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IntroductionThe COVID-19 pandemic is known to impact in-hospital processes for acute stroke patients, potentially resulting in delays due to quarantine and screening measures. The purpose of this study was to determine effects of changes in in-hospital quarantine policies on quality of care for acute stroke patients.MethodsHyperacute ischemic stroke patients who were admitted to Korea University Guro Hospital between January 2019 and February 2021 via the emergency department were included in this study. All had neurological symptoms within 6 h before arrival. As a mandatory COVID-19 real-time PCR screening test was implemented in March 2020, changes in quality indicators according to the progress of COVID-19 pandemic and changes in in-hospital quarantine policy, including door-to-image time (DIT), door-to-referral time, door-to-needle time (DNT), door-to-puncture time (DPT), and functional outcomes (discharge and 3-month modified Rankin’s scale) were determined.ResultsA total of 268 hyperacute stroke patients were analyzed. The number of hyperacute stroke patients gradually decreased as the pandemic progressed. Time indicators, including door-to-referral time, DIT, and DPT during the pandemic were increased. When pre-and post-COVID-19 screening epochs were compared, DIT, door-to-neurologist referral time, and DPT showed numerical increases. However, after accounting for potential confounders, a significant delay in DIT was found to be associated with the in-hospital COVID-19 quarantine policy.DiscussionOur study showed that enhancing in-hospital COVID-19 quarantine measures might increase the response time for hyperacute stroke care, suggesting an impact on the quality of care.

Abstract Background Glycated albumin (GA) is an indicator of glycemic variability over the past 2–4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). Methods We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). Results In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10–9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01–1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14–3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. Conclusions High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Background Perfusion imaging (PI) serves as a valuable tool for triaging patients with acute ischemic stroke for endovascular treatment (EVT). This study aims to investigate trends in PI use and its impacts on EVT rates and clinical outcomes, particularly focusing on variations across different time windows. Methods Data from a prospective, nationwide, acute stroke registry in South Korea were analyzed retrospectively. PI was regarded as treatment‐decision imaging when conducted either (1) prior to EVT, or (2) within 3 hours from hospital arrival in patients not receiving EVT. The study spanned 3 epochs: 2011–2014, 2015–2017, and 2018–2021. Based on the time from onset to arrival, patients were categorized into 2 time windows: early (0–6 hours) and late (6–24 hours). We evaluated EVT rates and clinical outcomes in patients with anterior large vessel occlusion. Results From 2011 to 2021 among 49 449 patients with acute ischemic stroke presenting within 24 hours of onset, PI use rates declined from 36.9% to 30.1%. In the early window, rates dropped from 48.4% to 32.4%, whereas in the late window, they increased from 23.5% to 27.8%. Factors such as older age, atrial fibrillation, anterior large vessel occlusion, and severe stroke were associated with higher rates in the late window. Conversely, younger age and male sex were associated with higher rates in the early window. For patients with anterior large vessel occlusion, PI use increased the likelihood of receiving EVT in the late window and minimized the risk of symptomatic intracranial hemorrhage in the early window. However, 3‐month functional outcomes and mortality were. unaffected. Conclusion The study revealed distinct trends in PI use across early and late time windows, indicating varying roles of PI in these time frames. However, the definitive value and necessity of PI in guiding EVT decision‐making remain unclear, underscoring the need for further research

Background and Purpose Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype. Methods Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical variable (DWI+AF algorithm). These models were tested: (1) internally against the opinion of the labeling experts, (2) against fresh external DWI data, and (3) against clinical trial dataset. Results In the training-and-validation datasets, the mean (±standard deviation) age was 68.0±12.5 (61.1% male). In internal testing, compared with the experts, the DWI-only and the DWI+AF algorithms respectively achieved moderate (65.3%) and near-strong (79.1%) agreement. In external testing, both algorithms again showed good agreements (59.3%–60.7% and 73.7%–74.0%, respectively). In the clinical trial dataset, compared with the expert consensus, percentage agreements and Cohen’s kappa were respectively 58.1% and 0.34 for the DWI-only vs. 72.9% and 0.57 for the DWI+AF algorithms. The corresponding values between experts were comparable (76.0% and 0.61) to the DWI+AF algorithm. Conclusion Our model trained on a large dataset of DWI (both with or without AF information) was able to classify ischemic stroke subtypes comparable to a consensus of stroke experts.

Background Although stroke is commonly perceived as occurring in older adults, traumatic brain injury, one of the risk factors for stroke, is a leading cause of death in the younger adults. This study evaluated stroke risk in young‐to‐middle‐aged adults based on traumatic brain injury severity and stroke subtypes. Methods and Results For this retrospective, population‐based, cohort study, data of adults aged 18 to 49 years who were diagnosed with traumatic brain injury were obtained from the Korean National Health Insurance Service between 2010 and 2017. Traumatic brain injury history was measured based on the International Classification of Diseases, Tenth Revision (ICD‐10), codes. Posttraumatic brain injury stroke risk was analyzed using a time‐dependent Cox regression model. At baseline, 518423 patients with traumatic brain injury and 518 423 age‐ and sex‐matched controls were included. The stroke incidence rate per 1000 person‐years was 3.82 in patients with traumatic brain injury and 1.61 in controls. Stroke risk was approximately 1.89 times as high in patients with traumatic brain injury (hazard ratio, 1.89 [95% CI, 1.84–1.95]). After excluding stroke cases that occurred within 12 months following traumatic brain injury, these significant associations remained. In the subgroup analysis, patients with brain injury other than concussion had an approximately 9.34‐fold risk of intracerebral hemorrhage than did the controls. Conclusions Stroke prevention should be a priority even in young‐to‐middle‐aged adult patients with traumatic brain injury. Managing stroke risk factors through regular health checkups and modifying health‐related behaviors is necessary to prevent stroke.

