Human embryonic stem cell-derived cerebral organoids for treatment of mild traumatic brain injury in a mouse model.

OBJECTIVE: There are no effective treatments for relieving neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated therapeutic efficacy of human embryonic stem cell-derived cerebral organoids (hCOs) in a mild TBI model, in terms of repair of damaged cortical regions, neurogenesis, and improved cognitive function. METHODS: Male C57BL/6 J mice were randomly divided into sham-operated, mild TBI, and mild TBI with hCO groups. hCOs cultured at 8 weeks were used for transplantation. Mice were sacrificed at 7 and 14 days after transplantation followed by immunofluorescence staining, cytokine profile microarray, and novel object recognition test. RESULTS: 8W-hCOs transplantation significantly reduced neuronal cell death, recovered microvessel density, and promoted neurogenesis in the ipsilateral subventricular zone and dentate gyrus of hippocampus after mild TBI. In addition, increased angiogenesis into the engrafted hCOs was observed. Microarray results of hCOs revealed neuronal differentiation potential and higher expression of early brain development proteins associated with neurogenesis, angiogenesis and extracellular matrix remodeling. Ultimately, 8W-hCO transplantation resulted in reconstruction of damaged cortex and improvement in cognitive function after mild TBI. CONCLUSION: hCO transplantation may be feasible for treating mild TBI-related neuronal dysfunction via reconstruction of damaged cortex and neurogenesis in the hippocampus.

Influence of renal impairment on neurologic outcomes following mechanical thrombectomy in acute vertebrobasilar stroke.

PURPOSE: Renal impairment (RI) has been regarded as a risk factor for unfavorable neurologic outcomes after mechanical thrombectomy (MT) in acute ischemic stroke. However, most of the previous studies were conducted on patients with anterior circulation stroke. Accordingly, the influence of RI on MT outcomes has not been well elucidated in detail in acute vertebrobasilar stroke. METHODS: Consecutive stroke patients with MT due to acute vertebrobasilar artery occlusion between March 2015 and December 2020 at four institutions were included. Multivariable logistic regression analysis was conducted to assess the associations between RI and outcomes and mortality at 3 months, and the development of intracerebral hemorrhage (ICH) after the procedure. Additionally, the multivariable Cox proportional hazards model was performed to determine the influence of RI on survival probability after patient discharge. RESULTS: A total of 110 patients were included in the final analysis. The presence of RI (OR = 0.268, 95% CI: 0.077-0.935), National Institute of Health Stroke Scale scores (OR = 0.849, 95% CI: 0.791-0.910), and puncture-to-recanalization time (OR = 0.981, 95% CI: 0.966-0.997) were related to outcomes. There was no significant association between RI and 3-month mortality or ICH. The cumulative survival probability after adjusting for relevant risk factors demonstrated that RI remained significantly associated with poorer survival after MT compared to patients without RI (HR = 2.111, 95% CI: 0.919-4.847). CONCLUSION: RI was an independent risk factor for poor 3-month neurologic outcomes and survival probability after MT in patients with acute vertebrobasilar stroke.

Ultrasonographic optic nerve sheath diameter to detect increased intracranial pressure in adults: a meta-analysis.

BACKGROUND: The optimal optic nerve sheath diameter (ONSD) cut-off for identifying increased intracranial pressure (IICP) remains unclear in adult patients. PURPOSE: To validate the diagnostic accuracy of ultrasonographic (US) ONSD > 5.0 mm as a cut-off for detecting IICP by computed tomographic (CT) through a meta-analysis. MATERIAL AND METHODS: A systemic literature review was performed of online databases from January 1990 to September 2017. A bivariate random-effects model was used to estimate pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs). A summary receiver operating characteristic (SROC) graph was used to provide summary points for sensitivity and specificity. Meta-regression tests were performed to estimate the influence of the study characteristics on DOR. Publication bias was assessed using Deeks' funnel plot asymmetry test. RESULTS: Six studies with 352 patients were included in the meta-analysis. US ONSD > 5.0 mm revealed pooled sensitivity of 99% (95% CI = 96-100) and specificity of 73% (95% CI = 65-80) for IICP detection. DOR was 178. The area under the SROC curve was 0.981, indicating a good level of accuracy. Meta-regression studies showed no significant associations between DOR and study characteristics such as probe mode (relative DOR [RDOR] = 0.60; P = 0.78), study quality (RDOR = 0.52; P = 0.67), IICP prevalence (RDOR = 0.04; P = 0.17), or pathology at admission (RDOR = 1.30; P = 0.87). CONCLUSION: US ONSD > 5.0 mm can be used to rapidly detect IICP in adults in emergency departments and intensive care units. Further meta-analysis based on individual patient-level databases is needed to confirm these results.

