Advancing glioblastoma treatment by targeting metabolism.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

Endovascular treatment of extracranial carotid artery aneurysms using self-expandable covered stent grafts: A single center retrospective study.

OBJECTIVES: This study was aimed to evaluate the safety and efficacy of endovascular treatment of extracranial carotid artery aneurysms (ECAAs) using self-expandable covered stent grafts. METHODS: All patients with ECAA at a single institution were reviewed from February 2014 to February 2020. Eight consecutive patients (three men, mean age 64.5 years) treated with endovascular repair with self-expandable covered stent graft were retrospectively reviewed. Patient characteristics, angiographic results, and follow-up outcomes were retrospectively recorded. Access to ECAA was gained via a femoral approach or a direct puncture of common carotid artery after surgical exposure because of kinking of the aortic arch and common carotid artery. A self-expandable covered stent graft (Viabahn; W. L. Gore, Flagstaff, AZ) was deployed to exclude the aneurysm. RESULTS: Based on imaging features, there were five peudoaneurysms and three true aneurysms. The technical success rate was 100%. Cerebral protection devices were not used in all the patients during the procedures. Immediate absolute obliteration of the ECAA with no endoleak was documented in all the patients. Perioperative complications included one internal carotid-cavernous sinus fistula, one bleeding at the puncture site, and one stroke. The mean follow-up period was 35.5 months (range, 9-72 months). All the patients were alive, with an obligation rate of 100%. No transient ischemia attack, stroke, or reoccurrence of symptoms was identified during the follow-up period. Radiological examinations identified patency of the stent grafts and revealed no endoleaks, stent fracture, stent migration, or aneurysm rupture. CONCLUSIONS: Endovascular treatment of ECAAs with self-expandable covered stent grafts appears to be a safe and feasible alternative for traditional open surgery, especially in the challenging anatomy and instable physical conditions. Although cerebrovascular accidents can occur as the result of hemodynamic changes during the perioperative period, the minimal alternative can yield satisfactory midterm follow-up clinical outcomes.

Transbrachial and transfemoral approaches combined with visceral protection for the treatment of juxtarenal aortoiliac occlusive disease: Technical issues and clinical outcomes.

PURPOSE: To evaluate the safety and efficacy of transbrachial and transfemoral approaches combined with visceral protection for the endovascular treatment of juxtarenal aortoiliac occlusive disease (AIOD) over an average 19-month follow-up period. METHODS: In this retrospective analysis, all patients with juxtarenal AIOD at a single institution were reviewed from June 2015 to January 2020. Patient characteristics, angiographic results, and follow-up outcomes were retrospectively recorded. The indications for treatment were critical limb threatening ischemia in 12 patients and bilateral claudication in five patients. Percutaneous access via the left brachial artery was first obtained to recanalize the infrarenal occluded lesions. After that, femoral accesses were achieved. A 4-Fr catheter, a 4 mm balloon, or a 6-Fr 90-cm-long sheath was used to complete visceral artery protection. RESULTS: A total of 17 juxtarenal AIOD patients (14 males; mean age, 63.4 ± 8.1 years) underwent endovascular treatment. The technical success rate was 100%. Complete reconstruction was achieved in 15 (88.2%) patients. The infrarenal aorta was reconstructed with kissing covered stent grafts (n = 7), kissing bare-metal stents (n = 2), covered stent grafts (n = 2), bare-metal stents (n = 1), or the off-label use of iliac limb stent grafts (n = 5). Renal embolization was found in 3 (17.6%) patients during intraoperative angiography. There was 1 (5.9%) case of distal runoff embolization after CDT and 1 (5.9%) case of left iliac artery rupture. One (5.9%) death occurred due to acute myocardial infarction 20 days after the operation. The average follow-up period was 19.3 ± 16.7 months (range, 1-54 months) in the remaining 16 cases. The renal artery patency rate was 100%. The estimated cumulative primary patency rates were 92.3% at 12 months and 59.3% at 36 months according to the Kaplan-Meier method. CONCLUSIONS: Transbrachial and transfemoral approaches combined with visceral protection offer a safe and effective alternative to open revascularization for the endovascular treatment of juxtarenal AIOD.

Chondroitin Sulfate/Polycaprolactone/Gelatin Electrospun Nanofibers with Antithrombogenicity and Enhanced Endothelial Cell Affinity as a Potential Scaffold for Blood Vessel Tissue Engineering.

