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).

To corset or not to corset after lumbar spine fixation surgery?: A prospective randomized clinical trial and literature review.

PURPOSE: Orthosis after lumbar fusion surgery is common. However, the evidence for benefit remains to be determined, especially in tropical areas with heavy workers. To investigate postoperative orthosis and whether it affects pain improvement, quality of life, and fusion rate. METHOD: From May 2021 to May 2022, this single-center prospective randomized clinical trial enrolled 110 patients. We excluded 9 patients, and 101 people were analyzed finally. Corset group, in which participants used a corset for 3 months postoperatively; Non-corset group, in which participants didn't wear any orthosis. ODI and VAS scale were recorded before the surgery: 2 weeks, 1 month, 3 months, half a year, and 1 year postoperatively. The lumbar X-ray was done before the surgery, 6 months postoperatively. All complications in 1 year were recorded. RESULTS: Significant decrease in VAS score in the non-corset group since post-operation day 5 (corset group 3.44 ±â€…1.77, non-corset group 3.36 ±â€…1.75, P = .0093) during admission, and also a decrease in admission duration (corset group 11.08 ±â€…2.39, non-corset group 9.55 ±â€…1.75, P = .0004) were found. There was a significantly better ODI score in the non-corset group since post-operation 1 month, while in the corset group until post-operation 3 months. Both groups had no significant difference in satisfaction, complication rates, and X-ray results, such as fusion, angular rotation, sagittal transition, and slip in the neutral position. CONCLUSION: After the transpedicular screw fixation with posterolateral fusion surgery for degenerative spondylolisthesis, non-orthosis is a safe strategy. It can reduce the admission duration and has the trend for better functional outcomes.

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.

The prevalence of chronic dehydration and associated with cardiometabolic risks among agriculture and aquaculture workers.

Background: Chronic dehydration is associated with complications and mortality in acute ischemic stroke patients. Prior literature indicates that farmers and fishery workers are commonly affected by cardiometabolic diseases and there is a need for early prevention of stroke. This study explores the prevalence of dehydration and the association of cardiometabolic risk profiles in agricultural and aquaculture workers. Methods: We conducted a community-based, cross-sectional study of agriculture and aquaculture workers in Yunlin County of Taiwan between August 1 and December 31, 2021. Data on demographic characteristics and health-related lifestyles were collected through one-on-one interviews using a questionnaire. The threshold for dehydration is defined as serum osmolality ≥295 mOsm/kg, and physiological biomarkers were collected from a collaborating hospital. Multivariable logistic regression analyses adjusted for demographic characteristics were performed to investigate the association between dehydration levels, cardiometabolic risks, and health-related behaviors. Results: A total of 962 Taiwanese agriculture and aquaculture workers who were predominantly women (65%) with a mean age of 64 years (SD = 13.8) were enrolled. The findings showed a high prevalence of dehydration (36%), metabolic syndrome (44.5%), abnormal waist circumference (64.4%), and abnormal blood pressure (68.5%). Multivariate logistic regression demonstrated that dehydration was significantly associated with metabolic syndrome (p < 0.001), 10-year stroke risk prediction (p < 0.001), and an unhealthy lifestyle (p < 0.001). Conclusion: The prevalence of chronic dehydration was higher in Taiwanese agriculture and aquaculture workers, which was significantly associated with cardiometabolic risks and unhealthy lifestyles.

A Novel Salivary Sensor with Integrated Au Electrodes and Conductivity Meters for Screening of Diabetes.

