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Association of an Endovascular-First Protocol for Ruptured Abdominal Aortic Aneurysms With Survival and Discharge Disposition. - JAMA surgery
Mortality after an open surgical repair of a ruptured abdominal aortic aneurysm (rAAA) remains high. The role and clinical benefit of ruptured endovascular aneurysm repair (rEVAR) have yet to be fully elucidated.To evaluate the effect of an endovascular-first protocol for patients with an rAAA on perioperative mortality and associated early clinical outcomes.Retrospective review of a consecutive series of patients presenting with an rAAA before (1997-2006) and after (2007-2014) implementation of an endovascular-first treatment strategy (ie, protocol) at an academic medical center.Early mortality, perioperative morbidity, discharge disposition, and overall survival.A total of 88 patients with an rAAA were included in the analysis, including 46 patients in the preprotocol group (87.0% underwent an open repair and 13.0% underwent an rEVAR) and 42 patients in the intention-to-treat postprotocol group (33.3% underwent an open repair and 66.7% underwent an rEVAR; Pâ€‰=â€‰.001). Baseline demographics were similar between groups. Postprotocol patients died significantly less often at 30 days (14.3% vs 32.6%; Pâ€‰=â€‰.03), had a decreased incidence of major complications (45.0% vs 71.8%; Pâ€‰=â€‰.02), and had a greater likelihood of discharge to home (69.2% vs 42.1%; Pâ€‰=â€‰.04) after rAAA repair compared with preprotocol patients. Kaplan-Meier analysis demonstrated significantly greater long-term survival in the postprotocol period (log-rank Pâ€‰=â€‰.002). One-, 3-, and 5-year survival rates were 50.0%, 45.7%, and 39.1% for open repair, respectively, and 61.9%, 42.9%, and 23.8% for rEVAR, respectively.Implementation of a contemporary endovascular-first protocol for the treatment of an rAAA is associated with decreased perioperative morbidity and mortality, a higher likelihood of discharge to home, and improved long-term survival. Patients with an rAAA and appropriate anatomy should be offered endovascular repair as first-line treatment at experienced vascular centers.
Regulation of cardiac cellular bioenergetics: mechanisms and consequences. - Physiological reports
The regulation of cardiac cellular bioenergetics is critical for maintaining normal cell function, yet the nature of this regulation is not fully understood. Different mechanisms have been proposed to explain how mitochondrial ATP production is regulated to match changing cellular energy demand while metabolite concentrations are maintained. We have developed an integrated mathematical model of cardiac cellular bioenergetics, electrophysiology, and mechanics to test whether stimulation of the dehydrogenase flux by Ca(2+) or Pi, or stimulation of complex III by Pi can increase the rate of mitochondrial ATP production above that determined by substrate availability (ADP and Pi). Using the model, we show that, under physiological conditions the rate of mitochondrial ATP production can match varying demand through substrate availability alone; that ATP production rate is not limited by the supply of reducing equivalents in the form of NADH, as a result of Ca(2+) or Pi activation of the dehydrogenases; and that ATP production rate is sensitive to feedback activation of complex III by Pi. We then investigate the mechanistic implications on cytosolic ion homeostasis and force production by simulating the concentrations of cytosolic Ca(2+), Na(+) and K(+), and activity of the key ATPases, SERCA pump, Na(+)/K(+) pump and actin-myosin ATPase, in response to increasing cellular energy demand. We find that feedback regulation of mitochondrial complex III by Pi improves the coupling between energy demand and mitochondrial ATP production and stabilizes cytosolic ADP and Pi concentrations. This subsequently leads to stabilized cytosolic ionic concentrations and consequentially reduced energetic cost from cellular ATPases.Â© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Snorkel/Chimney Stent Morphology Predicts Renal Dysfunction After Complex EVAR. - Annals of vascular surgery
Despite the high technical success and midterm patency of snorkel stents, concerns remain about structural durability and its effect on long-term renal function. We sought to evaluate the luminal stability of renal snorkel stents in order to investigate morphologic predictive factors of renal dysfunction following sn-EVAR.Patients with high quality CT-A after sn-EVAR between 2009-2013 were included for analysis. Luminal diameters of renal snorkel stents were measured on a 3D workstation at the proximal, main-body junction, and distal locations. Creatinine values and eGFR were recorded throughout the pre-, peri-, and post-operative course. Acute kidney injury and chronic renal decline were evaluated using the RIFLE criteria and CKD staging system, respectively.52 patients underwent Sn-EVAR (33 double renal, 19 single renal) with a two year primary patency of 95% at a mean