Fulminant cerebral infarction of anterior and posterior cerebral circulation after ascending type of facial necrotizing fasciitis.

Necrotizing fasciitis is a soft tissue infection that is characterized by extensive necrosis of the subcutaneous fat, neurovascular structures, and fascia. Cerebral infarction after facial necrotizing fasciitis has been rarely reported. A 61-year-old woman with diabetes was admitted with painful swelling of her right cheek. One day later, she was stuporous and quadriplegic. A computed tomographic scan of her face revealed right facial infection in the periorbital soft tissue, parotid, buccal muscle, and maxillary sinusitis. A computed tomographic scan of the brain revealed cerebral infarction in the right hemisphere, left frontal area, and both cerebellum. Four days later, she died from cerebral edema and septic shock. Involvement of the cerebral vasculature, such as the carotid or vertebral artery by necrotizing fasciitis, can cause cerebral infarction. Facial necrotizing fasciitis should be treated early with surgical treatment and the appropriate antibiotic therapy.

Value of CT angiography for the detection of intracranial vascular lesions in patients with acute severe headache.

OBJECTIVES: To retrospectively investigate the prevalence and characteristics of intracranial vascular lesions in patients with acute severe headache with the use of CT angiography (CTA). METHODS: We systematically searched for neurologically intact patients with acute severe headache and normal unenhanced head CT. The study group consisted of 512 patients; 251 male; mean age 46.2 ± 12.4 years. All patients underwent CTA between 1 day and 2 months after the headache attack. CTA images were interpreted by two experienced neuroradiologists for the presence of vascular lesions. RESULTS: Thirty-four (6.6 %) of the 512 patients had intracranial vascular lesions on CTA, including 33 aneurysms (2 patients had 2 aneurysms each), 2 moyamoya disease and 1 arterial dissection. No gender- or age-related differences were found. Aneurysms arose most commonly on the internal carotid artery (n = 12), followed by the anterior communicating artery (n = 7), and the middle cerebral artery (n = 7). Maximal diameters ranged from 2.0 to 13.1 mm (mean, 3.9 ± 2.6 mm). CONCLUSIONS: CTA is a feasible tool for diagnosing intracranial vascular lesions in patients with acute severe headache. The prevalence of vascular lesions in our series was 6.6 %, which is higher than that predicted in the general population. KEY POINTS: • Unruptured cerebral aneurysms may be a cause of acute severe headache • CTA assesses intracranial vascular lesions in patients with acute severe headache • The prevalence of vascular lesions in our series of patients was 6.6 %

Intravenous flat-detector computed tomography angiography for high-grade carotid stenosis.

AIM: The significant feature of intravenous flat-detector computed tomography (IV FDCT) angiography is its role in neurointerventional setting without patient transfer. However, few studies have addressed the accuracy of IV FDCT in estimating carotid stenosis and length. This study examined the reliability of IV FDCT in the diagnosis of high-grade carotid stenosis and stenosis length with digital subtraction angiography (DSA) as the reference. METHODS: Intravenous flat-detector CT and DSA were conducted simultaneously for 33 patients with 42 stenosed carotid arteries who were suspected of having symptomatic high-grade stenosis by carotid duplex ultrasound, magnetic resonance angiography, or CT angiography. The degree of stenosis and length discrepancy between 2 tests were recorded by 2 readers. RESULTS: The intraobserver and interobserver agreements were excellent for measuring high-grade carotid stenosis (κ = 0.87 and 0.82). Intravenous flat-detector CT had a sensitivity of 96.3%, specificity of 93.3%, and negative predictive value of 93.3% for detecting high-grade stenosis (≥70%) compared with DSA. Bland-Altman plots demonstrated excellent correlation of the degree of stenosis IV FDCT with DSA. Length discrepancy (IV FDCT - DSA, in millimeters) did not differ significantly according to degree of stenosis (Spearman rank test; r = 0.18, P = 0.26). CONCLUSIONS: Intravenous flat-detector CT can be a feasible and time-saving test for evaluating high-grade carotid stenosis and stenosis length.

