Intraoperative Stent-Graft-Induced Aortic Intimal Intussusception During TEVAR for Type B Aortic Dissection.

BACKGROUND: Aortic intimal intussusception is well described in the natural progression of type A aortic dissection. Only 3 cases of aortic intimal intussusception were reported to be related to thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection. In our study, we are reporting a rare but potentially fatal complication, the intraoperative stent-graft (SG)-induced aortic intimal intussusception (ISAII); this study reports a series of endovascular repair for ISAII cases. By presenting the ISAII definition, the diagnostic steps to rule out or to identify the condition, and the techniques to resolve it, we intended to raise the awareness of this severe complication, so that physicians can adapt to overcome the complications while performing TEVAR. MATERIALS AND METHODS: ISAII was defined as the partial or circumferential disruption of the distal intimal flap as an intraoperative complication of endovascular treatment. From January 2014 to June 2020, 1,096 patients underwent TEVAR for Stanford type B aortic dissection at our hospital. Among them, 14 ISAII complications were witnessed. All these patients underwent endovascular repair for ISAII lesions, and their data were extracted for analysis. RESULTS: The ISAII lesions were classified into 3 types according to their location in different aortic segments: type I, ISAII was limited within the intended SG coverage segment; type II, ISAII occurred after SG introduction or deployment, and the detached intimal flap extended beyond the intended SG coverage segment but did not affect the abdominal aortic visceral branches; type III, ISAII occurred during SG introduction or deployment, and the detached intimal flap descended to the abdominal aortic segment with visceral branches. Our results showed ISAII as a rare complication with an incidence of 1.28% (14/1096), and endovascular repair for all types of ISAII is an effective treatment. With a mean follow-up of 27.36 months (range 5-71 months), all the ISAII lesions were stable, and all the major aortic branches, SGs, and bare stents were patent. CONCLUSIONS: The management of this potentially devastating intraoperative complication relies on accurate diagnosis and prompt management. Our results suggested that endovascular repair for ISAII is effective and durable for correcting this complication. GRAPHICAL ABSTRACT: [Formula: see text].

Discovery of the EL-0052 as a potential anesthetic drug.

As a γ-aminobutyric acid A receptor (GABAAR) inhibitor, etomidate fulfills several characteristics of an ideal anesthetic agent, such as rapid onset with rapid clearance and high potency, along with cardiovascular stability. Unfortunately, etomidate has been reported to inhibit CYP11B1 at hypnotic doses, which is associated with a marked increase in patient deaths due to this unexpected off-target effect. In this study, molecular docking was used to simulate the binding mode of etomidate with GABAAR and CYP11B1. Based on the in-depth analysis of the binding mode, strong electron-withdrawing group on the C4 position of the imidazole ring was introduced to reduce the charge density of the nitrogen, which is beneficial in reducing the coordination bond between the imidazole nitrogen and heme iron in CYP11B1, as well as in reducing the adrenocortical suppression. Based on the results of ADMET property prediction, MEP analysis, and molecular docking simulation, 4-fluoroetomidate (EL-0052) was designed and synthesized. In vivo studies in rats and mice confirmed that EL-0052 had the efficacy similar to etomidate, but without adrenocortical suppression. These findings suggested that EL-0052 was superior to etomidate and support the continued development of EL-0052 as a preclinical candidate as an anesthetic.

Long-term results of extensive aortoiliac occlusive disease (EAIOD) treated by endovascular therapy and risk factors for loss of primary patency.

BACKGROUND: Although endovascular therapy has been widely used for focal aortoiliac occlusive disease (AIOD), its performance for extensive AIOD (EAIOD) is not fully evaluated. We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency. METHODS: Between January 2008 and June 2018, patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II (TASC II) C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled. Demographic, diagnosis, procedure characteristics, and follow-up information were reviewed. Univariate analysis was used to identify the correlation between the variables and the primary patency. A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency. Five- and 10-year primary and secondary patency, as well as survival rates, were calculated by Kaplan-Meier analysis. RESULTS: A total of 148 patients underwent endovascular treatment in our center. Of these, 39.2% were classified as having TASC II C lesions and 60.8% as having TASC II D lesions. The technical success rate was 88.5%. The mean follow-up time was 79.2 ±â€Š29.2 months. Primary and secondary patency was 82.1% and 89.4% at 5 years, and 74.8% and 83.1% at 10 years, respectively. The 5-year survival rate was 84.2%. Compared with patients without loss of primary patency, patients with this condition showed significant differences in age, TASC II classification, infrainguinal lesions, critical limb ischemia (CLI), and smoking. Multivariate logistic regression analysis showed age <61 years (adjusted odds ratio [aOR]: 6.47; 95% CI: 1.47-28.36; P = 0.01), CLI (aOR: 7.81; 95% CI: 1.92-31.89; P = 0.04), and smoking (aOR: 10.15; 95% CI: 2.79-36.90; P < 0.01) were independent risk factors for the loss of primary patency. CONCLUSION: Endovascular therapy was an effective treatment for EAIOD with encouraging patency and survival rate. Age <61 years, CLI, and smoking were independent risk factors for the loss of primary patency.