follow-up of 21 months, of which 34 had suitable imaging protocols. In this subset, snorkel stents had mean deformations of -0.14Â±0.52 (2.8%), -0.23Â±0.52 (4.6%) and -.04Â±0.16mm(1.8%) at the proximal, junction, and distal segments. Four cases of significant >50% stent collapse occurred during follow-up, all of which occurred at the junctional segment. In the total cohort, 17 (32.6%) and 16 (30.7%) patients developed AKI and chronic renal decline, respectively. Multivariate regression identified larger proximal luminal diameters at latest follow-up (OR 0.67 (CI .006-.740), p=.037) as the only protective morphologic risk factor for developing chronic renal decline. No independent predictor factors for acute kidney injury were found. Rates of renal decline were significantly worse with smaller measured proximal lumens with a one-year freedom from renal decline of 50% vs 77-83% for diameters measured less than 4mm versus greater than 4mm (p=.010). Degree of oversizing also affected rates of decline, with greater oversizing associated with improved freedom from renal decline at one year of 100% vs 57% (p=.012). Using a multivariate cox model, stent oversizing (HR 0.039, p=.018) and baseline CKD (HR 0.033, p=.004) were the only independent factors, both of which resulted in slower rates of renal decline during follow-up CONCLUSIONS: Renal snorkel stent-grafts maintain a high degree of patency and luminal stability at two year follow-up. However, stent collapse remains a rare but concerning risk, with the junctional segment most prone to significant stent deformation. Renal snorkel stents must be critically sized relative to native renal anatomy and we recommend employing at least stents sized â‰¥6mm to minimize the risk of renal dysfunction. Frequent and regular radiographic and laboratory follow-up remains important as we further optimize the approach to complex EVAR.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Safety and efficacy of antiplatelet/anticoagulation regimens after Viabahn stent graft treatment for femoropopliteal occlusive disease. - Journal of vascular surgery
We aimed to determine the safety and efficacy of antiplatelet/anticoagulation regimens after placement of Viabahn stent graft (W. L. Gore & Associates, Flagstaff, Ariz) for the treatment of femoropopliteal occlusive disease.Clinical, angiographic, and procedural data for patients undergoing endovascular treatment of femoropopliteal occlusive disease using Viabahn covered stent grafts at a single institution between 2006 and 2013 were retrospectively reviewed. Graft patency and freedom from thrombolysis, major adverse limb event, and reintervention were determined by Kaplan-Meier analysis. The influence of relevant variables on clinical outcome was determined through univariate and multivariate Cox proportional hazards analyses.Viabahn stent grafts were placed in a total of 91 limbs in 61 patients (66% men; mean age, 69 Â± 12 years) during the study period. Indication for intervention was either claudication (n = 59) or critical limb ischemia (n = 32), with the majority (70%) classified as TransAtlantic Inter-Society Consensus II C (n = 33) or D (n = 31) lesions. Mean follow-up was 38.3 months (range, 1-91 months). Postprocedural pharmacologic regimens included aspirin, clopidogrel, and warfarin (47%); indefinite aspirin and clopidogrel (46%); or aspirin and temporary clopidogrel (7%). Primary and secondary patency rates were 60%, 44%, and 36% and 95%, 82%, and 74% at 1 year, 3 years, and 5 years, respectively. Kaplan-Meier analysis demonstrated more aggressive antiplatelet/anticoagulation regimens to be associated with improved primary patency and freedom from reintervention. Cox proportional hazards analysis demonstrated TransAtlantic Inter-Society Consensus II D lesions, tobacco use, coronary artery disease, and smaller stent diameter to be independent risk factors for stent graft failure. Bleeding events were limited to those in the aspirin, clopidogrel, and warfarin group (11.6% [n = 5]; P = .052), although the majority of these events were not life-threatening, and only two cases required blood transfusion.Increasingly aggressive antithrombotic regimens after Viabahn stent graft placement trended toward improved overall clinical outcomes, although the marginal patency benefit observed with the addition of warfarin to dual antiplatelet therapy was tempered by an observed increased risk of bleeding complications. Longer term follow-up and multicenter studies are needed to further define optimal type and duration of antithrombotic therapy after endovascular peripheral interventions.Copyright Â© 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat. - Physiological reports
Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced.Â© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Renal function changes after snorkel/chimney repair of juxtarenal aneurysms. - Journal of vascular surgery
