A biomaterial-based therapy for lower limb ischemia using Sr/Si bioactive hydrogel that inhibits skeletal muscle necrosis and enhances angiogenesis.

Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases. In this study, a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis, regulating inflammation, and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases. In particular, sodium alginate, calcium silicate and strontium carbonate were used to prepare injectable hydrogels, which was gelled within 10 min. More importantly, this composite hydrogel sustainedly releases bioactive Sr2+ and SiO3 2- ions within 28 days. The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs, SMCs, C2C12 and Raw 264.7 cells in vitro, and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo. The results showed that the composite hydrogel stimulated angiogenesis, developed new collateral capillaries, and re-established the blood supply. In addition, the bioactive hydrogel directly promoted the expression of muscle-regulating factors (MyoG and MyoD) to protect skeletal muscle from necrosis, inhibited M1 polarization, and promoted M2 polarization of macrophages to reduce inflammation, thereby protecting skeletal muscle cells and indirectly promoting vascularization. Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases.

Dual genetic tracing reveals a unique fibroblast subpopulation modulating cardiac fibrosis.

After severe heart injury, fibroblasts are activated and proliferate excessively to form scarring, leading to decreased cardiac function and eventually heart failure. It is unknown, however, whether cardiac fibroblasts are heterogeneous with respect to their degree of activation, proliferation and function during cardiac fibrosis. Here, using dual recombinase-mediated genetic lineage tracing, we find that endocardium-derived fibroblasts preferentially proliferate and expand in response to pressure overload. Fibroblast-specific proliferation tracing revealed highly regional expansion of activated fibroblasts after injury, whose pattern mirrors that of endocardium-derived fibroblast distribution in the heart. Specific ablation of endocardium-derived fibroblasts alleviates cardiac fibrosis and reduces the decline of heart function after pressure overload injury. Mechanistically, Wnt signaling promotes activation and expansion of endocardium-derived fibroblasts during cardiac remodeling. Our study identifies endocardium-derived fibroblasts as a key fibroblast subpopulation accounting for severe cardiac fibrosis after pressure overload injury and as a potential therapeutic target against cardiac fibrosis.

Prognostic Value of the Systemic Immune Inflammation Index after Thoracic Endovascular Aortic Repair in Patients with Type B Aortic Dissection.

The study aimed at investigating the association between postoperative inflammatory scores and aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for patients with type B aortic dissection (TBAD). This single-centre, retrospective cohort included all patients who underwent TEVAR for TBAD between November 2016 and November 2020 at a university hospital. The risk factors for AAEs were analyzed by Cox proportional hazards model regression. Prediction accuracy was assessed using the area under the receiver operating characteristic curves. This study included 186 patients with a mean age of 58.5 years and a median follow-up period of 26 months. A total of 68 patients developed AAEs. Age and postoperative systemic immune inflammation index (SII) (>2893) were associated with post-TEVAR AAEs (hazard ratio (HR) 1.03, p = 0.003; HR 1.88, p = 0.043, respectively). Increased postoperative SII and age are independent risk factors for AAE post-TEVAR in patients with TBAD.

Comparison of techniques for left subclavian artery preservation during thoracic endovascular aortic repair: A systematic review and single-arm meta-analysis of both endovascular and surgical revascularization.

