Outcomes of Popliteal Stent-Graft Placement at the Artery Hinge Point for Popliteal Artery Aneurysm.

BACKGROUND: To assess whether stent-grafts crossing the hinge point (HP) in the popliteal artery are associated with increased complications and decreased patency rates, after endovascular treatment of the popliteal artery aneurysm. METHODS: This was a single-center, case-control study. Patients were allocated to either the HP group (subjects with stent-grafts crossing the HP) or the control group (subjects with stent-grafts above and/or below the HP) based on stent-graft location in the femoropopliteal artery. HP was defined as the main curve in the popliteal artery in the most acute angle toward the femur that appeared during knee flexion, which was identified by reviewing postoperative angiograms. Independent, blinded reviews were performed for all imaging data. Graft evaluation by CTA or duplex ultrasound was performed at 1, 3, 6, and 12 months and annually thereafter. Outcomes measured included: stent-graft patency, stent-graft fracture, other stent-related complications, and major adverse events, including reintervention, death, amputation, stroke, and myocardial infarction. RESULTS: A total of 44 limbs treated with placement of heparin-bonded Viabahn endoprostheses were included in this study. Twenty and twenty-four patients were allocated to the HP group and the control group, respectively. Primary patency rates of the HP group at 1, 2, 3, and 5 years were 84.1 ± 8.4%, 84.1 ± 8.4%, 84.1 ± 8.4%, and 72.1 ± 13.3%, respectively. The primary patency rates of the control group were 87.0 ± 7.0%, 82.4 ± 8.0%, 82.4 ± 8.0%, and 82.4 ± 8.0%, respectively. There was no significant difference between the 2 groups (P = 0.81). No reintervention was performed in the control group. In the HP group, 5 limbs (25.0%) developed endoleak, 3 (15.0%) developed thrombosis, and 1 (5.0%) developed a stent fracture followed by thrombosis. Thrombosis occurred in 2 limbs (8.3%) of the control group, and stent-graft migration was observed in another 2 cases (8.3%). Neither group demonstrated stent-graft infection or acute popliteal artery embolism. Overall, incidence of stent-related complications were significantly higher in the HP group (P= 0.04). Event-free survival rates of the HP group at 1, 2, 3, and 5 years were 75.0 ± 9.7%, 69.6 ± 10.4%, 61.9 ± 11.8%, and 29.0 ± 12.8%, respectively. Corresponding rates in the control group were 79.2 ± 8.3%, 79.2 ± 8.3%, 79.2 ± 8.3%, and 79.2 ± 8.3%, respectively. The difference was not statistically significant between the 2 groups (P = 0.20) CONCLUSIONS: crossing the HP with femoropopliteal artery stent-grafts increased the risk of stent-related complications and reinterventions but did not decrease stent patency or event-free survival.

A single nucleotide polymorphism-based formula to predict the risk of propofol TCI concentration being over 4 µg mL-1 at the time of loss of consciousness.

We aim to develop a formula based on single nucleotide polymorphisms (SNPs) to predict whether the propofol target-controlled infusion (TCI) concentration would be over 4 µg mL-1 at the time of loss of consciousness (LOC). We recruited 184 patients undergoing thyroid or breast surgeries with propofol anaesthesia. A total of 48 SNPs of CYP2B6, CYP2C9, UGT1A9, HNF4A, ABCB1, ABCC4, ABCG2, GABRA2, GABRA4, GABRB1, GABRB3, GABRG2, GABBR2, GAD1, SLC1A3, BDNF, and NRXN1, previously associated with propofol metabolic and pharmacology pathway, were genotyped. The formula was developed in the training cohort using the least absolute shrinkage and selection operator logistic regression model, and then validated in the testing cohort. The SNPs, GABBR2 rs1167768, GABBR2 rs1571927, NRXN1 rs601010, BDNF rs2049046, GABRA4 rs1512135, UGT1A9 rs11692021, GABBR2 rs2808536, HNF4A rs1884613, GABRB3 rs2017247, and CYP2B6 rs3181842 were selected to construct the SNP-based formula, which was used to calculate the risk score for over 4 µg mL-1 TCI concentration of propofol at the time of LOC. Patients in the high-risk group were more likely to require a propofol concentration higher than 4 µg mL-1 and presented a longer LOC latency. The SNP-based formula may significantly improve the safety and effectiveness of propofol-induced anaesthesia.