Electrospun polymer nanofibers have gained much attention in blood vessel tissue engineering. However, conventional nanofiber materials with the deficiencies of slow endothelialization and thrombosis are not effective in promoting blood vessel tissue repair and regeneration. Herein, biomimetic gelatin (Gt)/polycaprolactone (PCL) composite nanofibers incorporating a different amount of chondroitin sulfate (CS) were developed via electrospinning technology to investigate their effects on antithrombogenicity and endothelial cell affinity. Varying CS concentrations in PG nanofibers affects fiber morphology and diameter. The CS/Gt/PCL nanofibers have suitable porosity (~ 80%) and PBS solution absorption (up to 650%). The introduction of CS in Gt/PCL nanofibers greatly enhances their anticoagulant properties, prolongs their coagulation time, and facilitates cell responses. Particularly, 10%CS/Gt/PCL nanofibers display favorable cell attachment, elongation, and proliferation. Thus, the Gt/PCL nanofibers containing a certain amount of CS could be excellent candidates as a promising tissue-engineering scaffold in blood vessel repair and regeneration.

The impact of endovascular treatment on clinical outcomes of stable symptomatic patients with spontaneous superior mesenteric artery dissection.

OBJECTIVE: To evaluate the efficacy and clinical outcomes of endovascular treatment for superior mesenteric artery dissection (SMAD) and its effect on superior mesenteric artery (SMA) remodeling compared with medical management alone after successful initial medical management. METHODS: In this retrospective analysis, all patients with spontaneous SMAD at a single institution were identified from March 2007 to August 2019. The primary outcomes were freedom from major adverse events (MAEs, a composite of dissection-related death, the recurrence of mesenteric ischemia symptoms, and a requirement for intervention). The secondary outcomes were morphologic remodeling of the dissections and stenosis or occlusion of the SMA. RESULTS: A total of 94 patients with SMAD who underwent successful initial medical management (91 males; mean age, 50.4 ± 6.3 years) were enrolled in the study. Fifty-seven (60.6%) received medical management alone, and 37 (39.4%) underwent endovascular repair after initial medical management. In the endovascular group, the technical success rate was 86.5% (32 of 37). During a mean follow-up period of 33.6 ± 26.2 months (range, 1-120 months), nine (9.6%) patients experienced a recurrence of abdominal pain, and six had additional interventions for SMAD. The patients in the endovascular group showed more complete or partial remodeling (22 [81.1%] vs 24 [44.4%]; P < .0001) or unchanged dissections (5 [13.5%] vs 23 [42.6%]; P = .0001) than those in the conservative group. Survival analysis showed that the estimated MAE-free survival rates were 95.6%, 88.9%, and 85.4% at 1, 3, and 5 years, respectively. There was a higher freedom from SMA stenosis or occlusion in the endovascular group (log rank P = .046). CONCLUSIONS: Endovascular treatment and medical management alone result in similar MAE-free survival for patients with SMAD after successful initial medical management. Moreover, endovascular therapy is associated with a higher complete remodeling rate and greater freedom from SMA stenosis or occlusion.

Bone marrow stromal cells transplantation promotes the resolution and recanalization of deep vein thrombosis in rabbits through regulating macrophage infiltration and angiogenesis.

This study aims to validate whether bone marrow stromal cells (BMSCs) transplantation could promote the resolution and recanalization of deep vein thrombosis (DVT) and to explore the underlying mechanism. The right hind femoral vein was embolized to establish the DVT rabbit model. BMSCs from New Zealand white rabbits were isolated and identified, and then injected into DVT rabbits. After that, the extent of angiogenesis was determined by the amount of capillaries that were positive for antibody against vWF. Macrophage infiltration was measured by immunohistochemistry with F4/80 antibody. M1 or M2 macrophages were identified as F4/80 + CD11c + or F4/80 + CD206 + cells by using flow cytometry analysis, respectively. BMSCs were successfully isolated and identified. BMSCs transplantation promotes macrophage infiltration and angiogenesis in DVT rabbits. BMSCs transplantation causes M1/M2 polarization, altered cytokine production and increased monocyte chemotactic protein 1 (MCP-1) protein expression in DVT rabbits. However, injection of MCP-1 protein not only reversed the effects of BMSCs transplantation on macrophage infiltration and angiogenesis, but also reversed the effects of BMSCs transplantation on M1/M2 polarization and cytokine production in DVT rabbits. BMSCs transplantation promotes the resolution and recanalization of DVT in rabbits through regulating macrophage infiltration and angiogenesis, the underlying mechanism is associated with MCP-1 expression.

Technical issues and clinical outcomes of endovascular repair of isolated iliac artery aneurysms: A single-center experience.

