Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

The Role of Circadian Rhythms in Stroke: A Narrative Review.

Stroke, a debilitating condition often leading to long-term disability, poses a substantial global concern and formidable challenge. The increasing incidence of stroke has drawn the attention of medical researchers and neurologists worldwide. Circadian rhythms have emerged as pivotal factors influencing stroke's onset, pathogenesis, treatment, and outcomes. To gain deeper insights into stroke, it is imperative to explore the intricate connection between circadian rhythms and stroke, spanning from molecular mechanisms to pathophysiological processes. Despite existing studies linking circadian rhythm to stroke onset, there remains a paucity of comprehensive reviews exploring its role in pathogenesis, treatment, and prognosis. This review undertakes a narrative analysis of studies investigating the relationship between circadian variation and stroke onset. It delves into the roles of various physiological factors, including blood pressure, coagulation profiles, blood cells, catecholamines, cortisol, and the timing of antihypertensive medication, which contribute to variations in circadian-related stroke risk. At a molecular level, the review elucidates the involvement of melatonin, circadian genes, and glial cells in the pathophysiology. Furthermore, it provides insights into the diverse factors influencing stroke treatment and outcomes within the context of circadian variation. The review underscores the importance of considering circadian rhythms when determining the timing of stroke interventions, emphasizing the necessity for personalized stroke management strategies that incorporate circadian rhythms. It offers valuable insights into potential molecular targets and highlights areas that require further exploration to enhance our understanding of the underlying pathophysiology. In comparison to the published literature, this manuscript distinguishes itself through its coverage of circadian rhythms' impact on stroke across the entire clinical spectrum. It presents a unique synthesis of epidemiological, clinical, molecular, and cellular evidence, underscoring their collective significance.

Parkinson's disease patients combined with constipation tend to have higher serum expression of microRNA 29c, prominent neuropsychiatric disorders, possible RBD conversion, and a substandard quality of life.

INTRODUCTION: The symptom of constipation has been confirmed as an early diagnose criteria for Parkinson's disease (PD). Furthermore, evidences suggest that pathogenesis of PD initiates in gut, rather than brain. If so, identifying biomarkers for constipation in PD might have potentials to assist early diagnosis and initial treatment. METHOD: We first identified that microRNA 29c (miR-29c) was dysregulated both in PD and constipation patients through bioinformatics analysis. Then, serological analysis of the expression of miR-29c in 67 PD patients with constipation (PD-C), 51 PD patients without constipation (PD-NC), and 50 healthy controls (HC) was carried out by qPCR. Demographic and clinical features were also compared. Patients in PD-C group were further classified into two groups: those with prodromal stage constipation (PD-C-Pro) (n = 36) and those with clinical stage constipation (PD-C-Clinic) (n = 31), to explore their different characteristics. RESULTS: The levels of miR-29c in PD-C group were higher than that in PD-NC group, both higher than HC group. PD-C-Pro group's miR-29c levels were statistically higher compared with PD-C-Clinic group's. What is more, PD-C group had higher scores of MDS-UPDRS-I, NMSS, NMSS3, NMSS4, NMSS6, NMSS9, SCOPA-AUT, HAMD, HAMA, RBDSQ, CSS, and PACQOL compared with PD-NC party. Relative to the PD-C-Clinic, patients in PD-C-Pro group had higher MDS-UPDRS-I, NMSS, NMSS3, HAMD, and HAMA scores, and were more likely to have RBD. CONCLUSION: Our results indicated that miR-29c seems to be an underlying cause for developing constipation in patients with PD and PD-C identifies a group of patients with more severe non-motor impairment, prominent neuropsychiatric disorders, and possible RBD conversion as well as a substandard quality of life. We further confirmed that there is a close relationship between symptoms representing the same pathological origin, especially constipation and RBD.

Identifying the potential role of serum miR-20a as a biomarker for olfactory dysfunction in patients with Parkinson's disease.

INTRODUCTION: Olfactory dysfunction (OD), one of the most common non-motor symptoms in Parkinson's disease (PD), is a cardinal prodromal symptom that can appear years before the onset of motor symptoms. Ongoing studies have demonstrated that microRNAs (miRNAs) are suitable biomarkers for PD, while there is a lack of robust miRNAs that can serve as markers for OD in PD. METHODS: The concordantly differentially expressed miRNAs (DE miRNAs) in the damaged olfactory system were first identified in 2 OD-related Gene Expression Omnibus (GEO) datasets. Then, they were verified in another PD-related GEO dataset and only one miRNA (miR-20a) was found to be significantly altered. Serum levels of miR-20a were further measured by qPCR in 79 PD patients with OD (PD-OD), 52 PD patients without OD (PD-NOD), and 52 healthy controls (HC). Objective measure of OD was defined by 16-item Sniffin' Sticks odor identification test. All the participants underwent a demographic and comprehensive PD-related clinical assessment. RESULTS: Our results proved that miR-20a was significantly downregulated in PD-OD compared with PD-NOD and the area under curve (AUC) for OD detection by miR-20a was 0.803 (95% confidence interval, 0.724-0.883). In addition, PD-OD had higher scores of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (UPDRS) II, Hoehn and Yahr stage (H-Y), Non-Motor Symptoms Scale (NMSS) 3, NMSS 5, NMSS 9, Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), Activity of Daily Living (ADL), and lower scores of Mini-Mental State Examination (MMSE) and 39-item PD Quality of Life Questionnaire (PDQ-39) than PD-NOD. Binary regression model further presented that lower expressions of miR-20a and poorer cognitive function acted as promoting factors in the development of OD. CONCLUSION: Our results suggest that miR-20a could be a novel biomarker for OD in PD and PD-OD patients tend to have higher disease stage, poorer motor aspects of experiences of daily living, worse cognitive scores, and inferior quality of life, and were more likely to have mental disorders. Cognitive function, in particular, is strongly associated with OD in PD patients.

Association between Cognitive Decline and Altered Cerebral Perfusion in Adults with Moyamoya Disease after Revascularization.

INTRODUCTION: Certain studies have observed that patients with moyamoya disease (MMD) have cognitive decline after revascularization. Thus, this study analyzed the relationship between cognitive decline and altered cerebral perfusion after revascularization. METHODS: Here, 313 adult patients with MMD underwent single unilateral revascularization. First, cognitive function was scored using a Mini-Mental Scale (MMSE) and Montreal cognitive function scale (MoCA) before and 3 months after the operation (superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis). Then, computed tomography perfusion was performed before and 1 week after the operation to assess the cerebral perfusion. RESULTS: Our data showed that cognitive function decreased in 55 cases (17.6%) after revascularization. Furthermore, the incidence of cerebral hyperperfusion (CHP) was significantly higher in the cognitive decline group (49/55) than in the cognitive nondecline group (89.1% vs. 5.4%, p < 0.001). Results also showed that although all 55 patients had postoperative cognitive decline, 47 experienced relative cerebral blood flow (CBF) decrease at a relatively distant area of the anastomosis compared with that before the operation, which was significantly higher than in patients without cognitive decline (85.5% vs. 1.94%, p < 0.001). In addition, 41 patients had a simultaneous occurrence of local CHP and paradoxical CBF decrease at a relatively distant anastomosis area, which indicated the incident of watershed shift (WS). As observed, WS occurred in 74.5% of patients with cognitive decline, significantly higher than in patients without cognitive decline (74.5% vs. 0%, p < 0.0001). Through multiple logistic regression analysis, WS was also observed to be a strong independent risk factor for predicting postoperative cognitive decline 3 months after revascularization (odds ratio 17.780, 95% confidence interval 1.668-18.564; p = 0.017). CONCLUSION: Therefore, cognitive decline in patients with MMD after revascularization is related to WS, leading to an uneven distribution of CBF.

Benefits of Iron Chelators in the Treatment of Parkinson's Disease.

As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson's disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

Development an Inflammation-Related Factor-Based Model for Predicting Organ Failure in Acute Pancreatitis: A Retrospective Cohort Study.

