Approaching the Boundaries of Endovascular Treatment in Acute Ischemic Stroke : Multicenter Experience with Mechanical Thrombectomy in Vertebrobasilar Artery Branch Occlusions.

PURPOSE: Little is known about catheter-based endovascular treatment of vertebrobasilar artery branch occlusion (VEBABO) in acute ischemic stroke (AIS). Nonetheless, the experience of mechanical thrombectomy (MT) in distal small sized arteries of the anterior circulation seems promising in AIS. In this multicenter study, we report the feasibility, efficacy and safety of MT in VEBABO. METHODS: Retrospective analysis of consecutive AIS patients treated with MT due to VEBABO including posterior and anterior inferior cerebellar artery (PICA, AICA) and superior cerebellar artery (SCA) occlusions at seven tertiary care centers between January 2013 and May 2020. Baseline demographics and angiographic outcomes including recanalization success of the affected cerebellar arteries and procedural complications were recorded. Clinical outcomes were evaluated by the modified Rankin scale (mRS) at discharge and 90 days. RESULTS: Out of 668 endovascularly treated posterior circulation strokes we identified 16 (0.02%) cases with MT for VEBABO. Most frequently, MT of the SCA was done (13/16, 81%). Most VEBABOs occurred after MT of initial basilar/posterior cerebral artery occlusion (9/16, 56%). In 10/16 (63%) procedures, the affected VEBABO was successfully recanalized. Out of four patients three (75%) with isolated VEBABO had benefited from endovascular therapy. Subarachnoid hemorrhage was observed in 3/16 (19%) procedures. The rate of favorable outcome (mRS ≤2) was 40% at discharge and 47% at 90-day follow-up. Mortality was 13% (2/15). CONCLUSION: The use of MT for VEBABO is rare but appears to be feasible and effective; however, the comparatively high rate of procedure-related hemorrhage highlights that the indications for MT in these occlusion sites should be carefully weighed up.

Enhanced production of 6-aminopenicillanic acid in aqueous methyl isobutyl ketone system with immobilized penicillin G acylase.

Enzymatic hydrolysis of penicillin G for production of 6-amino-penicillanic-acid (6-APA) was achieved by using penicillin G acylase as catalyst in an aqueous-methylisobutyl ketone (MIBK) system. The optimization was carried out and it was found that the best conversion was improved 10% more than the aqueous system, which was obtained at the conditions: initial pH 8.0, 5.0% (W/V) substrate (penicillin G), and temperature at 35 degrees C, and the ratio of aqueous and organic phase was 3:1. The stability of the biocatalyst was studied at the operational conditions. After 5 cycles of semi-batch reactions, the residual activity of penicillin G acylase was 69.2% of the initial activity. There was no apparent loss of the yield of product. This process has a potential application in the industrial scale production of 6-APA because it simplifies the process effectively.

First-line crizotinib versus platinum-pemetrexed chemotherapy in patients with advanced ROS1-rearranged non-small-cell lung cancer.

OBJECTIVES: Food and Drug Administration (FDA) approved crizotinib for advanced ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) patients due to a single-arm study PROFILE 1001. However, there is no direct comparison between crizotinib and platinum-pemetrexed chemotherapy. MATERIALS AND METHODS: Clinical data of advanced ROS1+NSCLC patients treated with first-line crizotinib or platinum-pemetrexed chemotherapy between August 2010 and December 2017 were analyzed. RESULTS: Seventy-seven patients were eligible, including 30 (39.0%) in the crizotinib group and 47 (61.0%) in the platinum-pemetrexed chemotherapy group. The median follow-up was 28.1 months (95% confidence interval [CI]: 19.2-39.0). The objective response rate (ORR) of crizotinib (86.7%, 95% CI: 73.3-96.7) was higher than that of platinum-pemetrexed chemotherapy (44.7%, 95% CI: 29.8-57.4, P < .001). The disease control rate (DCR) was 96.7% (95% CI: 90.0-100) in the crizotinib group and 85.1% (95% CI: 74.5-95.7) in the chemotherapy group (P = .140). Significantly longer progression-free survival (PFS) was observed in the patients treated with crizotinib (18.4 months, 95% CI: 6.4-30.3) versus platinum-pemetrexed chemotherapy (8.6 months, 95% CI: 6.9-10.3, P < .001). Overall survival (OS) was also compared between the two groups and no significant difference was seen (Not reach vs 28.4 months [95% CI: 20.7-36.0], P = .176). Notably, a total of 37 patients have treatment crossover after the failure of first-line treatment. Among those patients, difference in OS was not statistically significant between seven patients who have given first-line crizotinib (38.6 months, 95% CI: 0-81.0) and 30 patients who have given platinum-pemetrexed chemotherapy initially (32.8 months, 95% CI: 11.9-53.8, P = .805). CONCLUSIONS: Our results suggested that first-line crizotinib had higher ORR and longer PFS than platinum-pemetrexed chemotherapy in patients with advanced ROS1+NSCLC, but the differences were not observed for OS.

Inflammatory Regulation by Driving Microglial M2 Polarization: Neuroprotective Effects of Cannabinoid Receptor-2 Activation in Intracerebral Hemorrhage.

The cannabinoid receptor-2 (CB2R) was initially thought to be the "peripheral cannabinoid receptor." Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response. Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10-15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate. The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms. Data showed that stimulation of CB2R using a selective agonist, JWH133, ameliorated brain edema, brain damage, and neuron death and improved neurobehavioral outcomes in acute phase after ICH. The neuroprotective effects were prevented by SR144528, a selective CB2R inhibitor. Additionally, JWH133 suppressed neuroinflammation and upregulated the expression of microglial M2-associated marker in both gene and protein level. Furthermore, the expression of phosphorylated cAMP-dependent protein kinase (pPKA) and its downstream effector, cAMP-response element binding protein (CREB), were facilitated. Knockdown of CREB significantly inversed the increase of M2 polarization in microglia, indicating that the JWH133-mediated anti-inflammatory effects are closely associated with PKA/CREB signaling pathway. These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH. Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH.