Search PubMed⌕ Search

Biomedical subjects

David J Cohen

Publications and source records attributed to David J Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2006

Association between thrombolysis in myocardial infarction myocardial perfusion grade, biomarkers, and clinical outcomes among patients with moderate- to high-risk acute coronary syndromes: observations from the randomized trial to evaluate the relative PROTECTion against post-PCI microvascular dysfunction and post-PCI ischemia among antiplatelet and antithrombotic agents-Thrombolysis In Myocardial Infarction 30 (PROTECT-TIMI 30).

BACKGROUND: A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs). METHODS: We hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI frame count would be associated with biomarker release, ischemia on Holter monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of patients with non-ST-elevation ACS undergoing percutaneous coronary intervention (PCI). RESULTS: The pre-PCI TMPG was correlated with the baseline as well as peak levels of troponin I (P < .001) and creatine kinase-MB (P < .001) and the post-PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by 48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs 7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after PCI on Holter monitoring trended longer among patients with an abnormal post-PCI TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post-PCI TMPG was the strongest correlate of death, myocardial infarction, or an ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as assessed angiographically using the TIMI frame count was not associated with the baseline, peak, or absolute rise of any biomarker, Holter findings, or clinical events. CONCLUSIONS: An abnormal TMPG, but not an angiographic CFR, is associated with biomarker status, the occurrence and duration of Holter ischemia, and adverse clinical outcomes among patients with moderate- to high-risk non-ST-elevation ACS undergoing PCI.

Acute Disease↗
PubMed2006

Influence of age, sex, and atrial fibrillation recurrence on quality of life outcomes in a population of patients with new-onset atrial fibrillation: the Fibrillation Registry Assessing Costs, Therapies, Adverse events and Lifestyle (FRACTAL) study.

BACKGROUND: Most quality of life (QoL) data in AF have been collected from clinical trial patients. We sought to characterize symptoms and QoL in a large inception cohort of unselected patients with AF and explore the impact of age, sex, and AF clinical course on QoL measures over time. METHODS: We collected symptom and QoL data on 963 patients with new onset AF enrolled in a multicenter observational registry. Patients were primarily managed with pharmacologic therapy and cardioversion. Quality of life instruments including the Medical Outcomes Study Short Form-12, University of Toronto AF Severity Scale, and the AF Symptom Checklist were completed at baseline and repeated over 2.5 years. Time-weighted QoL summary scores over the first year were calculated for each patient. Factors associated with those summary scores were explored in multivariable analyses. RESULTS: Quality of life was moderately impaired at baseline, but quickly approached population norms and remained stable thereafter. After multivariable adjustment, female sex was strongly associated with higher symptom scores and lower QoL scores. Older (age >65 years) patients reported less prominent disease-specific impairment in QoL than younger patients. In part because 73% of patients appeared to maintain sinus rhythm for the first year, AF clinical course had a comparatively small impact on QoL during this timeframe. CONCLUSIONS: Quality of life is impaired in newly diagnosed patients with AF, but improves to normal levels with standard treatments. Within the first year after diagnosis, sex, age, and comorbid conditions are more strongly associated with QoL outcomes than the clinical course of AF itself.

Age Factors↗
PubMed2006

Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure.

In the southern and southeastern United States, the 9-banded armadillo is an important reservoir for Mycobacterium leprae, the causative agent of leprosy (Hansen's disease). Here, we describe a woman living in Georgia with borderline tuberculoid leprosy who worked for many years in a garden where armadillos burrowed or were buried. There was no history of foreign travel or known exposure to a person with leprosy. Treatment with 6 once-monthly combined doses of rifampin, ofloxacin, and minocycline was successful.

Animals↗
PubMed2006

Protected carotid stenting in high-surgical-risk patients: the ARCHeR results.

