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We analyzed the influence of calculated physicochemical properties of more than 20,000 compounds on their P-gp and BCRP mediated efflux, microsomal stability, hERG inhibition, and plasma protein binding. Our goal was to provide guidance for designing compounds with desired pharmacokinetic profiles. Our analysis showed that compounds with ClogP less than 3 and molecular weight less than 400 will have high microsomal stability and low plasma protein binding. Compounds with logD less than 2.2 and/or basic pKa larger than 5.3 are likely to be BCRP substrates and compounds with basic pKa less than 5.2 and/or acidic pKa less than 13.4 are less likely to inhibit hERG. Based on these results, compounds with MW less then 400, ClogP less then 3, basic pKa less then 5.2 and acidic pKa less then 13.4 are likely to have good bioavailability and low hERG inhibition.Over activation of neutrophils has been linked to many inflammatory diseases; one of critical pathologic mechanisms is that generation and exocellular release of superoxide anion from neutrophils results in peripheral tissues damage. Besides, in this study, 2-(3,5-dimethoxyphenoxy)-5,7-dimethoxy-chromen-4-one (4), a 2-phexnoychromone from our compound bank, was demonstrated to have the moderate inhibitory effect on superoxide anion generating. Therefore, serial chromones substituted with phenols or 3-flourothiophenol were designed, synthesized, and examined for suppression of superoxide anion generation. In accordance with the results, the methoxy group at 7 position (R3) of the chromone, as well as a hydrogen bond donor at a meta site of the phenyl ring greatly impacted on the activity. 2-(3-fluorophenyl)sulfanyl-7-methoxy-chromen-4-one (16), a successful example of bioisosteres from a phenol to a thiophenol, exhibited prominent anti-inflammatory effects with the IC50 value against superoxide anion generation of 5.0 ± 1.4 μM.
To evaluate the short-term outcome of totally percutaneous endovascular aortic repair (pEVAR) of ruptured abdominal aortic aneurysms (AAAs) compared with femoral cut-down endovascular aortic repair (cEVAR).
The medical records of patients with ruptured AAAs that underwent EVAR between March 2010 and April 2017 were retrospectively reviewed. Demographic information, preoperative vital signs, preoperative laboratory data, method of anesthesia, procedure duration, aneurysm morphology, brand of device used, length of hospital stay, access complications, and short-term outcomes were recorded. Univariate as well as multivariate logistic regression was used to identify predictors of 30-day mortality.
Among 77 patients with ruptured AAAs, 17 (22.1%) received cEVAR and 60 (77.9%) received pEVAR. Significant differences in the procedure time (P = 0.004), method of anesthesia (P = 0.040), and 30-day mortality (P = 0.037) were detected between the cEVAR and pEVAR groups. Local anesthesia plus intravenous general anesthesia (odds ratio = 0.141, P = 0.018) was an independent factor associated with 30-day mortality and local anesthesia was better than general anesthesia for 24-hr mortality (P = 0.001) and 30-day mortality (P = 0.003).
In patients with ruptured AAAs, pEVAR procedures took less time than cEVAR procedures, but the length of hospital stay did not differ significantly. The 30-day mortality rate was lower with pEVAR than with cEVAR. Local anesthesia may be the key factor in EVAR to improved technical and clinical success.
In patients with ruptured AAAs, pEVAR procedures took less time than cEVAR procedures, but the length of hospital stay did not differ significantly. The 30-day mortality rate was lower with pEVAR than with cEVAR. Local anesthesia may be the key factor in EVAR to improved technical and clinical success.
Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are frequently employed for treating deep venous thrombosis (DVT). However, there have been relatively few studies comparing PMT outcomes to those associated with CDT. The present study was thus designed to compare short- and mid-term PMT and CDT patient outcomes following the treatment of DVT of the lower extremities.
This study was a retrospective analysis of 98 patients treated at the 3rd Affiliated Hospital of Shenzhen University (Shenzhen, China) and Beijing Chao Yang Hospital (Beijing, China). All patients had undergone treatment for symptomatic DVT of the lower legs via either CDT or PMT. Clinical records and outcome data between the patients in these 2 treatment groups were compared.
Of the 98 patients analyzed in this retrospective study, 50 had been treated via CDT while 48 had undergone PMT. These PMT and CDT operations were associated with mean treatment durations of 0.97 ± 0.20 hr and 32.48 ± 7.46 hr, respectivelalization duration, although it is also associated with higher rates of systemic complications.
PMT is an effective treatment modality in patients with symptomatic DVT. Relative to CDT it is associated with high treatment success rates, reduced treatment duration, and reduced hospitalization duration, although it is also associated with higher rates of systemic complications.
The aim of this study was to evaluate the safety, applicability and outcomes of the endovascular in situ fenestration (ISF) technique for patients with aortic arch pathologies by performing a systematic review.