Incidental thyroid lesions identified by ultrasound in patients with non-thyroidal head and neck cancer.

BACKGROUND: Thyroid cancer is one of the common head and neck malignancies and may be found incidentally with other head and neck cancers. PURPOSE: To evaluate the prevalence and risk of malignancy in incidental thyroid lesions identified by ultrasound (US) in patients with head and neck cancer. MATERIAL AND METHODS: We retrospectively reviewed medical records of all patients with head and neck cancer other than of thyroid origin between January 2004 and December 2011. A total of 690 patients (537 men and 153 women; mean age, 58.9 ± 12.9 years) underwent US of the neck for the evaluation of cervical lymph node status (including thyroid gland). We evaluated the prevalence of patients with incidental thyroid lesions identified by US and the risk of malignancy in these patients. RESULTS: Of the 690 patients with head and neck cancer, 234 (33.9%) had incidental thyroid lesions on US. Based on US findings, 61 patients underwent fine-needle aspiration, with 39 eventually undergoing thyroidectomy. Among these thyroid lesions, 24 incidental thyroid lesions of 22 patients were histologically proven to be malignant (23 papillary and 1 follicular carcinomas). The risk of malignancy was 9.4% on a patient-by-patient basis. CONCLUSION: Screening of the thyroid gland should be included in the preoperative US examination for cervical lymph node metastases in patients with non-thyroidal head and neck cancer.

Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm.

OBJECTIVE: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. METHODS: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. RESULTS: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. CONCLUSION: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Association of Haptoglobin Phenotypes with Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECT: We aimed to investigate the association of Haptoglobin (Hp) phenotypes with perihematomal edema (PHE) and neurological outcomes after intracerebral hemorrhage (ICH). METHODS: This prospective multicenter study enrolled patients that suffered ICH from March 2017 to February 2020. Hp phenotypes were determined using Western blotting; relative α1 intensity was calculated in patients with Hp2-1. A multivariable logistic regression analysis was then conducted to identify risk factors for increased relative PHE at 96 h and 3-month poor outcomes. RESULTS: In total, 120 patients were ultimately enrolled: Hp1-1 (n = 15, 12.5%); Hp2-1 (n = 51, 42.5%); and Hp2-2 (n = 54, 45.0%). Hp phenotype was significantly associated with PHE (p = 0.028). With Hp1-1 as a reference value, Hp2-2 significantly increased the likelihood of increased rPHE (OR = 6.294, 95% CI: 1.283-30.881), while Hp2-1 did not (OR = 2.843, 95% CI: 0.566-14.284). Poor outcomes were found to be closely associated with hematoma volume at admission (OR = 1.057, 95% CI: 1.015-1.101) and surgical treatment (OR = 5.340, 95% CI: 1.665-17.122) but not Hp phenotypes (p = 0.190). Further, a high level of relative α1 intensity was identified to be significantly associated with decreased rPHE (OR = 0.020, 95% CI: 0.001-0.358). However, the relative α1 intensity was not associated with poor outcomes (OR = 0.057, 95% CI: 0.001-11.790). CONCLUSIONS: ICH patients with Hp2-2 exhibited a higher likelihood of increased rPHE than those with Hp1-1. Higher relative α1 intensities were identified to be closely associated with rPHE in patients with Hp2-1.

Fine-mapping of intracranial aneurysm susceptibility based on a genome-wide association study.