PURPOSE: Isolated iliac artery aneurysms are the relatively uncommon condition. This study aims to evaluate the technical issues and clinical outcomes of endovascular repair in a cohort of isolated iliac artery aneurysms treated. METHODS: We retrospectively reviewed 22 consecutive patients with isolated iliac artery aneurysms between December 2006 and September 2016. Iliac artery aneurysms were treated in one of the three ways: (1) standard bifurcated aortic stent graft placement with limb extension; (2) coverage of iliac artery aneurysms with covered stent grafts; and (3) embolization of the arterial branches distal to the aneurysms with coils or vascular plugs. RESULTS: Twenty-two patients (20 men) with a mean age 64.7 years underwent endovascular repair during the study period. The median diameter of the isolated iliac artery aneurysms was 5.9 ± 1.7 cm (2.9-9.0 cm). Technical success was 95.5%. Conversion to open surgery was performed in one patient with bilateral internal iliac artery aneurysms. Four patients underwent placement of a bifurcated stent graft. A covered stent graft was deployed in 16 patients, with embolization of internal iliac artery in 14 patients. Simple coil embolization of isolated internal iliac artery aneurysm was performed in one patient. There was one sudden cardiac death on day 4 after the procedure due to heart failure. During the follow-up period (range: 1-50 months, mean 19.8 months), five patients died of causes not related to isolated iliac artery aneurysms, and transient buttock claudication was observed in one patient. CONCLUSIONS: Our study documents the safety and effectiveness of endovascular repair of isolated iliac artery aneurysms with low morbidity and mortality.

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms.

BACKGROUND AND AIMS: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). METHODS: AAA was induced in ApoE-/- mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. RESULTS: Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. CONCLUSIONS: Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA.

Endovascular repair of a Kommerell diverticulum anomaly.

A Kommerell diverticulum (KD) may predispose toward aortic aneurysm, dissection, or rupture, although they are primarily asymptomatic. We report a case of an aberrant left subclavian artery arising from a KD in a right-side aortic arch. The lesions were successfully treated by an endovascular approach involving Amplatzer vascular plug embolization of the aberrant left subclavian artery and endovascular repair of the KD.

Midterm outcomes of simultaneous hybrid coronary artery revascularization for left main coronary artery disease.

BACKGROUND: The purpose of this study was to evaluate the feasibility, safety, and midterm outcomes of a simultaneous hybrid revascularization strategy for left main coronary artery disease (LMCAD), compared with conventional off-pump coronary artery bypass grafting (OPCAB). METHODS: We compared the in-hospital and midterm outcomes of a simultaneous hybrid revascularization strategy (minimally invasive direct coronary bypass grafting of the left anterior descending coronary artery [LAD] and percutaneous intervention to non-LAD lesions) in 20 patients with LMCAD in an enhanced operating room. These patients were matched by propensity score to a group of 20 control patients who underwent standard OPCAB between September 2007 and December 2009. RESULTS: All baseline clinical characteristics of the 2 groups were similar. All of the patients in the 2 groups underwent surgery uneventfully without conversion to on-pump coronary artery bypass grafting. Compared with OPCAB, the patients in the hybrid group had shorter lengths of stay in the intensive care unit (34.8 ± 37.6 hours versus 50.7 ± 34.5 hours, P = .01). Transfusion requirements were reduced in the hybrid patients compared with the OPCAB patients (5% versus 40%, P = .01). The 2 groups did not differ with respect to the occurrence of other important morbidities. During the mean (±SD) follow-up of 18.5 ± 9.8 months, the group of patients who underwent the simultaneous hybrid procedure experienced an incidence of major adverse cardiac or cerebrovascular events that was similar to that of the OPCAB control group (100% versus 90%, respectively; P = .31). CONCLUSIONS: The midterm follow-up indicated that the simultaneous hybrid revascularization procedure for LMCAD is feasible, safe, and effective. These promising early findings warrant further prospective investigations.

Simultaneous hybrid revascularization versus off-pump coronary artery bypass for multivessel coronary artery disease.

BACKGROUND: This study sought to compare early and midterm clinical outcomes of a simultaneous hybrid coronary revascularization procedure with those in a propensity-matched subset of patients undergoing conventional off-pump coronary artery bypass grafting. METHODS: From June 2007 through December 2009, 104 consecutive patients (mean age 61.8 ± 10.2 years) with multivessel coronary artery disease underwent elective simultaneous coronary revascularization at Fuwai Hospital. Using propensity score methodology, these patients were matched with 104 patients who had undergone off-pump coronary artery bypass grafting through median sternotomy during the same period. We compared these groups' in-hospital clinical outcomes and freedom from major adverse cardiac or cerebrovascular events at a mean follow-up of 18 ± 7.9 months. RESULTS: The hybrid procedure required longer operative time and incurred higher in-hospital costs, but had shorter median intubation time (11.6 ± 6.3 vs 13.8 ± 6.8 hours, p = 0.02), intensive care unit length of stay (34.5 ± 35.6 vs 55.3 ± 46.4 hours, p < 0.001), and postoperative in-hospital length of stay (8.2 ± 2.6 vs 9.5 ± 4.5 days, p = 0.01). The hybrid group had significantly less chest tube drainage (789 ± 389 vs 834 ± 285 mL, p = 0.005) and need for blood transfusion (28.8% vs 51.9%, p > 0.001). At a mean follow-up of 18 months, the freedom from major adverse cardiac or cerebrovascular events is in favor of the hybrid group (99.0% vs 90.4%; p = 0.03). CONCLUSIONS: Compared with conventional off-pump coronary artery bypass grafting, simultaneous hybrid coronary revascularization shortens recovery time and has superior outcomes at a mean follow-up of 18 months. Simultaneous hybrid coronary revascularization provides a safe and reproducible alternative for selected patients with multivessel coronary artery diseases.

