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Background This study evaluated E-selectin inhibition with GMI-1271 (Uproleselan [GMI]) alone and in combination with the standard of care low-molecular-weight heparin (LMWH) to improve vein recanalization, decrease vein wall inflammation and protect against adverse bleeding in a primate model. We sought to examine this novel treatment of venous thrombosis. Methods Using a well-documented primate animal model, iliac vein thrombosis was induced by balloon occlusion of the iliac vein for 6 hours. Starting on day 2 after thrombosis, animals began treatment in two phases. In phase one, nontreated controls received no treatment (n = 5) vs animals treated with the E-selectin inhibitor GMI, 25 mg/kg, subcutaneous (SC), once daily (n = 4) for 21 days (previously published data). In phase two, animals were treated with GMI plus a combination of LMWH 1.5 mg/kg or 40 mg (GMI + LMWHc) SC once daily (n = 8) for 19 days; and animals treated with LMWH 1.5 mg/kg or 40 mg (LMWHc) SC once daily (n = 6) for 19 days. Animals were evaluated by magnetic resonance venography for vein recanalization and inflammation by gadolinium extravasation, duplex ultrasound, coagulation tests (thromboelastography, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen) and complete blood count at baseline, days 2, 7, 14, and 21 at euthanasia. Statistical analysis included using unpaired t test with Welch's correction for direct comparisons and one-way analysis of variance for comparison between the groups. Results Percent vein recanalization by magnetic resonance venography was highest in the GMI alone group followed by GMI + LMWHc, both significantly different from control. On ultrasound examination, animals treated with GMI alone had no decrease in open vein lumen by day 21, whereas decreases were observed in groups GMI + LMWHc (–26%), LMWHc (–27%), and controls (–80%). Vein wall inflammation decreased significantly in all treated groups. Intimal fibrosis and intimal thickness was best preserved in the GMI alone group. An analysis of total vein wall collagen revealed a trend in all treatment groups of decreasing vein wall collagen. No clinically significant bleeding events were noted in any group. The LMWH groups trended to have prolonged coagulation test values, whereas E-selectin inhibition with GMI did not cause clinically significant changes in coagulation measures. Conclusions Treatment with E-selectin inhibition results in improved vein recanalization, a decrease in vein wall inflammation and vein wall intimal thickness and fibrosis, with no changes in markers of coagulation. E-selectin inhibition with GMI alone is superior to E-selectin inhibition combined with LMWH, LMWH alone, and no treatment in this deep vein thrombosis model of iliac vein thrombosis.

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.

To explore the genetic basis for a child featuring idiopathic epilepsy and autism.Peripheral blood samples of the child and his parents were collected with informed consent for the extraction of genome DNA. Whole exome sequencing was carried out for the family trio. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.The proband was found to harbor a heterozygous nonsense c.3025CT (p.Arg1009Ter) variant in exon 7 of the CASR gene exon 7, which may produce a truncated protein. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be deleterious and classified as possibly pathogenic (PVS1+PM2).The c.3025CT (p.Arg1009Ter) variant of the CASR gene probably underlay the disease in this child.

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.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.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.

The optimal management of the aortic stump in open surgical conversion (OSC) after Abdominal aortic aneurysm (AAA) endovascular aneurysm repair (EVAR) is debated. Therefore, we aimed to compare the efficacies and safety between the bifurcated prosthetic vascular graft in situ stump reconstruction (p-graft ISSR) and aortic stump closure (ASC) in OSC.We analyzed 973 elective AAA patients admitted from January 01, 2001 to December 31, 2020, at the First Affiliated Hospital of Sun Yat-sen University. We conducted a statistical analysis of the clinical characteristics, procedural data, as well as outcomes and technique considerations of aortic stump management in OSC patients.A total of 24 male patients had OSC after EVAR. The rate of stent graft infection was 54.17% before OSC. Eleven patients underwent ASC, and 13 patients were treated with p-graft ISSR. The major complication after OSC was aortic stump bleeding (total incidence was 37.50%) (1 patient with a periaortic hematoma and 8 patients with a stump blowout). The total incidences of stump blowout between the patients with ASC and those with p-graft ISSR were significantly different (45.45% vs. 23.08%, P0.05). The total perioperative mortality was 25.00% (6 patients with stump blowouts). The perioperative survival rates between these 2 aortic stump management approaches were 72.72% and 76.92% (ASC vs. p-graft ISSR, P0.05). In total, 18 patients were followed up (3-180 months). There were 3 aorta-related deaths during the late follow-up period (including both of the 2 stump-blowout-related deaths just treated with ASC).If the condition of the aorta and peri-aortic tissue are suitable for a prosthetic graft bypass, the p-graft ISSR is highly recommended for OSC patients after EVAR.

In this study, the effect of direct water injection (DWI) was investigated on the performance of marine diesel engine based on the three-dimensional simulation model. The water injection quantity, temperature and timing were researched on the in-cylinder pressure and temperature, indicated power and NOx emissions. Then, the DWI strategies were compared with the exhaust gas recirculation (EGR). The results showed that the in-cylinder pressure, temperature, indicated power and NOx emissions decrease with increasing of water quantity. Reductions in NOx emissions up to 55.6% were obtained after applying DWI to the engine at the compression stroke. The water injection temperature has a little effect on the combustion and emissions of marine engine. The indicated power decreased when the water injection timing in the compression stroke. However, the indicated power increased when the water injection timing in the late combustion phase. The water injection timing in the compression stroke has more potential in reduction NOx emissions. The NOx emissions with water injection in the compression stroke decreased by 40% compared to the value with water injection in the later combustion phase. The ability of DWI and EGR were researched on the solve the trade-off between power and NOx emissions. The results showed that the DWI strategy can reduce NOx emissions at the higher indicated power compared with the results of EGR.

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.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.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).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.