Safety and efficacy of remote ischemic conditioning for the treatment of intracerebral hemorrhage: A proof-of-concept randomized controlled trial.

BACKGROUND: Remote ischemic conditioning can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage. AIMS: This study aimed to evaluate the safety and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage. METHODS: In this multicenter, randomized, controlled trial, 40 subjects with supratentorial intracerebral hemorrhage presenting within 24-48 h of onset were randomly assigned to receive medical therapy plus remote ischemic conditioning for consecutive seven days or medical therapy alone. The primary safety outcome was neurological deterioration within seven days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 days ([hematoma volume at 7 days - hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. RESULTS: The mean age was 59.3 ± 11.7 years and hematoma volume was 13.9 ± 4.5 mL. No subjects experienced neurological deterioration within seven days of enrollment, and no subject died or experienced remote ischemic conditioning-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19 ± 5.07 mL in the control group and 13.55 ± 3.99 mL in the remote ischemic conditioning group, and they were 8.54 ± 3.99 mL and 6.95 ± 2.71 mL at seven days after enrollment, respectively, which is not a significant difference (p > 0.05 each). The hematoma resolution rate in the remote ischemic conditioning group (49.25 ± 9.17%) was significantly higher than in the control group (41.92 ± 9.14%; MD, 7.3%; 95% CI, 1.51-13.16%; p = 0.015). The absolute PHE volume was 17.27 ± 8.34 mL in the control group and 12.92 ± 7.30 mL in the remote ischemic conditioning group at seven days after enrollment, which is not a significant between-group difference (p = 0.087), but the relative PHE in the remote ischemic conditioning group (1.77 ± 0.39) was significantly lower than in the control group (2.02 ± 0.27; MD, 0.25; 95% CI, 0.39-0.47; p = 0.023). At 90-day follow-up, 13 subjects (65%) in the remote ischemic conditioning group and 12 subjects (60%) in the control group achieved favorable functional outcomes (modified Rankin Scale score ≤ 3), which is not a significant between-group difference (p = 0.744). CONCLUSIONS: Repeated daily remote ischemic conditioning for consecutive seven days was safe and well tolerated in patients with intracerebral hemorrhage, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, the effects of remote ischemic conditioning on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.

Potential distribution of Notopterygium incisum Ting ex H. T. Chang and its predicted responses to climate change based on a comprehensive habitat suitability model.

Notopterygium incisum Ting ex H. T. Chang is a rare and endangered traditional Chinese medicinal plant. In this research, we built a comprehensive habitat suitability (CHS) model to analyze the potential suitable habitat distribution of this species in the present and future in China. First, using nine different algorithms, we built an ensemble model to explore the possible impacts of climate change on the habitat distribution of this species. Then, based on this model, we built a CHS model to further identify the distribution characteristics of N. incisum-suitable habitats in three time periods (current, 2050s, and 2070s) while considering the effects of soil and vegetation conditions. The results indicated that the current suitable habitat for N. incisum covers approximately 83.76 × 103 km2, and these locations were concentrated in the Tibet Autonomous Region, Gansu Province, Qinghai Province, and Sichuan Province. In the future, the areas of suitable habitat for N. incisum would significantly decrease and would be 69.53 × 103 km2 and 60.21 × 103 km2 in the 2050s and 2070s, respectively. However, the area of marginally suitable habitat would remain relatively stable. This study provides a more reliable and comprehensive method for modelling the current and future distributions of N. incisum, and it provides valuable insights for highlighting priority areas for medicinal plant conservation and resource utilization.

Association of Sex with Serum Potassium, Sodium, and Calcium Disorders after Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: To determine the association of sex with serum potassium, sodium, and calcium disorders in patients with hypertensive intracerebral hemorrhage, and meanwhile investigate other risk factors. METHODS: A total of 516 patients with hypertensive intracerebral hemorrhage were retrospectively enrolled. The clinical characteristics were collected. Serum potassium, sodium, and calcium levels were measured. Multivariate analysis was performed to identify risk factors. RESULTS: Hypokalemia is the most common electrolyte disorder (50.2%) after hypertensive intracerebral hemorrhage, followed by hyponatremia (19.8%), hypocalcemia (13.8%), hypernatremia (12.0%), hyperkalemia (2.5%), and hypercalcemia (0.4%). Most of the electrolyte disorders occurred within 1 week after the onset of hypertensive intracerebral hemorrhage. The incidence rate of hypokalemia was higher in women than in men (61.7% vs. 42.3%, χ2 = 18.676; P < 0.001), but the incidence rates of hyponatremia, hypocalcemia, and hypernatremia were not statistically different between women and men (all P > 0.05). Sex was associated with hypokalemia with women having increased risk, whereas sex was not associated with hypernatremia, hypocalcemia, and hyponatremia. In addition, surgical treatment was a risk factor of hypokalemia, hyponatremia, hypocalcemia, and hypernatremia, both breaking into ventricle and age were risk factors of hyponatremia and hypocalcemia, and bleeding site was a risk factor of hypocalcemia and hypernatremia. CONCLUSIONS: In the treatment of female patients with hypertensive cerebral hemorrhage, the clinician should pay attention to potassium chloride supplementation and monitor its intensity. Within 1 week after intracerebral hemorrhage, individuals most prone to electrolyte disorders determined according to the identified risk factors should be monitored as early as possible, and the disorders should be promptly corrected.

Remote Ischemic Conditioning for Intracerebral Hemorrhage (RICH-1): Rationale and Study Protocol for a Pilot Open-Label Randomized Controlled Trial.

