Search

Cell-cell interactions are important to numerous biological systems, including tissue microenvironments, the immune system, and cancer. However, current methods for studying cell combinations and interactions are limited in scalability, allowing just hundreds to thousands of multicell assays per experiment; this limited throughput makes it difficult to characterize interactions at biologically relevant scales. Here, we describe a paradigm in cell interaction profiling that allows accurate grouping of cells and characterization of their interactions for tens to hundreds of thousands of combinations. Our approach leverages high-throughput droplet microfluidics to construct multicellular combinations in a deterministic process that allows inclusion of programmed reagent mixtures and beads. The combination droplets are compatible with common manipulation and measurement techniques, including imaging, barcode-based genomics, and sorting. We demonstrate the approach by using it to enrich for chimeric antigen receptor (CAR)-T cells that activate upon incubation with target cells, a bottleneck in the therapeutic T cell engineering pipeline. The speed and control of our approach should enable valuable cell interaction studies., Competing Interests: Competing interest statement: J.L.M., N.G.S., C.S.P., C.A.S., M.S., R.H.C., and A.R.A. are shareholders in Scribe Biosciences, Inc., a company incorporated to commercialize the droplet assembly technology described in this paper. Patent applications 62/847,791 and 40/946,254 have been submitted to cover the technological developments described in this work., (Copyright © 2022 the Author(s). Published by PNAS.)

Atherosclerotic vascular disease is a leading cause of death worldwide. Atherosclerotic stenosis of the internal carotid or intracranial arteries causes up to 15% of strokes. Peripheral artery disease affects up to one in five people in the United States who are 60 years and older and nearly one-half of those who are 85 years and older. Renal artery stenosis may affect up to 5% of people with isolated hypertension and up to 40% of people with other atherosclerotic diseases. All patients with atherosclerotic vascular disease should receive a comprehensive program of guideline-directed medical therapy, including structured physical activity and lifestyle modification, an antiplatelet agent, a statin, antihypertensive therapy, and smoking cessation counseling. The U.S. Preventive Services Task Force recommends one-time screening for abdominal aortic aneurysm with ultrasonography in men 65 to 75 years of age who have smoked at least 100 cigarettes, but screening is not recommended for carotid, peripheral, and renal disease. Surgical revascularization decreases adverse outcomes and mortality in selected patients with advanced vascular disease. Endovascular repair has become more common for patients younger than 70 years because of decreased short-term mortality. Carotid revascularization with carotid endarterectomy or carotid artery stenting is recommended for symptomatic patients with greater than 50% internal carotid artery stenosis. Carotid artery stenting is preferred in patients with multiple comorbidities, tracheostomy, or previous neck radiation or dissection. In patients older than 70 years, carotid endarterectomy is associated with a lower risk of periprocedural stroke or death than carotid artery stenting. Revascularization is a reasonable treatment option for patients with lifestyle-limiting claudication and an inadequate response to guideline-directed therapies. Revascularization is indicated for patients with critical limb ischemia and is emergently indicated for acute limb ischemia. Renal artery revascularization offers no proven clinical benefit when added to optimal medical therapy.

The surgical management of advanced symptomatic atherosclerotic disease in multiple distributions including the coronary circulation presents unique challenges due to the high risk of perioperative ischemic complications in the setting of coronary artery bypass grafting. We present a novel case of the combined surgical management of symptomatic carotid, coronary and mesenteric ischemic disease. The patient underwent carotid endarterectomy followed by combined coronary and mesenteric revascularization using cardiopulmonary bypass during the same hospital admission. He had an uncomplicated post-operative course and was discharged to home on post-operative day 7 after the combined procedure. Ninety-day follow-up was also unremarkable with the patient having no recurrent symptoms of ischemia. This case demonstrates the feasibility and safety of our approach for this rare clinical presentation., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.)

Objectives: Studies have described the experiences of racial microaggressions in everyday life and on college campuses, yet prior research has not explored how microaggressions and microaffirmations are experienced by students who are first in their family to attend college., Method: This qualitative investigation of 296 open-ended survey responses described the lived experiences of first-generation college students at a large, public, predominately White institution., Results: Students experienced microaggressions in the form microinsults, microassaults, and microinvalidations, and microaffirmations in the form of microsupports, microcompliments, and microvalidations on campus., Conclusions: Study implications include the development and implementation of regular positive and intentional communications by faculty, staff, and peers on college campuses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Lower extremity peripheral artery disease (PAD) affects 12% to 20% of Americans 60 years and older. The most significant risk factors for PAD are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking; the presence of three or more factors confers a 10-fold increase in PAD risk. Intermittent claudication is the hallmark of atherosclerotic lower extremity PAD, but only about 10% of patients with PAD experience intermittent claudication. A variety of leg symptoms that differ from classic claudication affects 50% of patients, and 40% have no leg symptoms at all. Current guidelines recommend resting ankle-brachial index (ABI) testing for patients with history or examination findings suggesting PAD. Patients with symptoms of PAD but a normal resting ABI can be further evaluated with exercise ABI testing. Routine ABI screening for those not at increased risk of PAD is not recommended. Treatment of PAD includes lifestyle modifications-including smoking cessation and supervised exercise therapy-plus secondary prevention medications, including antiplatelet therapy, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Surgical revascularization should be considered for patients with lifestyle-limiting claudication who have an inadequate response to the aforementioned therapies. Patients with acute or limb-threatening limb ischemia should be referred immediately to a vascular surgeon.