The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction.

PURPOSE: Propofol is one of the most commonly used intravenous sedatives in general anesthesia, while the individual variations of propofol are apparent. The objective of this study was to investigate the influence of genetic variations in GABAergic neurons and glutamatergic neurons on time to loss of consciousness (LOC) and the incidence of hypotension during anesthesia induction. PATIENTS AND METHODS: A total of 140 Chinese patients undergoing thyroid surgery or breast surgery were recruited. Genotyping of candidate genes was carried out using the Agena Bioscience MassARRAY system. Anesthesia induction was initiated with a propofol target plasma concentration (Cp) of 4.0 µg mL-1. The LOC latency, systolic blood pressure, diastolic blood pressure, mean arterial pressure were documented. RESULTS: We found that GABRA2 rs35496835, GABRB1 rs1372496, GABRG2 rs11135176, GABRG2 rs209358, GAD1 rs3791878, SLC1A3 rs1049522 and gender were significant determinants of the patient's LOC latency following propofol administration. GABRA2 rs11503014 was highly correlated with blood pressure reduction during anesthesia induction. Multiple linear regression analysis revealed that GABRB1 rs1372496, GABRG2 rs11135176, and SLC1A3 rs1049522 accounted for 35.3% variations in LOC latency following propofol administration. CONCLUSION: Our findings indicate that genetic variants of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 may have influence on propofol susceptibility, which would be an important guidance towards building clinical models that can precisely predict the efficacy of propofol with various populations before surgery.

Interface pressure changes under compression bandages during period of wearing.

BACKGROUND: The aim of the present study was to investigate the changes in pressure over time under three different compression bandages and compare the temporal patterns of pressure changes among them. METHODS: The 4-hour changes in interface pressure were investigated in 10 volunteers with no venous disease or leg swelling. In 20 patients with venous ulcers, the change in interface pressure was measured after 4 hours, 1 day, and 7 days of bandage wearing. The three bandages tested were the Smart Sleeve compression system (SSB; Carolon, Rural Hall, NC), Coban 2 (C2; 3M, St Paul, Minn), and Profore Lite (PL; Smith & Nephew, London, United Kingdom). Pressure measurements were performed using the PicoPress transducer (Microlab, Padua, Italy) and the Juzo Pressure Monitor (Juzo, Cuyahoga Falls, Ohio). RESULTS: In the 10 volunteers, the mean pressure loss during the first 4 hours under the SSB, C2, and PL were 4.5, 3.7, and 6.6 mm Hg, respectively. No significant differences were seen in the pressure loss among the three bandages, whether in the supine (P = .59) or standing (P = .47) position. In the 20 patients with venous ulcers, the pressure had decreased gradually over 7 days under the C2 bandages. For the SSB and PL bandages, however, the interface pressure was relatively stable during the first day but decreased significantly afterward. The mean pressure loss during the 7 days was 4.7, 7.7, and 8.6 mm Hg for the SSB, PL, and C2, respectively (P = .017). Only the SSB maintained a desirable mean pressure >30.0 mm Hg on the seventh day in the patients with venous ulcers. CONCLUSIONS: The interface pressure had decreased over time under all three studied bandages. However, the temporal pattern of the pressure changes varied among the different bandages. Therefore, monitoring the interface pressure, allowing for adjustment or changes of the bandage at an accurate point, is essential to maintain a desirable interface pressure during compression therapy.

Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats.

Numerous studies have shown that the inhaled general anesthetic sevoflurane imposes toxicity on the central nervous system during the developmental period but the underlying mechanisms remain unclear. Neuropeptide Y (NPY) was reported to have important neuroprotective effects, which can attenuate neuronal loss under pathological conditions. However, the effects of NPY on sevoflurane-induced hippocampal neuronal apoptosis have not been investigated. In this study, postnatal day 7 (PND7) Sprague-Dawley rats and primary cultured cells separated from hippocampi were exposed to sevoflurane (2.4% for 4 h) and the NPY expression levels after treatment were analyzed. Furthermore, neuronal apoptosis assay was conducted via immunofluorescence staining of cleaved caspase-3 and flow cytometry after exogenous NPY administration to PND7 rats as well as cultured hippocampal neurons to elucidate the role of NPY in sevoflurane-induced neurotoxicity. Our results showed the level of NPY gradually decreased within 24 h after sevoflurane exposure in both the hippocampus of PND7 rats and cultured hippocampal neurons, but not in cultured astrocytes. In the exogenous NPY pretreatment study, the proportion of cleaved caspase-3 positive cells in the CA1 region of the hippocampus was increased significantly at 24 h after sevoflurane treatment, while NPY pretreatment could reduce it. Similarly, NPY could also reverse the apoptogenic effect of sevoflurane on cultured neurons. Herein, our results showed that sevoflurane caused a significant decrease in NPY expression, whereas exogenous NPY supplementation could reduce sevoflurane-induced hippocampal neuronal apoptosis both in vivo and in vitro.

