Impact of body mass index on outcomes after percutaneous coronary intervention in patients with acute myocardial infarction

Obesity is a widespread problem, particularly in the cardiovascular disease population. Obese patients have a lower incidence of cardiovascular mortality after elective percutaneous coronary interventions (PCIs); however, there is a paucity of data in the acute myocardial infarction (AMI) setting. This study investigated the effects of body mass index (BMI) on outcomes after percutaneous coronary revascularization in patients with AMI. Patients were categorized into 3 groups based on their BMI, i.e., normal, overweight, or obese. Most patients undergoing primary PCI for AMI (70%) were overweight or obese. Obese patients were significantly younger and more often diabetic, hypertensive, and hyperlipidemic compared with other groups. Angiographically, there was no difference in presence of multivessel disease, final Thrombolysis In Myocardial Infarction grade 3 flow, and presence of thrombus or dissection. Mortality was significantly lower in the hospital at 6 and 12 months in the obese group. Multivariate analysis demonstrated age>70 years, final Thrombolysis In Myocardial Infarction grade<3 flow, history of peripheral vascular disease, and ejection fraction to be the strongest predictors of mortality at 12 months. In conclusion, our data show that obese patients with AMI have a lower risk for in-hospital, 6-month, and 12-month mortality and cardiovascular events than patients with a normal BMI.     

Impact of baseline platelet count in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction (from the CADILLAC trial)

Despite the well-recognized role of platelets in the pathogenesis of acute myocardial infarction (AMI) and in the vascular responses to angioplasty, the relation between platelet count and outcomes after primary percutaneous coronary intervention (PCI) in AMI is unknown. We therefore determined the effect of baseline platelet count on clinical and angiographic outcomes of patients with AMI undergoing primary PCI. In the prospective, randomized CADILLAC trial, platelet count on admission was available in 2,021 of 2,082 patients (97.0%). Angiographic results and outcomes at 30 days and 1 year were stratified by quartiles of platelet count. Median platelet count was 231 x 10(9)/L (range 38 to 709). Primary PCI angiographic success rates were independent of platelet count. The 30-day incidence of target vessel thrombosis or reocclusion increased steadily across the higher quartiles of baseline platelet count (0.2%, 0.6%, 1.0%, and 2.0%, p = 0.027). At 1 year, patients with a baseline platelet count >or=234 versus <234 x 10(9)/L had higher rates of death or reinfarction (8.9% vs 4.5%, p <0.0001), death (5.8% vs 3.1%, p = 0.002), and reinfarction (3.4% vs 1.6%, p = 0.008). By multivariable analysis, a higher baseline platelet count was the strongest predictor of 1-year death or reinfarction (hazard ratio [HR] per 10,000 increase in platelet count 1.02, 95% confidence interval [CI] 1.02 to 1.07, p <0.0001) and independently predicted reinfarction (HR 1.06, 95% CI 1.02 to 1.09, p = 0.002) and cardiac mortality (HR 1.03, 95% CI 1.00 to 1.06, p = 0.055) at 1 year. In conclusion, a higher baseline platelet count in patients with AMI is a powerful independent predictor of death and reinfarction within the first year after primary PCI.     

Female urethral stricture disease

Female urethral stricture disease is a rare entity. The most common etiologies are traumatic injury, iatrogenic injury, and inflammatory disease resulting in periurethral fibrosis. Hallmark symptoms are frequency and urgency, and may also be dysuria, hesitancy, slow stream, incontinence, and recurrent urinary tract infections. Female bladder outlet obstruction is a difficult entity to define, and the subset representing stricture disease may also be elusive. The diagnosis of female urethral stricture disease is usually based on symptoms, meatal appearance, and difficult instrumentation of the patient. Other testing, such as urodynamics, voiding urography, or cystoscopy, may be helpful. Treatment options are conservative management with dilatation, endoscopic treatment, or open repair with various tissue flaps or grafts. Considerable controversy surrounds the efficacy of urethral dilatation in women with voiding dysfunction.     

Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures

BACKGROUND: Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown. METHODS: We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures. RESULTS: Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results. CONCLUSION: In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures.     

End points to establish the efficacy of new agents in the treatment of acute leukemia

Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure "reasonably likely" to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort.     

Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning

Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial "trichimerism," which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.