Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Role of Decompressive Craniectomy in the Treatment of Malignant Cerebral Venous Sinus Thrombosis: A Single Center Consecutive Case Series Study in China.

OBJECTIVE: Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST. METHODS: Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months. RESULTS: In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23-63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0-1), 2 (14.29%) patients had moderate disability (mRS 2-3), and 5 (35.71%) patients had severe disability (mRS 4-5). CONCLUSIONS: Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL).

Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes.

Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes.

Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p/Acyl-CoA oxidase 1(ACOX1) pathway.

6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative product of perfluorooctane sulfonate (PFOS), has been frequently detected in various environmental, wildlife, and human samples. A few studies revealed the hepatotoxicity of 6:2 Cl-PFESA in animals, but the underlying toxicity mechanisms remain largely unknown. In this study, we investigated the lipid metabolism disorders of 6:2 Cl-PFESA through miRNA-gene interaction mode in Huh-7 cells. Our results showed that 6:2 Cl-PFESA significantly promoted cellular lipid accumulation and increased the expression of Acyl-CoA oxidase 1 (ACOX1), with the lowest effective concentrations (LOECs) of 3 µM. In silico analysis showed that hsa-miR-532-3p is a potential miRNA molecule targeting ACOX1. Fluorescent-based RNA electrophoretic mobility shift assay (FREMSA) and ACOX1-mediated luciferase reporter gene assays showed that hsa-miR-532-3p could directly bind to ACOX1 and inhibit its transcription activity. Besides, 6:2 Cl-PFESA decreased the expression of hsa-miR-532-3p in the PPARα-independent manner. Overexpression of hsa-miR-532-3p promoted 6:2 Cl-PFESA-induced cellular lipid accumulation and decreased the ACOX1 production in Huh-7 cells. Taken together, at human exposure relevant concentrations, 6:2 Cl-PFESA might upregulate the expression levels of ACOX1 through downregulating hsa-miR-532-3p, and disturbed lipid homeostasis in Huh-7 cells, which revealed a novel epigenetic mechanism of 6:2 Cl-PFESA-induced hepatic lipid toxic effects.

Analysis of factors influencing hospital-acquired infection in postoperative patients with intracranial aneurysm.

BACKGROUND: Hospital-acquired infection (HAI) is a serious complication of neurosurgery. In recent years, the medical body has paid increasing attention to this issue. AIM: We investigated the status of HAIs in patients who had undergone surgery for intracranial aneurysms and analysed their risk factors. METHODS: A retrospective analysis was carried out on the medical records of 542 patients with intracranial aneurysms after they were admitted for neurosurgery at Xuanwu Hospital of Capital Medical University between January and December 2016. Cases studied were divided into an infection group and a control group. Logistic regression analysis of the data was carried out. FINDINGS: Of the 542 patients with intracranial aneurysms who underwent surgery, 77 HAIs occurred in 64 patients, with an infection prevalence of 11.8% and prevalence of infection cases of 14.2%. Logistic regression showed that an admission Glasgow Coma Scale (GCS) score of less than 8 points (odds ratio = 4.261, 95% confidence interval 1.102-16.476), hyperglycaemia (2.759, 1.159-6.564), hypothermia treatment (6.557, 2.244-19.159), and central venous catheterisation (CVC) (8.853, 2.860-27.398) were independent risk factors for HAIs in patients with intracranial aneurysm who underwent surgery. CONCLUSION: Being comatose upon hospital admission, having hyperglycaemia or hypothermia, and indwelling CVC are major risk factors for HAIs in patients undergoing surgery for intracranial aneurysms.

Recurrent Secondary Trigeminal Neuralgia Caused by Obliterated Tentorial Dural Arteriovenous Fistula Cured with Surgical Resection: Case Report and Literature Review.

