Publications

BACKGROUND

Although initiatives to regionalize cancer surgery are already under way, the relative importance of volume in cancer surgery is disputed.

HYPOTHESIS

We examined surgical mortality with 8 cancer resections in the US population to better quantify the influence of hospital volume.

METHODS

Using information from the all-payer Nationwide Inpatient Sample (1995-1997), we examined mortality with 8 cancer resections (N = 195 152). After dividing patients into 3 evenly sized volume groups based on hospital procedure volume (low, medium, and high), we used regression techniques to describe relationships between hospital volume and in-hospital mortality, adjusting for patient characteristics.

RESULTS

Trends toward lower operative risks at high-volume hospitals were observed for 7 of the 8 procedures. However, differences between low- and high high-volume hospitals were statistically significant for only 3 operations (esophagectomy, 15.0% vs 6.5%; pancreatic resection, 13.1% vs 2.5%; and pulmonary lobectomy, 10.1% vs 8.9%, respectively). Although they did not reach statistical significance, absolute differences in mortality between low- and high-volume hospitals were greater than 1% for the following 3 procedures: gastrectomy, 8.7% vs 6.9%; cystectomy, 3.6% vs 2.5%; and pneumonectomy, 10.6% vs 8.9%, respectively. Mortality reductions for nephrectomy and colectomy were small. In general, in terms of absolute differences in mortality, the effect of volume was greatest in elderly patients.

CONCLUSIONS

Operative mortality decreases with increasing hospital volume for several cancer resections. However, volume may be most important in patients who are older and at higher risk.

STUDY OBJECTIVES

To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS).

DESIGN

Double-blind, randomized, placebo-controlled trial.

SETTING

Multicenter, tertiary referral centers.

PATIENTS OR PARTICIPANTS

Forty-five subjects with asthma recruited from six medical centers in the United States.

INTERVENTIONS

The Asthma Clinical Research Network undertook a 28-week, randomized, multicenter, double-blind, placebo-controlled trial of 164 subjects with clinically stable, persistent asthma. A subset of subjects (n = 45) underwent bronchoscopy with endobronchial biopsy and BAL at the end of a 6-week run-in period, during which all subjects received triamcinolone acetonide (TAA), 400 microg bid. Airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells were quantified morphometrically along with determination of BAL tryptase. At the end of the run-in period, subjects were then randomized to receive salmeterol (42 micro g bid), placebo, or continue TAA for 16 weeks followed by a second bronchoscopy.

MEASUREMENTS AND RESULTS

Outcome variables included airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells that were quantified morphometrically and BAL tryptase. Thirty-five subjects completed the treatment phase; an additional 10 subjects, who were randomized to either salmeterol or placebo after the run-in, had treatment failure. When the bronchoscopy results performed at the end of the run-in, prior to randomization, were analyzed, the treatment failure group demonstrated significantly more tissue mast cells as compared to the nontreatment failure group despite 6 weeks of therapy with TAA (p = 0.04). BAL tryptase was also significantly higher in the treatment failure group (p < 0.0001). Of those subjects who completed the study, tissue mast cells and BAL tryptase did not change significantly within any of the treatment groups during the treatment phase (p > 0.05).

CONCLUSIONS

Persistent elevations in airway tissue mast cells and BAL tryptase after treatment with TAA predict treatment failure in patients for whom discontinuation of ICS is being considered.

BACKGROUND

Although C-reactive protein (CRP) predicts vascular risk, few data are available evaluating the relation between CRP and the Framingham Coronary Heart Disease Risk Score (FCRS).

METHODS AND RESULTS

CRP levels were compared with calculated 10-year FCRS in a cross-sectional survey of 1666 individuals free of cardiovascular disease. Among men and women not using hormone replacement therapy (HRT), CRP levels were significantly related to 10-year Framingham Coronary Heart Disease Risk categories [total cholesterol (TC) score for men and women: r=0.29 and r=0.22, respectively; LDL cholesterol score for men and women: r=0.29 and r=0.22, respectively, all probability values <0.01]. However, CRP levels correlated minimally with individual components of the FCRS, which included age (r(men)=0.17, r(women)=-0.003), TC (r(men)=-0.02, r(women)=-0.006), HDL-C (r(men)=0.13), LDL-C (r(men)=-0.0002, r(women)=0.012), blood pressure (rmen=0.18, r(women)=0.22), diabetes (r(men)=0.10, r(women)=0.07), and smoking (r(men)=0.16, r(women)=0.14) status. For women taking HRT, no significant relation was observed between CRP and the FCRS, although the power to detect effects in this subgroup is limited.

CONCLUSIONS

Our data demonstrate that CRP levels significantly correlate with calculated 10-year Framingham Coronary Heart Disease Risk in men and women not taking HRT but correlate minimally with most individual components of the FCRS. These data provide additional support for continued evaluation of CRP as a potential adjunct in the global prediction of cardiovascular risk.

Under different circumstances, natural killer T (NKT) cells can cause a T helper (Th) 1 or a Th2 polarization of immune responses. We show here, however, that mouse NKT cells with an invariant V alpha 14 rearrangement (V alpha 14i NKT cells) rapidly produce both IL-4 and IFN-gamma, and this pattern could not be altered by methods that polarize naive CD4+ T cells. Surprisingly, although cytokine protein was detected only after activation, resting V alpha 14i NKT cells contained IL-4 and IFN-gamma mRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by V alpha 14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The V alpha 14i NKT cells from primed mice retain the ability to produce IL-4 and IFN-gamma, but they are less effective at activating NK cells to produce IFN-gamma. Our data therefore indicate that V alpha 14i NKT cells have a relatively inflexible immediate cytokine response, but that changes in their ability to induce IFN-gamma secretion by NK cells may determine the extent to which they promote Th1 responses.