Background: Currently, the optimal technique to revascularize the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) remains controversial. Our study seeks to characterize early and late clinical results and to assess the advantages and disadvantages of endovascular vs. surgical strategies for the preservation of LSA. Methods: PubMed, Embase and Cochrane Library searches were conducted under the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) standards. Only literature published after January 1994 was included. Studies reporting on endovascular revascularization (ER), surgical revascularization (SR) for LSA preservation were included. 30-day mortality and morbidity rates, restenosis rates, and rates of early and late reintervention are measured as outcomes. Results: A total of 28 studies involving 2,759 patients were reviewed. All articles were retrospective in design. Single-arm analysis found no significant statistical differences in ER vs. SR in terms of 30-day mortality and perioperative complication rates. The mean follow-up time for the ER cohort was 12.9 months and for the SR cohort was 26.6 months, respectively. Subgroup analysis revealed a higher risk of perioperative stroke (4.2%) and endoleaks (14.2%) with the chimney technique compared to the fenestrated and single-branched stent approaches. Analysis of the double-arm studies did not yield statistically significant results. Conclusion: Both ER and SR are safe and feasible in the preservation of LSA while achieving an adequate proximal landing zone. Among ER strategies, the chimney technique may presents a greater risk of neurological complications and endoleaks, while the single-branched stent grafts demonstrate the lowest complication rate, and the fenestration method for revascularization lies in an intermediate position. Given that the data quality of the included studies were relatively not satisfactory, more randomized controlled trials (RCTs) are needed to provide convincing evidence for optimal approaches to LSA revascularization in the future.

Influence of alternating electric field on deep dewatering of municipal sludge and changes of extracellular polymeric substance during dewatering.

A self-prepared experimental device made of plexiglass with alternating power supply system was used to study the deep dewatering of municipal dewatered sludge. Considering the reduction rate of sludge water content (Wr) as the index, factors affecting enhanced electric settlement of sludge such as exchange electrode method, voltage gradient, sludge thickness, and mechanical pressure were studied, and the dewatering mechanism was elucidated. The single-factor experiment combined with the surface response method based on the Box-Behnken central experimental design was performed. With Wr as the response value, the voltage gradient conditions, time ratio, and sludge thickness were optimized. Pearson correlation analysis showed that the reduction of proteins/polysaccharides was beneficial to improving the sludge dewatering effect. Tightly bound extracellular polymeric substances (TB-EPSs) showed a significant influence on the sludge dewatering effect. Under the action of the external electric field, particles with negative charge moved toward the anode sludge, water with partial positive charge flowed to the cathode, and the sludge cellular structure was damaged. This resulted in the dissolution of a large number of EPSs and the release of bound water. The anode sludge cake got thickened due to the accumulation of the sludge particles, leading to the increase in resistance. The TB-EPS was deconstructed by the ohmic heating to improve the sludge dewatering effect and achieve deep dewatering. Scanning electron microscopy results showed that the drying problem of anode sludge was alleviated during the dewatering process.

Electrochemiluminescence aptasensor for vascular endothelial growth factor 165 detection based on Ru(bpy)32+/Au nanoparticles film modified electrode and double signal amplification.

Vascular endothelial growth factor (VEGF165) is a signal protein that plays a central role in the regulation of angiogenesis and can stimulate angiogenesis. The development of highly sensitive and selective detection method for VEGF165 is very important for disease diagnosis and follow-up treatment monitoring. In this study, an electrochemiluminescence (ECL) aptasensor for VEGF165 has been developed based on quench of H2O2 toward Ru(bpy)32+/TPrA ECL system and RecJf exonuclease induced target recovery and hybridization chain reaction (HCR) as amplification strategy. The presence of VEGF165 makes a large number of glucose oxidase (GOD) fixed on the electrode surface through the double signal amplification strategies. The present of GOD cause the production of a large amount of H2O2 near the electrode surface under excess amount of glucose, resulting in the inhibition of the ECL signal of Ru(bpy)32+/Au nanoparticles (Ru(bpy)32+/AuNPs) film fixed on the electrode surface. The ECL response of the designed biosensor has a good linear relationship with the logarithm of the concentration of VEGF165 in the range of 0.5 pg/mL to 500 ng/mL with a detection limit of 0.2 fg/mL. The VEGF165 in serum samples has been detected by the proposed aptasensor with satisfactory results.

Patients With Symptomatic AAAs Are More Likely to Develop Lumen Partial-Thrombus After Endovascular Aortic Repair Than Asymptomatic Patients.