Docking-based virtual screening of TßR1 inhibitors: evaluation of pose prediction and scoring functions.

To improve the reliability of virtual screening for transforming growth factor-beta type 1 receptor (TßR1) inhibitors, 2 docking methods and 11 scoring functions in Discovery Studio software were evaluated and validated in this study. LibDock and CDOCKER protocols were performed on a test set of 24 TßR1 protein-ligand complexes. Based on the root-mean-square deviation (RMSD) values (in Å) between the docking poses and co-crystal conformations, the CDOCKER protocol can be efficiently applied to obtain more accurate dockings in medium-size virtual screening experiments of TßR1, with a successful docking rate of 95%. A dataset including 281 known active and 8677 inactive ligands was used to determine the best scoring function. The receiver operating characteristic (ROC) curves were used to compare the performance of scoring functions in attributing best scores to active than inactive ligands. The results show that Ludi 1, PMF, Ludi 2, Ludi 3, PMF04, PLP1, PLP2, LigScore2, Jain and LigScore1 are better scoring functions than the random distribution model, with AUC of 0.864, 0.856, 0.842, 0.812, 0.776, 0.774, 0.769, 0.762, 0.697 and 0.660, respectively. Based on the pairwise comparison of ROC curves, Ludi 1 and PMF were chosen as the best scoring functions for virtual screening of TßR1 inhibitors. Further enrichment factors (EF) analysis also supports PMF and Ludi 1 as the top two scoring functions.

Discovery of New Inhibitors of Transforming Growth Factor-Beta Type 1 Receptor by Utilizing Docking and Structure-Activity Relationship Analysis.

The transforming growth factor-beta (TGF-ß) plays an important role in pathological fibrosis and cancer transformation. Therefore, the inhibition of the TGF-ß signaling pathway has therapeutic potential in the treatment of cancer. In this study, the binding modes between 47 molecules with a pyrrolotriazine-like backbone structure and transforming growth factor-beta type 1 receptor (TßR1) were simulated by molecular docking using Discovery Studio software, and their structure-activity relationships were analyzed. On the basis of the analysis of the binding modes of ligands in the active site and the structure-activity relationships, 29,254 new compounds were designed for virtual screening. According to the aforementioned analyses and Lipinski's rule of five, five new compounds (CQMU1901-1905) with potential activity were screened through molecular docking. Among them, CQMU1905 is an attractive molecule composed of 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), and 5-azacytosine. Interestingly, 5-FU, 6-MP, and 5-azacytidine are often used as anti-metabolic agents in cancer treatment. Compared with existing compounds, CQMU1901-1905 can interact with target proteins more effectively and have good potential for modification, making them worthy of further study.

Incidence and risk factors for retrograde type A dissection and stent graft-induced new entry after thoracic endovascular aortic repair.

OBJECTIVE: Stent graft (SG)-induced new entry (SINE) and retrograde type A dissection (RTAD) are serious device-related complications occurring after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection (TBAD) and may lead to endograft-related complications including retrograde dissection and death. The purpose of this study was to investigate the incidence and risk factors for the development of RTAD and SINE after TEVAR for TBAD and to identify the complications associated with this. METHODS: From April 2005 to October 2013, there were 997 patients who underwent TEVAR for TBAD; 852 were followed up (0-6 years; mean, 2.6 years), and 59 SINEs developed in 53 patients. The oversizing ratio and incidence of RTAD and SINE were compared between proximal bare stent (PBS) and non-PBS groups and RTAD and SINE and non-RTAD and non-SINE groups. The baseline characteristics and SG configurational factors potentially affecting both RTAD and distal SINE were analyzed. RESULTS: There was no significant difference between PBS and non-PBS groups in the incidence of RTAD. A greater oversizing ratio was related to a higher distal SINE rate. SINE was seen more frequently in smokers and in patients with hypertension, Marfan syndrome, and TEVAR in the chronic phase and less frequently in complicated dissection cases. Device-related factors for SINE were SG with a connecting bar and SG length <165 mm. The SG length <165 mm increased the overall proximal and distal SINE incidence in multivariate analysis. CONCLUSIONS: The presence of a PBS is not associated with a higher RTAD rate, whereas the use of an SG with a connecting bar and length <165 mm increases the risk of RTAD and SINE after TEVAR.