BACKGROUND: Carotid endarterectomy is the standard of care for most patients with severe extracranial carotid bifurcation disease. However, its safety and efficacy in patients with significant surgical risk are unclear. The ARCHeR (ACCULINK for Revascularization of Carotids in High-Risk patients) trial was performed to determine whether carotid artery stenting with embolic protection is a safe and effective alternative to endarterectomy in high-surgical-risk patients. METHODS: The ARCHeR trial is a series of three sequential, multicenter, nonrandomized, prospective studies. Forty-eight sites enrolled 581 high-surgical-risk patients between May 2000 and September 2003. Patients with severe carotid artery stenosis (angiographically defined, symptomatic > or =50%, or asymptomatic > or =80%) had an ACCULINK nitinol stent implanted. The ACCUNET filter embolic protection system was added to the procedure in the final 2 studies (422 patients). The primary efficacy end point was a composite of periprocedural (< or =30 days) death, stroke, and myocardial infarction, plus ipsilateral stroke between days 31 and 365. RESULTS: The 30-day rate of death/stroke/myocardial infarction was 8.3% (95% confidence interval [CI], 6.2%-10.8%), and that of stroke/death was 6.9% (95% CI, 5.0%-9.3%). Most (23/32) strokes were minor, of which more than half (12/23) returned to baseline National Institutes of Health Stroke Scale scores within 30 days. The 30-day major/fatal stroke rate was 1.5% (95% CI, 0.7%-2.9%). No hemorrhagic strokes were observed in the study. Ipsilateral cerebrovascular accident occurred in 1.3% between 30 days and 1 year, thus giving a primary composite end point of 30-day death/stroke/myocardial infarction plus ipsilateral stroke at 1 year of 9.6% (95% CI, 7.2%-12.0%), which is below the 14.4% historical control comparator. Target lesion revascularization at 12 months and 2 years was 2.2% and 2.9%, respectively. CONCLUSIONS: The ARCHeR results demonstrate that extracranial carotid artery stenting with embolic filter protection is not inferior to historical results of endarterectomy and suggest that carotid artery stenting is a safe, durable, and effective alternative in high-surgical-risk patients.

Angioplasty, Balloon↗
PubMed2006

Drug-eluting stents for ST[corrected]-elevation acute myocardial infarction: do we need randomized trials?

Since their introduction, drug-eluting stents have rapidly altered modern medicine's approach to coronary artery disease. Before the development of drug-eluting stents, standard bare-metal stents were plagued by in-stent restenosis, requiring repeat revascularization in as many as 15-20% of patients during the first 6-12 months following implantation [1]. The currently approved drug-eluting stents have dramatically reduced this complication by using a polymer-impregnated coating that elutes either paclitaxel or sirolimus to inhibit smooth muscle proliferation. The pivotal TAXUS-IV [2] and SIRIUS [3] trials compared drug-eluting stents with standard bare-metal stents and found rates of target vessel revascularization ranging from 3 to 4.1% in stable coronary artery disease patients - far lower than that had been seen previously with conventional standard bare-metal stents. After their approval in April 2003, drug-eluting stents use in clinical practice expanded rapidly. Within 9 months of their introduction, drug-eluting stents comprised 35% of all stent implantations in the United States [4]. In the last year at our own institution, drug-eluting stents comprised over 85% of all stents implanted. Despite their extensive use, data regarding the efficacy and safety of drug-eluting stents in certain clinical scenarios are limited. To date, the only published data supporting drug-eluting stents in ST[corrected]-elevation acute myocardial infarction come from the retrospective Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital registry [5] and the randomized, controlled single high-dose bolus tirofiban and sirolimus-eluting stent vs. abciximab and bare-metal stent in myocardial infarction study [6]. In this chapter, we discuss the theoretical risks and benefits of drug-eluting stents for ST elevation acute myocardial infarction, the available data regarding their use, and the areas in which future studies are needed.

Coated Materials, Biocompatible↗
PubMed2006

Newer pharmacotherapy in patients undergoing percutaneous coronary interventions: a guide for pharmacists and other health care professionals.

Significant advances in pharmacotherapy for patients undergoing percutaneous coronary intervention (PCI) have occurred during the past decade, including the introduction and approval of new antithrombin and antiplatelet therapies, as well as modifications in dosing, administration, and/or duration of older pharmacotherapy regimens. Also, off-label (i.e., not approved by the United States Food and Drug Administration) use of certain agents has become common. Given the novel nature of these agents and the nuances of therapy, the pharmacist and other health care professionals should play an integral role in collaboration with interventional cardiologists in development of hospital protocols, determination of appropriate agent selection, assessment of patient renal function and hematologic status, dosing, and monitoring for adverse effects. In this guide, the newer antiplatelet and antithrombin drugs that may be used during PCI are reviewed, and recommendations regarding the proper administration of these agents are provided.