IntroductionWe developed and externally validated a fully automated algorithm using deep learning to detect large vessel occlusion (LVO) in computed tomography angiography (CTA).MethodA total of 2,045 patients with acute ischemic stroke who underwent CTA were included in the development of our model. We validated the algorithm using two separate external datasets: one with 64 patients (external 1) and another with 313 patients (external 2), with ischemic stroke. In the context of current clinical practice, thrombectomy amenable vessel occlusion (TAVO) was defined as an occlusion in the intracranial internal carotid artery (ICA), or in the M1 or M2 segment of the middle cerebral artery (MCA). We employed the U-Net for vessel segmentation on the maximum intensity projection images, followed by the application of the EfficientNetV2 to predict TAVO. The algorithm’s diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsThe mean age in the training and validation dataset was 68.7 ± 12.6; 56.3% of participants were men, and 18.0% had TAVO. The algorithm achieved AUC of 0.950 (95% CI, 0.915–0.971) in the internal test. For the external datasets 1 and 2, the AUCs were 0.970 (0.897–0.997) and 0.971 (0.924–0.990), respectively. With a fixed sensitivity of 0.900, the specificities and PPVs for the internal test, external test 1, and external test 2 were 0.891, 0.796, and 0.930, and 0.665, 0.583, and 0.667, respectively. The algorithm demonstrated a sensitivity and specificity of approximately 0.95 in both internal and external datasets, specifically for cases involving intracranial ICA or M1-MCA occlusion. However, the diagnostic performance was somewhat reduced for isolated M2-MCA occlusion; the AUC for the internal and combined external datasets were 0.903 (0.812–0.944) and 0.916 (0.816–0.963), respectively.ConclusionWe developed and externally validated a fully automated algorithm that identifies TAVO. Further research is needed to evaluate its effectiveness in real-world clinical settings. This validated algorithm has the potential to assist early-career physicians, thereby streamlining the treatment process for patients who can benefit from endovascular treatment.

Abstract Background Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. Methods Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. Results Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30–1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12–2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23–2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19–2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. Conclusions We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Abstract Background The effect of amyloid-β (Aβ) on cognitive impairment in patients with small subcortical infarction remains controversial, although a growing body of evidence shows a substantial overlap between Alzheimer’s disease (AD) and subcortical ischemic vascular dementia, another form of cerebral small vessel disease (cSVD). Therefore, we investigated the relationships between Aβ positivity and the development of post-stroke cognitive impairment (PSCI) in patients with small subcortical infarction. Methods We prospectively recruited 37 patients aged ≥ 50 years, with first-ever small subcortical infarction, who underwent amyloid positron emission tomography, 3 months after stroke at Korea University Guro Hospital. We also enrolled CU participants matched for age and sex with stroke patients for comparison of Aβ positivity. Patients were followed up at 3 and 12 months after the stroke to assess cognitive decline. Logistic and linear mixed-effect regression analyses were performed to identify the effect of Aβ positivity on PSCI development and long-term cognitive trajectories. Results At 3 months after stroke, 12/37 (32.4%) patients developed PSCI, and 11/37 (29.7%) patients had Aβ deposition. Aβ positivity (odds ratio [OR] = 72.2, p = 0.024) was predictive of PSCI development regardless of cSVD burden. Aβ positivity (β = 0.846, p = 0.014) was also associated with poor cognitive trajectory, assessed by the Clinical Dementia Rating-Sum of Box, for 1 year after stroke. Conclusions Our findings highlight that Aβ positivity is an important predictor for PSCI development and cognitive decline over 1 year. Furthermore, our results provide evidence that anti-AD medications may be a strategy for preventing cognitive decline in patients with small subcortical infarctions.

A few cases of small fiber neuropathy (SFN) and tinnitus (TN) associated with coronavirus disease 2019 have been reported. However, the relationship between SFN and TN has not been studied. This study investigated a possible relationship between SFN and patients with TN (PwTNs) using autonomic function tests (AFTs) including quantitative sudomotor axon reflex tests (QSART). We performed QSARTs and other AFTs such as the Sympathetic skin response (SSR), Valsalva ratio (VR), and heart rate variability (HRV). The QSART results, obtained at seven hospitals using same protocols, were compared between PwTNs and healthy controls. We confirmed the abnormalities in SSR, VR, and HRV in PwTNs, although those parasympathetic AFTs were not performed in healthy controls. Additionally, we checked Tinnitus handicap inventory (THI) scores for PwTNs and ~50% of PwTNs had low-grade disability, whereas 9.3% had high-grade disability. Data from 57 PwTNs and 122 healthy controls were analyzed. The sweat volumes of QSART in the older age group tended to be higher in the PwTNs than in age-matched healthy controls, and significant differences between the PwTN and control groups were observed in the feet in both sexes (p < 0.001) and in the arms in women (p = 0.013). In the younger age group, the sweat volumes in the feet of men were higher in PwTNs than in healthy controls (p = 0.017). No association was observed between THI and QSART scores. In this study, the sweat volumes in QSARTs were higher in PwTNs than in healthy controls. However, abnormal SSR, HRV, and VR results were not commonly observed in PwTNs. Although the results should be interpreted with caution because of limitations in study, PwTNs might also have SFN apart from dysautonomia. This is the first study to perform QSART with other parasympathetic AFTs in PwTNs. However, larger and more rigorously controlled studies will be needed to reveal the relationship between SFN and TN in the future.