The snorkel approach for endovascular aneurysm repair (EVAR) has been found to be a safe and viable alternative to open repair for juxtarenal abdominal aortic aneurysms with good short-term outcomes. Concerns about long-term durability and renal branch patency with this technique have been raised with the increasing availability of fenestrated devices. We sought to evaluate renal function changes in patients undergoing "snorkel" EVAR (sn-EVAR).Patients who underwent sn-EVAR from 2009 to 2012 were included in this analysis. Creatinine values were obtained throughout the patient's preoperative, perioperative, and postoperative course. Glomerular filtration rate (GFR) was estimated by the simplified Modification of Diet in Renal Disease formula. Acute renal dysfunction was analyzed according to the RIFLE (Risk, Injury, Failure, Loss, End stage) criteria, whereas chronic renal dysfunction was stratified by the chronic kidney disease staging system.Forty-three consecutive patients underwent sn-EVAR (31 double renal, 12 single renal) for juxtarenal aortic aneurysms. Mean follow-up time was 21 months. Mean aneurysm size was 6.6 cm (range, 5.1-10.5 cm) with anatomy not suitable for treatment with standard EVAR (mean neck length, 1.6 mm); 74 renal snorkel stents were placed in these patients with a 2-year primary patency of 95%. On average, the cohort at baseline was stratified as having moderate renal dysfunction. Mean baseline, maximum postoperative, and latest follow-up creatinine concentrations were 1.20, 1.49, and 1.43, respectively (P = .004). Mean baseline, maximum postoperative, and latest follow-up GFRs were 57.4, 47.8, and 49.2, respectively (P = .014). With use of RIFLE criteria, 14 patients (32.6%) experienced some form of acute kidney injury, although 10 of these patients (23.3%) were classified as mild (25%-50% decline in GFR). On analysis without the RIFLE criteria, 21.4% of patients had postoperative creatinine concentration >1.5 mg/dL, 28.6% had postoperative creatinine concentration increase >30%, and 28.6% had postoperative GFR decline >30%. For the entire study cohort at latest follow-up, 51% experienced no decline of chronic renal dysfunction and 8.1% had improvement in renal function. Renal function declined by one stage in 35.2% of the cohort and by two stages in 5.4%. On analysis without chronic kidney disease staging, 24.3% of patients had latest follow-up creatinine concentration >1.5 mg/dL, 29.7% had latest follow-up creatinine concentration increase >30%, and 24.3% had latest follow-up GFR decline >30%. Mean survival time from significant renal decline was 23.4 months.sn-EVAR continues to demonstrate a high rate of technical success and results in only mild rates of acute and midterm renal function decline according to a number of established definitions for renal dysfunction. Continued monitoring of renal function, renal stent behavior, and abdominal aortic aneurysm sac changes remains critically important in the long-term management of patients undergoing sn-EVAR, particularly given the high comorbidities associated with juxtarenal aortic aneurysms.Copyright Â© 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Streptozotocin-induced diabetes prolongs twitch duration without affecting the energetics of isolated ventricular trabeculae. - Cardiovascular diabetology
Diabetes induces numerous electrical, ionic and biochemical defects in the heart. A general feature of diabetic myocardium is its low rate of activity, commonly characterised by prolonged twitch duration. This diabetes-induced mechanical change, however, seems to have no effect on contractile performance (i.e., force production) at the tissue level. Hence, we hypothesise that diabetes has no effect on either myocardial work output or heat production and, consequently, the dependence of myocardial efficiency on afterload of diabetic tissue is the same as that of healthy tissue.We used isolated left ventricular trabeculae (streptozotocin-induced diabetes versus control) as our experimental tissue preparations. We measured a number of indices of mechanical (stress production, twitch duration, extent of shortening, shortening velocity, shortening power, stiffness, and work output) and energetic (heat production, change of enthalpy, and efficiency) performance. We calculated efficiency as the ratio of work output to change of enthalpy (the sum of work and heat).Consistent with literature results, we showed that peak twitch stress of diabetic tissue was normal despite suffering prolonged duration. We report, for the first time, the effect of diabetes on mechanoenergetic performance. We found that the indices of performance listed above were unaffected by diabetes. Hence, since neither work output nor change of enthalpy was affected, the efficiency-afterload relation of diabetic tissue was unaffected, as hypothesised.Diabetes prolongs twitch duration without having an effect on work output or heat production, and hence efficiency, of isolated ventricular trabeculae. Collectively, our results, arising from isolated trabeculae, reconcile the discrepancy between the mechanical performance of the whole heart and its tissues.