Several inflammation-related factors (IRFs) have been reported to predict organ failure of acute pancreatitis (AP) in previous clinical studies. However, there are a few shortcomings in these models. The aim of this study was to develop a new prediction model based on IRFs that could accurately identify the risk for organ failure in AP. Methods. 100 patients with their clinical information and IRF data (levels of 10 cytokines, percentages of different immune cells, and data obtained from white blood cell count) were retrospectively enrolled in this study, and 94 patients were finally selected for further analysis. Univariate and multivariate analysis were applied to evaluate the potential risk factors for the organ failure of AP. The area under the ROC curve (AUCs), sensitivity, and specificity of the relevant model were assessed to evaluate the prediction ability of IRFs. A new scoring system to predict the organ failure of AP was created based on the regression coefficient of a multivariate logistic regression model. Results. The incidence of OF in AP patients was nearly 16% (15/94) in our derivation cohort. Univariate analytic data revealed that IL6, IL8, IL10, MCP1, CD3+ CD4+ T lymphocytes, CD19+ B lymphocytes, PCT, APACHE II score, and RANSON score were potential predictors for AP organ failure, and IL6 (P = 0.038), IL8 (P = 0.043), and CD19+B lymphocytes (P = 0.045) were independent predictors according to further multivariate analysis. In addition, a preoperative scoring system (0-11 points) was constructed to predict the organ failure of AP using these three factors. The AUC of the new score system was 0.86. The optimal cut-off value of the new scoring system was 6 points. Conclusions. Our prediction model (based on IL6, IL8, and CD19+ B Lymphocyte) has satisfactory working efficiency to identify AP patients with high risk of organ failure.

3D texture analyses within the substantia nigra of Parkinson's disease patients on quantitative susceptibility maps and R2∗ maps.

Iron accumulation in the substantia nigra (SN) is spatially heterogeneous, yet no study has quantitatively evaluated how the texture of quantitative susceptibility maps (QSM) and R2∗ might evolve with Parkinson's disease (PD) and healthy controls (HC). The aim of this study was to discriminate between patients with PD and HC using texture analysis in the SN from QSM and R2∗ maps. QSM and R2∗ maps were obtained from 28 PD patients and 28 HC on a clinical 3T MR imaging scanner using 3D multi-echo gradient-echo sequence. The first- and second- order texture features of the QSM and R2∗ images were obtained to evaluate group differences using two-tailed t-test. After correction for multiple comparisons, for the first-order analysis, the susceptibility of SN from patients with PD was significantly greater (p = 0.017) compared with the SN from HC. For the second-order texture analysis, angular second moment, entropy, and sum of entropy showed significant differences in QSM (p < 0.001) and R2∗ maps (p < 0.01). In addition, correlation, contrast, sum of variance and difference of variance, significantly separated the subject groups in QSM maps (p < 0.05) but not in R2∗ images. Receiver operating characteristic analysis showed that entropy and sum of entropy of the QSM maps in the SN yielded the highest performance for differentiating PD patients from HC (area under the curve = 0.89). In conclusion, most first- and second- order QSM texture features successfully distinguished PD patients from HC and significantly outperformed R2∗ texture analysis. The second-order texture features were more accurate and sensitive than first-order texture features for classifying PD patients.

Moderate- and Low-Dose of Atorvastatin Alleviate Cognition Impairment Induced by High-Fat Diet via Sirt1 Activation.