In addition to conventional genome-wide association studies (GWAS), a fine-mapping analysis is increasingly used to identify the genetic function of variants associated with disease susceptibilities. Here, we used a fine-mapping approach to evaluate candidate variants based on a previous GWAS involving patients with intracranial aneurysm (IA). A fine-mapping analysis was conducted based on the chromosomal data provided by a GWAS of 250 patients diagnosed with IA and 296 controls using posterior inclusion probability (PIP) and log10 transformed Bayes factor (log10BF). The narrow sense of heritability (h2) explained by each candidate variant was estimated. Subsequent gene expression and functional network analyses of candidate genes were used to calculate transcripts per million (TPM) values. Twenty single-nucleotide polymorphisms (SNPs) surpassed a genome-wide significance threshold for creditable evidence (log10BF > 6.1). Among them, four SNPs, rs75822236 (GBA; log10BF = 15.06), rs112859779 (TCF24; log10BF = 12.12), rs79134766 (OLFML2A; log10BF = 14.92), and rs371331393 (ARHGAP32; log10BF = 20.88) showed a completed PIP value in each chromosomal region, suggesting a higher probability of functional candidate variants associated with IA. On the contrary, these associations were not shown clearly under different replication sets. Our fine-mapping analysis suggested that four functional candidate variants of GBA, TCF24, OLFML2A, and ARHGAP32 were linked to IA susceptibility and pathogenesis. However, this approach could not completely replace replication sets based on large-scale data. Thus, caution is required when interpreting results of fine-mapping analysis.

Genome-wide polygenic risk impact on intracranial aneurysms and acute ischemic stroke.

Polygenic risk scores (PRSs) have an important relevance to approaches for clinical usage in intracranial aneurysm (IA) patients. Hence, we aimed to develop IA-predicting PRS models including the genetic basis shared with acute ischemic stroke (AIS) in Korean populations. We applied a weighted PRS (wPRS) model based on a previous genome-wide association study (GWAS) of 250 IA patients in a hospital-based multicenter cohort, 222 AIS patients in a validation study, and 296 shared controls. Risk predictability was analyzed by the area under the receiver operating characteristic curve (AUROC). The best-fitting risk models based on wPRSs were stratified into tertiles representing the lowest, middle, and highest risk groups. The weighted PRS, which included 29 GWASs (p < 5×10-8) and two reported genetic variants (p < 0.01), showed a high predictability in IA patients (AUROC = 0.949, 95% CI: 0.933-0.966). This wPRS was significantly validated in AIS patients (AUROC = 0.842, 95% CI: 0.808-0.876; p < 0.001). Two-stage risk models stratified into tertiles showed an increased risk for IA (OR = 691.25, 95% CI: 241.77-1976.35; p = 3.1×10-34; sensitivity/specificity = 0.728/0.963), which was replicated in AIS development (OR = 39.76, 95% CI: 16.91-93.49; p = 3.1×10-17; sensitivity/specificity = 0.284/0.963). A higher wPRS for IA may be associated with an increased risk of AIS in the Korean population. These findings suggest that IA and AIS may have a shared genetic architecture and should be studied further to generate a precision medicine model for use in personalized diagnosis and treatment.

Mitochondrial dysfunction associated with autophagy and mitophagy in cerebrospinal fluid cells of patients with delayed cerebral ischemia following subarachnoid hemorrhage.

Decreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied by delayed cerebral ischemia (DCI). However, whether abnormal mechanisms of mitochondria are associated with the development of DCI has not been reported yet. Under cerebral ischemia, mitochondria can transfer into the extracellular space. Mitochondrial dysfunction can aggravate neurologic complications. The objective of this study was to evaluate whether mitochondrial dysfunction might be associated with autophagy and mitophagy in CSF cells to provide possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n = 21; and non-DCI, n = 35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. Compared to non-DCI patients, DCI patients showed significantly increased mRNA expression levels (2-ΔCt) of DAPK1, BNIP3L, and PINK1, but not BAX, ULK1, or NDP52. Multivariable logistic regression analysis revealed that Hunt and Hess grade ≥ IV (p = 0.023), DAPK1 (p = 0.003), and BNIP3L (p = 0.039) were related to DCI. Increased mitochondrial dysfunction associated with autophagy and mitophagy could play an important role in DCI pathogenesis.

The Role of Consecutive Plasma Copeptin Levels in the Screening of Delayed Cerebral Ischemia in Poor-Grade Subarachnoid Hemorrhage.