Construction of an inexpensive, hand-held fundus camera through modification of a consumer "point-and-shoot" camera. - Investigative ophthalmology & visual science
To construct a low-cost, easy-to-use, high-image-quality mydriatic fundus camera with "point-and-shoot" operation, and to evaluate the efficacy of this camera to accurately document retinal disease.A prototype portable fundus camera was designed by interfacing a novel optical module with a Panasonic Lumix G2 consumer camera. Low-cost, commercially available optics were used to create even illumination of the fundus, providing a 50Â° retinal field of view. A comparative study assessing the image quality of the prototype camera against a traditional tabletop fundus camera was conducted under an Institutional Review Board (IRB)-approved study.A stand-alone, mydriatic camera prototype was successfully developed at a parts cost of less than $1000. The prototype camera was capable of operating in a point-and-shoot manner with automated image focusing and exposure, and the image quality of fundus photos was comparable to that of existing commercial cameras. Pathology related to both nonproliferative and proliferative diabetic retinopathy and age-related macular degeneration was easily identified from fundus images obtained from the low-cost camera.Early prototype development and clinical testing have shown that a consumer digital camera can be inexpensively modified to image the fundus with professional diagnostic quality. The combination of low cost, portability, point-and-shoot operation, and high image quality provides a foundational platform on which one can design an accessible fundus camera to screen for eye disease.
A metabolite-sensitive, thermodynamically constrained model of cardiac cross-bridge cycling: implications for force development during ischemia. - Biophysical journal
We present a metabolically regulated model of cardiac active force generation with which we investigate the effects of ischemia on maximum force production. Our model, based on a model of cross-bridge kinetics that was developed by others, reproduces many of the observed effects of MgATP, MgADP, Pi, and H(+) on force development while retaining the force/length/Ca(2+) properties of the original model. We introduce three new parameters to account for the competitive binding of H(+) to the Ca(2+) binding site on troponin C and the binding of MgADP within the cross-bridge cycle. These parameters, along with the Pi and H(+) regulatory steps within the cross-bridge cycle, were constrained using data from the literature and validated using a range of metabolic and sinusoidal length perturbation protocols. The placement of the MgADP binding step between two strongly-bound and force-generating states leads to the emergence of an unexpected effect on the force-MgADP curve, where the trend of the relationship (positive or negative) depends on the concentrations of the other metabolites and [H(+)]. The model is used to investigate the sensitivity of maximum force production to changes in metabolite concentrations during the development of ischemia.Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Why has reversal of the actin-myosin cross-bridge cycle not been observed experimentally? - Journal of applied physiology (Bethesda, Md. : 1985)
We trace the history of attempts to determine whether the experimentally observed diminution of metabolic energy expenditure when muscles lengthen during active contraction is consistent with reversibility of biochemical reactions and, in particular, with the regeneration of ATP. We note that this scientific endeavor has something of a parallel flavor to it, with both early and more recent experiments exploiting both isolated muscle preparations and exercising human subjects. In tracing this history from the late 19th century to the present, it becomes clear that energy can be (at least transiently) stored in a muscle undergoing an eccentric contraction but that this is unlikely to be due to the regeneration of ATP. A recently developed, thermodynamically constrained model of the cross-bridge cycle provides additional insight into this conclusion.
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8511 S Sam Houston Pkwy E Suite 101
8511 S Sam Houston Pkwy E Suite 101
8511 S Sam Houston Pkwy E 101