Background: According to their symptoms, abdominal aortic aneurysms (AAAs) can be divided into symptomatic and asymptomatic types. This study aimed to explore the differences and correlations between postoperative lumen thrombosis in these two groups after endovascular aortic repair (EVAR). Methods: A retrospective study using clinical data of 169 patients with AAA treated with EVAR collected in our hospital between January 2018 and January 2021 was conducted based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had clinical symptoms at admission and the presence of a complete lumen thrombus during follow-up, the patients were divided into two sets of groups: a complete-thrombus group (n = 44) and a partial-thrombus group (n = 125), and a group with clinical symptoms (n = 32) and a group without clinical symptoms (n = 137). The clinical data of these groups were compared, and a further stratified analysis was performed. Results: A total of 169 patients were included in the analysis. An abdominal aorta stent graft was successfully implanted in all patients. The complete-thrombus rate of the patients in this study was 73.96%. Univariate analysis showed that the maximal aortic diameter and preoperative peripheral blood neutrophil levels affected the clinical symptoms of patients with AAA (p < 0.05). The complete thrombus rate of the lumen of the AAA was lower in patients with clinical symptoms than in those without symptoms during the follow-up period (p < 0.05). Female sex, preoperative hyperuricemia, and symptoms at admission were independent risk factors for a partial thrombus in the lumen during follow-up. Based on these independent risk factors, we constructed a scoring system to differentiate patients into low- (0 points), middle- (1 point), and high-risk (2 points) groups. The scoring system could distinguish the complete lumen thrombosis rate after EVAR to a certain extent. Conclusions: Patients with symptomatic AAAs were more likely to develop incomplete lumen thrombosis than asymptomatic patients during follow-up after EVAR.

A systematic review and meta-analysis on endovascular treatment as an attractive alternative for acute superior mesenteric venous thrombosis.

OBJECTIVE: This systematic review and meta-analysis evaluated the published data on the efficacy and safety of therapies for superior mesenteric venous thrombosis (SMVT), aiming to provide a reference and set of recommendations for clinical treatment. METHODS: Relevant databases were searched for studies published from 2000 to June 2020 on SMVT treated with conservative treatment, surgical treatment, or endovascular approach. Different treatment types were grouped for analysis and comparison, and odds ratios with corresponding 95% confidence intervals were calculated. The outcomes were pooled using meta-analytic methods and presented by forest plots. RESULTS: Eighteen articles, including eight on SMVT patients treated with endovascular therapies, were enrolled. The treatment effectiveness was compared between different groups according to the change of symptoms, the occurrence of complications, and mortality as well. The conservative treatment group had better efficacy compared to the surgery group (89.0% vs. 78.6%, P <0.05), and the one-year survival rate was also higher (94.4% vs. 80.0%, P >0.05), but without statistical significance. As for endovascular treatment, the effectiveness was significantly higher than the surgery group (94.8% vs. 75.2%, P <0.05), and the conservative treatment group as well (93.3% vs. 86.3%, P >0.05), which still requires further research for the lack of statistical significance. CONCLUSIONS: Present findings indicate that anticoagulation, as conservative treatment should be the preferred clinical option in the clinic for SMVT, due to its better curative effect compared to other treatment options, including lower mortality, fewer complications, and better prognosis. Moreover, endovascular treatment is a feasible and promising approach that is worth in-depth research, for it is less invasive than surgery and has relatively better effectiveness, thus can provide an alternative option for SMVT treatment and may be considered as a reliable method in clinical.

Preoperative high lymphocyte-to-monocyte ratio is associated with intraoperative type I endoleak in patients with TAA with TEVAR.