The case being presented is a 35-year-old female with a 3-year history of progressive dyspnea and right-sided heart failure following spine surgery. Physical examination identified a continuous bruit in the lower abdomen radiating to her back which prompted further evaluation. Echocardiography showed normal left ventricle systolic function, enlarged right ventricle, functional tricuspid regurgitation, and moderate pulmonary hypertension. A computed tomography (CT) scan of the abdomen and pelvis demonstrated findings consistent with an arteriovenous fistula (AVF) between the right common iliac artery and the inferior vena cava. She underwent an uneventful endovascular repair without perioperative complication. The patient's symptoms resolved a few hours after the procedure and she continued to be symptom free at 3-month follow-up. This case illustrates an iatrogenic iliocaval fistula causing high-output cardiac failure which was successfully treated endovascularly with excellent clinical result., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Conventional wisdom holds that patients with a need for intervention for femoropopliteal occlusive disease at a younger age have more aggressive disease, although there is a paucity of support in the literature. The purpose of this study was to evaluate this assumption., Methods: A retrospective cohort of patients undergoing endovascular or open revascularization for femoropopliteal occlusive disease for critical limb ischemia during a 4-year period was assembled. Demographic information, comorbidities, disease characteristics, and time to last follow-up, repeat intervention, amputation, or death was recorded. The patients were stratified by age into a young (≤55 years) group, middle (56-77 years) group, and elderly (≥78 years) group. Univariate and multivariate statistical methods were used to evaluate the primary outcome., Results: The study included 124 patients with a mean age of 64.4 ± 0.8 years. Progression to reintervention or amputation occurred in 50% of the patients during the follow-up period, with 18% dying before having an outcome. Kaplan-Meier analysis showed a trend toward significance (P = .06) in time to reintervention, amputation, or death among the three groups, with time to event of 253, 1083, and 504 days for the young, middle, and elderly groups, respectively. However, differences based on age were not significant (P = .57) in Cox regression analysis., Conclusions: There does not appear to be an association between time to reintervention and patient age., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A 44-year-old man with a type A dissection repair 5 years earlier presented with progressive enlargement of the residual arch and thoracic aorta. Flow into the false lumen from the distal aortic suture line was evident on contrast-enhanced computed tomography. Through a redo hemisternotomy, the false lumen was accessed directly. An Amplatzer plug was deployed within the narrowed neck of the false lumen proximal to the enlarged false lumen within descending aorta. Interlocking coils were deployed proximal to the Amplatzer plug, resulting in thrombosis of the false lumen., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the 10-year outcome of patients presenting with asymptomatic moderate carotid artery stenosis, and to determine which factors correlate with progression of disease to stroke or revascularization., Methods: A retrospective review of all new patients presenting with asymptomatic moderate carotid artery stenosis from July 1998 to December 2001 was undertaken. Patients were consecutively identified and included by using duplex ultrasonography to identify moderate carotid disease. Variables were recorded for all patient encounters through June 2010. The primary end point was occurrence of ipsilateral cerebrovascular stroke or revascularization event (SORE). Statin therapy and angiotensin blockade (STAB) were categorized as follows: STAB(0)-medical treatment with neither statin therapy nor angiotensin blockade, STAB(1)-treatment with only one of the two, STAB(2)-treatment with both. An amortized cost model analyzed the cost of SORE-free survival., Results: Over a 42-month period, 468 carotids in 366 patients with an average age of 69.0 ± 8.7 years were evaluated. Over a mean follow-up of 6.6 ± 2.7 years, SORE occurred in 150 (32.1%) carotid arteries. Hyperlipidemia was predictive of SORE (hazard ratio [HR]: 1.543, 95% confidence interval [CI]: 1.053-2.262, P = 0.03). Medical therapies protective against SORE were beta-blockade (HR: 0.612, 95% CI: 0.435-0.861, P < 0.05), STAB(1) (HR: 0.487, 95% CI: 0.336-0.706, P < 0.01), and STAB(2) (HR: 0.149, 95% CI: 0.089-0.248, P < 0.01). At 10 years, SORE-free survival in STAB(2) was 82.7% ± 4.6%, STAB(1) was 56.3% ± 5.0%, and STAB(0) was 29.3% ± 5.4% (P < 0.01). The cost per SORE-free year in STAB(2) was $1,695.40 ± $275.60, STAB(1) was $3,916.80 ± $605.44, and STAB(0) was $4,126.40 ± $427.23 (P < 0.01)., Conclusion: These data demonstrate the clinical and financial advantage of using both statin therapy and angiotensin pathway blockage in patients with asymptomatic moderate carotid artery stenosis., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Thoracic endovascular aortic repair (TEVAR) devices are increasingly being utilized to treat aortic pathologies outside of the original Food & Drug Administration (FDA) approval for nonruptured descending thoracic aorta aneurysms (DTAs). The objective of this study was to evaluate the outcomes of patients undergoing TEVAR, elucidating the role of surgical and pathologic variables on morbidity and mortality., Methods: National Surgical Quality Improvement Program (NSQIP) data were reviewed for all patients undergoing endovascular thoracic aorta repair from 2005 to 2007. The patients' operative indication and surgical complexity were used to divide them into study and control populations. Comorbid profiles were assessed utilizing a modified Charlson Comorbidity Index (CCI). Thirty-day occurrences of mortality and serious adverse events (SAEs) were used as study endpoints. Univariate and multivariate models were created using demographic and clinical variables to assess for significant differences in endpoints (P ≤ .05)., Results: A total of 440 patients undergoing TEVAR were identified. When evaluating patients based on operative indication, the ruptured population had increased mortality and SAE rates compared to the nonruptured DTA population (22.6% vs 6.2%;P < .01 and 35.5% vs 9.1%;P < .01, respectively). Further analysis by surgical complexity revealed increased mortality and SAE rates when comparing the brachiocephalic aortic debranching population to the noncovered left subclavian artery population (23.1% vs 6.5%; P = .02 and 30.8% vs 9.1%; P < .01, respectively). Multivariate analysis demonstrated that operative indication was not a correlate of mortality or SAEs (odds ratio [OR], 0.95; P = .92 and OR, 1.42; P = .39, respectively); however, brachiocephalic aortic debranching exhibited a deleterious effect on mortality (OR, 8.75; P < .01) and SAE rate (OR, 6.67; P = .01)., Conclusion: The operative indication for a TEVAR procedure was not found to be a predictor of poor patient outcome. Surgical complexity, specifically the need for brachiocephalic aortic debranching and aortoiliac conduit, was shown to influence the occurrence of SAEs in a multivariate model. Comparative data, such as these, illustrate real-world outcomes of patients undergoing TEVAR outside of the original FDA-approved indications. This information is of paramount importance to various stakeholders, including third-party payers, the device industry, regulatory agencies, surgeons, and their patients., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: The objective of this study is to evaluate morbidity and mortality rates in surgical patients at the beginning of the academic year., Methods: The National Surgical Quality Improvement Program database was utilized to gather data on the 10 most common inpatient operative procedures from 2005-2007. Study end points included mortality, serious adverse events (SAE), and all morbidities. Statistical analysis of outcomes was conducted examining the total population, and then stratified by operation to assess for significant differences in end points (P < .05)., Results: A total of 89,473 patients were identified. During the first academic quarter, the mortality rate was no different in the study group than the control group (2.0% vs 2.2%, P = .793). Overall SAE and morbidity rates were similar between populations (11.5% vs 11.4%, P = .697 and 18.3% vs 17.8%, P = .076, respectively). When stratified by operation, "artery bypass graft" (3.7% vs 2.9%, P = .039) and "repair bowel opening" (1.1% vs 0.6%, P = .033) subsets had increases in mortality rate. Multivariate analysis confirmed the deleterious effect of first quarter admission in only the "artery bypass graft" subset (OR = 1.35, CI 1 = .023-1.774)., Conclusion: By in large, these data refute the "July Phenomenon." Multivariate analysis revealed patient disease to have a greater impact than timing of operation in the "repair bowel opening" subset. The "artery bypass graft" population was affected by timing of operation and the very small effect on mortality (<1%) may reflect new surgery residents being unfamiliar with the management of complex cardiovascular disease., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Introduction: Traumatic aortic injury (TAI) is a rare yet highly lethal injury associated with blunt force deceleration injury. The adoption of thoracic endovascular aortic repair (TEVAR) has become a safer option than traditional open repair. The purpose of this study is to review a rural trauma center experience with TAI., Methods: A retrospective analysis was performed, reviewing all patients who presented with TAI between 2000 and 2009. Clinical, anatomical, and procedural variables of all cases were systematically reviewed. Clinical endpoints included mortality, and aortic-related mortality, and hospital length of stay. The study population was stratified by those that underwent surgical repair (SR) and those managed medically (MM)., Results: Fifty-six patients presented with blunt TAI; 35 patients (62.5%) were surgically repaired (22 open, 13 TEVAR), while 21 (37.5%) were MM. The only difference in comorbidities was a higher rate of coronary artery disease in MM. Mean hospital arrival time (SR, 188.6 ± 30.3 minutes, MM, 253 ± 65.3 minutes), aortic injury grade (SR, 2.7 ± 0.1; MM, 2.3 ± 0.2), and injury severity score were not significantly different between the groups. Head Abbreviated Injury Score (AIS) was worse in the MM group, while chest AIS was worse in the SR group (P < .05). There were nine (42.9%) deaths in the MM group, while there were only two (5.7%) in the SR group (P < .001). There was no significant difference in aortic-related mortality. Mean follow-up time was not statistically different., Conclusion: These data provide a group of stable patients to examine the management of TAI in the endovascular era. The low aortic-related mortality in the MM group demonstrates that there is time for a thorough evaluation in patients sustaining TAI who arrive without hemodynamic instability., (Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Within the context of healthcare system reform, the cost efficacy of lower extremity revascularization remains a timely topic. The impact of an individual patient's socioeconomic status represents an under-studied aspect of vascular care, especially with respect to longitudinal costs and outcomes. The purpose of this study is to examine the relationship between socioeconomic status and clinical outcomes as well as inpatient hospital costs., Methods: A retrospective femoropopliteal revascularization database, which included socioeconomic factors (household income, education level, and payor status), in addition to standard demographic, clinical, anatomical, and procedural variables were analyzed over a 3-year period. Patients were stratified by income level (low income [LI] <200% federal poverty level [$42,400 for a household of 4], and higher income [HI] >200% federal poverty level) and revascularization technique (open vs endovascular) and analyzed for the endpoints of primary assisted patency, amortized cost-per-day of patency, and limb salvage. Data were analyzed with univariate and multivariate techniques., Results: A total of 187 cases were identified with complete data for analysis, 146 in the LI and 41 in the HI cohorts. LI patients differed from HI patients by mean age (66.2 +/- 1.0 vs 61.8 +/- 1.5 years, P = .04), high school graduate rate (51.4% vs 85.4%, P < .001), presence of tissue loss (30.1% vs 14.6%, P = .05), female gender (43.7% vs 22.0%, P = .01) and preoperative statin use (45.8% vs 75.6%, P < .001). There were no differences with respect to other comorbidities including smoking status, presence of diabetes, renal insufficiency, anatomic factors or treatment modality (open vs endovascular). Ninety-seven patients underwent endovascular revascularization. The following outcomes were noted in the endovascular subset of LI and HI patients respectively: primary assisted patency (66% vs 71%, P = NS) and 12-month cost-per-day of patency ($166.30 +/- 77.40 vs $22.45 +/- 12.45, P = .05). Ninety-eight patients underwent open revascularization, with the following outcomes in LI and HI patients respectively: primary assisted patency (78% vs 86%, P = NS) and 12-month cost-per-day of patency ($319.43 +/- 225.44 vs $40.47 +/- 4.63, P = .07). Of the 77 patients with critical limb ischemia, 19 underwent eventual amputation. Multivariate analysis demonstrated that income above 100% of the federal poverty line was protective against limb loss (odds ratio 0.06, 95% confidence interval 0.01-0.51, P < .001)., Conclusion: Income level correlates with advanced presentation, advanced age, and lack of statin use. Although primary assisted patency rate is not affected by income status, an increased cost-per-day of patency and inferior limb salvage is found in lower income patients.