BACKGROUND: Trigeminal neuralgia (TN) caused by a tentorial dural arteriovenous fistula (TDAVF) is quite rare. To date, only 10 cases and 2 small case series have been reported in this regard, and most were treated with either embolization or surgery. Here, we report a unique case of a TDAVF presented as TN, which was embolized with Onyx first and resected later. CASE DESCRIPTION: A 57-year-old male presented with right-sided TN. Magnetic resonance imaging revealed a variceal venous dilation occupying the right lateral pontine cistern and multiple venous flow void signals adjacent to the right trigeminal nerve root entry zone. Digital subtraction angiography revealed the right TDAVF, which was completely embolized with transarterial Onyx later. The patient remained symptom free for 1 year before TN recurred. Digital subtraction angiography did not exhibit the recurrence of fistula. After resection of embolized dilated veins, the symptom alleviated and the patient remained symptom free for the 5-month follow-up to date. CONCLUSIONS: Even complete obliteration of fistula could cause the recurrence of neuralgia, and resection of embolized dilated veins might be effective for the treatment of TN in such recurrent cases.

Intravenous delivery of adeno-associated viral vector serotype 9 mediates effective gene expression in ischemic stroke lesion and brain angiogenic foci.

BACKGROUND AND PURPOSE: Adeno-associated viral vector (AAV) is a powerful tool for delivering genes to treat brain diseases. Intravenous delivery of a self-complementary but not single-stranded AAV9 (ssAAV9) mediates robust gene expression in the adult brain. We tested if ssAAV9 effectively mediates gene expression in the ischemic stroke lesion and angiogenic foci. METHODS: Focal ischemic stroke was induced by permanent occlusion of the left middle cerebral artery (MCAO) and focal angiogenesis was induced by injecting an AAV expressing vascular endothelial growth factor (AAV-VEGF) into the basal ganglia. ssAAV vectors that have cytomegalovirus (CMV) promoter driving (AAV-CMVLacZ) or hypoxia response elements controlling (AAV-H9LacZ) LacZ expression were packaged in AAV9 or AAV1 capsid and injected into mice through the jugular vein 1 hour after MCAO or 4 weeks after the induction of angiogenesis. LacZ gene expression was analyzed in the brain and other organs 5 days after LacZ vector injection. RESULTS: LacZ expression was detected in the peri-infarct region of AAV9-CMVLacZ and AAV9-H9LacZ-injected MCAO mice and the brain angiogenic foci of AAV9-CMVLacZ-injected mice. Minimum LacZ expression was detected in the brain of AAV1-CMVLacZ-injected mice. Robust LacZ expression was found in the liver and heart of AAV-CMVLacZ-injected mice, but not in AAV9-H9LacZ-injected mice. CONCLUSIONS: ssAAV9 could be a useful tool to deliver therapeutic genes to the ischemic stroke lesion or brain angiogenic foci.

Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume.

Vascular endothelial growth factor (VEGF)-induced neovasculature is immature and leaky. We tested if coexpression of angiopoietin-1 (ANG1) with VEGF improves blood-brain barrier (BBB) integrity and VEGF neuroprotective and neurorestorative effects using a permanent distal middle cerebral artery occlusion (pMCAO) model. Adult CD-1 mice were injected with 2 × 10(9) virus genomes of adeno-associated viral vectors expressing VEGF (AAV-VEGF) or ANG1 (AAV-ANG1) individually or together in a 1:1 ratio into the ischemic penumbra 1 hour after pMCAO. AAV-LacZ was used as vector control. Samples were collected 3 weeks later. Compared with AAV-LacZ, coinjection of AAV-VEGF and AAV-ANG1 reduced atrophy volume (46%, P=0.004); injection of AAV-VEGF or AAV-ANG1 individually reduced atrophy volume slightly (36%, P=0.08 and 33%, P=0.09, respectively). Overexpression of VEGF reduced tight junction protein expression and increased Evans blue extravasation. Compared with VEGF expression alone, coexpression of ANG1 with VEGF resulted in upregulation of tight junction protein expression and reduction of Evans blue leakage (AAV-ANG1/AAV-VEGF: 1.4 ± 0.3 versus AAV-VEGF: 2.8 ± 0.7, P=0.001). Coinjection of AAV-VEGF and AAV-ANG1 induced a similar degree of angiogenesis as injection of AAV-VEGF alone (P=0.85). Thus, coexpression of ANG1 with VEGF improved BBB integrity and resulted in better neuroprotection compared with VEGF expression alone.