1 Barnes Jewish Hospital Plz
Saint Louis MO 63110
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Antithrombin nanoparticles inhibit stent thrombosis in exÂ vivo static and flow models. - Journal of vascular surgery
Despite significant advances in intravascular stent technology, safe prevention of stent thrombosis over prolonged periods after initial deployment persists as a medical need to decrease device failure. The objective of this project was to assess the potential of perfluorocarbon nanoparticles (NP) conjugated with the direct thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (PPACK-NP) to inhibit stent thrombosis.In a static model of stent thrombosis, 3Â Ã— 3-mm pieces of stainless steel coronary stents were cut and adsorbed with thrombin to create a procoagulant surface that would facilitate thrombus development. After treatment with PPACK-NP or control NP, stents were exposed to platelet-poor plasma (PPP) or platelet-rich plasma (PRP) for set time points up to 60Â minutes. Measurements of final clot weight in grams were used for assessing the effect of NP treatment on limiting thrombosis. Additionally, groups of stents were exposed to flowing plasma containing various treatments (saline, free PPACK, control NP, and PPACK-NP) and generated thrombi were stained and imaged to investigate the treatment effects of PPACK-NP under flow conditions.The static model of stent thrombosis used in this study indicated a significant reduction in thrombus deposition with PPACK-NP treatment (0.00067Â Â± 0.00026Â g; nÂ = 3) compared with control NP (0.0098Â Â± 0.0015Â g; nÂ = 3; PÂ = .026) in PPP. Exposure to PRP demonstrated similar effects with PPACK-NP treatment (0.00033Â Â± 0.00012Â g; nÂ = 3) vs control NP treatment (0.0045Â Â± 0.00012Â g; nÂ = 3; PÂ = .000017). In additional studies, stents were exposed to both PRP pretreated with vorapaxar and PPACK-NP, which illustrated adjunctive benefit to oral platelet inhibitors for prevention of stent thrombosis. Additionally, an inÂ vitro model of stent thrombosis under flow conditions established that PPACK-NP treatment inhibited thrombus deposition on stents significantly.This study demonstrates that antithrombin perfluorocarbon NPs exert marked focal antithrombin activity to prevent intravascular stent thrombosis and occlusion.Copyright Â© 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
Antithrombin nanoparticles improve kidney reperfusion and protect kidney function after ischemia-reperfusion injury. - American journal of physiology. Renal physiology
In the extension phase of acute kidney injury, microvascular thrombosis, inflammation, vasoconstriction, and vascular endothelial cell dysfunction promote progressive damage to renal parenchyma after reperfusion. In this study, we hypothesized that direct targeting and pharmaceutical knockdown of activated thrombin at the sites of injury with a selective nanoparticle (NP)-based thrombin inhibitor, PPACK (phenylalanine-proline-arginine-chloromethylketone), would improve kidney reperfusion and protect renal function after transient warm ischemia in rodent models. Saline- or plain NP-treated animals were employed as controls. In vivo 19F magnetic resonance imaging revealed that kidney nonreperfusion was evident within 3 h after global kidney reperfusion at 34 Â± 13% area in the saline group and 43 Â± 12% area in the plain NP group and substantially reduced to 17 Â± 4% (âˆ¼50% decrease, P < 0.05) in the PPACK NP pretreatment group. PPACK NP pretreatment prevented an increase in serum creatinine concentration within 24 h after ischemia-reperfusion, reflecting preserved renal function. Histologic analysis illustrated substantially reduced intrarenal thrombin accumulation within 24 h after reperfusion for PPACK NP-treated kidneys (0.11% Â± 0.06%) compared with saline-treated kidneys (0.58 Â± 0.37%). These results suggest a direct role for thrombin in the pathophysiology of AKI and a nanomedicine-based preventative strategy for improving kidney reperfusion after transient warm ischemia.Copyright Â© 2015 the American Physiological Society.
