Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

A survey of the enteral nutrition practices in patients with neurological disorders in the tertiary hospitals of China.

BACKGROUND AND OBJECTIVES: With the development of enteral nutrition in patients with neurological disorders in China, related guidelines were published in 2011. The Chinese Society for Parenteral and Enteral Nutrition conducted a survey to evaluate the status quo of enteral nutrition practices in these patients. METHODS AND STUDY DESIGN: This multicenter prospective investigation was conducted from April 2012 to April 2013 and involved 18 tertiary hospitals in China. The survey using standardized questionnaires sought information about the basic protocols for enteral nutrition (devices and staffing) and specific information about patients with neurological conditions who received nutrition by way of enteral feeding. RESULTS: In the 18 hospitals from 13 provinces, 83.3% patients were configured with an enteral nutrition infusion pump, 77.8% had a percutaneous endoscopic gastrostomy (PEG) device, and 88.9% had a clinical nutrition support group. Four hundred four patients participated in this survey (259 men, 145 women; mean age 61.3±14.7 years), 85.7% had suffered a stroke, 83.9% had impaired consciousness, and 98.0% had dysphagia. Of the 10 guidelines for enteral nutrition practices, setting the energy target, choosing the enteral nutrition tube, and monitoring the patient received unsatisfactory ratings were in poor compliance (56.2%, 30.0% and 38.9%, respectively); the remaining seven guidelines were in good compliance (each >75%). CONCLUSION: The survey suggested that configuration of the enteral nutritional devices and staffing was adequate in China's tertiary hospitals. However, some associated practices had not yet reached the desired levels of competency, indicating a need for this to be understood and for improved training.

Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional treatment (surgery, chemotherapy, and radiation). Dendritic cells (DCs) are the most powerful antigen presenting cells and DC-based vaccination has the potential to target and eliminate GBM cells and enhance the responses of these cells to the existing therapies with minimal damage to the healthy tissues around them. It can enhance recognition of GBM cells by the patients' immune system and activate vast, potent, and long-lasting immune reactions to eliminate them. Therefore, this therapy can prolong the survival of GBM patients and has wide and bright future in the treatment of GBM. Also, the efficacy of this therapy can be strengthened in several ways at some degree: the manipulation of immune regulatory components or costimulatory molecules on DCs; the appropriate choices of antigens for loading to enhance the effectiveness of the therapy; regulation of positive regulators or negative regulators in GBM microenvironment.

[Clinical features in 4 Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited cerebral arteriolar disease in adulthood, which is caused by NOTCH3 gene mutation. The main symptoms were migraine, cerebral stroke, later with mood disorders and dementia in Caucasian patients. Recently, the disease was also recognized in Asian patients, in whom the migraine is rarely reported. In order to give the clinical features of Chinese patients, we described the clinical symptoms in 4 CADASIL families. METHODS: CADASIL was diagnosed by the investigation of ultra-structure changes of arteriole in sural nerve and NOTCH3 gene mutation in the 4 index cases. Detailed clinical and routine laboratory examinations were performed in these 4 patients, including electrocardiography, nerve conduction velocity, serum glycogen, and serum homocysteine. Additionally, we also collected the clinical data of the other 83 family members through interviews and the available medical records. RESULTS: Of the 83 persons, 29 were classified as clinical suspected patients, who presented one or more of the disease-related neurological symptoms, such as cerebral ischemic events and the cognitive impairment. All of them showed no common risk factors for stroke, such as diabetic mellitus, hypertension, and heart disease. The clinical suspected patients distributed in every consecutive generations and involved both sexes, which was according to the autosomal dominant inherited pattern. The onset age of the disease ranged from 28 to 70-year-old and mainly between the 4th and the 5th decades. The main symptoms were recurrent episodic vertigo, with or without hemiplegia. At the same time or a little bit later, the cognitive impairment was developed in some patients. Compared with the typical presentations of the disease in European patients, none of our 29 patients showed migraine,one index case showed mild sensory disturbance in extremities. Elevated serum homocysteine level and abnormal of nerve conduction study in two index cases (3 and 4) were noticed. CONCLUSION: The onset age of the disease of our patients is similar to that of Caucasian patients. The main symptoms were stroke and dementia. Involvement of post circulation system was the main clinical feature for ischemic events in our patients. Dementia could be found in the early stage of disease. Migraine should not be regarded as a common clinical feature in our patients. The involvement of the peripheral nerves expanded the disease expression outside the central nervous system.

[NOTCH3 gene mutations in four Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

OBJECTIVES: To search for mutations in NOTCH3 gene in four Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: Four probands from four unrelated families with typical manifestations of CADASIL were studied. The 1 approximately 12 coding exons and their flanking intron sequences of NOTCH3 gene were amplified by PCR and sequenced. Some family members in the pedigree 2 and 4 were also examined for the NOTCH3 gene mutations. RESULTS: Four heterozygous missense mutations were identified in the four families: the proband 1 carrying a 268C-->T mutation in exon 3, the proband 2 a 322 C-->T mutation in exon 3, the proband 3 a 328 C-->T mutation inexon 3, and the proband 4 a 1819 C-->T mutation in exon 11, which resulted in the amino acid substitutions of R90C, C108R, R110C, and R607C respectively. Among them the C108R is a novel mutation not reported previously. Additionally, some members in the pedigree 2 and 4 also harbored the same mutations with the probands. CONCLUSION: Four heterozygous missense mutations in NOTCH3 gene have been found in four Chinese families with CADASIL. Different point mutations in NOTCH3 lead to similar phenotype of the disease. To search for mutations in NOTCH3 in related patients will help further understand and accurately diagnose the disease and perform prenatal diagnosis in CADASIL families.