Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma.

OBJECTIVE: Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma. METHODS: A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues. RESULTS: The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue. CONCLUSION: ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

Third ventricular width by transcranial sonography is associated with cognitive impairment in Parkinson's disease.

BACKGROUND: One-fourth of Parkinson's disease (PD) patients suffer from cognitive impairment. However, few neuroimaging markers have been identified regarding cognitive impairment in PD. OBJECTIVE: This study aimed to explore the association between third ventricular width by transcranial sonography (TCS) and cognitive decline in PD. METHOD: Participants with PD were recruited from one medical center in China. Third ventricular width was assessed by TCS, and cognitive function was analyzed by the Mini-Mental State Examination (MMSE). Receiver operating characteristic (ROC) analysis and Cox model analysis were utilized to determine the diagnostic and predictive accuracy of third ventricular width by TCS for cognitive decline in PD patients. RESULT: A total of 174 PD patients were recruited. Third ventricular width was negatively correlated with MMSE scores. ROC analysis suggested that the optimal cutoff point for third ventricular width in screening for cognitive impairment in PD was 4.75 mm (sensitivity 62.7%; specificity 75.6%). After 21.5 (18.0, 26.0) months of follow-up in PD patients without cognitive impairment, it was found that those with a third ventricular width greater than 4.75 mm exhibited a 7.975 times higher risk of developing cognitive impairment [hazard ratio = 7.975, 95% CI 1.609, 39.532, p = 0.011] compared with patients with a third ventricular width less than 4.75 mm. CONCLUSION: Third ventricular width based on TCS emerged as an independent predictor of developing cognitive impairment in PD patients.

Diagnostic Value of the Combination of Ultrasonographic Optic Nerve Sheath Diameter and Width of Crural Cistern with Respect to the Intracranial Pressure in Patients Treated with Decompressive Craniotomy.

BACKGROUND: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP. METHODS: This observational study enrolled 50 patients with brain injury after hemicraniectomy from January 2021 to December 2021. All patients underwent invasive ICP monitoring with microsensor, transcranial, and ocular ultrasound postoperatively. We measured the ONSD including the dura mater (ONSDI), the ONSD excluding the dura mater, the optic nerve diameter (OND), the eyeball transverse diameter (ETD), the WCC, and the flow velocities in the central retinal artery and middle cerebral artery. Then, we calculated the ONSDI-OND (the difference between ONSDI and OND) and ONSDI/ETD (the ratio of ONSDI to ETD). Patients were divided into a normal ICP group (n = 35) and an increased ICP group (≥ 20 mm Hg, n = 15) according to the ICP measurements. Correlations were then assessed between the values of the ultrasound parameters and ICP. RESULTS: The ONSDI, ONSDI-OND, and ONSDI/ETD were positively associated with ICP (r = 0.455, 0.482, 0.423 and p = 0.001, < 0.001, 0.002, respectively), whereas the WCC was negatively associated with ICP (r = - 0.586, p < 0.001). The WCC showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.904), whereas the ONSDI-OND and ONSDI also presented with acceptable predictive power among the ONSD-related parameters (AUC = 0.831, 0.803, respectively). The cutoff values for increased ICP prediction for ONSDI, ONSDI-OND, and WCC were 6.29, 3.03, and 3.68 mm, respectively. The AUC of the combination of ONSDI-OND and WCC was 0.952 (95% confidence interval 0.896-1.0, p < 0.001). CONCLUSIONS: The ONSDI, ONSDI-OND, and WCC were correlated with ICP and had acceptable accuracy levels in estimating ICP in patients after hemicraniectomy. Furthermore, WCC showed a higher diagnostic value than ONSD-related parameters, and the combination of ONSDI-OND and WCC was a satisfactory predictor of increased ICP.

Biomimetic calcium carbonate nanoparticles delivered IL-12 mRNA for targeted glioblastoma sono-immunotherapy by ultrasound-induced necroptosis.

Glioblastoma (GBM) is the most aggressive brain tumor, which owns the characteristics of high recurrence, low survival rate and poor prognosis because of the existence of blood brain barrier (BBB) and complicated brain tumor microenvironment. Currently, immunotherapy has attracted much attention on account of favorable therapeutic effect. In this study, we designed a cRGD-modified cancer cell membrane (CM) coated calcium carbonate nanoparticle to deliver interleukin-12 messenger RNA (IL-12 mRNA@cRGD-CM-CaCO3 NPs). The cRGD-modified CM as the shell can endow the nanoparticles with BBB crossing and tumor homing/homotypic targeting effect in the brain tumor microenvironment. IL-12 mRNA-loaded calcium carbonate nanoparticles as the core allow synergistic immunotherapy of necroptosis-induced immune response and IL-12 mRNA transfection under ultrasound irradiation. The as-prepared biomimetic nanoparticles showed superior target and immunotherapeutic outcomes, suggesting that this biomimetic nanoplatform provides a feasible strategy for promoting BBB-penetrating and antitumor immunity.