Background: Peripheral thrombolysis is an indispensible tool in the treatment of occlusive peripheral vascular disease (PVD). However, the use of intravascular thrombolytic agents carries a significant risk of morbidity and mortality. The aim of this study is to review a contemporary series of patients treated with catheter-directed thrombolytics in the treatment of occlusive PVD., Methods: A retrospective analysis was performed reviewing all patients who underwent catheter-directed thrombolytic therapy for PVD with recombinant tissue plasminogen activator (rt-PA) between 2005 and 2008. Data included clinical and demographic variables potentially associated with endpoints of technical success, hemorrhagic complications, and death. Data were analyzed with univariate and multivariate measures. Significance was assigned with p <0.05., Results: Over the 36-month study, 125 thrombolytic procedures were performed. Indication for treatment was occlusive thrombus in native artery (49 cases, 37.6%), vein (13 cases, 10.4%), or arterial bypass graft (63 cases, 49.6%). Twenty three cases (14.3%) used ultrasound-assisted catheter technology. Mean patient age was 57.9 +/- 1.1 years. Technical success was achieved in 82% of cases. Mean rt-PA dose was 47.3 +/- 1.4 mg (13.5 +/- 4.5 mg with ultrasound assisted catheter technology). Hemorrhagic complications occurred in 22.4% of patients with a 5.6% stroke rate. Intracranial hemorrhage (ICH) correlated with poor hypertensive control (systolic blood pressure >160 mmHg; OR, 13.67; CI, 1.59-117.68; p = 0.006) and advanced age (>80 years; OR, 9.04; CI, 1.40-58.57, p = 0.049). Hemorrhagic complications (including minor access site hematomas) correlated with poor hypertensive control (systolic blood pressure >180 mmHg; OR, 3.48; CI, 1.22-9.94; p = 0.021) and in patients with congestive heart failure (OR, 3.26; CI, 1.09-9.76; p = 0.036). Overall mortality occurred in 7 patients (5.6%), 4 as a result of hemorrhagic complications. Correlates of mortality were patients with diabetes mellitus (OR, 8.85; CI, 1.62-48.26; p = 0.003), end stage renal disease (OR, 15.33; CI, 2.07-113.39; p < .001) and congestive heart failure (OR, 6.06; CI, 1.22-30.13; p = .014). Serum fibrinogen levels, pre-procedural hypertension, and rt-PA dosage did not correlate with hemorrhagic complication or death., Conclusion: Peripheral thrombolysis with catheter-based technologies has a high incidence of technical success. However, the procedure continues to carry a significant complication rate. This study emphasizes the importance of periprocedural hypertensive control and identifies subgroups of patients at risk of untoward complications. On the basis of these data, the authors advocate stricter blood pressure parameters in patients undergoing peripheral thrombolysis., (Copyright (c) 2010. Published by Elsevier Inc.)