BackgroundDiabetes is associated with an increased risk of Parkinson’s disease dementia (PDD); however, it is unknown whether this association is dependent on continuous hyperglycemia, hypoglycemic events, or glycemic variability. We aimed to investigate the relationship between visit-to-visit fasting glucose variability and PDD development in patients with Parkinson’s disease (PD).MethodsUsing data from the Korean National Health Insurance Service, we examined 9,264 patients aged ≥40 years with de novo Parkinson’s disease (PD) who underwent ≥3 health examinations and were followed up until December 2019. Glucose variability was measured using the coefficient of variation, variability independent of the mean, and average real variability. Fine and Gray competing regression analysis was performed to determine the effect of glucose variability on incident PDD.ResultsDuring the 9.5-year follow-up period, 1,757 of 9,264 (19.0%) patients developed PDD. Patients with a higher visit-to-visit glucose variability had a higher risk of future PDD. In the multivariable adjusted model, patients with PD in the highest quartile (subdistribution hazard ratio [SHR] = 1.50, 95% CI 1.19 to 1.88), quartile 3 (SHR = 1.29, 95% CI 1.02 to 1.62), and quartile 2 (SHR = 1.30, 95% CI 1.04 to 1.63) were independently associated with a higher risk of PDD than those in the lowest quartile.ConclusionWe highlighted the effect of long-term glucose variability on the development of PDD in patients with PD. Furthermore, our findings suggest that preventive measures for constant glucose control may be necessary to prevent PDD.

Background and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods This randomized, open-label, controlled trial assigned patients with recent ischemic stroke

Abstract Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

Background Approximately 10% of patients with acute ischemic stroke with large‐vessel occlusion (LVO) have mild neurological deficits. Although leptomeningeal collaterals (LMCs) are the major determinant of clinical outcomes for patients with acute ischemic stroke with LVO, the contribution of baseline LMC status to subsequent infarct progression in patients with mild stroke with LVO is poorly defined. Methods This observational study included patients with acute anterior circulation LVO and mild stroke symptoms (National Institutes of Health Stroke Scale < 6) from a prospectively collected, multicenter, national stroke registry. The Alberta Stroke Program Early Computed Tomography Score was quantified on the initial and follow‐up images. An infarct progression, defined as any Alberta Stroke Program Early Computed Tomography Score decrease between the initial versus follow‐up scans, was categorized as either 0/1/2+. The LMCs on the baseline images were graded as good, fair, or poor. Results Of the 623 included patients (mean age, 67.6±13.4 years; 380 [61.0%] men; 186 [29.9%] with reperfusion treatment), the baseline LMC was graded as good in 331 (53.1%), fair in 219 (35.2%), and poor in 73 (11.7%). The Alberta Stroke Program Early Computed Tomography Score decrement was noted as 0 in 288 (46%) patients, 1 in 154 (24%), and 2+ in 181 (29%). A poor LMC was associated with an infarct progression (adjusted odds ratio, 2.05 [95% CI, 1.22–3.47]). Conclusions Poor collateral blood flow was associated with infarct progression in patients with acute ischemic stroke with LVO and mild symptoms. In this selective population, early assessment of collateral blood flow status can help in early detection of patients susceptible to infarct progression.

Background: In August 2020, 17 healthcare workers (HCWs) were simultaneously diagnosed with severe fever with thrombocytopenia syndrome (SFTS) at a university hospital in Daegu, Republic of Korea. Methods: An epidemiologic investigation using questionnaires was conducted for all suspected HCWs who had viral infection symptoms or who had the possibility of exposure to the index patient. Results: A total of 17 HCWs infected with the SFTS virus (SFTSV) (28.8%) were identified among the 59 HCWs who had contact with the patient. Operating a bag valve mask during cardiopulmonary resuscitation (CPR) (OR 7.50, 95% CI 1.75–41.07), cardiac massage during CPR (OR 12.00, 95% CI 1.76–241.94), exposure to the patient's body fluids (OR 7.43, 95% CI 1.91–34.69), and shorter individual hospital work experience periods (OR 6.79, 95% CI 1.70–32.10) were significantly associated with SFTS infection in the univariate analysis. However, exposure to body fluids was found to be the only statistically significant risk factor when multivariate analysis was conducted (OR 6.27. 95% CI 1.23–42.81, p = 0.036). Conclusions: This finding illustrates the importance of wearing appropriate personal protective equipment in treatment areas and when conducting any medical procedures, including CPR for patients with SFTS, and any procedure that involves potential exposure to body fluids.

Background Hypomagnesemia is associated with stroke severity and increased in-hospital mortality in patients with acute ischemic stroke. This study aimed to assess whether serum magnesium concentration could predict functional outcomes of patients with acute ischemic stroke. Methods A total of 1,006 patients with acute ischemic stroke were analyzed. A serum magnesium level

Abstract In acute ischemic stroke (AIS), the hemodynamics around the lesion are important because they determine the recurrence or prognosis of the disease. This study evaluated the effects of perfusion deficits in multiphase arterial spin labeling (ASL) and related radiological parameters on the occurrence of early recurrent ischemic lesions (ERILs) in AIS. We assessed AIS patients who underwent multiphase ASL within 24 h of symptom onset and follow-up diffusion-weighted imaging within 7 days. ASL perfusion deficit, arterial transit artifact (ATA), and intra-arterial high-intensity signal (IAS) were manually rated as ASL parameters. A total of 134 patients were evaluated. In the multivariable analyses, ASL perfusion deficit [adjusted odds ratio (aOR) = 2.82, 95% confidence interval = 1.27–6.27] was positively associated with ERIL. Furthermore, when ATA was accompanied, the ASL perfusion deficit was not associated with ERIL occurrence. Meanwhile, IAS showed a synergistic effect with ASL perfusion deficit on the occurrence of ERIL. In conclusion, we demonstrated the association between perfusion deficits in multiphase ASL with ERIL in patients with AIS. This close association was attenuated by ATA and was enhanced by IAS. ASL parameters may help identify high-risk patients of ERIL occurrence during the acute period.