Application of Intraoperative Contrast-Enhanced Ultrasound in the Resection of Brain Tumors.

OBJECTIVE: To investigate the value of routine intraoperative ultrasound (IU) and intraoperative contrast-enhanced ultrasound (ICEUS) in the surgical treatment of brain tumors, and to explore the utilization of ICEUS for the removal of the remnants surrounding the resection cavity. METHODS: In total, 51 patients who underwent operations from 2012 to 2018 due to different tumors in the brain were included in this study. The clinical data were evaluated retrospectively. IU was performed in all patients, among which 28 patients underwent ICEUS. The effects of IU and ICEUS on tumor resection and recurrence were evaluated. Semiquantitative analysis was performed to compare ICEUS parameters of the brain tumor with those of the surrounding tissue. RESULTS: In total, 36 male and 15 female patients were included in this study. The average age was 43 years (range: 14-68 years). The follow-up period was from 7 to 74 months (mean follow-up 32 months). IU was used in all patients, and no lesion was missed. Among them, 28 patients underwent ICEUS. The rate of total removal of the ICEUS group (23/28, 82%) was significantly higher than that of the IU group (11/23, 48%) (P<0.05). The recurrence rate of ICEUS and IU was 18% (5/23), and 22% (5/28), respectively, and the difference did not reach statistical significance (P>0.05). The semiquantitative analysis showed that the intensity and the transit time of microbubbles reaching the lesions were significantly different from the intensity and the transit time of microbubbles reaching the surrounding tissue (P<0.05) and reflected indirectly the volume and the speed of blood perfusion in the lesions was higher than those in the surrounding tissue. CONCLUSION: ICEUS is a useful tool in localizing and outlining brain lesions, especially for the resection of the hypervascular lesions in the brain. ICEUS could be more beneficial for identifying the remnants and improving the rate of total removal of these lesions than routine intraoperative ultrasound.

Essential tremor vs idiopathic Parkinson disease: Utility of transcranial sonography.

Substantia nigra (SN) hyperechogenicity measured by transcranial sonography (TCS) is a promising biomarker for Parkinson disease (PD). The aim of this study was to explore the diagnostic accuracy of SN hyperechogenicity (SN) for differentiating PD from essential tremor (ET). A total of 119 patients with PD, 106 ET patients and 112 healthy controls that underwent TCS from November 2016 to February 2019 were included in this single-center retrospective case-control study. Two reviewers who were blinded to clinical information independently measured the SN by TCS imaging. The diagnostic sensitivity, specificity, and accuracy of TCS imaging were evaluated between the PD and healthy controls and between patients with PD and ET. Interrater agreement was assessed with the Cohen κ statistic. TCS imaging of the SN allowed to differentiate between patients with PD and ET with a sensitivity (91.6% and 90.8%) and specificity (91.5% and 89.6%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.87). In addition, measurement of the SN allowed to differentiate between patients with PD and healthy subjects with a sensitivity (91.6% and 90.8%) and specificity (88.4% and 89.3%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.91). Measurement of SN on TCS images could be a useful tool to distinguishing patients with PD from those with ET.

Diagnostic Performance of Transcranial Sonography for Evaluating Substantia Nigra Hyper-echogenicity in Patients with Parkinson's Disease.

To determine the diagnostic performance of transcranial sonography (TCS) in assessing increased echogenic area of the substantia nigra (SN) in patients with Parkinson's disease (PD). Institutional review board approval was obtained for this retrospective study. A total of 278 PD patients (mean age: 64.7 ± 9.8 y, 100 women) and 300 healthy control patients (mean age: 63.6 ± 9.3 y, 97 women) were referred for TCS assessment of SN hyper-echogenicity (SN+) from June 2016 to December 2018. Two sonographers independently measured the sizes of the echogenic areas of the SN by TCS imaging in both PD patients and healthy controls. The diagnostic sensitivity, specificity and accuracy of TCS imaging were compared between PD patients and healthy controls. Inter-rater agreement was assessed with the Cohen's κ statistic. The sensitivity, specificity and accuracy of readers 1 and 2, respectively, for the identification of SN+ in TCS were 90.3% and 89.6% (251 and 249 of 278), 89.3% and 88.3% (268 and 265 of 300) and 89.8% and 88.9% (519 and 514 of 578). Inter-observer agreement was excellent (к = 0.84). The area under the receiver operating characteristic curve (AUC) for differentiation of PD patients from healthy controls was 0.92 for reader 1 and 0.91 for reader 2. Cutoff values of 0.20 and 0.21 cm2 were derived from the assessments performed by readers 1 and 2, respectively. We defined 0.20 cm2 as the optimal cutoff value because it had a higher AUC. TCS is a promising diagnostic technique and can be very helpful in differentiating PD patients from healthy individuals.