Endovascular Management of a Ruptured Aortic Arch Pseudoaneurysm Using the Snorkel Technique and Coil Embolization.

We report a reoperation case of a ruptured infectious aortic arch pseudoaneurysm, which was stabilized with thoracic endovascular aortic repair and snorkel bypass of the innominate artery (IA) and the left common carotid artery (LCCA). A 57-year-old Chinese woman with multiple comorbidities and previous open repair for Stanford type A aortic dissection 5 years ago presented with a ruptured 10.7 cm × 7.3 cm aortic arch pseudoaneurysm involving the origins of the LCCA and the left subclavian artery. The patient underwent emergent endovascular aortic repair with placement of a stent graft in both IA and left carotid artery coursing parallel to the aortic arch endograft.

Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self-nanoemulsifying Drug Delivery System.

Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.

[Endovascular repair for isolated iliac artery aneurysm].

OBJECTIVE: To evaluate the short and middle-term efficacies of endovascular repair for isolated iliac artery aneurysms (IIAAs). METHODS: Retrospective analyses were performed for the clinical and follow-up data of 27 patients undergoing endovascular repair at Department of Vascular Surgery, Affiliated Zhongshan Hospital, Fudan University from January 2008 to December 2012. For asymptomatic aneurysms, repair criterion was a diameter over 3 cm while under 3 cm for symptomatic aneurysms. RESULTS: There were 19 asymptomatic and 8 symptomatic cases. And 25 selective and 2 emergent operations were performed. The interventions included endovascular stent grafts (n = 17), coil embolization (n = 1), both stent grafts and coils (n = 7) and hybrid operations (n = 2). Technical success was achieved in all cases. No delayed healing or infection of inguinal access sites occurred. In-stent thrombosis could be observed in 2 cases. Buttock claudication was observed in one case. Sexual dysfunction occurred in three cases. Endoleaks were confirmed by intraoperative digital subtraction angiography in three cases. There was no occurrence of colorectal ischemia or postoperative aneurysmal rupture. Patients were followed up for a mean period of 33 ± 18 months. One patient died of recurrent renal cell carcinoma. CONCLUSION: Endovascular repair of isolated iliac artery aneurysms provides good short and middle-term patency. It may become a first-choice for treating isolated iliac artery aneurysms in the future.

Vitamin D: preventive and therapeutic potential in Parkinson's disease.

Vitamin D is one of the important nuclear steroid transcription regulators that controls transcriptions of a large number of genes. Vitamin D supplement is commonly recommended for the elderly to prevent bone diseases. Amounting new evidence has indicated that vitamin D plays a crucial role in brain development, brain function regulation and neuroprotection. Parkinson's disease (PD) is a degenerative disorder commonly seen in the elderly, characterized by movement disorders including tremor, akinesia, and loss of postural reflexes. The motor symptoms largely result from the continued death of dopaminergic neurons in the substantia nigra, despite use of current therapeutic interventions. The cause and mechanism of neuron death is currently unknown. Vitamin D deficiency is common in patients with PD suggesting its preventive and therapeutic potential. Vitamin D may exert protective and neurotropic effects directly at cellular level, e.g. protection of dopamine system, and/or by regulating gene expression. This review summarizes the epidemiological, genetic and translational evidence implicating vitamin D as a candidate for prevention and treatment for PD.

An experimental model of Stanford type B aortic dissection with intravenous epinephrine injection.

