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Hemorrhagic complications have been reported after repeated exposures to bovine thrombin products due to development of factor V inhibitors. Our patient underwent emergency repair of acute aortic dissection and coronary artery bypass grafting. The patient developed leg wound infection at the saphenous vein harvest site, which was debrided and left open. Attempt to reclose the leg wound 1 month later was complicated by a life-threatening hemorrhage with markedly elevated activated partial thromboplastin time. There was no evidence of infection or disseminated intravascular coagulation, and further study identified low factor V level with positive factor V inhibitor. Treatment with plasmapheresis and steroid successfully reversed the coagulopathy. Detailed case review failed to reveal exposure to any thrombin products other than the one used for the aortic dissection repair. This case was unusual because only a single exposure to this product resulted in severe hemorrhagic complication 1 month after surgery.

OBJECTIVES This study compared survival after percutaneous coronary intervention (PCI) with survival after coronary artery bypass graft surgery (CABG) among diabetics in the Veterans Affairs AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) study randomized trial and registry of high-risk patients. BACKGROUND Previous studies indicate that CABG may be superior to PCI for diabetics, but no comparisons have been made for diabetics at high risk for surgery. METHODS Over five years (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior CABG, myocardial infarction within seven days, left ventricular ejection fraction 70 years, or an intra-aortic balloon being required to stabilize) were identified. A total of 781 were acceptable for CABG and PCI, and 454 consented to be randomized. The 1,650 patients not acceptable for both CABG and PCI constitute the physician-directed registry, and the 327 who were acceptable but refused to be randomized constitute the patient-choice registry. Diabetes prevalence was 32% (144) among randomized patients, 27% (89) in the patient-choice registry, and 32% (525) in the physician-directed registry. The CABG and PCI survival rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS The respective CABG and PCI 36-month survival rates for diabetic patients were 72% and 81% for randomized patients, 85% and 89% for patient-choice registry patients, and 73% and 71% for the physician-directed registry patients. None of the differences was statistically significant. CONCLUSIONS We conclude that PCI is a relatively safe alternative to CABG for diabetic patients with medically refractory unstable angina who are at high risk for CABG.

OBJECTIVES This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction 70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients.

BACKGROUNDPercutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups.OBJECTIVESThis five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents.METHODSPatients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction

Patients with documented history of heparin-induced thrombocytopenia (HIT) pose a difficult problem during surgery using cardiopulmonary bypass (CPB). Several alternatives to heparin exist, but these products either are not approved for use in the United States or have more side effects than heparin. We report on a patient with documented heparin-induced antibody and left main coronary artery disease who underwent uneventful coronary artery bypass surgery and recovery by using preoperative plasmaphresis and limited use of porcine intestinal heparin during CPB.

We reviewed our experience with second primary lung cancer (SPLC) at the Little Rock Veterans Affairs Medical Center from 1966 to 1993. Fifty-four patients were found to have 65 such lesions after 1,572 "curative" resections for lung cancer (4.1%). Eleven patients had at least a third primary tumor (3 having more). Metachronous SPLCs comprised 60% (39/65) and synchronous 40% (26/65). The mean interval between first and second tumors was 54.63 +/- 8 (standard error) months (range, 5 to 218 months), and that between second and third was 26.1 +/- 7.4 (standard error) (range, 5.5 to 51 months). Squamous cell carcinoma comprised 58.4% (38/65), adenocarcinoma 30.8% (20/65), and small cell carcinoma 10.8% (7/65). Histology of the SPLC was the same as that of the first tumor in 50.7% (33/65). Stage I primary tumors comprised 76% (41/54) of index tumors, 61.1% (33/54) of SPLCs, and 72.2% (8/11) of third primary tumors. Second primary lung cancer followed minimal resection in 44% (24/54), lobectomy in 37% (20/54), and pneumonectomy in 13% (7/54) of cases. There was no evidence that minimal resection for the first primary tumor predisposed to SPLC. After 1983 the majority of SPLCs were diagnosed with computed tomographic scanning. After resection of SPLCs, survival rates at 3 and 5 years were 26% and 18%, metachronous 39% and 23.4%, and synchronous 12.25% and 12.25%.