OBJECTIVES: Various inflammatory factors are closely associated with the incidence of thoracic aortic aneurysms (TAAs). Furthermore, the severity of inflammation is closely related to the absolute value and proportion of each leukocyte subgroup. Only few reports have analyzed the importance of lymphocyte-monocyte ratio (LMR) as a potential inflammatory marker in vascular diseases. Therefore, we aimed to investigate the effect of peripheral blood LMR on thoracic endovascular aortic repair (TEVAR) in patients with TAA. METHODS: A retrospective study of the clinical data collected in our hospital between January 2016 and January 2021 was performed on 162 patients with TAA treated with TEVAR, based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had the clinical symptoms at admission and the occurrence of type I endoleaks during operation, patients were divided into two groups, respectively: an intraoperative type I endoleak group (n = 34) and a group without intraoperative type I endoleak (n = 128), and a group with clinical symptoms (n = 31) and a group without clinical symptoms (n = 131). The clinical data of these two groups were compared, the free from second intervention rates related to endoleak and the preoperatively LMR of the two groups was calculated. LMR was calculated preoperatively. Receiver-operating characteristic curve analysis was used to determine the cut-off for preoperative LMR values. Based on the cut-off point, patients were divided into a high LMR group (n = 34) and a low LMR group (n = 128). The clinical data of the two groups were compared, and further stratified analysis was performed. RESULTS: A total of 162 patients were included in the analysis. All patients were successfully implanted with a thoracic aorta stent graft. The preoperative LMR level and postoperative endoleak-related secondary intervention rate were higher in the type I endoleak group than those in the group without intraoperative type I endoleaks. The preoperative C-reactive protein (CRP) level of patients with TAA with clinical symptoms was higher than that of asymptomatic patients. There was a negative correlation between preoperative CRP and LMR levels. In addition, in symptomatic or asymptomatic patients, the LMR level was associated with the occurrence of intraoperative type I endoleaks. After excluding the influence of type of endografts, our results showed that the clinical symptoms did not affect the occurrence of the intraoperative type I endoleak, and patients with intraoperative type I endoleak had a higher rate of postoperative secondary intervention. CONCLUSION: Patients with TAA with type I endoleaks during TEVAR had an increased rate of secondary intervention related to endoleaks. Patients with TAA with high LMR levels before TEVAR were more likely to have endoleaks during operation.

Midterm Outcomes of an Adjustable Puncture Device for In Situ Fenestration During Thoracic Endovascular Aortic Repair.

OBJECTIVE: To evaluate the midterm outcomes of in situ fenestration (ISF) with an adjustable puncture device for aortic arch branch preservation during thoracic endovascular aortic repair (TEVAR). METHODS: From October 2016 to April 2019, patients with complicated type B aortic dissection, thoracic aortic aneurysm > 5.5 cm in diameter, or aortic penetrating ulcer with a base > 20 mm or depth > 15 mm, who received TEVAR requiring a proximal sealing beyond zone 3 and underwent ISF using an adjustable puncture device, were included. After the procedure, patients were monitored at one, three, six, and 12 months, and annually thereafter. Peri-operative and follow up data were collected and analysed. RESULTS: Fifty of 51 patients (98%) received successful ISFs. One, two, or three aortic arch branches were preserved in 44, six, and one patient, respectively. Intra-operatively, eight type Ia endoleaks and one type II endoleak were found on angiography. One patient died of cerebral hernia three days post-procedure from a severe stroke; one patient suffered from transient paraplegia but recovered in two weeks; one patient had a non-disabling stroke. The median follow up was 31 months (22.5 - 36.5 months). At six month follow up, all nine unmanaged endoleaks had disappeared. One new type Ia endoleak was identified in a patient at the one month follow up which resolved spontaneously one year later. All revascularised arteries were patent at the last follow up. No fractures, migrations, or bridging stent kinks were found. CONCLUSION: In this largest mechanical based ISF study to date, an adjustable puncture device was shown to facilitate the procedure of ISF during endovascular repair of aortic diseases involving the aortic arch, with high success. The midterm outcome demonstrates the efficacy and safety of the device in assisting with preservation of aortic arch branches.

Transcollateral Recanalization of an Occluded Superior Mesenteric Artery.