Biases of Villalta scale in classifying post-thrombotic syndrome in patients with pre-existing chronic venous disease.

OBJECTIVE: The Villalta scale (VS) is a recommended and widely used clinical severity score for diagnosis and grading of post-thrombotic syndrome (PTS). However, patients with primary chronic venous disease (CVD) who have a history of deep venous thrombosis (DVT) may be classified as having PTS even though post-thrombotic disease is not actually present. The purpose of this study was to investigate the biases of the VS with use in patients with pre-existing CVD. METHODS: This single-center, prospective, observational study included patients who were diagnosed with CVD during a 12-month period from 2016 to 2017. The VS and the Venous Clinical Severity Score (VCSS) were completed, and bilateral lower extremity venous duplex ultrasound studies were performed. The correlation of the VS with the VCSS was analyzed. Sensitivity, specificity, positive bias, and negative bias of the VS combined with a history of DVT were calculated. For patients in whom DVT developed during the study, the VS score was taken 12 months after the onset of DVT and compared with the score before DVT. RESULTS: A total of 288 patients were included. The VS score correlated well with the VCSS, with a correlation coefficient of 0.86 (P < .001). The two scores changed similarly over time. The accuracy of the VS combined with a history of DVT was 94.1%, with a sensitivity of 71.4% and a specificity of 95.9%. The positive bias was as high as 42.3%, although the negative bias was 2.3%. The VS score decreased to a normal level during follow-up in 41.7% of the CVD patients in whom a new DVT developed (n = 12). CONCLUSIONS: The use of the VS for defining PTS appeared to misclassify those with primary CVD and a history of DVT as having PTS by 42.3%. Using the VS at follow-up in patients with PTS and pre-existing CVD may be misleading. Re-evaluation of the results of previous studies that used the VS may be needed.

Stimulatory Effects of Boron Containing Bioactive Glass on Osteogenesis and Angiogenesis of Polycaprolactone: In Vitro Study.

Polycaprolactone (PCL) has attracted great attention for bone regeneration attributed to its cost-efficiency, high toughness, and good processability. However, the relatively low elastic modulus, hydrophobic nature, and insufficient bioactivity of pure PCL limited its wider application for bone regeneration. In the present study, the effects of the addition of boron containing bioactive glass (B-BG) materials on the mechanical properties and biological performance of PCL polymer were investigated with different B-BG contents (0, 10, 20, 30, and 40 wt.%), in order to evaluate the potential applications of B-BG/PCL composites for bone regeneration. The results showed that the B-BG/PCL composites possess better tensile strength, human neutral pH value, and fast degradation as compared to pure PCL polymers. Moreover, the incorporation of B-BG could enhance proliferation, osteogenic differentiation, and angiogenic factor expression for rat bone marrow stromal cells (rBMSCs) as compared to pure PCL polymers. Importantly, the B-BG also promoted the angiogenic differentiation for human umbilical vein endothelial cells (HUVECs). These enhanced effects had a concentration dependence of B-BG content, while 30 wt.% B-BG/PCL composites achieved the greatest stimulatory effect. Therefore the 30 wt.% B-BG/PCL composites have potential applications in bone reconstruction fields.

Determination of dexmedetomidine by UHPLC-MS/MS and its application to evaluate the effect of dexmedetomidine concentration on the target-controlled infusion concentration of propofol.

The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA® MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v) at a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive selection reaction monitoring mode. The 201.12 → 95.12 and 515.29 → 275.68 mass transitions of DEX and IS (telmisartan), respectively, were monitored. The calibration curve of DEX was linear over the concentrations of 0.1-10 ng/mL. The intra-batch and inter-batch precisions of quality control samples were less than 10.05% and had accuracies of less than 6.25%. The newly developed method was successfully applied to quantify the DEX concentrations of plasma samples from 34 patients who were co-medicated with DEX prior to receiving anaesthesia by PPF. Results showed that comedication with DEX could reduce the requirements of PPF. Specifically, it was firstly found that the concentration of DEX is negatively correlated with the TCI concentration of PPF at the time of loss of consciousness.