A recently identified lectin-like oxidized low-density lipoprotein receptor (LOX-1) mediates endothelial cell injury and facilitates inflammatory cell adhesion. We studied the role of LOX-1 in myocardial ischemia-reperfusion (I/R) injury. Anesthetized Sprague-Dawley rats were subjected to 60 min of left coronary artery (LCA) ligation, followed by 60 min of reperfusion. Rats were treated with saline, LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat IgG (10 mg/kg) before I/R. Ten other rats underwent surgery without LCA ligation and served as a sham control group. LOX-1 expression was markedly increased during I/R ( P < 0.01 vs. sham control group). Simultaneously, the expression of matrix metalloproteinase-1 (MMP-1) and adhesion molecules (P-selectin, VCAM-1, and ICAM-1) was also increased in the I/R area ( P < 0.01 vs. sham control group). There was intense leukocyte accumulation in the I/R area in the saline-treated group. Treatment of rats with the LOX-1 antibody prevented I/R-induced upregulation of LOX-1 and reduced MMP-1 and adhesion molecule expression as well as leukocyte recruitment. LOX-1 antibody, but not nonspecific IgG, also reduced myocardial infarct size ( P < 0.01 vs. saline-treated I/R group). To explore the link between LOX-1 and adhesion molecule expression, we measured expression of oxidative stress-sensitive p38 mitogen-activated protein kinase (p38 MAPK). The activity of p38 MAPK was increased during I/R ( P < 0.01 vs. sham control), and use of LOX-1 antibody inhibited p38 MAPK activation ( P < 0.01). These findings indicate that myocardial I/R upregulates LOX-1 expression, which through p38 MAPK activation increases the expression of MMP-1 and adhesion molecules. Inhibition of LOX-1 exerts an important protective effect against myocardial I/R injury.

Background Intractable hemorrhage is a dreaded complication after cardiovascular surgery often requiring re-exploration and the administration of large quantities of blood products. In view of problems with aprotinin, a new safer effective agent is needed. Recombinant activated FVII is approved for use in patients with hemophilia A and B who have inhibitors to factors VIII and IX, and has shown promise in off-label use for the management of life-threatening hemorrhage in several clinical scenarios including cardiac surgery. It may help control bleeding, reduce blood product usage, and avoid potential morbidity. Its exact place in the management of bleeding during and after cardiac surgery is not yet fully known. Methods. We performed a retrospective review of patients who were given recombinant factor VIIa (rFVIIa; Novoseven, NovoNordisk, Copenhagen, Denmark) to control bleeding after major cardiovascular surgery requiring cardiopulmonary bypass (CPB) at our institution. The decision to administer rFVIIa was made empirically based on the observation by the surgeons of refractory bleeding that appeared unresponsive to conventional hemostasis agents including the requirement of large volumes of blood components, and was at least severe enough to prevent chest closure. We compared blood loss and blood component usage in patients before and after rFVIIa. We also performed a detailed review of the English literature to determine the role of rFVIIa in the treatment of bleeding after cardiac surgery. Results. Between August 2002 to February 2006, 1295 patients underwent open heart surgery at our institution; of these, 28 were given Novoseven either to control intractable bleeding, or to prevent major bleeding. Table 1 shows the patient characteristics. Satisfactory hemostasis was achieved in all but 3 patients after a single 90 μg/kg intravenous dose of rFVIIa. In all patients, there was a dramatic reduction in the amount of blood components (PRBCs, Platelets and FFP) used after rFVIIa infusion (Table 2). Cryoprecipitate was administered routinely with rFVIIa and its usage did not change significantly (Table 2). No thromboembolic or other complications directly related to rVIIa occurred. Conclusions. We have demonstrated that intravenous rFVIIa is effective, safe, and valuable in the management of intractable bleeding after complicated cardiac surgeries. There are several reports and reviews in the literature which corroborate our experience and indicate that recombinant factor VIIa is a potent pro-hemostatic agent which has a role in the treatment of life-threatening refractory hemorrhage associated with cardiac surgery. Earlier preemptive administration of rFVIIa during or before surgery may be of value in patients at high risk of intractable bleeding in order to limit blood loss, and to avoid potential morbidity from large volume blood component transfusions. Randomized, controlled trials are warranted to assess the efficacy, safety, and cost-benefit of this intervention in cardiac surgical patients. TABLE 1. Characteristics and operative course of the 28 patients Mean age 60 yrs (range 22–85) Male, M 24(85%); F 4(15%) Total number of surgical procedures performed: 34 Aortic valve: 7; Bentall or modified Bentall: 9 (3 emergent) Mitral Valve Replacement: 4; CABG: 10; Redo 2 Left pneumonectomy/resection of L Atrial cuff & pericardium: 1 Removal of Inferior vena cava tumor (Renal cell ca): Re-exploration: 6; Delayed closure: 5; Both re-exploration and delayed closure: Median bypass time: 214 min (65–358) Timing of Novoseven: intra op: 21 including elective use in 2 pts; post op: 7 Dose of Novoseven: 90mcg/kg in 22; 45 mcg/kg 2 patients Responders 25(89%) Outcome: Deaths 11(38%) Autopsies: 2; no evidence of systemic thrombosis Table 2. Details of the blood products administered both before and after rFVIIa infusion. Componen Mean units Before rVIIa Mean units After rVIIa Difference; p value PRBC usage 15.9 5.033333 0.045 Platelet usage 4.448276 1.37931 0.005 FFP Usage 9.931034 5.793103 0.042 Cryoppt 21.71429 12.54167 0.091