Abstract To assess the safety and efficacy of navigation-guided balloon Eustachian tuboplasty (BET) compared to medical management (MM) alone in patients with chronic Eustachian tube dilatory dysfunction (ETD). This is a prospective, multicenter, 1:1 parallel-group, randomized controlled trial (RCT). It aims to assess the efficacy of navigation-guided BET compared to MM alone in patients with chronic ETD. The primary outcome measure was an improvement in the Eustachian tube dysfunction questionnaire (ETDQ)-7 score at the 6-week follow-up compared with baseline. Secondary outcome measures included changes in the signs and symptoms during the follow-up, changes in the score for each subcategory of ETDQ-7, type of tympanometry, pure tone audiometry, and the availability of a positive modified Valsalva maneuver. Navigation-guided BET was safely performed in all patients. A total of 38 ears of 31 patients (19 ears of 16 patients in the BET group and 19 ears of 15 patients in the control group) completed the planned treatment and 6 weeks of follow-up. More patients in the BET group (1.99 ± 0.85) had less symptomatic dysfunction than in the control group (3.40 ± 1.29) at 6 weeks post-procedure (P = 0.001). More patients experienced tympanogram improvement in the BET group at 6 weeks compared to the control group (36.5% vs. 15.8%) with a positive modified Valsalva maneuver (36.6% vs. 15.8%, P = 0.014). Additionally, air–bone gap change was significantly decreased in the BET group compared to the control group at the 6-week follow-up visit (P = 0.037). This prospective, multicenter, RCT study suggests that navigation-guided BET is a safe and superior treatment option compared to MM alone in patients with chronic ETD.

Abstract We aimed to develop a novel prediction model for early neurological deterioration (END) based on an interpretable machine learning (ML) algorithm for atrial fibrillation (AF)-related stroke and to evaluate the prediction accuracy and feature importance of ML models. Data from multicenter prospective stroke registries in South Korea were collected. After stepwise data preprocessing, we utilized logistic regression, support vector machine, extreme gradient boosting, light gradient boosting machine (LightGBM), and multilayer perceptron models. We used the Shapley additive explanation (SHAP) method to evaluate feature importance. Of the 3,213 stroke patients, the 2,363 who had arrived at the hospital within 24 h of symptom onset and had available information regarding END were included. Of these, 318 (13.5%) had END. The LightGBM model showed the highest area under the receiver operating characteristic curve (0.772; 95% confidence interval, 0.715–0.829). The feature importance analysis revealed that fasting glucose level and the National Institute of Health Stroke Scale score were the most influential factors. Among ML algorithms, the LightGBM model was particularly useful for predicting END, as it revealed new and diverse predictors. Additionally, the effects of the features on the predictive power of the model were individualized using the SHAP method.

Background and purposeThere is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits.MethodsFrom a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS

Abstract Insulin resistance is associated with the occurrence of stroke and atherosclerotic disease. However, the relationship between insulin resistance and the prognosis of acute ischemic stroke in non-diabetic patients is unclear. We hypothesized that insulin resistance might affect short-term functional recovery after acute ischemic stroke in non-diabetic patients. Between May 2014 and December 2016, 1377 consecutive patients with acute ischemic stroke were enrolled from a prospectively maintained stroke registry. After excluding patients with transient ischemic attacks (TIA), pre-stroke disabilities, diabetes mellitus, and patients with incomplete evaluations, 517 patients were included in the study. The homeostasis model assessment of insulin resistance (HOMA-IR) score was used to evaluate the degree of insulin resistance. The patients with the highest quartile of log HOMA-IR index scores were younger and had higher fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and HbA1c levels. Multivariable logistic regression analysis revealed that log HOMA-IR scores were independently associated with poor prognosis after adjusting for age and sex and p

Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF‐related stroke. Methods and Results We included consecutive patients with AF‐related stroke between 2013 and 2015 from the registry of a real‐world prospective cohort from 11 large centers in South Korea. A 3‐month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF‐related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01–1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60–6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF‐related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF‐related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

BackgroundAlthough many electrocardiography wearable devices have been released recently for the detection of atrial fibrillation (AF), there are few studies reporting prospective data for wearable devices compared to the strategy of the existing guidelines in the detection of atrial fibrillation (AF) after cryptogenic stroke. A tiny single-patch monitor is more convenient than a conventional Holter monitor recording device and, therefore, longer duration of monitoring may be acceptable.Methods and DesignThe CANDLE-AF study is a multicenter, prospective, randomized controlled trial. Patients with transient ischemic attack or ischemic stroke without any history of AF will be enrolled. The superiority of the 72-h single-patch monitor to standard strategy and non-inferiority of the 72-h single-patch monitor to an event-recorder-type device will be investigated. Single-patch monitor arm will repeat monitoring at 1, 3, 6, and 12 months, event-recorder-type arm will repeat monitoring twice daily for 12 months. The enrollment goal is a total of 600 patients, and the primary outcome is the detection of AF which continues at least 30 s during study period. The secondary outcome is the rate of changes from antiplatelet to anticoagulant and major adverse cardiac and cerebrovascular events within 1 year.ConclusionsThe results of CANDLE-AF will clarify the role of a single-lead patch ECG for the early detection of AF in patients with acute ischemic stroke. In addition, the secondary outcome will be analyzed to determine whether more sensitive AF detection can affect the prognosis and if further device development is meaningful. (cris.nih.go.kr KCT0005592).