The prognostic value of copeptin in subarachnoid hemorrhage (SAH) has been reported, but the prognosis was largely affected by the initial clinical severity. Thus, the previous studies are not very useful in predicting delayed cerebral ischemia (DCI) in poor-grade SAH patients. Here, we first investigated the feasibility of predicting DCI in poor-grade SAH based on consecutive measurements of plasma copeptin. We measured copeptin levels of 86 patients on days 1, 3, 5, 7, 9, 11, and 13 using ELISA. The primary outcome was the association between consecutive copeptin levels and DCI development. The secondary outcomes were comparison of copeptin with C-reactive protein (CRP) in predicting DCI. Additionally, we compared the prognostic value of transcranial Doppler ultrasonography (TCD) with copeptin using TCD alone to predict DCI. Increased copeptin (OR = 1.022, 95% CI: 1.008-1.037) and modified Fisher scale IV (OR = 2.841; 95% CI: 0.998-8.084) were closely related to DCI. Consecutive plasma copeptin measurements showed significant differences between DCI and non-DCI groups (p < 0.001). Higher CRP and DCI appeared to show a correlation, but it was not statistically significant. Analysis of copeptin changes with TCD appeared to predict DCI better than TCD alone with AUCROC differences of 0.072. Consecutive measurements of plasma copeptin levels facilitate the screening of DCI in poor-grade SAH patients.

Multi-View Convolutional Neural Networks in Rupture Risk Assessment of Small, Unruptured Intracranial Aneurysms.

Auto-detection of cerebral aneurysms via convolutional neural network (CNN) is being increasingly reported. However, few studies to date have accurately predicted the risk, but not the diagnosis itself. We developed a multi-view CNN for the prediction of rupture risk involving small unruptured intracranial aneurysms (UIAs) based on three-dimensional (3D) digital subtraction angiography (DSA). The performance of a multi-view CNN-ResNet50 in accurately predicting the rupture risk (high vs. non-high) of UIAs in the anterior circulation measuring less than 7 mm in size was compared with various CNN architectures (AlexNet and VGG16), with similar type but different layers (ResNet101 and ResNet152), and single image-based CNN (single-view ResNet50). The sensitivity, specificity, and overall accuracy of risk prediction were estimated and compared according to CNN architecture. The study included 364 UIAs in training and 93 in test datasets. A multi-view CNN-ResNet50 exhibited a sensitivity of 81.82 (66.76-91.29)%, a specificity of 81.63 (67.50-90.76)%, and an overall accuracy of 81.72 (66.98-90.92)% for risk prediction. AlexNet, VGG16, ResNet101, ResNet152, and single-view CNN-ResNet50 showed similar specificity. However, the sensitivity and overall accuracy were decreased (AlexNet, 63.64% and 76.34%; VGG16, 68.18% and 74.19%; ResNet101, 68.18% and 73.12%; ResNet152, 54.55% and 72.04%; and single-view CNN-ResNet50, 50.00% and 64.52%) compared with multi-view CNN-ResNet50. Regarding F1 score, it was the highest in multi-view CNN-ResNet50 (80.90 (67.29-91.81)%). Our study suggests that multi-view CNN-ResNet50 may be feasible to assess the rupture risk in small-sized UIAs.

Association Between Copeptin and Six-Month Neurologic Outcomes in Patients With Moderate Traumatic Brain Injury.