The rise in diabetes cases is a growing concern due to the aging of populations. This not only places a strain on healthcare systems but also creates serious public health problems. Traditional blood tests are currently used to check blood sugar levels, but they are invasive and can discourage patients from regularly monitoring their levels. We recently developed nano-sensing probes that integrate Au microelectrodes and conductivity meters, requiring only 50 µL of saliva for measurement. The usage of the co-planar design of coating-free Au electrodes makes the measurement more stable, precise, and easier. This study found a positive correlation between the participant's fasting blood sugar levels and salivary conductivity. We observed a diabetes prevalence of 11.6% among 395 adults under 65 years in this study, using the glycated hemoglobin > 6.5% definition. This study found significantly higher salivary conductivity in the diabetes group, and also a clear trend of increasing diabetes as conductivity levels rose. The prediction model, using salivary conductivity, age, and body mass index, performed well in diagnosing diabetes, with a ROC curve area of 0.75. The study participants were further divided into low and high groups based on salivary conductivity using the Youden index with a cutoff value of 5.987 ms/cm. Individuals with higher salivary conductivity had a 3.82 times greater risk of diabetes than those with lower levels, as determined by the odds ratio calculation. In conclusion, this portable sensing device for salivary conductivity has the potential to be a screening tool for detecting diabetes.

ADAM17 Confers Temozolomide Resistance in Human Glioblastoma Cells and miR-145 Regulates Its Expression.

Glioblastoma (GBM) is a malignant brain tumor, commonly treated with temozolomide (TMZ). Upregulation of A disintegrin and metalloproteinases (ADAMs) is correlated to malignancy; however, whether ADAMs modulate TMZ sensitivity in GBM cells remains unclear. To explore the role of ADAMs in TMZ resistance, we analyzed changes in ADAM expression following TMZ treatment using RNA sequencing and noted that ADAM17 was markedly upregulated. Hence, we established TMZ-resistant cell lines to elucidate the role of ADAM17. Furthermore, we evaluated the impact of ADAM17 knockdown on TMZ sensitivity in vitro and in vivo. Moreover, we predicted microRNAs upstream of ADAM17 and transfected miRNA mimics into cells to verify their effects on TMZ sensitivity. Additionally, the clinical significance of ADAM17 and miRNAs in GBM was analyzed. ADAM17 was upregulated in GBM cells under serum starvation and TMZ treatment and was overexpressed in TMZ-resistant cells. In in vitro and in vivo models, ADAM17 knockdown conferred greater TMZ sensitivity. miR-145 overexpression suppressed ADAM17 and sensitized cells to TMZ. ADAM17 upregulation and miR-145 downregulation in clinical specimens are associated with disease progression and poor prognosis. Thus, miR-145 enhances TMZ sensitivity by inhibiting ADAM17. These findings offer insights into the development of therapeutic approaches to overcome TMZ resistance.

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.

In-hospital outcomes of patients with spontaneous supratentorial intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) in the brain parenchyma accounts for 16.1% of all stroke types in Taiwan. It is responsible for high morbidity and mortality in some underlying causes. The objective of this study is to discover the predicting factors focusing on in-hospital outcomes of patients with spontaneous supratentorial ICH. Between June 2014 and October 2018, there were a total of 159 patients with spontaneous supratentorial ICH ranging from 27 to 91 years old in our institution. Twenty-three patients died during hospitalization, whereas 59 patients had an extended length of stay of >30 days. The outcomes were measured by inpatient death, length of stay, and activity of daily living (ADL). Both univariate and multivariate binary logistic regression, as well as multivariate linear regression, were used for statistical analysis. Multivariate binary linear regression analysis showed the larger hematoma in initial computed tomography scan of >30 cm3 (odds ratio [OR] = 2.505, P = .013) and concurrent in-hospital infection (OR = 4.173, P = .037) were both statistically related to higher mortality. On the other hand, in-hospital infection (≥17.41 days, P = .000) and surgery (≥11.23 days, P = .001) were correlated with a longer length of stay. Lastly, drastically poor change of ADL (ΔADL <-30) was associated with larger initial ICH (>30 cc, OR = 2.915, P = .049), in-hospital concurrent infection (OR = 4.695, P = .01), and not receiving a rehabilitation training program (OR = 3.473, P = .04). The results of this study suggest that age, prothrombin, initial Glasgow Coma Scale, computed tomography image, location of the lesion, and surgery could predict the mortality and morbidity of the spontaneous ICH, which cannot be reversed at the time of occurrence. However, effective control of international normalized ratio level, careful prevention against infection, and the aid of rehabilitation programs might be important factors toward a decrease of inpatient mortality rate, the length of stay, and ADL recovery.