We conducted a systematic search using the PubMed, Embase, and Cochrane databases to identify English language articles between January 2004 and March 2019 on the management of aortic arch pathologies using an in situ fenestration technique. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The studies included all investigated the clinical outcomes and postprocedural complications of using ISF techniques.
Seven studies reported on a total of 117 aortic arch pathologies patients. Including fifty-two dissection patients, forty-seven aneurysm patients, eighteen intramural hematomas and penetrating ulcers patients. Needle fenestration and laser fenestration were performed in sixty-two and forty-five patients respectively, and the rest ten patients received radiofrequency fenestration. The follow-up period ranged from 1 to 55 months. The pooled technical success rates were 94% (95% confidence interval [CI] 79-98%). The stroke rate was 6% (95% CI 3-13%). The 30-day MAE was 11% (95% CI 6-18%).
The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.
The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.
It is recommended that patients with ≥50% carotid artery stenosis undergo surveillance imaging and atherosclerotic risk reduction medical therapies, regardless of whether revascularization is performed. The objective of this study was to determine rates of adherence to these recommended measures and to identify risk factors for nonadherence.
A retrospective analysis was performed of all carotid duplex ultrasound (DUS) from 2016 to 2017 at a single institution. Patients with unilateral or bilateral ≥50% carotid stenosis were included. Primary outcomes were rates and timing of surveillance imaging and medication regimen. Patient and study characteristics were compared using univariate and multivariable analyses. click here A subgroup analysis of patients with a new finding of carotid stenosis was also performed.
Carotid stenosis >50% was detected in 340 patients. Overall, 182 patients (54%) had follow-up imaging (median 261 days [IQR 166-366]) and 158 patients (46%) had no imaging follow-up (NIFU). NIFU patients e on recommended statin therapy. The benefits of nonrevascularization-based treatments for carotid disease require adherence to therapy. Forgoing surveillance imaging in patients with hemodynamically significant carotid stenosis should be a shared decision between provider and patient and does not obviate the need for medical therapies.
The purpose of this study was to identify the independent risk factors for ipsilateral new ischemic lesions (NILs) during carotid artery stenting (CAS).
In patients treated with CAS, the association between postoperative ipsilateral NILs on diffusion-weighted imaging (DWI) and patient demographics, intraoperative factors, the presence of plaque components, the semiquantitative grading of component size on multicontrast magnetic resonance imaging (MRI) were retrospectively analyzed.
Ipsilateral NILs on DWI were detected in 85 (39.2%) patients. The debris was observed on the surface embolic protection devices in 70.97% of patients. Univariate analysis showed that different stages of intraplaque hemorrhage (IPH) (along with lipid-rich necrotic core [LRNC]) (P < 0.001), size of IPH (P < 0.001), calcification (CA) (P = 0.045), and LRNC (without IPH) (P < 0.001) as well as postdilation (P < 0.001)), stent type (P = 0.001), and aortic arch ulcer (P = 0.004) were associated with postoperative ipsilarch ulcer, postdilation and open cell stent are associated with increased risk of ipsilateral NILs on DWI after CAS procedure. Preoperative staging of IPH and semiquantitative grading of size of plaque components based on multi-contrast MRI may be useful for predicting ipsilateral cerebral ischemic events after CAS.
Mycotic abdominal aorta aneurysm (MAAA) is a rare and life-threatening condition. Because of its rarity, there is a lack of adequately powered studies and consensus on its treatment and follow up. This study aimed to review the outcomes following surgical intervention for MAAA in a single tertiary centre and to formulate a management protocol based on available evidence and expert opinion.
Data were collected by retrospective review of case records of all patients who underwent repair of MAAA in a single tertiary referral centre from 2001 to 2018. Demographic, clinical and outcome data were analysed and compared with previously published series in the literature. A management protocol was formulated based on available literature which was then reviewed and modified as per expert opinion from multidisciplinary discussions.
Seventeen patients underwent repair of MAAA during the study period including 4 Open repairs, 4 surgeon modified fenestrated endovascular aortic aneurysm repairs (SM FEVAR) and 9 endovnsideration individual patient variability and local expertise.
Treatment of chronically occluded infrainguinal venous bypass grafts in patients presenting with recurrent chronic limb threatening limb ischemia (CLTI) represent a clinical challenge. Recent case reports have suggested the use of endovascular recanalization techniques without preceding thrombolysis. This study assesses feasibility and mid-term outcomes of this technique.
A retrospective review of 5 consecutive patients (3 men, 2 women, mean age 70 ± 5 years) presenting with chronic venous bypass graft occlusion and recurrence of CLTI during 1 year was performed. Patients were treated with relining of the bypass grafts. Patients were followed up at median 26 (6-36) months. All patients were treated successfully with restoration of flow in the grafts using recanalization and relining technique without thrombolysis. In 4 patients, a Viabahn stentgraft (SG) was used with the addition of interwoven nitinol stents (INS) in 3. In 1 patient, the graft was treated with INS without the addition of a stentgraft. No peripheral embolization was encountered during the procedures.