≥ 90 bpm). CONCLUSIONS: High initial in-hospital heart rate is an independent predictor of all-cause mortality and cardiovascular death in patients with AIS.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study.

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

INTRODUCTION: Branch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent stroke in acute small subcortical infarction caused by BAD. METHODS AND ANALYSIS: In this prospective, single-centre, open-label, non-randomised, single-arm study using a historical control, we will compare early DAPT and high-intensity statin treatment with a historical control group of patients with BAD who were treated with single antiplatelet therapy without high-intensity statin treatment. Patients will be eligible for enrolment if they are admitted for acute ischaemic stroke within 24 hours, have a National Institutes of Health Stroke Scale (NIHSS) score of 1-8 and are diagnosed with BAD by MRI. Patients will take aspirin, clopidogrel and high-intensity statins (atorvastatin or rosuvastatin) within 24 hours of stroke onset, followed by aspirin or clopidogrel alone from day 22. The primary endpoint is the percentage of patients who develop END within 7 days of stroke onset (defined as an increase in the NIHSS score ≥2 points) and recurrent stroke within 30 days. The total sample sizes will be 138 for the intervention group and 277 for the control group. A historical control group will be drawn from previous prospective observation studies. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (202001386A3). All participants will have to sign and date an informed consent form. The findings arising from this study will be disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT04824911.

Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study.

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study. Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed. Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04-2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3-12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001). Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

The influence of constipation on asthma: A real-world, population-based cohort study.

BACKGROUND: Among respiratory diseases, asthma is one of the most burdensome disorder worldwide. Growing evidence disclose gut dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microflora. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess the risk of asthma in constipated patients by a nationwide population-based cohort study. METHODS: We analysed 86 860 constipated patients and 86 860 individuals without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Analysis of propensity score was utilised to match age, gender, comorbidities and medications at a ratio of 1:1. Besides, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and stratified analysis were conducted. RESULTS: The incidence of asthma was 10.4 per 1000 person-years in the constipation group, which was higher than the rate of 5.7 per 1000 person-years observed in the non-constipation group. After adjustment for age, gender, urbanisation, comorbidities and medications, constipated patients had a 1.81-fold greater risk of asthma compared with those without constipation (adjusted hazard ratio [aHR]: 1.81, 95% CI: 1.74-1.88). In subgroup analyses, patients aged 20-39 years had a 2.01-fold highest risk of asthma in the constipation cohort (aHR: 2.01, 95% CI: 1.82-2.22). Besides, the severity of constipation is associated with an increased risk of asthma; the aHR was 1.92 (1.84-2.00), 2.07 (1.94-2.21) and 2.10 (1.96-2.25) for ≤ 30 days, 31-120 days and >120 days of laxatives prescription within 1 year after the index date, respectively (P < .001). CONCLUSION: Constipation relates to a significantly increased risk of asthma. Physicians should be aware of the possibility of asthma in constipated people. Further research is warranted to investigate the possible pathological mechanisms of this association.

Initial in-hospital heart rate is associated with three-month functional outcomes after acute ischemic stroke.

BACKGROUND: Increased heart rate (HR) has been associated with stroke risk and outcomes. MATERIAL AND METHODS: We analyzed 1,420 patients from a hospital-based stroke registry with acute ischemic stroke (AIS). Mean initial in-hospital HR and the coefficient of variation of HR (HR-CV) were derived from the values recorded during the first 3 days of hospitalization. The study outcome was the 3-month functional outcome. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analysis. RESULTS: A higher mean HR level was significantly and continuously associated with a higher probability of unfavorable functional outcomes. Compared with the reference group (mean HR < 70 beats per minute), the multivariate-adjusted OR for an unfavorable outcome was 1.81 (95% CI, 1.25-2.61) for a mean HR ≥ 70 and < 80 beats per minute, 2.52 (95% CI, 1.66 - 3.52) for a mean HR ≥ 80 and < 90 beats per minute, and 3.88 (95% CI, 2.20-6.85) for mean HR ≥ 90 beats per minute. For stroke patients with a history of hypertension, the multivariate-adjusted OR for patients with a HR-CV ≥ 0.12 (versus patients with a HR-CV < 0.08 as a reference) was 1.73 (95% CI, 1.11-2.70) for an unfavorable outcome. CONCLUSIONS: Our results indicated that a high initial in-hospital HR was significantly associated with unfavorable 3-month functional outcomes in patients with AIS. In addition, stroke patients with a HR-CV ≥ 0.12 also had unfavorable outcomes compared with those with a HR-CV < 0.08 if they had a history of hypertension.