Influencing factors of futile recanalization after endovascular therapy for cerebral infarction with posterior circulation occlusion of large vessels: a retrospective study.

BACKGROUND: The optimal treatment for cerebral infarction caused by posterior circulation occlusion of large vessels has not yet been determined. Intravascular interventional therapy is an important treatment for cerebral infarction with posterior circulation occlusion of large vessels. However, endovascular therapy (EVT) of some posterior circulation cerebrovascular is ineffective and eventually become futile recanalization. Therefore, we performed a retrospective study to explore the factors influencing futile recanalization after EVT in patients with posterior circulation large-vessel occlusion. METHODS: Eighty-six patients with acute cerebral infarction and posterior circulation large vessel occlusion after intravascular intervention were divided into two groups according to their modified Rankin scale (mRS) scores after 3 months: group 1, mRS scores less than or equal to 3 (the effective recanalization group); group 2, mRS scores greater than 3 (the ineffective recanalization group). The basic clinical data, imaging index scores, time from onset to recanalization, and operation time between the two groups were compared and analyzed. Logistic regression was used to analyze the factors influencing indicators of good prognosis, and the ROC curve and Youden index were used to determine the best cutoff value. RESULTS: Between the two groups, there were significant differences in the posterior circulation CT angiography (pc-CTA) scores, GCS scores, pontine midbrain index scores, time from discovery to recanalization, operation time, NIHSS score and incidence of gastrointestinal bleeding. The logistic regression revealed that the NIHSS score and time from discovery to recanalization were associated with good prognoses. CONCLUSION: NIHSS score and recanalization time were independent influencing factors of ineffective recanalization of cerebral infarctions caused by posterior circulation occlusion. EVT is relatively effective for cerebral infarction caused by posterior circulation occlusion when the NIHSS score is less than or equal to 16 and the time from onset to recanalization is less than or equal to 570 min.

Discovery of Novel Potent and Fast BTK PROTACs for the Treatment of Osteoclasts-Related Inflammatory Diseases.

Bruton's tyrosine kinase (BTK) is an attractive target in inflammatory and autoimmune diseases. However, the effectiveness of BTK inhibitors is limited by side effects and drug resistance. In this study, we report the development of novel BTK proteolysis targeting chimeras (PROTACs) with different classes of BTK-targeting ligands (e.g., spebrutinib) other than ibrutinib. Compound 23 was identified as a potent and fast BTK PROTAC degrader, exhibiting outstanding degradation potency and efficiency in Mino cells (DC50, 4 h = 1.29 ± 0.3 nM, t1/2, 20 nM = 0.59 ± 0.20 h). Furthermore, compound 23 forms a stable ternary complex, as confirmed by the HTRF assay. Notably, 23 down-regulated the BTK-PLCγ2-Ca2+-NFATc1 signaling pathway activated by RANKL, thus inhibiting osteoclastogenesis and attenuating alveolar bone resorption in a mouse periodontitis model. These findings suggest that compound 23 is a potent and promising candidate for osteoclast-related inflammatory diseases, expanding the potential of BTK PROTACs.

Acute cerebral infarction of posterior circulation in a patient with vertebral artery fenestration deformity: A case report.

Introduction: Cerebrovascular fenestration malformation is a rare congenital vascular variation. Cerebrovascular fenestration malformation rarely directly leads to cerebral infarction, and the mechanism of cerebral infarction is not clear. Cases of young patients with vertebral artery fenestration malformation who suffered from acute cerebral infarction of posterior circulation are rare and have not been reported widely. Patient concerns: A 36-year-old male patient, who had been in good health and without a family history of stroke, was admitted to our hospital with a 6-h history of dizziness and unstable walking. Diagnosis: Brain MR examination showed multiple irregular high signal lesions in the left thalamus, left occipital lobe and left cerebellum. Brain MR enhancement examination confirmed multiple cerebral infarction in left thalamus, left occipital lobe and left cerebellum. CT angiography of head and neck showed fenestration deformity of V2-V3 segment of left vertebral artery. Interventions: Considering that the patient was suffering from acute cerebral infarction of posterior circulation, he was treated with antiplatelet, lipid-lowering and plaque stabilization, etc. Outcomes: After receiving our treatment, the patient's symptoms were relieved. At 3 and 6 months after discharge, there was no dizziness, unstable walking, no acute cerebral infarction, which meant that the patient recovered well. Conclusion: In the absence of traditional risk factors and other evidence of cryptogenic stroke, the cerebral infarction in the blood supply area of fenestration malformation should be considered to be related to fenestration malformation, but its pathogenesis is not clear. Antiplatelet therapy, lipid-lowering and plaque stabilization, etc. are effective in prevention of new infarction for such patients.

Astrocytoma with myelin oligodendrocyte glycoprotein antibody associated encephalomyelitis: A case report.

BACKGROUND: Demyelination is similar with malignancy in clinical symptoms. Magnetic resonance imaging (MRI) is an important auxiliary examination in the diagnosis of demyelinating diseases and malignancy. Since MRI and symptoms can be difficult to distinguish demyelination from malignancy, other auxiliary examinations, such as demyelinating disease-specific antibodies, play an important role in distinguishing them. Previous studies have reported demyelinating disease-specific antibodies in patients with malignancy. What's more, it is more difficult to confirm the diagnosis when the malignant tumor co-occurs with demyelinating diseases, which has never been reported in previous studies. We report the diagnosis of myelin oligodendrocyte glycoprotein antibody associated encephalomyelitis (MOG-EM) in a patient who had astrocytoma for several years. CASE PRESENTATION: Patient's concerns and diagnoses: our case report records a 49-year-old woman with astrocytoma for more than 4 years, who recently developed the symptoms of MOG-EM, including dizziness, vomiting, and vision loss. This astrocytoma patient was diagnosed with MOG-EM according to comprehensive evidence, including MRI, visual evoked potential (VEP), serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG), and therapeutic effect. Interventions and outcomes: this patient was diagnosed with astrocytoma by surgical biopsy 4 years earlier. This patient has been treated with tumor resection, postoperative radiation treatment and chemotherapy. After treatment, the patient was left with right limb weakness while other symptoms were improved. Recently, the intravenous steroid agent was used to treat this patient after being diagnosed with MOG-EM. Dizziness, vomiting, and vision loss have gone into remission. This patient did not relapse in 7 months after discharge. This patient is still being followed up at the outpatient clinic. And the patient will next be treated with azathioprine. CONCLUSIONS: In previous studies, polyclonal antibody has been found in cancer patients, such as aquaporin-4 and MOG-IgG in astrocytoma patients. But the case of our study finds that astrocytoma can coexist with MOG-EM. Therefore, MOG-EM should not be excluded easily in astrocytoma patients when the relative antibody of encephalomyelitis is positive. What's more, it reminds us that the pathogenesis of MOG-EM might be related to astrocytoma.