The aim of this study was to create an experimental model of aortic dissection (AD) with a long-term patent false lumen to develop new treatments for Stanford type B aortic dissection. Sixteen adult beagle dogs (weight 14-18 kg) were used. After exposure and partially clamping, the descending aorta was cut through the adventitia to one-third of the depth of the tunica media. The aortic wall was divided into two layers by raspatory. Then half the circumference of the inner layer was cut transversely. All of the proximal layers and the distal outer layers were anastomosed together. Epinephrine was immediately used to expand the false lumen, and the effect was terminated using nitroglycerin when necessary. All dogs underwent both digital subtraction angiography (DSA) and computed tomography angiography (CTA) immediately after and 1 week and 1 month after surgery. The dogs were followed up at 1 day, 3 months, 1 year, and 2 years. The surgery was successful in 12 dogs. Dissection formation was observed immediately after epinephrine administration and confirmed by DSA and CTA. Our results showed typical characteristics of AD, such as a tear, septum, and true and false lumens. This is an easy and feasible way of developing a Stanford type B AD model by intravenous injection of epinephrine. In this canine model of AD, the false lumen has excellent long-term patency and the dissection plane is histologically similar to that in human AD. This model may contribute to the development of new treatments for Stanford type B AD.

Evaluation of acute kidney injury as defined by the risk, injury, failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Acute kidney injury (AKI) is considered as a common and significant complication following abdominal aortic aneurysm (AAA) repair. This study aimed to assess the associated risk factors of AKI in the critically ill patients undergoing AAA repair and to evaluate the appropriate AKI management in the specific population. METHODS: We retrospectively examined data from all critically ill patients undergoing AAA repairs at our institution from April 2007 to March 2012. Multivariable analysis was used to identify factors associated with postoperative AKI, which was defined by risk, injury, failure, loss and end-stage (RIFLE) kidney disease criteria. The goal-directed hemodynamic optimization (maintenance of optimal hemodynamics and neutral or negative fluid balance) and renal outcomes were also reviewed. RESULTS: Of the 71 patients enrolled, 32 (45.1%) developed AKI, with 30 (93.8%) cases diagnosed on admission to surgical intensive care unit (SICU). Risk factors for AKI were ruptured AAA (odds ratio (OR) = 5.846, 95% confidence interval (CI): 1.346 - 25.390), intraoperative hypotension (OR = 6.008, 95%CI: 1.176 to 30.683), and perioperative blood transfusion (OR = 4.611, 95%CI: 1.307 - 16.276). Goal-directed hemodynamic optimization resulted in 75.0% complete and 18.8% partial renal recovery. Overall in-hospital mortality was 2.8%. AKI was associated with significantly increased length of stay ((136.9 ± 24.5) hours vs. (70.4 ± 11.3) hours) in Surgical Intensive Care Unit. CONCLUSIONS: Critically ill patients undergoing AAA repair have a high incidence of AKI, which can be early recognized by RIFLE criteria. Rupture, hypotension, and blood transfusion are the significant associated risk factors. Application of goal-directed hemodynamic optimization in this cohort appeared to be effective in improving renal outcome.

Management of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair.

We reported a case of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair. The patient was undergoing warfarin therapy. Duplex ultrasound was applied as the sole surveillance method during follow-up and provided the concerned information for reintervention. The endoleaks were successfully repaired by coil embolization of the collaterals from the internal iliac artery feeding the fourth lumbar artery.

[The development of a type II endoleak domesticated pig model with continuous pressure monitor].

OBJECTIVE: To develop a type II endoleak porcine model with continuous pressure monitor by the strain-gauge pressure transducer and the patch. METHODS: Nine tamed porcine was randomized as the experiment group of 6 domesticated pigs and the control group of 3 domesticated pigs. When the abdominal aortic aneurysm (AAA) was created, the 2(nd) and 3(rd) pair of infrarenal lumber arteries were preserved in the experiment group, while ligated in the control group. The stent-graft was implanted in the endovascular repair. CT angiography was performed to seek endoleak, and the angiography was performed to excluded the type I and type III endoleak. The pressure in the excluded AAA monitored by the strain-gauge pressure transducer was recorded and compared in both groups to evaluated the effect of type II endoleak in the experiment group. RESULTS: The AAA porcine model with pressure monitor were successfully developed in all 9 porcine. The endoleak and the retrograde flow of the lumber arteries were confirmed by CT angiography in the experiment group. The ratio of the average pressure after the procedure to before the procedure was higher in the experiment group than the control group (U = 0.000, P = 0.020). The ratio of the pulse pressure after the procedure to the average pressure before the procedure was higher in the experiment group than the control group (U = 0.000, P = 0.020). CONCLUSION: It is feasible to develop type II endoleak domesticated pig model by preserving the lumber arteries for the retrograde flow, and the AAA model with pressure monitor by the strain-gauge pressure transducer and the patch.

[Complications in endovascular repair of abdominal aortic aneurysms: treatment and prevention].