Introduction: This study hypothesized that preoperative statin therapy would have a protective effect on patients undergoing elective abdominal aortic aneurysm (AAA) repair and that the risk-reduction effect of these agents would result in a reduction in subsequent total hospital costs., Methods: All patients who underwent an elective endovascular AAA repair (EVAR) or open AAA repair (OAR) between 2004 and 2007 were retrospectively reviewed. Clinical end points included postoperative days, length of hospital stay, postoperative complications (myocardial infarction, stroke, renal failure, hemorrhage, pneumonia, urinary tract infection, wound infection), and 30-day mortality. The financial end point was total hospital cost associated with the procedure., Results: We identified 401 patients, consisting of 173 EVAR patients (43%) and 228 OAR (57%). Despite a higher Society for Vascular Surgery risk score, the EVAR statin cohort had significantly reduced postoperative days (1.9 +/- 0.2 vs 2.3 +/- 0.3, P < .05) and hospital length of stay (2.3 +/- 0.3 vs 2.8 +/- 0.4, P < .05) compared with the nonstatin EVAR cohort. Postoperative complications (4.4% vs 14.7%, P < .05) and the mortality rate (0.0% vs 5.9%, P < .05) were significantly decreased in the OAR statin cohort compared with the nonstatin OAR cohort and trended to be decreased in the EVAR statin group. Statin therapy translated into a lower total cost per patient of $3,205 for EVAR and $3,792 for OAR (P < .05)., Conclusion: With respect to both clinical outcome measures and subsequent resource utilization, statin therapy is associated with a beneficial effect in patients undergoing elective AAA repair. These data suggest that preoperative statin therapy should be an integral part of the risk optimization for patients undergoing AAA repair., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Healthcare resource utilization is an understudied aspect of vascular surgery. Initial cost of a given procedure is not an accurate reflection of resource utilization because it does not account for procedural durability and efficacy. Herein we describe an amortized cost model that accounts for procedural costs, durability, and re-intervention costs., Methods: A cost model was developed using patency data endpoints and total hospital costs (direct and indirect) associated with an inital revascularization and subsequent re-interventions. This model was applied to a retrospective database of femoropopliteal reconstructions. One hundred and eighty-three open cases were compared with 198 endovascular cases; and the endpoints of initial cost, amortized cost at 12 months, and assisted patency were examined., Results: The open and endovascular cases were not statistically different with respect to indication, patient co-morbid profiles, or post-procedural pharmacotherapy. Primary assisted patency was better in the open revascularization group at 12 months (78% versus 66%, P < .01). There was a statistically significant higher initial cost for open reconstruction when compared with endovascular ($12,389 +/- $408 versus $6,739 +/- $206, P < .001). However, at 12 months post-procedure, the initial cost benefit was lost for endovascular patients ($229 +/- $106 versus $185 +/- $124, P = .71). There was, however, a trend for endovascular cost savings in claudicants, though this did not reach significance ($259 +/- $189 versus $86 +/- $52, P = .31). For patients with critical limb ischemia, renal dysfunction, and end stage renal disease, the trend favored open surgery., Conclusions: An amortized cost model provides insight into the healthcare resource utilization associated with a particular revascularization and assistive procedures. The initial cost savings of endovascular therapies are not sustained over time. Cost-savings trends were noted, however, longer follow-up is required to see if these will reach statistical significance.