Background: Ischemic stroke with atrial fibrillation (AF) may recur despite appropriate treatment. It may be AF-related or AF-unrelated. We compared the factors associated with AF-related and AF-unrelated recurrences among ischemic stroke patients with AF.Methods: Patients with ischemic stroke and AF were enrolled from 11 centers in Korea. Ischemic stroke recurrence was classified as AF-related if the lesion pattern was compatible with cardioembolism without significant stenosis or as AF-unrelated if the lesion was more likely due to small vessel disease or arterial stenosis. Factors associated with stroke recurrence (AF-related and AF-unrelated) were investigated.Results: Among the 2,239 patients, 115 (5.1%) experienced recurrence (75 AF-related and 40 AF-unrelated). Factors independently associated with any stroke recurrence included AF diagnosed before stroke, small subcortical infarctions, and small scattered lesions in a single vascular territory. Type of AF was associated with the type of stroke recurrence, with persistent AF being associated with AF-related stroke [hazard ratio (HR) = 2.94, 95% confidence interval (CI) 1.69–5.26; p < 0.001]. By contrast, paroxysmal AF (HR = 3.76, 95% CI 1.56–9.04; p = 0.003), AF diagnosed before stroke (HR = 2.38, 95% CI 1.19–4.55; p = 0.014), small scattered lesions in a single vascular territory (reference: corticosubcortical lesion, HR = 3.19, 95% CI 1.18–8.63; p = 0.022), and the use of antiplatelet agents (HR = 2.11, 95% CI 1.11–4.03; p = 0.024) were independently associated with AF-unrelated stroke.Conclusion: Persistent AF was more associated with AF-related stroke recurrence, whereas paroxysmal AF was more associated with AF-unrelated stroke recurrence. A scattered lesion in a single vascular territory may predict AF-unrelated stroke recurrence.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a newer delivery system using a non-invasive stimulation device placed at the ear. taVNS research is focused on clinical trials showing potential therapeutic benefits, however the neurophysiological effects of this stimulation on brain activity are still unclear. We propose a systematic review that aims to describe the effects of taVNS on EEG measures and identify taVNS parameters that can potentially lead to consistent EEG-mediated biomarkers for this therapy. A systematic literature review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Cochrane handbook for systematic reviews. Clinical trials examining EEG parameters were considered, including absolute and relative power, coherence, degree of symmetry, evoked potentials, and peak frequency of all bands. According to our criteria, 18 studies (from 122 articles) were included. Our findings show a general trend towards increased EEG power spectrum activity in lower frequencies, and changes on early components of the ERP related to inhibitory tasks. This review suggests that quantitative electroencephalography can be used to assess the effects of taVNS on brain activity, however more studies are needed to systematically establish the specific effects and metrics that would reflect the non-invasive stimulation through the auricular branch of the vagus nerve.

Background There is insufficient evidence on the effect of statins, particularly high‐intensity statins, in patients with acute ischemic stroke and atrial fibrillation. We investigated the impact of statins on the outcomes in these patients, including those who might be vulnerable to statin therapy and those without clinical atherosclerotic cardiovascular diseases. Methods and Results A total of 2153 patients with acute ischemic stroke and atrial fibrillation were enrolled in the present nationwide, multicenter, cohort study. The primary composite end point was the occurrence of net adverse clinical and cerebral events (NACCE; death from any cause, stroke, acute coronary syndrome, or major bleeding) over a 3‐year period based on statin intensity. NACCE rates were lower in patients receiving low‐ to moderate‐intensity (adjusted hazard ratio 0.64; 95% CI: 0.52‐0.78) and high‐intensity statins (hazard ratio 0.51; 95% CI 0.40‐0.66) than in those not receiving statin therapy. High‐intensity statins were associated with a lower risk for NACCE than low‐ to moderate‐intensity statins (hazard ratio 0.76; 95% CI 0.59‐0.96). Subgroup analyses showed that the differences in hazard ratio for 3‐year NACCE favored statin use across all subgroups, including older patients, those with low cholesterol levels, patients receiving anticoagulants, and patients without clinical atherosclerotic cardiovascular diseases. Magnified benefits of high‐intensity statins compared with low‐ to moderate‐intensity statins were observed in patients who underwent revascularization therapy and those under 75 years of age. Conclusions Statins, particularly high‐intensity statins, could reduce the risk for NACCE in patients with acute ischemic stroke and atrial fibrillation; this needs to be further explored in randomized controlled trials.

Background and aims: Atrial fibrillation (AF) is a major cause of ischemic stroke; however, detailed clinical data and prognostic factors for stroke patients with AF are lacking in Korea. We aimed to investigate clinical information and factors associated with functional outcomes of stroke patients with AF from the Korean nationwide ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) database.Methods: From January 2013 to December 2015, consecutive clinical information from acute stroke patients with AF or history of AF was collected from 11 centers in Korea. Collected data included demographics, risk factors, pre-stroke medication, stroke severity, stroke subtypes, concomitant cerebral atherosclerosis, brain image findings, recanalization therapy, discharge medication, and functional outcome at 3 months after index stroke.Results: A total of 3,213 stroke patients (mean age, 73.6 ± 9.8 years; female, 48.6%) were included. The mean CHA2DS2-VASc score was 4.9. Among the 1,849 (57.5%) patients who had brain image and functional outcome data, poor outcome (modified Rankin scale > 2) was noted in 53.1% (981/1,849) of patients. After adjusting for age, sex, and variables that had a p < 0.05 in univariate analysis or well-known factors for functional outcome, presence of asymptomatic extracranial cerebral atherosclerosis [odd ratio (OR): 1.96, 95% confidence interval (CI): 1.36–2.82, p = 0.001] and less frequent prior stroke statin intake (OR: 0.69, 95% CI: 0.49–0.98, p = 0.038) were associated with poor functional outcome.Conclusion: Our results suggest that presence of non-relevant extracranial cerebral atherosclerosis may affect poor functional outcome and prior stroke statin therapy may be feasible in Korean stroke patients with AF.

Fulminant hepatic failure (FHF) is often accompanied by a myriad of neurologic complications, which are associated with high morbidity and mortality. Although appropriate neuromonitoring is recommended for early diagnosis and to minimize secondary brain injury, individuals with FHF usually have a high chance of coagulopathy, which limits the ability to use invasive neuromonitoring. Jugular bulb venous oxygen saturation (JvO2) monitoring is well known as a surrogate direct measures of global brain oxygen use. We report the case of a patient with increased intracranial pressure due to FHF, in which JvO2 was used for appropriate brain oxygen monitoring.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p

The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality. Second, we obtained data from the Korean National Health Information Service-National Sample Cohort (NHIS-NSC) database for external validation and analyzed the effect of statins on mortality, taking compliance into consideration. For the stroke registry cohort, statin use was independently associated with reduced mortality in a multivariable model [hazard ratio (HR) = 0.675, 95% confidence interval (CI) = 0.457–0.996]. There was no interaction between statin use and cancer characteristics, vascular risk factors, or laboratory findings. A dose-dependent relationship between statin use and survival was also demonstrated. Analysis of the NHIS-NSC database found a similar association between statin therapy and reduced mortality (adjusted HR = 0.64, 95% CI = 0.45–0.90) and this effect persisted even after controlling for the adherence of statin use (HR = 0.60, 95% CI = 0.41–0.89). Statin therapy could be associated with reduced mortality in patients with acute stroke and active cancer.