OBJECTIVE: To report the technique of transcollateral retrograde recanalization of a superior mesenteric artery flush occlusion. METHODS: The technique of a patient undergoing transcollateral retrograde recanalization for acute symptomatic superior mesenteric artery flush occlusion was reviewed and presented. Other adjunctive methods to facilitate the endovascular treatment of the superior mesenteric artery total occlusion lesion were also compared and discussed. RESULTS: The patient was a 47-year-old woman, acute onset of symptomatic chronic mesenteric ischemia with flush occlusion of the superior mesenteric artery which was unable to be revascularized in a routine operation. A collateral was found to connect celiac artery and superior mesenteric artery (gastroduodenal arch). The guidewire was retrograde crossed the occluded lesion via this collateral and recaptured by the catheter from the same single brachial sheath followed by balloon angioplasty and stent implantation. The patient recovered well and the symptoms completely disappeared after the procedure. CONCLUSION: The technique of retrograde recanalization through collateral pathway is an applicable alternative option for patients with superior mesenteric artery flush occlusion who have failed attempts by conventional antegrade approaches.

A Multicenter Assessment of Anatomic Suitability for Iliac Branched Devices in Eastern Asian Patients With Unilateral and Bilateral Aortoiliac Aneurysms.

Objective: This study aims to assess the suitability of four types of commercial iliac branch device systems to treat Eastern Asian abdominal aortic aneurysm (AAA) patients with bilateral or unilateral common iliac artery aneurysms (CIAAs). Methods: Patients with a coexisting AAA and a unilateral or bilateral CIAAs who underwent endovascular aneurysm repair (EVAR) at two tertiary centers in China from 2015 to 2017 were reviewed. Morphology of lesions was measured and the anatomic suitability for Cook iliac branch device (IBD), Gore iliac branch endoprosthesis (IBE), Lifetech iliac branch stent graft (IBSG), and Jotec IBD was evaluated according to the latest instructions for use. Results: Seventy-six patients with AAA were enrolled, including 35 bilateral CIAAs, 41 unilateral CIAAs. A hundred and eleven lesions were investigated aggregately: 16.2, 28.8, 21.6, and 19.8% met the criteria for Cook IBD, Gore IBE, Lifetech IBSG, and Jotec IBD, respectively. A total of 34 (44.7%) patients could be treated for at least one lateral lesion. The diameter of the internal iliac artery (IIA) was the most common restriction for IBD application. Additionally, the IIA diameter of lesions in the bilateral group was significantly larger compared with the unilateral group (P < 0.001). Based on the anatomical characteristics alone, it is likely that IBDs will be more suitable for unilateral lesions than bilateral ones (P < 0.05). However, there was no difference between the suitability for patients with unilateral or bilateral CIAAs (P > 0.05). Conclusions: Less than half of Eastern Asian patients with aortoiliac aneurysms were eligible for IBD application. This was primarily due to the IIA diameter failing to meet the criteria. And thus, the suitability of lesions in bilateral group was significantly lower than that in the unilateral group. Aiming to expand the indications and optimize the design of the iliac branch devices, IIA diameter and the anatomical characteristics of the bilateral lesions should be considered deliberately.

Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic Repair: Incidence, Time Trends and Risk Factors.

To review the incidence of retrograde type A aortic dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) of patients with type B aortic dissection, and to investigate its time trends and underlying risk factors. The incidence rate of RTAD after TEVAR for type B aortic dissection was gathered as a cumulative pool for each year in meta-analysis. Linear regression was used to establish the temporal trend of RTAD incidence. Annual decrease rate was calculated for the fulltime frame. Sixty-six articles were included in this study, which represented 11,149 patients enrolled since 1994, and the research published between 2000 and 2019. The overall pooled rate of RTAD incidence is 2.20% (95% confidence interval 0.0162-0.0284; P < 0.0001). The incidence numbers fluctuated for many years while continuing to decline, ultimately reaching a valley in 2016-2017. The linear regression analysis identified a 0.4% decrease in incidence rate along with a declining oversize rate of stent-grafts. The overall average incidence of RTAD in the past 21 years was 2.2%. The downward incidence trend may be attributed to the lower oversize rate and the improved design of stent-grafts, as well as sophisticated manipulation and delayed TEVAR intervention.