Presented is a patient with an iatrogenic hepatic artery pseudoaneurysm that was treated by endovascular stent grafting. Endovascular stent grafting of a hepatic artery pseudoaneurysm offers a safe and potentially less morbid alternative to an open repair. The report stresses the necessity of careful preoperative evaluation with angiography to determine the feasibility of the procedure. An aggressive approach to treating hepatic artery pseudoaneurysms is advocated because of the poor correlation between size and their tendency to rupture. With an increasing rate of diagnosis of visceral artery aneurysms in elderly, debilitated patients, endovascular repair is anticipated to have an increasing role and should be considered a first-line therapy in anatomically suitable candidates.

Arteritis and mycotic aneurysms have been well described for more than 100 years. The authors report a case of bacterial arteritis that presented with pneumatosis of the aortic wall and that evolved over 1 week into an infected abdominal aortic aneurysm. This case documents the rapid progression from arteritis to mycotic aneurysm, highlighting the need for close radiologic follow-up and aggressive medical and surgical management.

Bacterial lipopolysaccharide (LPS) causes acute lung injury (ALI) and contributes to inflammation in the acute respiratory distress syndrome (ARDS) and sepsis, making mechanisms of resistance to LPS critically important in clinical settings. The authors postulated that intratracheal administration of a plasmid (pcDNA3. 0-rTNFalpha) encoding rat tumor necrosis factor-alpha (TNF-alpha) would increase resistance of mice to LPS-induced ALI or mortality. They investigated the time course and dose-response for development of LPS-induced ALI in C57/BL6 mice and sought possible protective effects of 100 microg pcDNA3.0-rTNFalpha intratracheally 1, 2, or 3 weeks before LPS challenge. Lung myeloperoxidase (MPO) activity and alveolar lavage fluid (BALF) cell counts increased significantly 48 hours after intraperitoneal (IP) LPS challenges. After pcDNA3.0-rTNFalpha pretreatment, mice challenged with LPS had lower lung/body weight ratios than mice treated with pcDNA3.0; however, other indices of lung injury did not differ. Survival of mice challenged with lethal IP LPS 2 weeks after intratracheal pcDNA3.0-rTNFalpha vector improved significantly, compared to mice pretreated with the control vector, pcDNA3.0. However, pcDNA3.0-pretreated mice tolerated LPS challenge less well than saline-pretreated controls. LPS causes neutrophilic lung injury and mortality, but pcDNA3.0-TNFalpha does not prevent ALI due to LPS. Intratracheal pcDNA3.0-rTNFalpha pretreatment significantly improves survival of mice after LPS challenge, compared to those pretreated with pcDNA3.0.

Lung epithelial cells produce increased reactive oxygen species (ROS) after hypoxia exposure, and they are more susceptible after hypoxia to injury by agents that generate superoxide [O2-; e.g., 2,3-dimethoxy-1,4-naphthoquinone (DMNQ)]. Cellular GSH and MnSOD both decrease in hypoxic lung epithelial cells, altering the redox state. Because ROS participate in signaling pathways involved in cell death or survival, we tested the hypothesis that mitogen-activated protein kinases (MAPK) were involved in a protective response against cellular injury during reoxygenation. Human lung epithelial A549 cells were incubated in hypoxia (<1% O2 for 24 h) and then reoxygenated by return to air. p38mapk and MKK3 phosphorylation both decreased after hypoxia. During reoxygenation, cells were incubated with DMNQ (0-50 microM), a redox cycling quinone that produces O2-. Hypoxia preexposure significantly increased epithelial cell lysis resulting from DMNQ. Addition of the p38mapk inhibitors SB-202190 or SB-203580 markedly increased cytotoxicity, as did the mitogen/extracellular signal-regulated kinase (MEK) 1/2 inhibitor PD-98059 (all 10 microM), suggesting a protective effect of downstream molecules activated by the kinases. Transfection of A549 cells with a dominant active MKK3 plasmid (MKK3[Glu]) partially inhibited cytolysis resulting from DMNQ, whereas the inactive MKK3 plasmid (MKK3[Ala]) had less evident protective effects. Stress-related signaling pathways in epithelial cells are modulated by hypoxia and confer protection from reoxygenation, since hypoxia and chemical inhibition of p38mapk and MEK1/2 similarly increase cytolysis resulting from O2-.