Angioplasty, Balloon, Coronary↗
PubMed2006

Cost effectiveness of the sirolimus-eluting stent in high-risk patients in Canada: an analysis from the C-SIRIUS trial.

BACKGROUND: The cost effectiveness of drug-eluting stents in Canada is debated and deserves further evaluation in high-risk patients. METHODS: We performed an economic analysis from the third-party payer perspective based on the clinical results and resource-utilization data of the C-SIRIUS (The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients with Long De Novo Lesions in Small Native Coronary Arteries) trial, which examined the safety and efficacy of sirolimus-eluting stents (SES) versus bare metal stents (BMS) in high-risk patients with single long de novo lesions in small coronary arteries. Only inpatient costs were considered, including physician fees. We postulated that the incremental cost required to avoid a repeat revascularization (RR) procedure with BMS versus simple balloon angioplasty (BA) could be considered the willingness to pay (WTP) to avoid restenosis in Canada. We assessed the incremental cost-effectiveness ratio (ICER) of SES compared with BMS in these high-risk patients compared with WTP. Results are expressed in 2003 Canadian dollars. RESULTS: With a 7% absolute reduction in the need for RR compared with BA, BMS are associated on average with an ICER of US dollars 12,551/RR avoided (RRA) in Canada. In C-SIRIUS, SES further reduced the need for RR at 1 year from 22% to 4% (p = 0.015) compared with BMS. With a 1.5 stent-to-lesion (STL) ratio and an SES retail price of US dollars 2,700 compared with US dollars 700 for BMS, the ICER of SES versus BMS was US dollars 11,275/RRA -- borderline cost effective compared with the implicit WTP of US dollars 12,551 for such health benefit in Canada. Using a lower STL ratio (1.2) would improve the ICER to US dollars 7941/RRA. CONCLUSIONS: Treatment of long lesions in small vessels with SES increases net healthcare costs. However, the ICER for SES compares favorably with the currently accepted comparator, i.e. BMS, to reduce coronary restenosis -- at least for higher risk patients undergoing single-vessel revascularization.

Adult↗
PubMed2006

Economic implications of bivalirudin in the cardiac catheterization laboratory.

More than 1.2 million percutaneous coronary intervention (PCI) procedures are performed each year in the United States, with average hospital costs of more than $10,000 per procedure. Despite ongoing improvements in device technology and adjunct pharmacology, both ischemic complications (eg, periprocedural myocardial infarction) and bleeding complications remain relatively common and are associated with both increased costs (in the short term) and mortality (in the longer term). Recently, the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 clinical trial demonstrated that the use of the direct thrombin inhibitor, bivalirudin, with provisional glycoprotein (GP) IIb/IIIa inhibitor for selected patients in place of a conventional anticoagulation strategy of heparin and routine use of a GP IIb/IIIa inhibitor, resulted in comparable rates of ischemic complications and a significant reduction in the frequency of both major and minor bleeding complications. A prospectively designed economic analysis was performed using data from 4651 US patients who participated in REPLACE-2. In this analysis, patients who were assigned to the bivalirudin and provisional GP IIb/IIIa inhibitor strategy had anticoagulation costs during PCI that were approximately $400 per patient lower than those with heparin plus routine GP IIb/IIIa inhibition. Bivalirudin also produced corresponding decreases in total in-hospital costs and aggregate 30-day medical care costs. These cost savings derived both from the lower acquisition cost of the antithrombotic therapy and the reduced rate of bleeding complications, which accounted for approximately 20% of the cost offsets. These results suggest that for patients similar to those studied in REPLACE-2 (ie, low to moderate risk PCI procedures), use of bivalirudin and provisional GP IIb/IIIa inhibition compared with heparin and routine GP IIb/IIIa inhibition can result in similar rates of ischemic complications, reduced bleeding, and substantial cost savings to both hospitals and the healthcare system. Whether these benefits can be extended to higher risk patient subsets including patients with non-ST elevation or ST elevation myocardial infarction is currently under investigation.

Angioplasty, Balloon, Coronary↗
PubMed2005

Standards for statistical models used for public reporting of health outcomes: an American Heart Association Scientific Statement from the Quality of Care and Outcomes Research Interdisciplinary Writing Group: cosponsored by the Council on Epidemiology and Prevention and the Stroke Council. Endorsed by the American College of Cardiology Foundation.

