Despite advances in stem cell research, cell transplantation therapy for liver failure is impeded by a shortage of human primary hepatocytes (HPH), along with current differentiation protocol limitations. Several studies have examined the concept of co-culture of human induced pluripotent cells (hiPSCs) with various types of supporting non-parenchymal cells to attain a higher differentiation yield and to improve hepatocyte-like cell functions both in vitro and in vivo . Co-culturing hiPSCs with human endothelial cells (hECs) is a relatively new technique that requires more detailed studies. Using our 3D human embryoid bodies (hEBs) formation technology, we interlaced Human Adipose Microvascular Endothelial Cells (HAMEC) with hiPSCs, leading to a higher differentiation yield and notable improvements across a wide range of hepatic functions. We conducted a comprehensive gene and protein secretion analysis of our HLCs coagulation factors profile, showing promising results in comparison with HPH. Furthermore, a stage-specific glycomic analysis revealed that the differentiated hepatocyte-like clusters (HLCs) resemble the glycan features of a mature tissue rather than cells in culture. We tested our HLCs in animal models, where the presence of HAMEC in the clusters showed a consistently better performance compared to the hiPSCs only group in regard to persistent albumin secretion post-transplantation.

OBJECTIVEThe Pipeline embolization device (PED) is a routine choice for the endovascular treatment of select intracranial aneurysms. Its success is based on the high rates of aneurysm occlusion, followed by near-zero recanalization probability once occlusion has occurred. Therefore, identification of patient factors predictive of incomplete occlusion on the last angiographic follow-up is critical to its success.METHODSA multicenter retrospective cohort analysis was conducted on consecutive patients treated with a PED for unruptured aneurysms in 3 academic institutions in the US. Patients with angiographic follow-up were selected to identify the factors associated with incomplete occlusion.RESULTSAmong all 3 participating institutions a total of 523 PED placement procedures were identified. There were 284 procedures for 316 aneurysms, which had radiographic follow-up and were included in this analysis (median age 58 years; female-to-male ratio 4.2:1). Complete occlusion (100% occlusion) was noted in 76.6% of aneurysms, whereas incomplete occlusion (≤ 99% occlusion) at last follow-up was identified in 23.4%. After accounting for factor collinearity and confounding, multivariable analysis identified older age (> 70 years; OR 4.46, 95% CI 2.30–8.65, p < 0.001); higher maximal diameter (≥ 15 mm; OR 3.29, 95% CI 1.43–7.55, p = 0.005); and fusiform morphology (OR 2.89, 95% CI 1.06–7.85, p = 0.038) to be independently associated with higher rates of incomplete occlusion at last follow-up. Thromboembolic complications were noted in 1.4% and hemorrhagic complications were found in 0.7% of procedures.CONCLUSIONSIncomplete aneurysm occlusion following placement of a PED was independently associated with age > 70 years, aneurysm diameter ≥ 15 mm, and fusiform morphology. Such predictive factors can be used to guide individualized treatment selection and counseling in patients undergoing cerebrovascular neurosurgery.

No abstract

Background The ISAT (International Subarachnoid Aneurysm Trial) has generated a paradigm shift towards endovascular treatment for intracranial aneurysms but remains unclear if this has led to a true reduction in the risk for aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between the treatment burden of unruptured and ruptured aneurysms in the post‐ISAT era. Methods and Results Admissions data from the National Inpatient Sample (2004–2014) were extracted, including patients with a primary diagnosis of aSAH or unruptured intracranial aneurysms treated by clipping or coiling. Within each year, this combined group was randomly matched to non‐aneurysmal control group, based on age, sex, and Elixhauser comorbidity index. Multinomial regression was performed to calculate the relative risk ratio of undergoing treatment for either ruptured or unruptured aneurysms in comparison with the reference control group, adjusted for time. After adjusting for National Inpatient Sample sampling effects, 243 754 patients with aneurysm were identified, 174 580 (71.6%) were women; mean age, 55.4±13.2 years. A total of 121 882 (50.01%) patients were treated for unruptured aneurysms, 79 627 (65.3%) endovascularly and 42 256 (34.7%) surgically. A total of 121 872 (49.99%) patients underwent procedures for aSAH, 68 921 (56.6%) endovascular, and 52 951 (43.5%) surgically. Multinomial regression revealed a significant year‐to‐year decrease in aSAH procedures compared with the control group of non‐aneurysmal hospitalizations (relative risk ratio, 0.963 per year; P <0.001), while there was no statistical significance for unruptured aneurysms procedures (relative risk ratio, 1.012 per year; P =0.35). Conclusions With each passing year, there is a significant decrease in relative risk ratio of undergoing treatment for aSAH, concomitant with a stable annual risk of undergoing treatment for unruptured intracranial aneurysms.

Seventeen daucane esters have been isolated from the seeds of Ferula hermonis Boiss (Apiaceae). Three of these sesquiterpenes, 4beta-hydroxy-6alpha-benzoyl-7-daucen-9-one (1), 4beta, 8beta-dihydroxy-6alpha-benzoyl-dauc-9-ene (2), and 4beta, 9alpha-dihydroxy-6alpha-benzoyl-dauc-7-ene (4), named feruhermonins A-C, respectively, are novel natural products. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. Although 4beta, 8beta-dihydroxy-6alpha-(4-hydroxy-3-methoxybenzoyl)-dauc-9-ene (3) was reported previously, the complete spectroscopic data for this compound are presented here for the first time.

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0–1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0–2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61–3.32]; P <0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14–12.76]; P <0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31–0.96]; P =0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42–2.34]; P =0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16–6.57]; P <0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11–28.92]; P <0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25–0.94]; P =0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31–2.42]; P =0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

Objectives There is limited data on upfront middle meningeal artery (MMA) embolization in the context of significant midline shift (MLS) (greater than 5mm) for the treatment of chronic subdural hematomas (cSDH). This study reports the temporal changes following MMA embolization as an upfront treatment of cSDH in patients with or without MLS and either mild, no symptoms or mild and stable neurological deficits. Methods A retrospective series of patients with a cSDH from a single institution in the United States between 2018-2020 was conducted. Eligible patients were treated with upfront MMA embolization. Results 27 upfront MMA embolization procedures in 23 patients were included. Twelve patients had MLS of 5 millimeters or more (52%). The median maximal thickness at diagnosis was 18 mm [11-22]. The mean distance of MLS was 5 mm ±4. There were no procedural complications. The overall rescue surgery rate was 15%. A single rescue surgery secondary to an increase in hematoma thickness was required (4%). The temporal changes for both hematoma and MLS showed gradual improvement between 2 weeks and 4 weeks post-procedure. The average time-to-resolution of MLS was 46 days in patients with less than 5 mm MLS and 51 days in those with 5 mm or more. Conclusion Upfront MMA embolization for cSDH with a thickness up to 25 mm provides adequate symptom relief, stabilization and/or progressive resorption of the cSDH during follow-up in carefully selected asymptomatic or mildly symptomatic patients even in the presence of a MLS greater than 5 mm.

No abstract