The impact of coronary artery endarterectomy on outcomes during coronary artery bypass grafting

Abstract Background: The impact of coronary artery endarterectomy during coronary artery bypass grafting (CABG) has been debated. We examined the early and late outcomes of CABG with endarterectomy (CE) compared to CABG alone. Methods: Patients undergoing isolated CABG operations from 2003 to 2008 were retrospectively reviewed. We identified 99 patients who underwent CE and 3:1 propensity matched them to 297 CABG‐alone patients based upon clinical factors: Society of Thoracic Surgeons (STS) predicted risk of mortality, age, gender, year of surgery, and ejection fraction. Patient risk factors as well as short‐ and long‐term outcomes were compared by univariate and Kaplan‐Meier analysis. Results: Preoperative risk factors were similar between patients undergoing CE or CABG alone. Cross‐clamp times (95.6 vs. 71.8 minutes, p = 0.0001) and perfusion times (121.8 vs. 92.7 minutes, p = 0.0001) were longer in patients undergoing CE. Operative mortality (4.0% vs. 1.3%, p = 0.112) and postoperative complications were not significantly different between groups. Patients undergoing coronary endarterectomy incurred longer ICU (75.06 vs. 48.64 hours, p = 0.001) and hospital stays (9.01 vs. 7.7 days, p = 0.034). Long‐term mortality (mean follow‐up = 27.7 ± 17.7 months) was equivalent despite revascularization technique (p = 0.13); however, patients undergoing CE encountered worse overall freedom from myocardial infarction (MI) (p = 0.03). Conclusion: Patients undergoing CABG with coronary CE required longer ventilatory support and ICU stay yet have comparable operative mortality, major complication rates, and long‐term survival to isolated CABG. Coronary endarterectomy should be considered an acceptable adjunct to CABG for patients with extensive coronary artery disease to achieve complete revascularization. (J Card Surg 2011;26:247‐253)     

Modeling cytoplasmic release of encapsulated oligonucleotides from cationic liposomes

Transfection activity of antisense oligodeoxynucleotides (ODN)-loaded cationic liposomes is mainly restricted by uptake and ODN release into cytoplasm, which is difficult to evaluate in cell culture studies. Well-designed models of cellular membranes, aim of the present study, might facilitate investigation of such processes. In this investigation, a phosphorothioate ODN was actively encapsulated in a DODAP-containing cationic liposome by ethanol injection with 73% efficiency. ODN release was determined by fluorescence dequenching of FITC-ODN upon incubation of liposomes with early endosomal (EE), late endosomal (LE) and plasma membranes (PM) models. LE provided the highest release (up to 76%) in a temperature-dependent manner. Release by EE (<16%), total PM (<11%) and PM external layer ( approximately 0) were not temperature sensitive. These differences are attributed to lipid charge, chain mobility, critical packing parameter and cholesterol content of the models. Intracellular distribution of FITC-ODN, determined by fluorescence microscopy and flowcytometry in the presence and absence of sodium azide, confirmed that liposomes were internalized mainly via endocytosis; hence inability of our PL models to simulate such active processes. Instead, release of ODN from endosomes into cytoplasm was pH-sensitive and in good agreement with model membrane studies in terms of amount and mechanism.     

Structure of retracted tendons after staged repair following continuous traction

Purpose  

The effect of staged repair involving continuous re-lengthening of the retracted musculotendinous unit after rotator cuff tear is not known. We quantified changes in chronically retracted tendons undergoing no repair or a staged repair involving an initial re-lengthening of the musculotendinous unit by traction in a sheep model of massive rotator cuff tear.     

Design,synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase

BackgroundAcetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease.MethodsColorimetric Ellman’s method was used for determination of IC₅₀ value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action.Result and discussionA new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC₅₀ = 11.51 μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC₅₀ = 1.95 μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10 μM.ConclusionIt is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstractOpen in a separate windowA new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00346-9) contains supplementary material, which is available to authorized users.     

Vertebral fractures following stereotactic body radiotherapy for spine metastases

Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long‐term control from lesion irradiation. Post‐treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post‐radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as ‘vertebral compression fracture’, ‘stereotactic body radiotherapy’ and ‘spine metastases’. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post‐treatment fracture rate and statistical identification of associated risk factors. Rates of post‐treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre‐existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture.     

Cross-validated models of the relationships between neck muscle electromyography and three-dimensional head kinematics during gaze behavior

The object of this study was to model the relationship between neck electromyography (EMG) and three-dimensional (3-D) head kinematics during gaze behavior. In two monkeys, we recorded 3-D gaze, head orientation, and bilateral EMG activity in the sternocleidomastoid, splenius capitis, complexus, biventer cervicis, rectus capitis posterior major, and occipital capitis inferior muscles. Head-unrestrained animals fixated and made gaze saccades between targets within a 60° × 60° grid. We performed a stepwise regression in which polynomial model terms were retained/rejected based on their tendency to increase/decrease a cross-validation-based measure of model generalizability. This revealed several results that could not have been predicted from knowledge of musculoskeletal anatomy. During head holding, EMG activity in most muscles was related to horizontal head orientation, whereas fewer muscles correlated to vertical head orientation and none to small random variations in head torsion. A fourth-order polynomial model, with horizontal head orientation as the only independent variable, generalized nearly as well as higher order models. For head movements, we added time-varying linear and nonlinear perturbations in velocity and acceleration to the previously derived static (head holding) models. The static models still explained most of the EMG variance, but the additional motion terms, which included horizontal, vertical, and torsional contributions, significantly improved the results. Several coordinate systems were used for both static and dynamic analyses, with Fick coordinates showing a marginal (nonsignificant) advantage. Thus, during gaze fixations, recruitment within the neck muscles from which we recorded contributed primarily to position-dependent horizontal orientation terms in our data set, with more complex multidimensional contributions emerging during the head movements that accompany gaze shifts. These are crucial components of the late neuromuscular transformations in a complete model of 3-D head-neck system and should help constrain the study of premotor signals for head control during gaze behaviors.