Background: The most frequent site of metastases from prostate cancer is bone. Bisphosphonates reduce excessive bone turnover while preserving bone structure and mineralization in patients with other tumor types. We conducted a double-blind, placebo-controlled, randomized trial to determine whether the first-generation bisphosphonate sodium clodronate could improve bone progression-free survival (BPFS) times among men with bone metastases from prostate cancer., Methods: Between June 1994 and July 1998, 311 men who were starting or responding to first-line hormone therapy for bone metastases were randomly assigned to receive oral sodium clodronate (2080 mg/day) or placebo for a maximum of 3 years. The primary endpoint of the trial was symptomatic BPFS. Secondary endpoints included overall survival, treatment toxicity, and change in World Health Organization (WHO) performance status. Time-to-event data were analyzed using the log-rank chi-square test and Kaplan-Meier curves. All statistical tests were two-sided., Results: Baseline characteristics were balanced across the two groups. After a median follow-up of 59 months, the sodium clodronate group showed statistically nonsignificant better symptomatic BPFS (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.61 to 1.02; P =.066) and overall survival (HR = 0.80, 95% CI = 0.62 to 1.03; P =.082) than the control group. Patients in the clodronate group were less likely to have a worsened WHO performance status (HR = 0.71, 95% CI = 0.56 to 0.92; P =.008). However, the clodronate group reported more gastrointestinal problems and increased lactate dehydrogenase levels and required more frequent modification of the trial drug dose (HR for any adverse event = 1.71, 95% CI = 1.21 to 2.41; P =.002). Results of subgroup analyses suggested that clodronate might be more effective the sooner after diagnosis of metastatic bone disease it is started., Conclusion: These results suggest that further studies of the effect of newer generation bisphosphonates on BPFS in men with metastatic prostate cancer are warranted.

Both NADH dehydrogenase (complex I) and aconitase are inactivated partially in vitro by superoxide (O2-.) and other oxidants that cause loss of iron from enzyme cubane (4Fe-4S) centers. We tested whether hypoxia-reoxygenation (H-R) by itself would decrease lung epithelial cell NADH dehydrogenase, aconitase, and succinate dehydrogenase (SDH) activities and whether transfection with adenoviral vectors expressing MnSOD (Ad.MnSOD) would inhibit oxidative enzyme inactivation and thus confirm a mechanism involving O2-. Human lung carcinoma cells with alveolar epithelial cell characteristics (A549 cells) were exposed to <1% O2-5% CO2 (hypoxia) for 24 h followed by air-5% CO2 for 24 h (reoxygenation). NADH dehydrogenase activity was assayed in submitochondrial particles; aconitase and SDH activities were measured in cell lysates. H-R significantly decreased NADH dehydrogenase, aconitase, and SDH activities. Ad.MnSOD increased mitochondrial MnSOD substantially and prevented the inhibitory effects of H-R on enzyme activities. Addition of alpha-ketoglutarate plus aspartate, but not succinate, to medium prevented cytotoxicity due to 2,3-dimethoxy-1,4-naphthoquinone. After hypoxia, cells displayed significantly increased dihydrorhodamine fluorescence, indicating increased mitochondrial oxidant production. Inhibition of NADH dehydrogenase, aconitase, and SDH activities during reoxygenation are due to excess O2-. produced in mitochondria, because enzyme inactivation can be prevented by overexpression of MnSOD.

Isolated iliac artery aneurysms are rare but dangerous aneurysms associated with a high incidence of rupture (between 14 and 70%). Rupture is frequently associated with an exceedingly high mortality primarily because of the elusive nature of the presenting symptoms and the resulting major delays in treatment. Accordingly these aneurysms are best managed aggressively. Although emerging endovascular techniques show promise surgical resection and reconstruction remains the gold standard for definitive management and has withstood the test of time with excellent durable and unparalleled results. That said, from an operative perspective these aneurysms are technically demanding and remain one of the more formidable technical challenges in vascular surgery. To highlight the key elements involved in a successful repair we present a right internal iliac artery aneurysm with an associated contralateral common iliac artery occlusion, review the necessary preoperative planning and the available surgical treatment options, and detail the technical steps leading to a successful reconstruction. Careful operative planning is critical. Inadequate preoperative studies, inadequate preoperative decision making, and a poorly formulated operative strategy can lead to catastrophic results. Some of the most feared complications include pelvic venous injury with resulting massive hemorrhage and postoperative pelvic ischemia (with resulting rectal and/or spinal cord ischemia) which occurs as a result of inadequate contralateral collateral pelvic blood flow when the internal iliac artery is not reimplanted. Accordingly the preoperative workup must include a careful analysis of the adequacy of the contralateral pelvic blood flow to supply collateral flow in the event that the internal iliac is not reimplanted. In the presence of compromised contralateral internal iliac perfusion, resection and reconstruction or an alternative form of pelvic revascularization is mandatory. Excellent and unencumbered exposure is mandatory for a safe and successful repair. The retroperitoneal approach as illustrated in this case is strongly recommended. Although it is challenging excellent results can be achieved by resection of the aneurysm and reconstruction.

