Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly

OBJECTIVE: Progress in the treatment of acromegaly with drugs is making it necessary to improve the prediction of the outcome of transsphenoidal surgery. DESIGN: We evaluated clinical, hormonal and radiologic predictors based on magnetic resonance imaging (MRI) of surgical outcome in patients with acromegaly. METHODS: This retrospective analysis included 125 consecutive patients investigated for acromegaly in a single endocrine unit since the use of MRI imaging began (1988). Eighty-three of these patients (50 women) underwent transsphenoidal surgery and were investigated before and after surgery in our department. A neuroradiologist unaware of the surgical outcome analyzed the results of pituitary gland MRI investigations. RESULTS: Surgical remission rates were 44%, 43%, 61% and 59% based on mean basal GH concentration under 2.5 microg/l, GH/oral glucose tolerance test (OGTT) of <1 microg/l, GH/OGTT of <2 microg/l or IGF-I concentration normal for age and sex respectively. In univariate logistic regression analysis with IGF-I concentration used as the criterion for cure, young age (P<0.001), high IGF-I concentration before surgery (P<0.01), high basal GH concentration before surgery (P<0.02), and high nadir GH/OGTT before surgery (P=0.03) were predictors of poor outcome. The following results in standardized MRI analysis were associated with a higher probability of not being cured: adenoma greater than 15 mm in diameter (P<0.02), infrasellar extension (P=0.04), suprasellar extension (P<0.005) and invasive adenoma (0.02) according to MRI staging. MRI analysis of the intracavernous extension showed that stages above B2 (possible sinus extension with sign of invasion of the space below the carotid artery) were associated with a lower probability of postoperative normal GH plasma levels (P=0.01). In multivariate analysis, age, preoperative hormonal levels and adenoma size remained the major predictors of surgical outcome. CONCLUSIONS: This report provides the first evidence that detailed MRI analysis of adenoma size, location and potential invasion, together with preoperative clinical and hormonal parameters, can be used for the prediction of hormonal outcome after transsphenoidal surgery for acromegaly.     

Predicting mortality in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PAMI risk score)

We performed a pooled analysis of the Primary Angioplasty in Myocardial Infarction (PAMI) trials to examine predictors of death after primary percutaneous coronary intervention. Using these data, we developed a risk score with a range of 0 to 15 points. The PAMI risk score was found to be a strong predictor of late mortality.     

Declining length of hospital stay for acute myocardial infarction and postdischarge outcomes: a community-wide perspective

BACKGROUND: The objectives of this population-based study were to describe trends of more than a decade (1986-1999) in duration of hospitalization after acute myocardial infarction (AMI), patient characteristics associated with varying lengths of stay, and the impact of declining length of stay on postdischarge mortality. METHODS: The study sample consisted of 4551 patients discharged after AMI from all greater Worcester, Mass, hospitals in 8 annual periods during the study period. Regression models were used to examine the influence of demographic, clinical, and treatment variables on length of stay and the association between declining length of hospital stay and postdischarge mortality. RESULTS: Marked declines were observed in the average length of stay between the 1986-1988 (11.7 days) and 1997-1999 (5.9 days) periods. Factors associated with a longer hospital stay included advanced age, female sex, anterior and Q-wave MI, and occurrence of clinically important cardiac complications. Patients with health maintenance organization, Medicare, Medicaid, or no insurance coverage were less likely to have an increased length of stay. Increased 30- and 90-day mortality was associated with a length of stay of greater than 14 days (odds ratio, 2.08; 95% confidence interval, 1.18-3.66) relative to those with a length of stay of 6 to 8 days (odds ratio, 2.01; 95% confidence interval, 1.34-3.01). Patients with a length of stay of less than 6 days exhibited no significant increases in postdischarge mortality. Similar trends were observed in patients with a complicated AMI. CONCLUSIONS: We found marked decreases in length of stay for patients hospitalized with AMI during the past decade. However, we found no negative association between declining length of stay and short-term mortality after hospital discharge for AMI.     

s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line

s-Thalidomide has proven efficacy in multiple myeloma. Although it has both antiangiogenic and pro-apoptotic effects, its primary mode of therapeutic action remains unclear. We have investigated the changes to the expression of genes involved with these cellular processes following culture with s-thalidomide in the U266 MM cell line. Cells were cultured with s-thalidomide (0-1000 microM), and cell parameters, including apoptosis, were assessed on day 3. RNA was extracted from cells cultured for 24 h at the IC(50) concentration of s-thalidomide, and changes to gene expression were investigated by microarray methodologies. A reduction in cell viability was observed in U266 cells cultured with s-thalidomide (IC(50): 362 microM), which were mirrored by significant increases in apoptosis (for example, 200 microM on day 3: 40.3+/-3.1% vs. 3.2+/-0.4% on day 0; P<0.001). There were changes in the expression profile of genes involved in angiogenesis and apoptosis, but the changes were most dramatic in the apoptotic genes. In particular, the expression of I-kappaB kinase was decreased by two-fold, which was associated with a four-fold decrease in NF-kappaB expression. These data correlated with immunoblotting analyses, which showed significant increases in I-kappaB protein levels and decreased NF-kappaB activity. Additionally, the Bax : Bcl-2 ratio was significantly increased. Our data suggest that both angiogenic and apoptotic genes and proteins are affected by s-thalidomide. Additionally, a dramatic decrease in Bcl-2 expression with s-thalidomide suggests a possible enhancement of cytotoxic effect if combined with other cytotoxic agents.