Postapproval outcomes of juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft. - Journal of vascular surgery
The objective of this study was to evaluate postapproval outcomes of patients with juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft (Cook Inc, Bloomington, Ind).We reviewed clinical data of consecutive patients treated with the Zenith fenestrated endovascular graft in the United States at seven institutions with early commercial access from July 2012 to December 2012. Clinical outcomes and compliance to anatomic guidelines were compared with results of the U.S. fenestrated trial (USFT).Fifty-seven patients were treated. There were significantly more (P < .05) patients with coronary artery disease, myocardial infarction, and preoperative renal insufficiency than in the USFT. Thirty-six patients (63.2%) did not meet the USFT anatomic criteria of a >4-mm infrarenal neck, and there were significantly more mesenteric stents (13 vs 0; P < .05) used in this group than in the USFT, reflecting the higher anatomic complexity of these patients. The total operative time was 250.2 Â± 14.8 minutes, the fluoroscopy time was 68.9 Â± 4.47 minutes, and the average volume of contrast material was 108.6 Â± 5.6 mL. Technical success was 100% in regard to aneurysm exclusion, although the left renal fenestration was not able to be aligned in two patients, and one patient had a kinked renal stent that was successfully restented. During this time period, there were a total of 10 endoleaks, of which two were type III and eight were type II.Despite higher rates of comorbidities and more challenging anatomy, early 30-day outcomes of juxtarenal aortic aneurysms treated postapproval with the Zenith fenestrated endovascular graft compare well with USFT data. Future studies are needed to assess durability of this treatment modality as the technology diffuses and data mature.Published by Mosby, Inc.
The effect of extremity vascular complications on the outcomes of cardiac support device recipients. - Journal of vascular surgery
To assess the effect of extremity vascular complications (EVCs, including ischemia or vessel trauma) on the outcomes of patients receiving cardiac support devices (CSDs, including ventricular assist device [VAD] and extracorporeal membrane oxygenation [ECMO]).Institutional Review Board-approved, retrospective review of a prospectively maintained database of all temporary and permanent CSD recipients from 7/1/10 to 6/30/12. Patient demographics, procedural data, and outcomes were analyzed. The primary endpoint was all-cause mortality at 30-days post-CSD initiation.Of 208 patients who received CSDs, 31 (14.9%) experienced EVC: 13 (8.9%) of the 146 permanent VADs, 10 (26.3%) of the 38 temporary VADs, and 8 (33.3%) of the 24 ECMO patients. The 30-day mortality for CSD-EVC patients was not significantly higher than that of the CSD patients who did not experience EVC for permanent VAD (15.4% vs 4.5%; P = .15) and ECMO patients (50.0% vs 68.75%; P = 1.00), but was significantly higher for temporary VAD patients (80.0% vs 35.7%; P = .03). Within the CSD-EVC cohort, patients who received a temporary VAD had a significantly higher 30-day mortality and decision to withdraw care after EVC compared with those who received a permanent VAD (P = .01 and P < .01, respectively). Looking beyond the 30-day window, EVC was associated with higher mortality rates in the permanent VAD population (53.8% vs 25.6%; P = .025) but not the temporary VAD or ECMO groups.In temporary VAD recipients, EVCs result in higher 30-day mortality, more frequent withdrawal of care, and shortened survival time relative to the global temporary VAD group. EVC in permanent VAD recipients did not affect early (30-day) mortality rates, but strongly predicted a higher cumulative mortality risk for the 2-year study period. Overall ECMO mortality rates were high, and not significantly impacted by the occurrence of EVC. The nature of the EVC (cannulation site complication vs embolic injury) did not impact mortality. This data provides quality improvement targets for VAD programs.Copyright Â© 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Early effectiveness of isolated pectoralis minor tenotomy in selected patients with neurogenic thoracic outlet syndrome. - Journal of vascular surgery