Background and rationale: Although many therapies have been investigated for intracerebral hemorrhage (ICH), none have succeeded in improving the functional outcomes. Remote ischemic conditioning (RIC) has been proven to promote hematoma resolution and improve neurological outcomes in an ICH model; whether it is safe and feasible in patients with ICH remains unknown. This trial aims to assess the safety, feasibility, and preliminary efficacy of RIC in patients with ICH and to plan for a phase-2 study. Methods: A proof-of-concept, assessor-blinded, pilot open-label randomized controlled trial will be carried out with patients with ICH within 24-48 h of ictus. All participants will be randomly allocated to the intervention group and the control group with a 1:1 ratio (n = 20) and will be treated with standard managements according to the guidelines. Participants allocated to the intervention group will receive RIC once daily for 7 consecutive days. Cranial computed tomography examinations will be performed at baseline, and on days 3, 7, and 14. Neurological outcomes will be assessed at baseline, and on days 1 to 14, 30, and 90. The primary outcome to be tested is safety. Secondary tested outcomes include changes of hematoma and perihematomal edema volume, incidence of hematoma expansion, functional outcomes, and frequency of adverse events. Discussions: This study will be the first proof-of-concept randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of RIC in patients with ICH, results of which will provide parameters for future studies and provide insights into the treatment of ICH. Trial Registration: Clinicaltrials.gov, identifier: NCT03930940.

A prognostic signature based on three non-coding RNAs for prediction of the overall survival of glioma patients.

Recent studies have identified certain non-coding RNAs (ncRNAs) as biomarkers of disease progression. Glioma is the most common primary intracranial cancer, with high mortality. Here, we developed a prognostic signature for prediction of overall survival (OS) of glioma patients by analyzing ncRNA expression profiles. We downloaded gene expression profiles of glioma patients along with their clinical information from the Gene Expression Omnibus and extracted ncRNA expression profiles via a microarray annotation file. Correlations between ncRNAs and glioma patients' OS were first evaluated through univariate Cox regression analysis and a permutation test, followed by random survival forest analysis for further screening of valuable ncRNA signatures. Prognostic signatures could be established as a risk score formula by including ncRNA signature expression values weighted by their estimated regression coefficients. Patients could be divided into high risk and low risk subgroups by using the median risk score as cutoff. As a result, glioma patients with a high risk score tended to have shorter OS than those with low risk scores, which was confirmed by analyzing another set of glioma patients in an independent dataset. Additionally, gene set enrichment analysis showed significant enrichment of cancer development-related biological processes and pathways. Our study may provide further insights into the evaluation of glioma patients' prognosis.

Endovascular management of ruptured basilar artery dissection with two overlapping Low-profile Visualized Intraluminal Support stents.

The optimal endovascular treatment method of ruptured basilar artery dissection still remains controversial. We reported a case with ruptured basilar artery dissection involving the left anterior inferior cerebellar artery. The dissecting aneurysm was successfully treated with two overlapping Low-profile Visualized Intraluminal Support stents and the preservation of antegrade blood flow of the anterior inferior cerebellar artery was achieved. Three-month and six-month follow-ups revealed good clinical and angiographic results, although controversies regarding long-term stability remained to be addressed.

[Complications of stent-assistant angioplasty of symptomatic intracranial artery stenosis].

OBJECTIVE: To discuss the safety of intracranial stenting for refractory symptomatic intracranial artery stenosis. METHODS: Forty-eight patients with symptomatic intracranial artery stenosis were treated by transluminal stent-assistant angioplasty. Of them, 40 cases were selected because they had recurrent TIAs or mild stroke despite of antiplatelet or anticoagulation therapy; 8 cases with high-grade stenosis after acute cerebral artery theromblysis. Lesions involved MCA (17/48); Basilar artery (8/48); intracranial vertebral artery (18/18); and distal ICA (5/18). RESULTS: For 46 of 48 cases the flexible coronary stent were successfully deployed. The average stenosis reduced from 83% to 5%, short-term follow-up showed good clinical improvement. Complications include vessel rupture (1/18); acute thrombosis within stent (1/48); perforation of cortical artery (1/18) and perforate vessel occlusion (1/18). CONCLUSION: Stent-assistant angioplasty are effective for treatment of symptomatic intracranial stenosis, the higher rate of complications may be because of the limited experiences of this technique. it need further practise and long term follow-up study.

Correlation between TSP-1, TGF-ß and PPAR-γ expression levels and glioma microvascular density.

Gliomas are the most common type of primary tumor in the central nervous system and are characterized by abundant capillary angiogenesis. It is important to study the underlying molecular mechanisms of angiogenesis in order to aid the identification of potential therapeutic targets. The aim of the current study was to investigate the expression levels of thrombospondin-1 (TSP-1), transforming growth factor-ß (TGF-ß) and peroxisome proliferator-activated receptor-γ (PPAR-γ) in gliomas, and determine their relationships with angiogenesis. Immunohistochemical methods were used to detect TSP-1, TGF-ß and PPAR-γ expression levels and to assess microvascular density (MVD) in 99 glioma tissue samples of various grades. The total positive expression rates of TSP-1 and PPAR-γ were 78.4 and 94.1% in low-grade gliomas and 45.8 and 39.6% in high-grade gliomas. These values suggest that their expression negatively correlated with tumor grade. However, TGF-ß expression positively correlated with tumor grade; the total positive expression rate of TGF-ß in high-grade gliomas (93.8%) was significantly increased compared with that in low-grade gliomas (43.1%). The MVD in the low-grade group was 28±7.2 vessels/field, which was significantly lower than in the high-grade group (45±6.2 vessels/field). TSP-1 and PPAR-γ expression levels were negatively correlated with MVD (P<0.05), while the TGF-ß expression level was positively correlated with MVD (P<0.05). These results indicate that the TSP-1, TGF-ß and PPAR-γ expression levels in gliomas are correlated with MVD, which suggests that these proteins may be involved in the regulation of glioma angiogenesis.