Popliteal vascular trauma has historically been an urban phenomenon. We hypothesized that rural popliteal artery injury would result more often from blunt mechanisms of injury (MOI), have a longer time to operation, and result in a higher amputation rate. We retrospectively reviewed all cases of popliteal artery injury from December 1994 to May 2001 at our rural trauma center. Age, gender, Injury Severity Score (ISS), MOI, scene transport versus transfer from a referring hospital, time to operation, and operative times were studied. Significance was determined by Student's t test with a P value < or = 0.05. Thirty-two popliteal artery injuries were found. Blunt trauma accounted for 50 per cent of the injuries. Eighty-eight per cent of the patients were transferred from a referring hospital. Patients transported directly from the scene had a higher ISS. Longer operative times translated into an increased need for fasciotomy. The amputation rate was 19 per cent. This is the first attempt to delineate the specific nature of rural popliteal artery trauma. The amputation rate was not different between the two different MOI and was independent of the time to operation. Of those patients receiving an amputation 83 per cent were transferred from another hospital and despite a statistically lower ISS still required an amputation.

Objective: To determine the role of total energy expenditure (TEE) and its components in the ability of collared lemmings to increase weight in response to a decrease in photoperiod., Research Methods and Procedures: Energy expenditure was measured by 24-hour indirect calorimetry concurrent with food-intake studies. TEE and resting and nonresting energy expenditure (REE and NREE, respectively) were adjusted for body weight by analysis of covariance (ANCOVA). Uncoupling protein 1 (Ucp1) mRNA levels from interscapular brown adipose tissue were determined by Northern blot., Results: TEE and REE of lemmings exposed to a short photoperiod for 10 days were significantly lower than that of lemmings exposed to a long photoperiod (p < 0.05), whereas NREE was not significantly different (p = 0.44). Ucp1 mRNA levels in interscapular brown adipose tissue were 50% lower in short- vs. long-photoperiod lemmings (p < 0.01). Ucp1 mRNA levels were positively related to REE (r2 = 0.79, p < 0.01). After adjustment of REE for differences in Ucp1 mRNA levels, there was no longer a significant difference attributable to photoperiod treatment (p = 0.54)., Discussion: The results of this study indicate that the increase in body mass that occurs when collared lemmings are exposed to a short photoperiod may be primarily fueled by a decrease in REE and is correlated with a decrease in Ucp1 mRNA levels.

Purpose: We report our experience with the holmium laser in the endoscopic management of primary obstructive megaureter (POM) in adults., Patients and Methods: From February 1997 to September 1998, three women and one man 26 to 63 years old underwent ureteroscopic endoureterotomy for POM with symptomatic vesicoureteral junction obstruction. The left ureter was more commonly affected than the right (R:L 1:3). The diagnosis of POM was based on a clinical history, intravenous urography, diuretic renography (T 1/2), and micturating cystogram. Endoureterotomy of the juxtavesical and intramural part of the ureter was performed in a retrograde fashion using the holmium laser. Incision of the subepithelial part of the ureter and the ureteral orifice was avoided. A pigtail stent was left in situ for 6 weeks. Postoperatively, patients were assessed at 3 months and yearly thereafter. The mean follow-up was 30.5 months., Results: All patients demonstrated symptomatic and radiologic improvement., Conclusions: Endoscopic incision of POM in adults with the holmium laser is safe, simple, and minimally invasive. This procedure should be considered as an initial approach for patients who have failed conservative treatment. However, further follow-up is necessary to determine its long-term efficacy.

Purpose: To review our initial experience with the holmium laser in patients with recurrent superficial bladder cancer., Patients and Methods: We treated 41 patients having 71 recurrent superficial transitional-cell tumors of the bladder between December 1994 and September 1997 using the holmium:YAG laser under local anesthesia. The laser treatment was carried out as a part of the follow-up flexible cystoscopy protocol, and topical anesthesia was used. The mean follow-up was 14 months (range 3-33 months)., Results: There were 13 recurrent tumors in the treated area and 38 recurrences in the untreated areas. Of interest, a subgroup of 10 patients were treated before 1994 with cystodiathermy and later on with the holmium:YAG laser at various times during their follow-up. The local recurrence rate with cystodiathermy was 32% compared with 10% after laser treatment (P = 0.39). A questionnaire study of 33 patients showed complete satisfaction with the treatment. Only 2 (6%) elected to have a further procedure under general anesthesia. In the series, 83% scored their pain as 2 or less of 10 on a visual analog scale., Conclusions: The absence of complications, high patient satisfaction, and ability to be used in the outpatient setting make the holmium:YAG laser an attractive alternative in the treatment of recurrent superficial cancer of the bladder.

Much of the multicultural counseling research has pointed out the need for counselors to become culturally competent to appropriately address the needs of an emerging diverse community. To date, however, this body of research has largely focused on counselor competencies, with little attention being given to the client perspective of multicultural counseling competencies. This article discusses the importance of integrating the client perspective within the historical context of the multicultural literature by examining client preferences and expectations, as well as the adequacy of the current empirical data. The authors also raise the issue of politics inherent in multiculturalism and discuss how this affects the research. A number of recommendations are made as a guide for future research.

Objective: Various modalities ranging from acucise balloon to endoincision with electrocautery, cold knife, and lasers have been used to treat ureteropelvic junction obstruction (UPJO). We assessed the intermediate effectiveness of endopyelotomy with the holmium(Ho):YAG laser., Patients and Methods: Between November 1994 and May 1998, 20 patients with 16 primary and 4 secondary symptomatic UPJO were treated. All patients were evaluated clinically and radiologically before and after the procedure at 3 months, and yearly thereafter. The mean follow-up was 34 months (12-38 months)., Results: A total of 22 procedure were performed on 20 patients with an average operating time of 44.3 min and mean hospital stay of 1.9 days. All patients were stented after the procedure for 6 weeks. Complication included urinoma (1) and guidewire fracture in 1 patient. 15 patients had a successful outcome determined by a diuretic renography and/or Whitaker test. Three patients with poor preoperative renal function (<25%) had an unsatisfactory outcome. There were 2 failures and they were treated with nephrectomy (1) and open pyeloplasty (1)., Conclusions: A controlled, precise, safe and almost 'bloodless' endopyelotomy can be performed with the holmium laser. Success rate tends to be poor in patients with poor renal function.