With the proliferation of efforts to report publicly the outcomes of healthcare providers and institutions, there is a growing need to define standards for the methods that are being employed. An interdisciplinary writing group identified 7 preferred attributes of statistical models used for publicly reported outcomes. These attributes include (1) clear and explicit definition of an appropriate patient sample, (2) clinical coherence of model variables, (3) sufficiently high-quality and timely data, (4) designation of an appropriate reference time before which covariates are derived and after which outcomes are measured, (5) use of an appropriate outcome and a standardized period of outcome assessment, (6) application of an analytical approach that takes into account the multilevel organization of data, and (7) disclosure of the methods used to compare outcomes, including disclosure of performance of risk-adjustment methodology in derivation and validation samples.

American Heart Association↗
PubMed2005

Cost-effectiveness analysis of hypertension guidelines in South Africa: absolute risk versus blood pressure level.

BACKGROUND: Hypertension is responsible for more deaths worldwide than any other cardiovascular risk factor. Guidelines based on blood pressure level for initiation of treatment of hypertension may be too costly compared with an approach based on absolute cardiovascular disease (CVD) risk, especially in developing countries. METHODS AND RESULTS: Using a Markov CVD model, we compared 6 strategies for initiation of drug treatment--2 different blood pressure levels (160/95 and 140/90 mm Hg) and 4 different levels of absolute CVD risk over 10 years (40%, 30%, 20%, and 15%)--with one of no treatment. We modeled a hypothetical cohort of all adults without CVD in South Africa, a multiethnic developing country, over 10 years. The incremental cost-effectiveness ratios for treating those with 10-year absolute risk for CVD >40%, 30%, 20%, and 15% were 700 dollars, 1600 dollars, 4900 dollars, and 11,000 dollars per quality-adjusted life-year gained, respectively. Strategies based on a target blood pressure level were both more expensive and less effective than treatment decisions based on the strategy that used absolute CVD risk of >15%. Sensitivity analysis of cost of treatments, prevalence estimates of risk factors, and benefits expected from treatment did not change the ranking of the strategies. CONCLUSIONS: In South Africa, current guidelines based on blood pressure levels are both more expensive and less effective than guidelines based on absolute risk of cardiovascular disease. The use of quantitative risk-based guidelines for treatment of hypertension could free up major resources for other pressing needs, especially in developing countries.

Adult↗
PubMed2005

Treatment of recalcitrant atopic dermatitis with omalizumab.

Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.

Antibodies, Anti-Idiotypic↗
PubMed2005

Excessive weight gain in cardiac transplant recipients.

BACKGROUND: Substantial weight gain frequently occurs after cardiac transplant (CT) and increases the risk of secondary disease. It is unclear, however, if weight gain after CT is related to glucocorticoid immunosuppressive therapy. METHODS: A retrospective chart review was performed on the first 200 patients undergoing CT and the first 200 patients undergoing renal transplant (RT) at Columbia Presbyterian Medical Center, starting in January 2000. Patients who survived 1 year and had their weight recorded at transplant were included in the study. Rejection episodes and prednisone treatment was recorded for CT patients. Regression analysis was used to determine predictors of weight gain. RESULTS: A total of 158 CT patients and 128 RT patients were included in the data analysis. The weight of CT patients at time of transplant was (mean +/- SD) 76.3 +/- 14.6 kg and increased by 10.3 +/- 10.6 kg (p < 0.05) by 1-year post-transplant. Pre-transplant weight of the RT patients was 74.1 +/- 20.1 kg; by 1-year post-RT, weight increased by 3.5 +/- 8.6 kg (p < 0.05). The weight gain in CT patients was significantly greater than in the RT patients (p < 0.001). Post-transplant weight change in multiple regression models was related to age, gender (male) and transplant type (cardiac), but not to prednisone dose or pre-transplant weight. CONCLUSIONS: CT results in substantial post-surgical weight gain, which is greater than that observed for RT. Overweight and obesity development was not related to prednisone dose alone. This observation may have important clinical and research implications.

Adult↗
PubMed2005

Optimal timing of intervention in non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Registry.