Background: Copeptin has been reported as a predictive biomarker for the prognosis after traumatic brain injury (TBI). However, most of them were in patients with severe TBI and limited value in predicting outcomes in patients with moderate TBI defined as Glasgow Coma Scale (GCS) score from 9 to 12. We aimed to investigate the predictive value of copeptin in assessing the neurologic outcome following moderate TBI. Methods: Patients were prospectively enrolled between May 2017 and November 2020. We consecutively measured plasma copeptin within 24 h after trauma, days 3, 5, and 7 using ELISA. The primary outcome was to correlate plasma copeptin levels with poor neurologic outcome at 6 months after moderate TBI. The secondary outcome was to compare the prognostic accuracy of copeptin and C-reactive protein (CRP) in assessing the outcome of patient. Results: A total of 70 patients were included for the final analysis. The results showed that 29 patients (41.4%) experienced a poor neurologic outcome at 6 months. Multivariable logistic regression analysis revealed that increased copeptin (odds ration [OR] = 1.020, 95% CI: 1.005-1.036), GCS score of 9 or 10 (OR = 4.507, 95% CI: 1.266-16.047), and significant abnormal findings on CT (OR = 4.770; 95% CI: 1.133-20.076) were independent risk factors for poor outcomes. Consecutive plasma copeptin levels were significantly different according to outcomes (p < 0.001). Copeptin on day 7 exhibited better prognostic performance than CRP with an area under receiver operating characteristic curve (AUROC) difference of 0.179 (95% CI: 0.032-0.325) in predicting 6-month poor outcomes. Conclusion: Plasma copeptin level can be a useful marker in predicting 6-month outcomes in patients with moderate TBI.

Small atypical cervical nodes detected on sonography in patients with squamous cell carcinoma of the head and neck: probability of metastasis.

OBJECTIVE: The purpose of this study was to assess the probability of metastasis of small atypical cervical lymph nodes detected on sonography in patients with squamous cell carcinoma (SCC) of the head and neck. METHODS: We reviewed, retrospectively and blindly, sonographic findings of 148 patients (118 men and 30 women; mean age, 58.2 years) who underwent curative neck dissection. Each lymph node was classified by using a 4-point scale: 1, definitely benign; 2, indeterminate (small [short-axis diameter <10 mm for levels I and II and <7 mm for levels III-VI] atypical node); 3, definitely metastatic; and 4, large (>3-cm) metastatic. Lymph nodes were considered atypical if they met at least 1 of the following criteria: a long- to short-axis diameter ratio of less than 2.0, absence of a normal echogenic hilum, and heterogeneous echogenicity of the cortex. These results were verified, on a level-by-level basis, with histopathologic findings. RESULTS: Small atypical nodes were found on sonography in 63 cervical levels of 48 patients, of which 18 (28.6%) were proved to have metastatic nodes. The probability of metastasis was significantly higher with than without a large (>3-cm) ipsilateral metastatic node (0.50 versus 0.20; P = .038) and marginally higher with than without an ipsilateral metastatic node (0.41 versus 0.16; P = .061) but not significantly associated with the T stage of the primary tumor (P = .238) or the presence of an ipsilateral tumor (P = .904). CONCLUSIONS: Metastasis was encountered in about 30% of small atypical cervical nodes on sonography in patients with SCC of the head and neck. Our results indicate that small atypical nodes must be interpreted with consideration of metastatic nodes in the ipsilateral neck.

A randomized comparison of estimated radiation exposure between Low and conventional dose protocol during invasive coronary angiography (ERICA trial): Pilot study.

PURPOSE: Radiation exposure during coronary angiography is potentially harmful to patients and operators. However, there are limited data on the effects of a low-dose radiation angiography. We evaluated the feasibility and effectiveness of a reduced radiation dose protocol during invasive coronary angiography. METHODS: One hundred three consecutive patients who underwent coronary angiography were enrolled and randomized to low- or conventional dose protocols (LDP versus CDP). The LDP consists of 10 frames per second during fluoroscopy and half the radiation dose of CDP during cineangiography. Image quality was assessed using a Likert rating scale by an independent radiologist. The radiation dose was estimated with dose-area product (DAP) and air-kerma (AK). RESULTS: Body weight and waist circumference are well correlated with the level of DAP and AK. Exposure time and total images and frame counts in cineangiography were similar in both groups. There was a marked reduction of the estimated radiation dose (DAP and AK) in the LDP group compared to the CDP group without significant compromise in image quality (total DAP: LDP 1980.1 ±â€¯1163.7 vs. CDP 3434.2 ±â€¯2188.1 µGym2 p = 0.001; total AK: 279.6 ±â€¯159.3 vs. 493.8 ±â€¯280.6 mGy, p < 0.001). CONCLUSION: The LDP reduced the total estimated radiation dose compared to the CDP without a significant loss of diagnostic information. A LDP may be a viable strategy to protect patients and medical staff from the hazards of radiation in the cardiac catheterization laboratory.

Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage.

Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epigenome-wide association study (EWAS) and quantitative real-time PCR (qRT-PCR) were conducted in 40 SAH patients (DCI, n = 13; non-DCI, n = 27). A replication study using bisulfite modification and methylation-specific PCR was further performed in 36 patients (DCI, n = 12; non-DCI, n = 24). The relative degree of methylation was described as the median and 25th-75th percentile. No significant differences in clinical characteristics between DCI and non-DCI groups were observed. Among the top 10 differentially methylated genes analyzed via EWAS, two aberrantly methylated CpG sites of cg00441765 (INSR gene) and cg11464053 (CDHR5 gene) were associated with decreased mRNA expression (2-ΔCt). They include INSR [0.00020 (0.00012-0.00030) in DCI vs. 0.00050 (0.00030-0.00068) in non-DCI] and CDHR5 [0.114 (0.053-0.143) in DCI vs. 0.170 (0.110-0.212) in non-DCI]. Compared with non-DCI cases, patients with DCI exhibited an increased degree of methylation in the replication study: INSR, 0.855 (0.779-0.913) in DCI vs. 0.582 (0.565-0.689) in non-DCI; CDHR5, 0.786 (0.708-0.904) in DCI vs. 0.632 (0.610-0.679) in non-DCI. Hypermethylation of two novel genes, INSR and CDHR5 may serve as a biomarker for early detection of DCI following SAH.

The Effects of Balloon-Guide Catheters on Outcomes after Mechanical Thrombectomy in Acute Ischemic Strokes : A Meta-Analysis.

OBJECTIVE: Mechanical thrombectomies with balloon-guide catheters (BGC) are thought to improve successful recanalization rates and to decrease the incidence of distal emboli compared to thrombectomies without BGC. We aimed to assess the effects of BGC on the outcomes of mechanical thrombectomy in acute ischemic strokes. METHODS: Studies from PubMed, EMBASE, and the Cochrane library database from January 2010 to February 2018 were reviewed. Random effect model for meta-analysis was used. Analyses such as meta-regression and the "trim-and-fill" method were additionally carried out. RESULTS: A total of seven articles involving 2223 patients were analyzed. Mechanical thrombectomy with BGC was associated with higher rates of successful recanalization (odds ratio [OR], 1.632; 95% confidence interval [CI], 1.293-2.059). BGC did not significantly decrease distal emboli, both before (OR, 0.404; 95% CI, 0.108-1.505) and after correcting for bias (adjusted OR, 1.165; 95% CI, 0.310- 4.382). Good outcomes were observed more frequently in the BGC group (OR, 1.886; 95% CI, 1.564-2.273). Symptomatic intracranial hemorrhage and mortality did not differ significantly with BGC use. CONCLUSION: Our meta-analysis demonstrates that BGC enhance recanalization rates. However, BGC use did not decrease distal emboli after mechanical thrombectomies. This should be interpreted with caution due to possible publication bias and heterogeneity. Additional meta-analyses based on individual patient data are needed to clarify the role of BGC in mechanical thrombectomies.

miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4.

Recent studies show that dysregulated miRNAs play an important role in breast cancer initiation and progression. Here, we identified upregulated expression of miR-1307-3p in breast cancer tissues and that increased level of miR-1307-3p was closely correlated with lower survival rate in breast cancer patients. Consistent with clinical data, our in vitro data show that expression level of miR-1307-3p was significantly increased in breast cancer cell lines compared to human mammary epithelial cell line MCF10A. Overexpression of miR-1307-3p in MCF10A stimulated cell proliferation and caused their growth in soft agar and tumor formation in nude mice. In contrast, inhibition of miR-1307-3p suppressed breast cancer cell proliferation and their growth in soft agar and inhibited tumor formation in nude mice. Further, we identified that miR-1307-3p plays its oncogenic role through targeting SET and MYND domain-containing 4 (SMYD4) expression in breast cancer. Taken together, our findings suggest that miR-1307-3p is a oncogenic miRNA that significantly contributes to breast cancer development and progression, and inhibition of miR-1307-3p may be a novel strategy for inhibits breast cancer initiation and progression.