Aneurysms of the superior mesenteric artery (SMA) are rare, accounting for 5.5% of all splanchnic aneurysms and <0.5% of all intraabdominal aneurysms. Previous reports have characterized these aneurysms among splanchnic artery aneurysms. However, these aneurysms are quite different in terms of etiology, presentation, and treatment, and their independent consideration is warranted. We report a patient with a traumatic SMA aneurysms who was successfully treated with surgical resection and distal revascularization. We also present an alternative technique of retrograde aorto-SMA bypass using autologous vein that prevents kinking. Also included is a review of the recent literature as it pertains specifically to SMA aneurysms.

Autogenous reconstruction is one option available for patients with aortic graft infection or mycotic aneurysms. We reviewed our recent institutional experience with all patients undergoing aortic reconstruction using autologous superficial femoral vein (SFV). Between February 1995 and November 1997, eight patients (five with prosthetic aortic graft infection and three with mycotic aneurysms, including one ruptured mycotic aneurysm) underwent single-stage aortic reconstruction using autologous SFV. Therapy for graft infection included graft excision and replacement with aortobifemoral or aortofemoral (with subsequent cross femoral) grafts fashioned from the SFV. The two patients undergoing elective repair of mycotic aneurysms were treated with extensive SFV patches, and the patient with a ruptured mycotic aneurysm underwent SFV tube grafting. Autogenous reconstruction of the aorta using the SFV in infected fields shows promise for salvage of life and limb during early experiences and short-term follow-up. Morbidity and mortality rates compare favorably with those from existing series, reconstruction is anatomic, and reinfection potential is low. Long-term follow-up and more extensive experience with this technique are needed to establish its role relative to other conventional methods.

Endovascular aortic grafting represents a minimally invasive approach to aortic aneurysm repair. The technique requires a variety of new skills and extensive training. Telemedicine enhances mentoring and technical support for surgeons performing the technique.

Endovascular grafting represents a minimally invasive approach to prosthetic aortic grafting for abdominal aortic aneurysms (AAA). We reviewed our initial experience with a bifurcated endovascular graft that shares with conventional grafts the characteristics of discrete transaortic fixation and unitary unsupported woven polyester construction. Twenty-eight patients (26 male, 2 female; age: 58-93) with infrarenal aortic aneurysms between 41 and 82 mm in greatest diameter (x = 55.4 mm) underwent bifurcated endovascular grafting (Guidant/EVT, Menlo Park, CA) over an 18-month period. We concluded that bifurcated endovascular grafting with the EVT(R) device provides reliable and reproducible aneurysm exclusion with short hospital recovery and low morbidity.

Nephroblastoma is an infantile neoplasia with a low incidence in adults. A case of Wilms' tumour in a 76-year-old male is reported. In a literature review the current status of knowledge in the geriatric population is discussed.

Purpose: Transurethral incision of the prostate is a well established technique for relieving bladder outflow obstruction caused by prostate glands less than 30 gm. We present data showing that the holmium:YAG laser can prevent postoperative catheterization without compromising the outcome of surgery., Materials and Methods: We prospectively followed 100 men an average of 62 years old with symptomatic bladder outflow obstruction and a benign prostate gland less than 30 gm. clinically in whom serum prostate specific antigen was less than 4 microg./l. They were assessed using International Prostate Symptom Score, urinary flow rate, post-void residual estimation and sexual function questionnaires preoperatively, and 6 weeks, and 1 and 2 years postoperatively. With the patient under general anesthesia a single incision was made from the ureteral orifice to the verumontanum and out to fat using holmium:YAG laser energy transmitted through a 400 nm. fiber sheathed in a ureteral catheter., Results: A total of 97 patients voided without postoperative catheterization. Average International Prostate Symptom Score decreased from 19.2 to 3.7 at 6 weeks and it remained improved at 2 years (average 3.5). Reciprocal results were achieved with improvement in average urinary flow rate from 9.79 to 19.23 and 18.27 ml. per second at 6 weeks and 2 years, respectively. Residual urine measurement decreased from 133.6 ml. preoperatively to 27 and 10 ml. at 6 weeks and 2 years, respectively. All 77 patients potent preoperatively remained so, although retrograde ejaculation developed in 8., Conclusions: The holmium:YAG laser allows transurethral prostatic incision to be performed without the need for postoperative catheterization while maintaining efficacy.

The clinic benefits of the Holmium: YAG laser include a pronounced haemostatic effect, fibreoptic delivery system and a wide range of power-setting options. We review our initial experience in treating 48 patients with ureteric stones. Stones were located in the upper, middle and lower ureter in 27%, 21% and 52% of patients respectively. The Holmium laser successfully fragmented all calculi and there were no major complications. We have found the Holmium laser to be a safe, effective and reliable alternative for the management of urolithiasis.

A guidewire fracture is a rare complication of laser surgery. We report that this rare complication occurred during a retrograde endoureteropyelotomy with the holmium:YAG laser. No data are available about the safety of commonly used guidewires. A comparative in vitro study was performed with two types of guidewires to assess their resistance. At all energy levels tested, a Teflon-coated guidewire performed best in the present safety test.