Mounting evidences have demonstrated that diet-induced obesity is associated with cognition impairment via increasing oxidative stress and inflammation in the brain. Atorvastatin (Ator, a HMG-CoA reductase inhibitor) is a cholesterol lowering drug. Studies have reported that Ator can ameliorate the development and progression of cognition impairment. Additionally, silent information regulator 1 (SIRT1) has been demonstrated to be beneficial in cognition impairment. However, the interaction between Ator and SIRT1 activation for cognition impairment remains unclear. This study aimed to identify a relationship between the use of Ator and cognition impairment induced by high-fat diet via Sirt1 activation. A total of 60 healthy male C57BL/6J mice were purchased and then divided into 6 groups, including normal diet group (control), a high-fat diet group (40%HFD, 40% energy from fat), a model group (60%HFD, 60% energy from fat), and model group treated with different doses of Ator (high-dose (80 mg), moderate-dose (40 mg), and low-dose (20 mg) groups). All interventions took place for 7 months. Metabolic phenotypes were characterized for body weight and analysis of serum lipid level. The level of cognition development was examined by Morris water maze (MWM) approach and novel object recognition test (NORT); besides, the expression of Creb1, Gap-43, BDNF, CaMKII, and ERKs of frontal cortex and hippocampus was determined by reverse transcription polymerase chain reaction (RT-PCR). Then, the levels of factors related to inflammation (TNF-a, IL-1ß, HMGB1 and IL-6) and oxidation stress (SOD, MDA, CAT and GSH-Px) were assessed using commercially available kits. Finally, SIRT1 and its downstream molecules (Ac-FoxO1, Ac-p53, Ac-NF-κB, Bcl-2 and Bax) were evaluated by Western blot analysis. Compared with the 60% HFD group, body weight and serum lipid levels were significantly decreased in the Ator treated groups. The results of MWM and NORT, as well as the levels of Creb1, Gap-43, BDNF, CaMKII, and ERKs were markedly reversed in the moderate- and low-dose of Ator treated groups. Meanwhile, the expression of IL-1ß, TNF-a, IL-6, HMGB1, and MDA was notably decreased, whereas the activity of SOD, CAT, and GSH-Px was increased. It was also revealed that the expression of SIRT1 was remarkably unregulated, the level of Bcl-2 was upregulated, and the content of Ac-FoxO1, Ac-p53, Ac-NF-κB, and Bax was downregulated in the moderate- and low-dose of Ator. Furthermore, results showed that the effect of moderate-dose of Ator was significantly greater than the low-dose of Ator. However, these effects were not observed in the high-dose of Ator. Our results showed that moderate- and low-dose of Ator can significantly attenuate cognition impairment induced by HFD through its antioxidant and anti-inflammatory functions related to SIRT1 activation.

Seed point discontinuity-based segmentation method for the substantia nigra and the red nucleus in quantitative susceptibility maps.

BACKGROUND: The automatic segmentation of cerebral nuclei in the quantitative susceptibility mapping (QSM) images can provide assistance for surgical treatment and pathological mechanism studies. However, as the most frequently used segmentation method, the atlas method provides unsatisfactory results when segmenting the substantia nigra (SN) and the red nucleus (RN). PURPOSE: To propose and evaluate an improved automatic method based on seed points-discontinuity for segmentations of the SN and the RN in QSM images. STUDY TYPE: Prospective. SUBJECTS: In all, 22 subjects, 11 patients with Parkinson's disease (PD), and 11 healthy subjects (mean age of 68.0 ± 6.9 years) underwent MR scans. FIELD STRENGTH/SEQUENCE: 3T system and a 3D multiecho gradient echo sequence with monopolar readout gradient. ASSESSMENT: Manual segmentations by two radiologists (both with over 10 years of experience in neuroimaging) were used to establish a baseline for assessment. The Dice coefficient and the center-of-gravity distance was employed to evaluate the segmentation accuracy. STATISTICAL TESTS: The mean value and standard deviation of the Dice coefficient and center-of-gravity distance were calculated separately to compare segmentation results from the proposed method, the level set method, the atlas method (including the single-atlas method and the multi-atlas majority voting method). RESULTS: The statistical results of Dice coefficient of the SN and the RN between the ground truth and the segmentation were 0.79 ± 0.14 and 0.77 ± 0.06 for the proposed method, 0.40 ± 0.10 and 0.65 ± 0.09 for the level set method, 0.68 ± 0.09 and 0.64 ± 0.07 for the single-atlas method, 0.70 ± 0.06 and 0.68 ± 0.05 for the multi-atlas majority voting method, respectively. The proposed method also provides the lowest center-of-gravity distance value (1.05 ± 0.71 for the SN and 0.74 ± 0.35 for the RN). DATA CONCLUSION: The segmentation results of the proposed method performed well on the in vivo data and were closer to the manual segmentation than the atlas method. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1112-1119.

Prognostic aspects of dynamic contrast-enhanced magnetic resonance imaging in synchronous distant metastatic rectal cancer.

