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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.

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.

The objective of our study was to scrutinize the learning experiences of Korean neurology residents, with an emphasis on the implications of the novel competency-based curriculum implemented in 2021. We hypothesized that this revised curriculum could modulate residents' cognitive conduct, primarily the manifestation of overconfidence, in distinctive ways across different stages of training. Our investigative framework was three-fold. Initially, we began with a qualitative inquiry involving in-depth interviews with a purposively selected cohort of eight residents from four training sites. This approach facilitated comprehensive insight into their perceptions of their competence and confidence across the continuum of a four-year residency program. Subsequently, we incorporated the K-NEPA13 assessment instrument, administered to the residents and their overseeing supervisors. This stage aimed to dissect potential cognitive biases, particularly overconfidence and consistency, within the resident population. The final study involved a comprehensive survey administered to a group of 97 Korean neurology residents, allowing us to consolidate and validate our preceding findings. Our findings revealed that junior residents portrayed heightened confidence in their clinical capabilities compared to their senior peers. Intriguingly, junior residents also displayed a stronger inclination towards reevaluating their clinical judgments, a behavior we hypothesize is stimulated by the recently introduced competency-based curriculum. We identified cognitive divergence between junior and senior residents, with the latter group favoring more consistent and linear cause-and-effect reasoning, while the former demonstrated receptiveness to introspection and reconsideration. We speculate this adaptability might be engendered by the supervisor assignment protocol intrinsic to the new curriculum. Our study highlights the essentiality of incorporating cognitive behaviors when devising medical education strategies. Acknowledging and addressing these diverse cognitive biases, and instilling a spirit of adaptability, can nurture a culture that persists in continuous learning and self-reflection among trainee doctors.

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.

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

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

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.

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.

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.