BACKGROUND: Recent studies indicate that a routine invasive approach for patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) yields improved outcomes compared with a conservative approach, but the optimal timing of this approach remains open to debate. METHODS AND RESULTS: We used day of hospital presentation as an instrumental variable to study the impact of timing of cardiac catheterization and revascularization therapy on acute outcomes (death, reinfarction, stroke, cardiogenic shock, or congestive heart failure) among patients with UA and NSTEMI. Between January 2001 and September 2003, 56,352 patients with UA or NSTEMI were treated at 310 US hospitals participating in the CRUSADE national quality improvement initiative. Weekend patients were defined as those who presented to the hospital between 5 PM on Friday and 7 AM on Sunday. All other patients were classified as weekday. Weekday patients were similar to weekend patients in terms of demographics, clinical characteristics, and the use of medical therapies in the first 24 hours. Although overall rates of cardiac catheterization and revascularization were similar for the 2 groups, median time to catheterization was significantly longer for weekend than for weekday patients (46.3 versus 23.4 hours, P<0.0001). This delay was not associated with increased in-hospital adverse events, including death (weekend 4.4% versus weekday 4.1%, P=0.23), recurrent MI (2.9% versus 3.0%, P=0.36), or their combination (6.6% versus 6.6%, P=0.86). These findings were not affected by risk adjustment or use of alternative definitions of weekend versus weekday presentation. When weekend presentation was used as the basis for an instrumental variable analysis, we found that catheterization within the first 12 hours of presentation was associated with a nonsignificant trend toward reduced in-hospital mortality (absolute risk reduction 1.9%; 95% CI 6.7% lower to 2.9% higher; P=0.43) that decreased with longer treatment delays. CONCLUSIONS: Although weekend presentation is associated with a delay in invasive management among patients with UA and NSTEMI, in the context of contemporary medical therapy, this does not increase adverse events. Weekend presentation appears to fulfill accepted criteria as an instrumental variable for studying the optimal timing of invasive management for acute coronary syndrome patients. Using weekend status as an instrumental variable, we found no significant benefit to early catheterization, although we could not exclude an important risk reduction, particularly for catheterization within 12 hours of presentation.

Aged↗
PubMed2005

A blinded, randomized, placebo-controlled trial of percutaneous laser myocardial revascularization to improve angina symptoms in patients with severe coronary disease.

OBJECTIVES: This study was a randomized, patient- and evaluator-blinded, placebo-controlled trial in patients treated using percutaneous myocardial laser revascularization. BACKGROUND: Previous studies using similar therapies have been confounded by placebo bias. METHODS: A total of 298 patients with severe angina were randomly assigned to receive low-dose or high-dose myocardial laser channels or no laser channels, blinded as a sham procedure. The primary end point was the change in exercise duration from baseline examination to six months. RESULTS: The incidence of 30-day death, stroke, myocardial infarction, coronary revascularization, or left ventricular perforation occurred in two patients in the placebo, eight patients in the low-dose, and four patients in the high-dose groups (p = 0.12); 30-day myocardial infarction incidence was higher in patients receiving either low-dose or high-dose laser (nine patients) compared with placebo (no patients, p = 0.03). At six months, there were no differences in the change in exercise duration between those receiving a sham (28.0 s, n = 100), low-dose laser (33.2 s, n = 98), or high-dose laser (28.0 s, n = 98, p = 0.94) procedure. There were also no differences in the proportion of patients improving to better than Canadian Cardiovascular Society class III angina symptoms at six months. The follow-up visual summed stress single-photon-emission computed tomography scores were not significantly different from baseline in any group and were no different between groups. The modest improvement in angina symptoms assessed by the Seattle Angina Questionnaire also was not statistically different among the arms. CONCLUSIONS: Treatment with percutaneous myocardial laser revascularization provides no benefit beyond that of a similar sham procedure in patients blinded to their treatment status.

Angina Pectoris↗
PubMed2005

Frequency, predictors, and outcomes of drug-eluting stent utilization in patients with high-risk non-ST-segment elevation acute coronary syndromes.

