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891.

Objectives

In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects: 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve.

Background

A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied.

Methods

Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR.

Results

Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s; p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR; p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR; p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR; p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR; p = 0.001).

Conclusions

Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free period of diastole did not change post-TAVR, suggesting that indices calculated during this period are not vulnerable to the confounding effect of the stenotic aortic valve.  相似文献   
892.
Faithful separation of chromosomes prior to cell division at mitosis is a highly regulated process. One family of serine/threonine kinases that plays a central role in regulation is the Aurora family. Aurora B plays a role in the spindle assembly checkpoint, in part, by destabilizing the localization of BubR1 and Mad2 at centrosomes and responds to changes in tension caused by aberrant microtubule kinetochore attachments. Aurora B is overexpressed in a subset of cancers and is required for mitosis, making it an attractive anticancer target. Here, we use mathematical modeling to extend a current model of the spindle assembly checkpoint to incorporate all signaling kinetochores within a cell rather than just one and the role of Aurora B within the resulting model. We find that the current model of the spindle assembly checkpoint is robust to variation in its key diffusion-limited parameters. Furthermore, when Aurora B inhibition is considered within the model, for a certain range of inhibitor concentrations, a prolonged prometaphase/metaphase is observed. This level of inhibitor concentrations has not yet been studied experimentally, to the authors' best knowledge. Therefore, experimental verification of the results discussed here could provide a deeper understanding of how kinetochores and Aurora B cooperate in the spindle assembly checkpoint.  相似文献   
893.
The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal muscles. Such short term effects have since been extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also been convincingly demonstrated in man in vivo. More recently a longer term effect of fatty acid metabolism to decrease glucose oxidation (hours) has been shown in heart and skeletal muscle and liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspects of glucose metabolism could be important in the development of insulin resistance in diabetes mellitus in man.  相似文献   
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Management of patients with nonischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) remains challenging. The role of catheter ablation for VT continues to evolve for these patients. Prior reports have described the location of the arrhythmogenic substrate for patients with NICM to be frequently located along the basal left ventricle, with an epicardial predilection. Furthermore, predictors for identifying whether mapping the endocardium or epicardial surface of the heart have been identified for improved success of VT ablation in this patient population. This chapter will review the latest advances in catheter ablation of ventricular tachycardia in patients with NICM.  相似文献   
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899.
Within the United Kingdom , a recent change in “Best Practice Guidance” has suggested that mammograms for symptomatic breast patients, with a clinically benign examination, should be limited to those over 40 years . This has led to anxiety over missing cancer diagnoses in the 35–39 year‐old age group. This study aimed to assess the impact of the new guidance upon a NHS Breast unit with a particular focus on safety. Two cancer data bases (BASO and SOMERSET) were used to identify thirty‐three patients aged 35–39 years diagnosed with breast cancer between January 2007 and June 2011. Case notes were retrieved and retrospectively analyzed for trends during clinical (P1–P5) and radiological assessment (using Royal College Radiologists Breast Group classification—M1‐5, U1‐5). Sensitivity and false‐negative rates for each modality were calculated. Sensitivities of clinical examination, mammography, and ultrasound for detecting malignancy were 72.7%, 78.8%, and 93.9%, respectively. Within the clinically benign group (P1 and P2), mammography and ultrasound showed sensitivities of detecting malignancy of 55.5% and 88.9%, respectively, with three extra cancers being identified by ultrasound when mammography was graded less than M3 (indeterminate lesion—requiring biopsy). Importantly, no cancers would have been missed if the new guidance had been adhered to. This study has shown that mammography has no additional diagnostic benefit as first‐line imaging in symptomatic breast patients aged 35–39 years. It has confirmed that implementation of the new Best Practice Guidance is safe, when used in the setting of triple assessment, to ensure cancer diagnoses are not missed.  相似文献   
900.
Breakage of K-wires and stainless steel wires which are used for fracture fixation is not uncommon, but migration is rare. We report a case of migration of broken K-wire used for patella tension band wiring to the popliteal fossa. The broken hardware was removed surgically. We would like to suggest that K-wire and wire fixation used for treatment of patellar fractures can migrate into the posterior compartment of the knee and cause clinical symptoms. Close clinical and radiological follow-up after internal fixation to identify the presence of hardware breakage or movement and removal of wires once fracture has united can avert such complications.  相似文献   
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