[Efficacy of one-stop hybrid revascularization for treatment of unprotected left main coronary artery disease].

OBJECTIVE: To evaluate the efficacy of one-stop hybrid coronary revascularization [simultaneous minimally invasive direct coronary artery bypass surgery (MIDCAB) and percutaneous coronary intervention (PCI) procedures performed in an enhanced (or called "hybrid") operative unit] for the treatment of unprotected left main coronary artery (ULMCA) disease. METHODS: From June 2007 to April 2009, 14 patients [13 male, mean age: (60.4 +/- 15.4) years] underwent the one-stop hybrid approach in the "hybrid" operating room. Proximal lesions were evidenced in 5 patients and distal or bifurcation lesions in 11 patients. MIDCAB procedure for grafting of the left intramammary artery (LIMA) with the left anterior descending (LAD) artery was first performed via lower partial ministernotomy on the beating heart, followed by PCI on the LMCA disease and non-LAD coronary lesions. RESULTS: Operation was successful in all patients underwent the one-stop hybrid procedure. LIMA grafts were used in all 14 patients and confirmed to be patent by angiography. A total of 25 non-LAD coronary lesions were treated by PCI and 29 stents (27 drug-eluting stents and 2 bare-mental stents) were implanted to 23 lesions and coronary angioplasty was performed in the remaining lesions. There was no death, perioperative myocardial infarction, stroke or repeat revascularization during the procedure and the follow-up period. All the patients remained free from angina during the 7.9 months (range 1 - 15 months) follow-up period. LIMA grafts and stents were patent in 5 patients at 1-year follow-up. CONCLUSIONS: Our initial experience demonstrates that one-stop hybrid coronary revascularization provides a reasonable, feasible and safe alternative for selected patients with LMCA diseases.

Evaluation of antiplatelet effects of a modified protocol by platelet aggregation in patients undergoing "one-stop" hybrid coronary revascularization.

"One-stop" hybrid coronary revascularization has emerged to be a reliable and attractive alternative for selected patients with multivessel coronary artery disease. However, the optimal antiplatelet regimen of the one-stop hybrid procedure still remains controversial. We modified the antiplatelet protocol in order to reduce the risk of perioperative bleeding and maximally inhibit platelet activity. This study sought to investigate whether the inhibition of platelet activity by this modified antiplatelet protocol is comparable with the conventional protocol widely used and recommended in percutaneous coronary interventions (PCI). Twenty three patients undergoing one-stop hybrid procedure and 20 patients undergoing conventional PCI were enrolled in this prospective study. The modified antiplatelet protocol included perioperative use of aspirin; clopidogrel was administered immediately before PCI with a 300 mg loading dose, followed by a maintenance dose of 75 mg/day for 12 months. Blood samples were obtained before the operation and 2 hours, day 1 and day 3 after operation. Platelet aggregation was induced with: 1) arachidonic acid (AA) (final concentration 0.5 mmol/L) to assess the efficacy of aspirin; 2) adenosine diphosphate (ADP) (final concentration 10 micromol/L) to assess the specific efficacy of clopidogrel. Platelet counts were statistically lower in the hybrid group than in the PCI control group (p = 0.0018) on day 1 after operation. AA-induced platelet aggregation increased significantly in comparison with the preoperative baseline values (p = 0.0079) and the PCI control group (p = 0.0023) on day 1 after operation. ADP-induced platelet aggregation gradually decreased in the hybrid group, and achieved similar platelet inhibition with the PCI group on 2 hours and day 1 after operation. No major adverse clinical events such as death, perioperative myocardial infarction, stent thrombosis or reoperation for bleeding occurred in both groups within 30 days after procedure. These results demonstrate that our modified antiplatelet therapy can sufficiently inhibit platelet activity similarly as the conventional protocol for PCI early after operation. Thus, this modified protocol, with continuous use of aspirin and intraoperative administration of loading dose clopidogrel, might be a safe and effective antiplatelet strategy for the one-stop hybrid coronary revascularization.