OBJECTIVES: To explore the correlations between DCE-MRI quantitative parameters and synchronous distant metastasis and the clinicopathological factors in rectal cancers. METHODS: Sixty-three patients with rectal cancer (synchronous distant metastasis, n = 31; non-metastasis, n = 32) were enrolled in this study. Student's t test and ANOVA were used to compare DCE-MRI parameters (K trans , K ep and V e ). The receiver operating characteristic (ROC) analysis was used to find the reasonable threshold of DCE-MRI parameters to differentiate lesions with synchronous distant metastasis from those without metastasis. RESULTS: The K trans , K ep , and V e value were significantly higher in the lesions with distant metastasis than in the lesions without distant metastasis (0.536 ± 0.242 vs. 0.299 ± 0.118 min-1, p < 0.001; 1.598 ± 0.477 vs. 1.341 ± 0.390 min-1, p = 0.022; and 0.324 ± 0.173 vs. 0.249 ± 0.091, p = 0.034; respectively). The K trans showed the highest AUCs of 0.788 (p < 0.001), with sensitivity of 61.29 % and specificity of 87.5 %, respectively. CONCLUSIONS: DCE-MRI parameters may represent a prognostic indicator for synchronous distant metastases in patients with rectal cancer. KEY POINTS: • The K trans , K ep and V e values correlated with synchronous distant metastasis. • Higher K trans , K ep and V e values were noted among patients with metastasis. • DCE-MRI parameters might represent a prognostic indicator for synchronous distant metastases.

The value of diffusion kurtosis magnetic resonance imaging for assessing treatment response of neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To evaluate the feasibility and value of diffusion kurtosis (DK) imaging in assessing treatment response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). METHODS: Forty-one patients were included. All patients underwent pre- and post-CRT DCE-MRI on a 3.0-Tesla MRI scanner. Imaging indices (D app , K app and ADC values) were measured. Change value (∆X) and change ratio (r∆X) were calculated. Pathological tumour regression grade scores (Mandard) were the standard reference (good responders: pTRG 1-2; poor responders: pTRG 3-5). Diagnostic performance was compared using ROC analysis. RESULTS: For the pre-CRT measurements, pre-D app-10th was significantly lower in the good responder group than that of the poor responder group (p = 0.036). For assessing treatment response to neoadjuvant CRT, pre-D app-10th resulted in AUCs of 0.753 (p = 0.036) with a sensitivity of 66.67 % and a specificity of 77.78 %. The r∆D app had a relatively high AUC (0.859) and high sensitivity (100 %) compared with other image indices. CONCLUSIONS: DKI is feasible for selecting good responders for neoadjuvant CRT for LARC. KEY POINTS: • LARC responded well after neoadjuvant chemoradiotherapy with lower pre-D app-10th . • LARC responded well with greater increases in mean ADC and D app . • The change ratio of D app (r∆D app ) had a relatively better diagnostic performance.

Correlation of standard diffusion-weighted imaging and diffusion kurtosis imaging with distant metastases of rectal carcinoma.

PURPOSE: To investigate the correlation of standard diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) with distant metastases of rectal carcinoma. MATERIALS AND METHODS: Fifty-eight patients with rectal carcinoma (27 with distant metastasis and 31 with no metastasis) were included in this study. The apparent diffusion coefficient (ADC) value from standard DWI (b values of 0 and 1000 sec/mm(2) ), Dapp , and Kapp from DKI (b values of 0, 700, 1400, and 2000 sec/mm(2) ) were acquired with a 3.0T magnetic resonance imaging (MRI) scanner. These quantitative parameters were calculated from the entire tumors. Receiver operating characteristic curve analyses were conducted to assess the utility for discrimination of tumor with distant metastasis and those without metastasis. Parameters were compared using the independent-samples t-test. RESULTS: The histogram metrics 10th percentile of Dapp (Dapp-10th ) and ADC values (ADC10th ) were significantly lower in the distant metastasis group than those without metastasis (972.5 ± 118.8 vs. 1121.3 ± 133.8 × 10(-6) mm(2) /s, P = 0.03; 809.2 ± 67.1 vs. 856.2 ± 72.1 × 10(-6) mm(2) /s, P = 0.03). Dapp-10th showed relatively higher area under the curve (AUC) (0.856 vs. 0.669, P = 0.024), and higher specificity (100% vs. 68%) than ADC10th did for differentiation of lesions with distant metastasis from those without metastasis. CONCLUSION: DKI was relatively better than standard DWI in discriminating rectal carcinoma with distant metastasis from those without metastasis. J. Magn. Reson. Imaging 2016;44:221-229.

Potential Utility of Visually AcceSAble Rembrandt Images Assessment in Brain Astrocytoma Grading.