Despite the established benefit of drug-eluting stents (DESs) in improving clinical and angiographic outcomes in pivotal, randomized trials, relatively little is known regarding the frequency and patterns of DES use in clinical practice. To characterize DES use in a broad, unselected high-risk non-ST-segment elevation acute coronary syndrome population, we evaluated the frequency, patterns, and predictors of DES use among patients in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Quality Improvement Initiative who were selected to undergo percutaneous coronary intervention. Of 8,852 patients with high-risk non-ST-segment elevation acute coronary syndromes who underwent percutaneous revascularization at 262 hospitals between October 2003 and June 2004, 5,858 (66.2%) were treated with DESs and 2,994 (33.8%) were not. During a 9-month period, DES use increased considerably from 52.6% of cases in October 2003 to 78.5% in June 2004. Compared with the bare metal stent cohort, patients receiving DESs were more likely to be women and to have private insurance, but were less likely to present with positive cardiac markers or ST-segment depression. In adjusted analysis, death and recurrent infarction were significantly lower among the patients with a DES, yet early revascularization and treatment with guideline-recommended therapies were less frequent. In a multivariate model, significant (p <0.05) predictors of DES use included hyperlipidemia, elevated systolic blood pressure, private insurance, and treatment at a larger hospital. In conclusion, these findings not only identified differences in the selection and treatment of patients receiving bare metal stents versus DESs, but also demonstrated the increasing use of DESs in higher risk patients who have previously been excluded from randomized, pivotal trials.

Acute Disease↗
PubMed2005

Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutaneous coronary intervention (a subanalysis of the REPLACE-2 trial).

Among patients who undergo percutaneous coronary intervention, renal impairment is associated with an excessive risk of bleeding and ischemic events. Bivalirudin provides comparable suppression of ischemic events with a decrease in bleeding events compared with heparin and glycoprotein IIb/IIIa inhibition. We examined the relation between adverse events, renal impairment, and antithrombotic therapy within a randomized comparison. The Second Randomized Evaluation in PCI Linking Bivalirudin to Reduced Clinical Events per-protocol study population was assessed. Renal function was defined as calculated creatinine clearance <60 ml/min. Events within the overall study population and within each study arm were assessed. Thirty-day events by renal function were compared by chi-square test and logistic regression. Late mortality was compared by log-rank test. Interaction analyses were performed. Among 5,710 patients, renal impairment was associated with increased ischemic events (hazard ratio 1.45, 95% confidence interval 1.13 to 1.88, p = 0.004), bleeding complications (hazard ratio 1.72, 95% confidence interval 1.06 to 2.80, p = 0.028), and excessive 12-month mortality (hazard ratio 3.85, 95% confidence interval 2.67 to 5.54, p <0.001). Bivalirudin provided suppression of ischemic events that was comparable to heparin and glycoprotein IIb/IIIa inhibition regardless of renal impairment. Fewer bleeding events with bivalirudin were also evident irrespective of renal dysfunction. No interaction between treatment assignment, bleeding or ischemic complications, and renal impairment was observed. The safety and efficacy of bivalirudin compared with heparin and planned glycoprotein IIb/IIIa inhibition in this high-risk group are comparable and consistent with the results of the overall trial.

Abciximab↗
PubMed2005

Acute and hyperacute humoral rejection in kidney allograft recipients treated with anti-human thymocyte antibodies.

Equine and rabbit antihuman thymocyte globulins (ATGs) have been used in renal transplantation for prevention and treatment of acute rejection. We now report that hyperacute and acute antibody-mediated rejection of renal allografts occurred in three newly transplanted patients who received ATG for induction therapy. Antibody studies performed using complement-dependent cytotoxicity, flow cytometry, enzyme-linked immunosorbent assay, and Luminex yielded negative results for antilymphocytic and antiendothelial cell antibodies in the pretransplant sera obtained from these patients. ATG treatment was initiated at the time of transplantation. One of the patients experienced hyperacute rejection and required transplant nephrectomy within 24 h of transplantation. The other two patients developed acute antibody-mediated rejection within 14 days after transplantation. None of the patients developed antihuman leukocyte antigen antibodies when humoral rejection occurred. However, xenoantibodies that strongly bound to human lymphocytes and, importantly, to activated endothelial cells, were identified in the sera obtained at the time of humoral rejection. Hence, our results strongly implicate ATG in the induction of antibody-mediated rejection of kidney allografts. Flow cytometry testing of ATG reactivity to endothelial cells may be useful in identifying and discarding the ATG lots containing xenoantibodies that can bind to activated endothelial cells of the transplant.

Adolescent↗