This study evaluated the early effectiveness of isolated pectoralis minor tenotomy (PMT) in the surgical treatment of selected patients with neurogenic thoracic outlet syndrome (NTOS) compared with supraclavicular decompression (SCD; as scalenectomy, neurolysis, and first rib resection) plus PMT (SCD+PMT).Data were obtained for 200 patients undergoing operative treatment for disabling NTOS between 2008 and 2011. Isolated PMT was offered to 57 patients with physical examination findings limited to the subcoracoid space, and SCD+PMT was offered to 143 with scalene triangle and subcoracoid findings. Functional outcomes were assessed before and 3 months after surgery using the Disabilities of the Arm, Shoulder and Hand (DASH) survey and related instruments.There were no significant differences (P > .05) between PMT and SCD+PMT patients with respect to age (overall, 37 Â± 1 years), sex (73% women), side affected (52% right, 14% bilateral), or the frequency of various NTOS symptoms, but fewer PMT patients had a bony anomaly (0% vs 18%; P < .01) or a history of injury (35% vs 61%; P < .01). Mean preoperative DASH scores were similar between PMT and SCD+PMT groups (49.9 Â± 3.6 vs 50.8 Â± 1.6), but previous use of opiate pain medications was higher in PMT patients (47% vs 20%; P = .0004). PMT was conducted as an outpatient procedure, whereas the mean hospital stay after SCD+PMT was 4.8 Â± 0.1 days, with two patients (1%) requiring early reoperations for persistent lymph leaks. Mean DASH scores 3 months after surgery were significantly improved after isolated PMT (29.6 Â± 4.2; P < .01) and SCD+PMT (41.5 Â± 2.2; P < .01), but the mean extent of improvement in DASH scores was not significantly different in PMT (32% Â± 9%) vs SCD+PMT (19% Â± 5%). There were also no significant differences in the proportion of PMT vs SCD+PMT patients demonstrating improvement in functional outcome measures (75% vs 72%) or in overall use of opiate medications (35% vs 27%).Isolated PMT is a low-risk outpatient procedure that is effective for the treatment of selected patients with disabling NTOS, with early outcomes similar to SCD+PMT. These findings emphasize the importance of recognizing subcoracoid brachial plexus compression as part of the spectrum of NTOS and support the role of PMT in surgical management.Copyright Â© 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Supraclavicular decompression for neurogenic thoracic outlet syndrome in adolescent and adult populations. - Journal of vascular surgery
This study was conducted to better define clinical results and understand factors determining responsiveness to surgical treatment for neurogenic thoracic outlet syndrome (NTOS) in adolescent and adult populations.A retrospective review was conducted for 189 patients with disabling NTOS who underwent primary supraclavicular decompression (scalenectomy, brachial plexus neurolysis and first rib resection, with or without pectoralis minor tenotomy) from April 2008 to December 2010. Clinical characteristics were compared between 35 adolescent patients (aged<21 years) and 154 adults (aged>21 years). Functional outcome measures were assessed before surgery and at 3- and 6-month follow-up using a composite NTOS Index combining the Disabilities of the Arm, Shoulder and Hand (DASH) survey, the Cervical-Brachial Symptom Questionnaire (CBSQ), and a 10-point visual analog scale (VAS) for pain.Adolescent and adult patients were not significantly different with respect to sex (overall 72.5% female), side affected (58.7% right, 60.3% dominant limb), bony anomalies (23.3%), previous injury (55.6%), coexisting pain disorders (11.1%), and positive responses to scalene muscle anesthetic blocks (95.6%). Compared with adults, adolescent patients had a significantly (P<.05) lower incidence of depression (11.4% vs 41.6%), motor vehicle injury (5.7% vs 20.1%), previous operations (11.4% vs 29.9%), preoperative use of opiate medications (17.1% vs 44.8%), and symptom duration>2 years (24.2% vs 50.0%). Mean preoperative NTOS Index (scale 0-100) was significantly lower in adolescent vs adult patients (46.5Â±3.6 vs 58.5Â±1.7; P=.009), and hospital length of stay was 4.4Â±0.2 vs 4.9Â±0.1 days (P=.03), but the rate of postoperative complications was no different (overall, 4.2%). Although both groups exhibited significant improvement in functional outcome measures at 3 and 6 months, adolescent patients had significantly lower NTOS Index (10.4Â±3.1 vs 39.3Â±3.3; P<.001) and use of opiate medications (11.4% vs 47.4%; P<.001) compared with adults.Adolescents undergoing supraclavicular decompression for NTOS had more favorable preoperative characteristics and enhanced 3-month and 6-month functional outcomes than adults. Further study is needed to delineate the age-dependent and independent factors that promote optimal surgical outcomes for NTOS.Copyright Â© 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Effect of increasing patient age on complication rates following intact abdominal aortic aneurysm repair in the United States. - The Journal of surgical research