OBJECTIVE: The aim of this study was to evaluate the predictive value of multivariate factors of Visually AcceSAble Rembrandt Images (VASARI) in brain astrocytoma grading. METHODS: Presurgical magnetic resonance images of 126 patients with brain astrocytomas (World Health Organization grade 2, n = 38; grade 3, n = 36; grade 4, n = 52) were rated by 2 neuroradiologists for tumor size, location, and tumor morphology by using a standardized imaging feature set VASARI. RESULTS: Significant differences were noted in 12 factors of VASARI including enhancement quality, enhancing proportion, noncontrast enhancing tumor proportion, necrosis proportion, edema proportion, hemorrhage, thickness of enhancing margin, definition of the enhancing margin, pial and ependymal invasion, enhanced tumor crossing midline, and satellites between brain astrocytoma grades (grades 1-IV, P < 0.05). On multivariate regression analysis, enhancement quality was an independent diagnostic factor for high-grade brain astrocytoma, whereas edema proportion was an independent diagnostic factor in differentiating grade 2 and grade 3. Noncontrast enhancing tumor proportion was a predictive factor in the diagnosis of grade 4 astrocytoma. Receiver operating characteristic analysis illustrates edema proportion score higher than 2 with sensitivity of 86.1% in differentiating grade 2 and grade 3 astrocytoma. Noncontrast enhancing tumor proportion scores 4 or lower has high sensitivity (92.3%) but moderate specificity (50.0%) in differentiating grade 3 and grade 4 astrocytoma. CONCLUSIONS: Our data illustrate that magnetic resonance features of VASARI especially enhancement quality, edema proportion, and noncontrast enhancing tumor proportion provided precise and detailed information of astrocytoma grading and suggested that prediction of astrocytoma grading is based on VASARI as an adjunct to biopsy.

Correlation Between Magnetic Resonance Imaging-Based Evaluation of Extramural Vascular Invasion and Prognostic Parameters of T3 Stage Rectal Cancer.

PURPOSE: The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. METHODS: Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. RESULTS: Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). CONCLUSIONS: Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

Distribution of ischemic infarction and stenosis of intra- and extracranial arteries in young Chinese patients with ischemic stroke.

BACKGROUND: The distribution of cerebral ischemic infarction and stenosis in ischemic stroke may vary with age-group, race and gender. This study was conducted to understand the risk factors and characteristics of cerebral infarction and stenosis of vessels in young Chinese patients with ischemic stroke. METHODS: This was a retrospective study, from January 2007 to July 2012, of 123 patients ≤50 years diagnosed with acute ischemic stroke. Patient characteristics were compared according to sex (98 males and 25 females) and age group (51 patients were ≤45 years and 72 patients were 46-50 years). Characteristics of acute ischemic infarction were studied by diffusion weighted imaging. Stenosis of intra- and extracranial arteries was diagnosed by duplex sonography, head magnetic resonance angiography (MRA) or cervical MRA. RESULTS: Common risk factors were hypertension (72.4 %), dyslipidemia (55.3 %), smoking (54.4 %) and diabetes (33.3 %). Lacunar Infarction was most common in our patients (41.5 %). Partial anterior circulation infarction was predominant in females (52.0 vs 32.7 %; P = 0.073) and posterior circulation infarction in males (19.8 vs 4 %; P = 0.073). Multiple brain infarctions were found in 38 patients (30.9 %). Small artery atherosclerosis was found in 54 patients (43.9 %), with higher prevalence in patients of the 46-50 years age-group. Intracranial stenosis was more common than extracranial stenosis, and middle cerebral artery stenosis was most prevalent (27.3 %). Stenosis in the anterior circulation was more frequent than in the posterior circulation (P < 0.001). CONCLUSIONS: In these young patients, hypertension, smoking, dyslipidemia and diabetes were common risk factors. Intracranial stenosis was most common. The middle cerebral artery was highly vulnerable.

Bidirectional association between hypothyroidism and myasthenia gravis: a Mendelian randomized study.

OBJECTIVES: Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study. METHODS: Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences (p ≤ 5 × 10-8) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results. RESULTS: Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, p = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, p = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, p = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, p = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, p = 0.170). DISCUSSION: This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.

Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons (MN) in the motor cortex, brain stem, and spinal cord. In the present study, we established an ALS in vitro model of purified embryonic MNs, derived from non-transgenic and mutant SOD1-G93A transgenic mice, the most commonly used ALS animal model. MNs were cultured together with either non-transgenic or mutant SOD1-G93A astrocyte feeder layers. Cell viability following exposure to kainate as excitotoxic stimulus was assessed by immunocytochemistry and calcium imaging. We then examined the neuroprotective effects of N-acetyl-GLP-1(7-34) amide (N-ac-GLP-1), a long-acting, N-terminally acetylated, C-terminally truncated analog of glucagon-like peptide-1 (GLP-1). GLP-1 has initially been studied as a treatment for type II diabetes based on its function as insulin secretagogue. We detected neuroprotective effects of N-ac-GLP-1 in our in vitro system, which could be attributed to an attenuation of intracellular calcium transients, not only due to these antiexcitotoxic capacities but also with respect to the increasing knowledge about metabolic deficits in ALS which could be positively influenced by N-ac-GLP-1, this compound represents an interesting novel candidate for further in vivo evaluation in ALS.

Parkinson's Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. Gene expression profiles were screened from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) were selected for the enrichment analysis. A protein-protein interaction (PPI) network was built with the STRING database (Search Tool for the Retrieval of Interacting Genes), and two ML approaches, namely least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were employed to identify candidate genes. The external validation dataset further tested the expression degree and diagnostic value of candidate biomarkers. To assess the validity of the diagnosis, we determined the receiver operating characteristic (ROC) curve. A convolution tool was employed to evaluate the composition of immune cells by CIBERSORT, and we performed correlation analyses on the basis of the training dataset. Twenty-seven DEGs were screened in the PD and control samples. Our results from the enrichment analysis showed a close association with inflammatory and immune-associated diseases. Both the LASSO and SVM algorithms screened eight and six characteristic genes. AGTR1, GBE1, TPBG, and HSPA6 are overlapping hub genes strongly related to PD. Our results of the area under the ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 (AUC = 0.967), TPBG (AUC = 0.767), and HSPA6 (AUC = 0.633), suggested that these genes have good diagnostic value, and these genes were significantly associated with the degree of immune cell infiltration. AGTR1, GBE1, TPBG, and HSPA6 were identified as potential biomarkers in the diagnosis of PD and provide a novel viewpoint for further study on PD immune mechanism and therapy.

A Risk Score for Predicting the Necessity of Surgical Necrosectomy in the Treatment of Infected Necrotizing Pancreatitis.

BACKGROUND: For infected necrotizing pancreatitis (INP), percutaneous catheter drainage (PCD) is now widely acknowledged as the initial intervention in a step-up approach, followed, if necessary, by minimally invasive necrosectomy or even open pancreatic necrosectomy. However, an overemphasis on PCD may cause a patient's condition to deteriorate, leading to missed surgical opportunities or even death. This study aimed to develop a simple and convenient scoring tool for assessing the need for surgery in INP patients who received PCD procedures. METHODS: In an observational study conducted between April 2015 and December 2020, PCD was utilized as the initial step to treat 143 consecutive INP patients. A surgical necrosectomy was performed when the patient failed to respond. Risk factors of PCD failure (i.e., need for surgical necrosectomy) were identified by multivariate logistic regression models. An integer-based risk scoring tool was developed using the ß coefficients derived from the logistic regression model. RESULTS: In 62 (43.4%) patients, PCD was successful, while the remaining 81 (56.6%) individuals required subsequent surgical necrosectomy. In the multivariate model, organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume were associated with a need for surgical necrosectomy. A predictive scoring tool based on these four factors demonstrated an area under the receiver operating characteristic curve (AUC) of 0.893. Under the scoring tool, a total score of 4 or more indicates a high possibility of surgical necrosectomy being required (at least 80%). Using the coordinates of the receiver operating characteristic curve (ROC), the sensitivity and specificity at this threshold are 0.802 and 0.903, respectively. CONCLUSIONS: A risk score model integrating organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume can identify INP patients at high risk for necrosectomy. The straightforward risk assessment tool assists clinicians in stratifying INP patients and making more judicious medical decisions.