Accuracy of Transcranial Sonography of the Substantia Nigra for Detection of Parkinson's Disease: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of substantia nigra hyper-echogenicity by transcranial sonography (TCS) for the diagnosis of Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were electronically searched from inception to June 2018 for all relevant studies. The methodological quality of each study was evaluated by two independent reviewers, who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Articles reporting information sufficient to calculate the sensitivity and specificity of TCS to diagnose PD were included. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses and forest meta-regression. Thirty-nine studies (3123 participants with PD) were analyzed. The pooled sensitivity and specificity of TCS were 0.84 (95% confidence interval: 0.81-0.87) and 0.85 (0.80-0.88), respectively, for differentiating PD from normal controls or participants with other parkinsonian syndromes. In the secondary outcome, PD participants exhibited a significant increase in substantia nigra areas than either normal controls (0.14 [0.12-0.16], p < 0.0001) or participants with other parkinsonian syndromes (0.11 [0.08-0.13], p < 0.0001). This meta-analysis revealed the high diagnostic performance of TCS in differentiating patients with PD from both normal controls and participants with other parkinsonian syndromes.

Effectiveness of N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N-acetylcysteine (NAC) pretreatment in the prevention of contrast-induced nephropathy (CIN). In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN. METHODS AND RESULTS: PubMed, EMBASE, and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk (RR) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN. The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group (RR: 0.76, 95% CI: 0.66-0.88, P=0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% (RR: 0.74, 95% CI: 0.63-0.87, P=0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% (RR: 1.00, 95% CI: 0.42-2.40, P=1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% (RR: 0.51, 95% CI: 0.29-0.89, P=0.02). CONCLUSIONS: Our meta-analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious.

Association between vitamin E and non-alcoholic steatohepatitis: a meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) generally has a relatively favorable clinical course; however, non-alcoholic steatohepatitis (NASH) was much more frequently progresses to cirrhosis and hepatocellular carcinoma. We performed a systematic review and meta-analysis of clinical trials to examine the effects of vitamin E supplementation in improving liver histology in NASH. We performed a comprehensive search of the PubMed, Embase and Cochrane databases through October 2014. Weighted mean differences (WMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the efficacy of vitamin E in improving liver histological scores by using fixed effects or random effects. Standard methods were performed to explore statistical heterogeneity and publication bias. Compared with controls, vitamin E supplementation significantly improved all histological parameters, including steatosis (WMD = -0.62, 95% CI: -0.95, -0.77, P = 0.0002), hepatocyte ballooning (WMD = -0.30, 95% CI: -0.56, -0.04, P = 0.03), lobular inflammation (WMD = -0.39, 95% CI: -0.67, -0.11, P = 0.007) and fibrosis (WMD = -0.39, 95% CI: -0.72, -0.06, P = 0.02). Our analysis also indicated the absence of publication bias between NASH and Vitamin E intake. This meta-analysis indicates that vitamin E supplementation had a significant and positive effect in the improvement of steatosis, ballooning degeneration, lobular inflammation and fibrosis in patients with NASH.

Association between patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and nonalcoholic fatty liver disease: a HuGE review and meta-analysis.

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57-4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39-5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.

Influence of vitamin E supplementation on glycaemic control: a meta-analysis of randomised controlled trials.

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (-0.58%, 95% CI -0.83 to -0.34) and fasting insulin (-9.0 pmol/l, 95% CI -15.90 to -2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.

Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice.

Non-alcoholic fatty liver disease (NAFLD) is hepatic manifestation of a metabolic syndrome and includes a spectrum of hepatic steatosis, steatohepatitis, and fibrosis. Interleukin-17 (IL-17) has been reported to play a critical role in inflammatory progression of some liver diseases. The present study was designed to investigate the role of IL-17 on high fat diet-induced NAFLD in C57BL/6 mice. IL-17 blockade with anti-IL-17mAb significantly improved liver function, attenuated hepatic lipid accumulation, suppressed Kuffer cells activation, and decreased pro-inflammatory cytokines levels, which were associated with inhibition of NF-κB signaling cascades activation. Our data suggested that IL-17 was related to disease progression in NAFLD mouse model and blocking IL-17 may be a promising novel therapeutic approach for patients with NAFLD.