Background and PurposeThrombolysis is underused in acute ischemic stroke, mainly due to the reluctance of physicians to treat thrombolysis patients. However, a computerized clinical decision support system can help physicians to develop individualized stroke treatments.MethodsA consecutive series of 958 patients, hospitalized within 12 hours of ischemic stroke onset from a representative clinical center in Korea, was used to establish a prognostic model. Multivariable logistic regression was used to develop the model for global and safety outcomes. An external validation of developed model was performed using 954 patients data obtained from 5 university hospitals or regional stroke centers.ResultsFinal global outcome predictors were age; previous modified Rankin scale score; initial National Institutes of Health Stroke Scale (NIHSS) score; previous stroke; diabetes; prior use of antiplatelet treatment, antihypertensive drugs, and statins; lacunae; thrombolysis; onset to treatment time; and systolic blood pressure. Final safety outcome predictors were age, initial NIHSS score, thrombolysis, onset to treatment time, systolic blood pressure, and glucose level. The discriminative ability of the prognostic model showed a C-statistic of 0.89 and 0.84 for the global and safety outcomes, respectively. Internal and external validation showed similar C-statistic results. After updating the model, calibration slopes were corrected from 0.68 to 1.0 and from 0.96 to 1.0 for the global and safety outcome models, respectively.ConclusionsA novel computerized outcome prediction model for thrombolysis after ischemic stroke was developed using large amounts of clinical information. After external validation and updating, the model's performance was deemed clinically satisfactory.

Ischemic stroke patients with active cancer frequently experience early neurological deterioration (END); however, the predictors of END are not well studied. The neutrophil to lymphocyte ratio (NLR) has recently been described as a predictor of poor outcomes in cancer and stroke. However, its role in cancer-related stroke has not been addressed.We aimed to evaluate the association between the NLR and END in cancer-related stroke patients.We included 85 cryptogenic stroke patients with active cancer. END was defined as an increase ≥ 4 on the total National Institutes of Health Stroke Scale (NIHSS) score within 72 hours of admission. The NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. We obtained the NLR during the following three periods: at admission, 1-3 days after admission (D 1-3 NLR) and 4-7 days after admission (D 4-7 NLR).END occurred in 15 (18%) of the 85 patients. END was significantly associated with the initial NIHSS score, infarction volume, and the D 1-3 NLR. In multivariate analysis, a higher D 1-3 NLR, measured before END events, remained an independent predictor of END [adjusted odds ratio = 2.78, 95% confidence interval = 1.09-7.08, P = 0.032]. In terms of temporal changes in the NLR, the END group showed a tendency toward temporal increase in the NLR at D 1-3 (P = 0.061) with subsequent decrements in the D 4-7 NLR (P = 0.088), while the non-END group showed no significant changes in the NLR between periods.This study demonstrated that a higher NLR could predict END events in cryptogenic stroke patients with active cancer. However, the results should be confirmed in further large prospective studies.

BackgroundThe current guideline recommends moderate‐ to vigorous‐intensity physical activity (PA) at least 40 min/day for 3 to 4 days/week. Although recent evidence has demonstrated that low‐dose PA could reduce cardiovascular mortality, the relationship between low‐dose PA and the risk of stroke remains uncertain. Methods and ResultsUsing data from a nation‐wide sample cohort in Korea, we examined 336 326 individuals who received a general health examination between 2009 and 2010. Level of PA was assessed using a questionnaire for weekly PA frequencies regarding 3 intensity categories: light, moderate, and vigorous. Moderate‐ to vigorous‐intensity PA (MVPA) was classified into 4 frequency categories: none, 1 to 2, 3 to 4, or ≥5 times/week. Cox proportional hazard models were constructed to estimate the risk of stroke. During the average follow‐up of 3.6 years, 2213 stroke cases occurred. MVPA was none in 50%, 1 to 2 times/week in 20%, 3 to 4 times/week in 13%, and ≥5 times/week in 18% of the cohort. Individuals with MVPA 1 to 2 times/week had a 16% reduced risk of stroke (adjusted hazard ratio, 0.84; 95% confidence interval, 0.73–0.96) compared with those with no MVPA. The population attributable fraction of no MVPA was 12%, which was the second most important risk factor for a stroke after hypertension. ConclusionsEven 1 to 2 times a week of MVPA might be beneficial to prevent a first‐ever stroke in the general population, although a quantitative validation of the questionnaire is needed. From a public health perspective, we need to encourage inactive people to start exercising with more‐achievable goals.

Stroke associated with non-valvular atrial fibrillation (NVAF) is one of the most important subtypes of ischemic stroke, and its importance is becoming even more apparent in an aging population. To assess the risk of stroke associated with NVAF, the CHADS2 and CHA2DS2-VASc scores are mainly used. Such scores can be used to predict the recurrence and prognosis of ischemic stroke. In addition, new oral anticoagulants (NOACs) and devices are being evaluated in the prevention of stroke associated with NVAF in addition to treatment with the conventional oral anticoagulant, warfarin. Since clinical experience with NOACs is not globally sufficient, a cautious approach is needed.

BACKGROUND:Stroke in cancer patients is not rare but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. AIM:In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. METHODS:We included 210 ischemic stroke patients with active cancer. The 30-day mortality data were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. RESULTS:Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS scores, D-dimer levels, and CRP levels as well as frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. The initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independent of D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease in D-dimer levels, despite treatment, while the survivor group showed the opposite response. CONCLUSIONS:D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

We report a case of a 36-year-old woman with progressive generalized myoclonus that first became apparent 9 years ago. Her younger brother had similar problems. Examination of her eyes revealed cherry-red spots. Hexosaminidase A, β-galactosidase and neuraminidase activity were normal. Although the laboratory findings were negative, cherry-red spots, progressive myoclonus and autosomal recessive inheritance pattern suggested that she had an unknown type of lysosomal storage disease.

Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16-3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43-5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients.

Abstract Background Gastric outlet obstruction (GOO) caused by unresectable gastric cancer is a challenging aspect of patient care. There have been no reports involving patients with obstructing gastric cancer and several incurable factors curatively treated by multimodal treatments. Case presentation We report a case of 55-year-old man who was diagnosed with a poorly differentiated adenocarcinoma in the pre-pyloric antrum with GOO by gastroscopy. An abdominal computed tomography (CT) scan revealed thickening of the gastric wall and adjacent fat infiltration, and a large amount of food in the stomach suggesting a passage disturbance, enlarged lymph nodes along the common hepatic and left gastric arteries, and multiple hepatic metastases. The serum carcinoembryonic antigen (CEA) level was 343 ng/ml and the carbohydrate antigen (CA) 19-9 level was within normal limits. The patient underwent a laparoscopic gastrojejunostomy for palliation of the GOO. On the 3rd and 12th days after surgery, he received intraperitoneal chemotherapy with 40 mg of docetaxel and 150 mg of carboplatin. Simultaneously, combined chemotherapy with 85 mg/m2 of oxaliplatin for the 1st day and 600 mg/m2 of 5-FU for 2 days (FOLFOX regimen) was administered from the 8th post-operative day. After completion of nine courses of FOLFOX, the patient achieved a complete response (CR) with complete disappearance of the primary tumor and the metastatic foci. He underwent a radical subtotal gastrectomy with D3 lymph node dissection 4 months after the initial palliative surgery. The pathologic results revealed no residual primary tumor and no lymph node metastasis in 43 dissected lymph nodes. He has maintained a CR for 18 months since the last operation. Conclusion Combination chemotherapy with systemic and intraperitoneal chemotherapy following laparoscopic bypass surgery showed marked efficacy in the treatment for unresectable advanced gastric cancer with GOO.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are anti-diabetes agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxaneinduced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidas e-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity scorematched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540,258 patients with 270,129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs. 7.6 events per 1000 patient-years, hazard ratio [HR], 0.78 [95% CI: 0.73-0.83]). This was similar for PE (2.9 vs. 3.8 events per 1000 patient-years, HR, 0.74 [95% CI: 0.68-0.82]) and DVT (3.9 vs. 4.7 events per 1000 patient-years, HR, 0.81 [95% CI: 0.75-0.88]). In this propensity scorematched, target trial emulation study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at one year compared with patients who received DPP4i., (Copyright © 2025 American Society of Hematology.)

Background: Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular and thromboembolic events. However, the incidence of cardiovascular and thromboembolic events associated with ICIs in gastroesophageal cancers is unknown., Methods: We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 130 participating healthcare institutions. Patients who received ICI and chemotherapy were compared with those who received only chemotherapy. The primary outcomes were cardiovascular events including pericarditis, myocarditis, heart failure, myocardial infarction, ischemic stroke, atrial fibrillation, conduction disorders as well as venous thromboembolism (VTE) within 1-year of ICI or chemotherapy. We matched the cohorts based on predetermined variables including demographics, metastatic disease, chemotherapy, underlying comorbidities, and the use of cardiovascular and lipid-lowering medications., Results: We identified 1,448 patients who received ICI and chemotherapy and 11,966 patients who received chemotherapy only. After matching, 1,425 patients remained in each cohort. The mean age was 63.1 ± 12.7 years in the ICI and chemotherapy cohort and 62.9 ± 12.1 years in the chemotherapy-only cohort. ICI was associated with a higher incidence of pericarditis (45.6 vs. 30.9 cases per 1000 patient-years; HR 1.51 [95% CI 1.03-2.22]) and VTE (102.5 vs. 75.1 cases per 1000 patient-years; HR 1.40 [95% CI 1.09-1.80]). The incidence of other cardiovascular outcomes were similar between the two cohorts., Conclusion: In this cohort study, the use of ICI and chemotherapy was associated with an approximately 40-50% increased risk of pericarditis and VTE than patients on chemotherapy only., Competing Interests: Declarations. Conflict of interest: No conflicts of interest to declare. Ethical approval: This database is compliant with the General Data Protection Regulation and Health Insurance Portability & Accountability Act (HIPPA). This study has been deemed exempt by the Taipei Medical University Hospital's Institutional Review Board (IRB)., (© 2025. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to a placebo. We aim to comprehensively evaluate the safety of using Inclisiran in patients with dyslipidemia and ASCVD or an ASCVD risk equivalent., Methods: Four electronic databases, namely, Pubmed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, were searched from inception to June 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of Inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACEs), injection-site adverse events, new-onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using the risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens., Results: The study included 7 RCTs, enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2% females) who received Inclisiran. Compared to the control group, Inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I 2 = 0%), MACEs (RR, 0.98; 95% CI, 0.82 to 1.17; I 2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I 2 = 0%), and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I 2 = 0%). However, Inclisiran use demonstrated a significant increase in injection-site adverse events (RR, 6.50; 95% CI, 3.20 to 13.20; I 2 = 29%)., Conclusions: Inclisiran use significantly increased injection-site reactions, with no increase in mortality, T2DM, or nasopharyngitis. It demonstrates a generally favorable safety profile, making it a promising option for lipid management in individuals at high cardiovascular risk, such as those with ASCVD or equivalent conditions. While it effectively improves dyslipidemia, decision-makers should be aware of an increased incidence of injection-site reactions, which, though typically mild, warrant consideration in clinical practice. Further trials are required to assess the safety of Inclisiran, particularly the association of the severity of injection-site adverse events over longer treatment durations.