Percutaneous radiofrequency trigeminal rhizotomy benefits in patients with refractory trigeminal neuralgia.

ABSTRACT: A significant number of patients suffers from refractory trigeminal neuralgia (TN) after receiving microvascular decompression (MVD) or other neuro-destructive procedure such as gamma knife radiosurgery (GKRS). This study aims to demonstrate a remediable, reproducible approach to treating refractory pain effectively by percutaneous radiofrequency trigeminal rhizotomy (RF-TR).A total of 392 patients with TN were treated by RF-TR during the past 10 years. Among these patients, 48 cases who had received either MVD, GKRS alone, or a combination of both were assigned to group A. Those who had not received any form of treatment (125 patients) or failed to respond medically (130 patients) were assigned as the control group (group B). All the RF-TR were performed by a single surgeon with the aid of intraoperative computed tomography (iCT)-based neuronavigation with magnetic resonance (MR) image fusion. The outcome measure was the numerical rating scale (NRS) expressed subjectively by patients. The paired Student t test and the analysis of covariance (ANCOVA) were used for statistical analysis.In group A, 21 of 24 patients (88%) had significant improvement (NRS change ≥5) in facial pain after RF-TR. The average NRS score was 9.75 ±â€Š0.53 before the procedure and 1.92 ±â€Š3.35 post-treatment (significant NRS decrease [P = .000]). On the other hand, in group B, 226 of 255 patients (89%) also had dramatic amelioration of facial pain after RF-TR. The average NRS score was 9.46 ±â€Š0.69 before the procedure and 1.62 ±â€Š2.85 post-treatment (7.84 ±â€Š2.82 in NRS decrease [P = .008]). By using a univariate ANCOVA, no statistical significance was found in NRS score improvement between the two groups.Repeated MVD and GKRS for refractory TN may be less desirable due to a greater risk of mortality (up to 0.8%) and morbidity (4% of serious complications). Conversely, RF-TR administration with the novel navigation technique by using iCT and MR image fusion is free from any remarkable and irreversible morbidities. In this study, RF-TR not only provided an alternative and effective strategy if TN recurred but also resulted in the same NRS score improvement regardless of the status of prior treatment.

The impact of needle location on clinical outcome of radiofrequency rhizotomy for trigeminal neuralgia.

BACKGROUND: Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors. METHODS: The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures. RESULTS: Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p < 0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern. CONCLUSIONS: This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

Application of a Novel Biosensor for Salivary Conductivity in Detecting Chronic Kidney Disease.

The prevalence of chronic kidney disease (CKD) is increasing, and it brings an enormous healthcare burden. The traditional measurement of kidney function needs invasive blood tests, which hinders the early detection and causes low awareness of CKD. We recently designed a device with miniaturized coplanar biosensing probes for measuring salivary conductivity at an extremely low volume (50 µL). Our preliminary data discovered that the salivary conductivity was significantly higher in the CKD patients. This cross-sectional study aims to validate the relationship between salivary conductivity and kidney function, represented by the estimated glomerular filtration rate (eGFR). We enrolled 214 adult participants with a mean age of 63.96 ± 13.53 years, of whom 33.2% were male. The prevalence rate of CKD, defined as eGFR < 60 mL/min/1.73 m2, is 11.2% in our study. By multivariate linear regression analyses, we found that salivary conductivity was positively related to age and fasting glucose but negatively associated with eGFR. We further divided subjects into low, medium, and high groups according to the tertials of salivary conductivity levels. There was a significant trend for an increment of CKD patients from low to high salivary conductivity groups (4.2% vs. 12.5% vs. 16.9%, p for trend: 0.016). The receiver operating characteristic (ROC) curves disclosed an excellent performance by using salivary conductivity combined with age, gender, and body weight to diagnose CKD (AUC equal to 0.8). The adjusted odds ratio of CKD is 2.66 (95% CI, 1.10−6.46) in subjects with high salivary conductivity levels. Overall, salivary conductivity can serve as a good surrogate marker of kidney function; this real-time, non-invasive, and easy-to-use portable biosensing device may be a reliable tool for screening CKD.