OBJECTIVE: To review the prevention and treatment strategies in the complications after endovascular repair (EVAR) of abdominal aortic aneurysms, retrospectively in a single medical center. METHODS: From January 2003 to December 2010, clinical data of 344 EVAR cases were analyzed retrospectively, including postoperative period and long-term results. There were 302 male and 42 female patients, with a mean age of (69 ± 8) years. Patients were followed up at 3 months, 6 months, and then every year with abdominal x-ray and spiral CT angiography. RESULTS: The surgical success rate was 99.7% (343/344). The mortality with elective and emergency surgery was 0.30% (1/334) and 1/10 respectively. The average follow-up time was 3 to 84 months with a mean of 32.9 months. The follow-up rate was 81.8% (279/341). The mortality was 1.1% (3/279), the re-intervention rate was 10.4% (29/279) and the overall complication rate was 12.9% (36/279), including endoleak 5.7% (16/279), stent-graft migration 1.1% (3/279), aneurysm expansion or rupture 5.4% (15/279), limb occlusion 2.5% (7/279) and stent-graft infection 1.4% (4/279). CONCLUSION: EVAR has allowed a minimally invasive approach to aortic pathology. A careful preoperative assessment is the key for EVAR. Endoleak continues to be the major long-term complication of the endoluminal grafting technique, and the major cause for re-intervention. Life-long follow-up is an integral part of EVAR.

[Analysis of contrast medium induced pancreatitis].

OBJECTIVE: To report the contrast medium induced pancreatitis after angiography or endovascular therapy, analyze the possible cause of this complication, the treatment specialty and the prognosis. METHOD: The patients suffered from contrast medium induced pancreatitis after angiography or endovascular therapy during last 10 years were retrospectively analyzed. The patients' comorbidity, the onset time of the pancreatitis, the specialty of the pancreatitis, the treatment method and the prognosis were documented. The relative literature was retrieved and reviewed. The clinical data was compared with the relative literature and analyzed. RESULTS: Three cases of contrast medium induced pancreatitis were documented. One case was a young man, received angiography because of renal artery stenosis. He was suffered from moderate abdominal pain 2 hours after the procedure. Pancreatitis of edema type was confirmed by CT scan. He recovered thoroughly after the medical treatment. One case was an old man, underwent angiography for renal artery stenosis and abdominal aortic aneurysm. He was suffered from acute abdominal pain during the procedure. The CT scan revealed as edema pancreatitis. He died from cardiac infarction during the treatment. The last case was an old female, suffered from sustained abdominal distension after endovascular treatment of endoleak post AAA EVAR. Edema pancreatitis was confirmed by CT scan. The symptom was not alleviated well after the treatment. Finally she was died from MOSF. CONCLUSION: The incidence of contrast medium induced pancreatitis is relatively low. It's not easy to detect in early stage. Early diagnosis and treatment is the key to improve the therapeutic effect. The prognosis of patient with multiple comorbidity is poor.

Retrograde type A aortic dissection after endovascular stent graft placement for treatment of type B dissection.

BACKGROUND: Retrograde type A aortic dissection has been deemed a rare complication after endovascular stent graft placement for type B dissection. However, this life-threatening event appears to be underrecognized and is worth being investigated further. METHODS AND RESULTS: Eleven of 443 patients developed retrograde type A aortic dissection during or after stent grafting for type B dissection from August 2000 to June 2007. Of these 11 patients, 3 had Marfan syndrome. The Kaplan-Meier estimate of the rate of freedom from this event at 36 months is 97.4% (95% confidence interval, 0.95 to 0.99). The new entry was located at the tip of the proximal bare spring of the stent graft in 9 patients, was within the anchoring area of the proximal bare spring in 1, and remained unknown in 1 patient. Eight patients were converted to open surgery, and 2 received medical treatment. One patient suddenly died 2 hours after the primary stent grafting, and 2 died within 1 week after the surgical conversion, so mortality reached 27.3%. During the follow-up from 3 to 50 months, type I endoleak was identified in 1 patient 3 months after the surgical exploration and disappeared at 6 months. CONCLUSIONS: Retrograde type A aortic dissection after stent grafting for type B dissection appears not to be rare and results from mixed causes. Fragility of the aortic wall and disease progression may predispose to it, whereas stent grafting-related factors make important and provocative contributions. Avoiding aortic arch stent grafting in Marfan patients, preferably selecting the endograft without the proximal bare spring for patients with a kinked aortic arch or with Marfan syndrome (if endografting is used), improving the device design, and standardizing endovascular manipulation might lessen its occurrence.