Advanced age is generally acknowledged as a risk factor for adverse surgical outcomes, but little information exists to define the magnitude of this association from a population-based perspective. This study was undertaken to determine the relation of patient age to complications following abdominal aortic aneurysm (AAA) repair in a population-based experience.This study was based upon data from 6397 patients with a primary diagnosis of intact AAA and a procedure code for repair of AAA from the Nationwide Inpatient Sample (NIS) in 2000. The NIS is a 20% stratified random sample representative of all United States hospitals. Primary outcome variables were postoperative complications determined from secondary diagnostic codes. Adjustment for confounding variables was performed using multiple logistic regression.At least one complication affected 29% of patients. Increasing age correlated with a higher risk of having one or more complications (51-60 years, 18.8%; 61-70 years, 27.3%; 71-80 years, 31.2%; >80 years, 34.3%; P < 0.01). Comparison of the oldest to the youngest age group revealed an increased incidence of pulmonary insufficiency (13.9% versus 6.4%), pneumonia (7.7% versus 3.0%), reintubation (9.5% versus 3.9%), acute renal failure (8.8% versus 2.5%), myocardial infarction (4.3% versus 1.6%), and mortality (7.9% versus 1.1%). The association of increasing age to complications and mortality persisted after adjusting for patient case-mix.Older patient age is independently associated with an increased risk of major postoperative complications after AAA repair. The increasing age of the United States population will compound this healthcare problem. Quality improvement efforts must focus on minimizing complication rates in elderly patients undergoing common vascular surgical procedures including AAA repair.
Oximetric angiosome imaging in diabetic feet. - Journal of magnetic resonance imaging : JMRI
To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet.In four healthy and five subjects with diabetes, the feasibility of foot oximetry was examined using a 3T clinical magnetic resonance imaging (MRI) scanner. The subjects' feet were scanned at rest and during a toe-flexion isometric exercise. The oxygen extraction fraction of skeletal muscle was measured using a susceptibility-based MRI method. Our newly developed MR foot oximetric angiosome model was compared with the traditional angiosome model in the assessment of the distribution of oxygen extraction fraction.Using the traditional angiosome during the toe-flexion exercise, the oxygen extraction fraction in the medial foot of healthy subjects increased (4.9â€‰Â±â€‰3%) and decreased (-2.7â€‰Â±â€‰4.4%) in subjects with diabetes (differenceâ€‰=â€‰7.6%; 95% confidence intervalâ€‰=â€‰-13.7â€‰Â±â€‰1.4; Pâ€‰=â€‰0.02). Using the oximetric angiosome, the percent difference in the areas of oxygen extraction fraction within the 0.7-1.0 range (expected oxygen extraction fraction during exercise) between rest and exercise was higher in healthy subjects (8â€‰Â±â€‰4%) than in subjects with diabetes (4â€‰Â±â€‰4%; Pâ€‰=â€‰0.02).This study demonstrates the feasibility of measuring skeletal muscle oxygen extraction fraction in the foot muscle during a toe-flexion isometric exercise. Instead of assessing oxygen extraction fraction in a foot muscle region linked to a supplying artery (traditional angiosome), the foot oximetric angiosome model assesses oxygen extraction fraction by its different levels in all foot muscle regions and thus may be more appropriate for assessing local ischemia in ulcerated diabetic feet. J. Magn. Reson. Imaging 2016.Â© 2016 Wiley Periodicals, Inc.
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1 Barnes Jewish Hospital Plz Saint Louis, MO 63110
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1 Barnes Jewish Hospital Plz
660 S Euclid Ave Box 8121
660 S Euclid Ave Campus Box 8134
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1 Barnes Jewish Hospital Plz