Hepatic organoids (HOs), primarily composed of hepatobiliary cells, do not represent the pathogenesis of liver diseases due to the lack of non-parenchymal cells. Multi-lineage liver organoids (mLOs) containing various cell types found in the liver offer a promising in vitro disease model. However, their structural complexity remains challenging to achieve due to the difficulty in optimizing culture conditions that meet the growth need of all component cell types. Here, we demonstrate that cystic HOs generated from hPSCs can be expanded long-term and serve as a continuous source for generating complex mLOs. Assembling cystic HOs with hPSC-derived endothelial and hepatic stellate cell-like cells under conventional HO culture conditions failed to support the development of multiple cell types within mLOs, resulting in biased differentiation towards specific cell types. In contrast, modulating the cAMP/Wnt/Hippo signaling pathways with small molecules during assembly and differentiation phases efficiently generate mLOs containing both hepatic parenchymal and non-parenchymal cells. These mLOs exhibited structural complexity and functional maturity, including vascular network formation between parenchymal lobular structures, cell polarity for bile secretion, and the capacity to respond to fibrotic stimuli. Our study underscores the importance of modulating signaling pathways to enhance mLO structural complexity for applications in modeling liver pathologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute recurrent myopericarditis, characterized by the occurrence of a new myopericarditis event following a symptom-free interval of 4-6 weeks, is relatively rare lacking definitive guidelines for management. Understanding its prevalence, causes, and optimal management is challenging due to limited data and insufficient guidelines. This case outlines the diagnostic work-up and different management modalities for recurrent myopericarditis. A 44-year-old African American man with a past medical history of myopericarditis a year ago presented with fever and chest pain for 4 days. The patient was found to have elevated troponin, CRP, and ESR; pericardial effusion along with a Coxsackie A virus titer of 1:800, suggestive of Coxsackie A virus-induced recurrent myopericarditis. The patient responded well to colchicine and a tapering dose of ibuprofen, achieving significant resolution in the pericardial effusion. Recurrent myopericarditis caused by Coxsackie A virus is a relatively rare phenomenon. New onset myopericarditis can be caused by various factors such as infections, autoimmune disorders, neoplasms, metabolic issues, trauma, and drugs, with recurrence rates of 15%-50% in pericarditis patients. Coxsackie A virus is an important and rare etiology of recurrent myopericarditis due to its unique immune evasive traits. The treatment modalities guided by definitive guidelines for recurrent pericarditis can be applied in recurrent myopericarditis with significant resolution of symptoms. Although there are no specific guidelines for managing recurrent myopericarditis, using approaches designed for recurrent pericarditis has shown promising results, and the immune evasive nature of Coxsackie A virus underscores the need for further research to improve our understanding and treatment of this condition., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: Current guidelines recommend limiting the rate of correction in patients with severe hyponatremia to avoid severe neurologic complications such as osmotic demyelination syndrome (ODS). However, published data have been conflicting. We aimed to evaluate the association between rapid sodium correction and ODS in patients with severe hyponatremia., Materials and Methods: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to November 2023. The primary outcome was ODS and the secondary outcomes were in-hospital mortality and length of hospital stay., Results: We identified 7 cohort studies involving 6,032 adult patients with severe hyponatremia. Twenty-nine patients developed ODS, resulting in an incidence rate of 0.48%. Seventeen patients (61%) had a rapid correction of serum sodium in the first or any 24-hour period of admission. Compared with a limited rate of sodium correction, a rapid rate of sodium correction was associated with an increased risk of ODS (RR, 3.91 [95% CI, 1.17 to 13.04]; I 2 = 44.47%; p = 0.03). However, a rapid rate of sodium correction reduced the risk of in-hospital mortality by approximately 50% (RR, 0.51 [95% CI, 0.39 to 0.66]; I 2 = 0.11%; p < 0.001) and the length of stay by 1.3 days (Mean difference, -1.32 [95% CI, -2.54 to -0.10]; I 2 = 71.47%; p = 0.03)., Conclusions: Rapid correction of serum sodium may increase the risk of ODS among patients hospitalized with severe hyponatremia. However, ODS may occur in patients regardless of the rate of serum sodium correction., Competing Interests: Conflict of interest None to declare., (© 2024 Xin Ya See et al., published by Sciendo.)

Background: To implement the ACGME Anesthesiology Milestone Project in a non-North American context, a process of indigenization is essential. In this study, we aim to explore the differences in perspective toward the anesthesiology competencies among residents and junior and senior visiting staff members and co-produce a preliminary framework for the following nation-wide survey in Taiwan., Methods: The expert committee translation and Delphi technique were adopted to co-construct an indigenized draft of milestones. Descriptive analysis, chi-square testing, Pearson correlation testing, and repeated-measures analysis of variance in the general linear model were employed to calculate the F values and mean differences (MDs)., Results: The translation committee included three experts and the consensus panel recruited 37 participants from four hospitals in Taiwan: 9 residents, 13 junior visiting staff members (JVSs), and 15 senior visiting staff members (SVSs). The consensus on the content of the 285 milestones was achieved after 271 minor and 6 major modifications in 3 rounds of the Delphi survey. Moreover, JVSs were more concerned regarding patient care than were both residents (MD = - 0.095, P < 0.001) and SVSs (MD = 0.075, P < 0.001). Residents were more concerned regarding practice-based learning improvement than were JVSs (MD = 0.081; P < 0.01); they also acknowledged professionalism more than JVSs (MD = 0.072; P < 0.05) and SVSs (MD = 0.12; P < 0.01). Finally, SVSs graded interpersonal and communication skills lower than both residents (MD = 0.068; P < 0.05) and JVSs (MD = 0.065; P < 0.05) did., Conclusions: Most ACGME anesthesiology milestones are applicable and feasible in Taiwan. Incorporating residents' perspectives may bring insight and facilitate shared understanding to a new educational implementation. This study helped Taiwan generate a well-informed and indigenized draft of a competency-based framework for the following nation-wide Delphi survey., (© 2024. The Author(s).)

There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I 2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I 2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I 2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.