The effect of quercetin delivery system on osteogenesis and angiogenesis under osteoporotic conditions.

Bone regeneration under osteoporotic conditions with impaired angiogenesis, osteogenesis and remodeling represents a great challenge. In the present study, the effects of quercetin on proliferation, osteogenic differentiation and angiogenic factor secretion as well as on the osteoclastogenic factor secretion of ovariectomized (OVX) rat bone marrow-derived mesenchymal stem cells (rBMSCs) were first evaluated in vitro. The role of mitogen-activated protein kinase (MAPK) signaling pathways and the protein kinase B (AKT) signaling pathway in these processes was also investigated. Finally, hydroxyapatite (HA) bioceramic microspheres with a micro-nano hybrid surface (nHA bioceramic microspheres) were fabricated and used as drug delivery carriers of quercetin, and the ability to induce osteogenesis and angiogenesis in vivo was confirmed in an OVX rat critical-sized femur defect model. In vitro studies showed that quercetin significantly promoted cell proliferation, ALP activity and the expression of osteogenic and angiogenic factors of OVX rBMSCs as well as inhibited the expression of receptor activator of nuclear factor-κB ligand (RANKL) in a dose-dependent manner, with a concentration of 1 µM yielding the greatest effect. Moreover, the activation of the extracellular signal-regulated protein kinase (ERK), p38 and AKT signaling pathways was observed in quercetin-treated OVX rBMSCs, and the crosstalk among these signaling pathways was evident. Furthermore, the nHA bioceramic microspheres could efficiently release quercetin in a sustained manner, and quercetin loaded in the nHA bioceramic microspheres could promote new bone formation and blood vessel formation in vivo. The present study revealed that quercetin could promote osteogenesis and angiogenesis while inhibiting osteoclastogenesis both in vitro and in vivo under osteoporotic conditions. Moreover, HA bioceramic microspheres with a micro-nano hybrid surface could act as injectable drug delivery carriers of quercetin and could be applied for osteoporotic bone regeneration.

Evaluation of osteogenesis and angiogenesis of icariin loaded on micro/nano hybrid structured hydroxyapatite granules as a local drug delivery system for femoral defect repair.

Icariin has been identified to promote osteogenic differentiation of bone mesenchymal stem cells (BMSCs). However, whether icariin could enhance angiogenic factor expression of BMSCs, which may be vital for bone repair, needs to be explored. Moreover, how to construct a delivery system of icariin and its repair capability in bone defects are still unknown. In the present study, the effects of icariin on the osteogenic differentiation and angiogenic factor expression of BMSCs were firstly evaluated. Moreover, new micro/nano hybrid structured HAp (micro/nano HAp) granules were fabricated to construct the delivery system of icariin, and the osteogenesis and angiogenesis of icariin loaded on micro/nano HAp granules in a rat femoral plug defect model were evaluated by micro-CT measurements, sequential fluorescent labeling and the histological assay. The in vitro results showed that icariin significantly improved osteogenic differentiation of rat BMSCs demonstrated by the enhanced alkaline phosphatase (ALP) activity and gene expression of runt-related transcription factor-2 (Runx2), ALP, collagen type I (Col I), osteocalcin (OCN) and OCN protein secretion. Moreover, icariin induced the angiogenic genes expression of BMSCs, such as vascular endothelial growth factor (VEGF) and angiotensin 1 (ANG1). Furthermore, the activation of the AKT signaling pathway was observed in BMSCs upon treatment with icariin, and these enhancement effects could be blocked by LY294002, which suggested that the AKT signaling pathway was involved in the osteogenic differentiation and angiogenic factor expression of BMSCs induced by icariin. More importantly, micro/nano HAp granules with rod-like shapes were successfully fabricated and acted as delivery carriers for icariin. Consequently, icariin loaded on micro/nano HAp granules could promote new bone formation and blood vessel formation. These results demonstrated that icariin could enhance osteogenic differentiation and angiogenic factor expression of BMSCs via the AKT signaling pathway, moreover, the novel micro/nano HAp granules could act as carriers for icariin to repair bone defects via enhancing osteogenesis and angiogenesis.