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.

Percutaneous Radiofrequency Rhizotomy Is Equally Effective for Trigeminal Neuralgia Patients with or Without Neurovascular Compression.

BACKGROUND: Neurovascular compression (NVC) in patients with trigeminal neuralgia (TN) can be a factor of treatment outcome, especially in microvascular decompression and stereotactic radiosurgery. No such effect has been reported in percutaneous radiofrequency rhizotomy (RF). This study aims to investigate whether NVC affects the efficacy of RF in patients with TN. METHODS: We retrospectively reviewed patients with TN who received RF in our institution. Pretreatment magnetic resonance imaging was performed in every patient, and the presence of NVC was reviewed independently by two physicians. The patients were followed up at least for a year after the treatment. Pain severity was assessed with a numeric rating scale (NRS). RESULTS: Sixty-two patients were included in the study. All of the patients had single-sided lesions, and 35 patients had NVC. There were no significant differences between these two groups of patients in terms of gender distribution, age, and pretreatment pain severity. Comparable pain severity improvement was found at 1-year follow-up between these two groups (NRS 7.93 ± 0.492 without compression vs 7.57 ± 0.451 with compression, P = 0.600). No significant difference in posttreatment pain severity at 1 year was found between these two patient groups (NRS 1.37 ± 0.466 without compression vs 1.66 ± 0.458 with compression, P = 0.667). CONCLUSIONS: For patients with TN treated by RF, the presence or absence of NVC is not likely to affect the 1-year pain control rate.

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.

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line.

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat.

BACKGROUND: Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke. Standard-dose rt-PA (0.9 mg/kg) is known to achieve good recanalization but carries a high bleeding risk. Lower dose of rt-PA has less bleeding risk but carries a high re-occlusion rate. We investigate if induced pluripotent stem cells (iPSCs) can improve the thrombolytic effect of low-dose rt-PA (0.45 mg/kg). METHODS: Single irradiation with 6 mW/cm2 light-emitting diode (LED) for 4 h at rat common carotid artery was used as thrombosis model according to our previous report. Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and interleukin 1 beta (IL-1 beta) were used as the inflammatory markers for artery endothelial injury. Angiopoietin-2 (AP-2), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were examined in artery wall and iPSCs culture. Animal ultrasound was used to evaluate the stenosis degree of common carotid artery before and at 2 h, 24 h, 4 days and 7 days after LED irradiation. RESULTS: After LED irradiation alone, there was a persistent occlusion from 2 h to 7 days. Standard-dose rt-PA alone could recanalize the occluded artery from 24 h to 7 days to stenotic degree ≤ 50%. Low-dose rt-PA or 1 × 106 mouse iPSCs alone could not recanalize the occluded arteries from 2 h to 7 days. Combination use of low-dose rt-PA plus 1 × 106 mouse iPSCs caused better recanalization from 24 h to 7 days. ET-1, ICAM-1 and IL-1 beta were strongly expressed after LED irradiation but reduced after iPSCs treatment. AP-2, BDNF and VEGF were rarely induced after LED irradiation but strongly expressed after iPSCs treatment. In vitro study showed iPSCs could express AP-2, BDNF and VEGF. CONCLUSION: The adjuvant use of iPSCs may help improving the thrombolytic effect of low-dose rt-PA by suppressing inflammatory factors and inducing angiogenic trophic factors. Stem cells could be a potential regimen in acute thrombolytic therapy to improve recanalization and reduce complications.

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured -34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 µg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.