In vivo intervertebral disc mechanical deformation following a treadmill walking "stress test" is inversely related to T1rho relaxation time.

OBJECTIVE: To assess the in vivo relationship between the mechanical response of intervertebral discs (IVDs) to dynamic activity and IVD biochemical composition assessed via T1rho relaxation imaging. DESIGN: Eighteen asymptomatic participants with no history of low back pain (LBP), injury, or surgery underwent magnetic resonance (MR) imaging of their lumbar spine prior to and immediately following a treadmill walking "stress test." Anatomic (SPACE, FLASH) MR images were obtained pre- and post-exercise and utilized to measure IVD mechanical deformation. Quantitative (T1rho) imaging was performed pre-exercise to reflect IVD composition. Pre-exercise anatomic images were also utilized to assess IVD degenerative status based on the modified Pfirrmann scale. To quantify mechanical response, 3D surface models of the L1-L2-L5-S1 IVDs were created from manual segmentations of pre- and post-exercise anatomic images and utilized to assess changes in IVD height. IVD strain (%) was defined as change in IVD height normalized to pre-activity height. Linear mixed models were used to assess the relationships between IVD mechanical deformation (strain), composition (T1rho relaxation time), and degenerative status (Pfirrmann grade). RESULTS: Increased compressive IVD strain was associated with lower T1rho relaxation times in the nucleus pulposus (NP) of the disc (ßT1rho=5.07,CI:[1.52,7.77],Rmarg2=0.52,p=0.005). Thus, an inverse relationship between IVD strain and NP T1rho relaxation time was observed. CONCLUSION: The in vivo mechanical response of the IVD to the "stress test" was sensitive to differences in NP composition. The results of this study suggest that quantification of in vivo IVD mechanical function and composition may provide insight into IVD health.

Improving vasomotor symptoms; psychological symptoms; and health-related quality of life in peri- or post-menopausal women through yoga: An umbrella systematic review and meta-analysis.

OBJECTIVES: Vasomotor symptoms (VMS), commonly reported during menopausal transition, negatively affect psychological health and health-related quality of life (HRQoL). While hormone therapy is an effective treatment, its use is limited by concerns about possible harms. Thus, many women with VMS seek nonhormonal, nonpharmacologic treatment options. However, evidence to guide clinical recommendations is inconclusive. This study reviewed the effectiveness of yoga, tai chi and qigong on vasomotor, psychological symptoms, and HRQoL in peri- or post-menopausal women. DESIGN: MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, CINAHL and the Allied and Complementary Medicine Database were searched. Researchers identified systematic reviews (SR) or RCTs that evaluated yoga, tai chi, or qigong for vasomotor, psychological symptoms, and health-related quality of life (HRQoL) in peri- or post-menopausal women. Data were abstracted on study design, participants, interventions and outcomes. Risk of bias (ROB) was assessed and updated meta-analyses were performed. RESULTS: We identified one high-quality SR (5 RCTs, 582 participants) and 3 new RCTs (345 participants) published after the SR evaluating yoga for vasomotor, psychological symptoms, and HRQoL; no studies evaluated tai chi or qigong. Updated meta-analyses indicate that, compared to controls, yoga reduced VMS (5 trials, standardized mean difference (SMD) -0.27, 95% CI -0.49 to -0.05) and psychological symptoms (6 trials, SDM -0.32; 95% CI -0.47 to -0.17). Effects on quality of life were reported infrequently. Key limitations are that adverse effects were rarely reported and outcome measures lacked standardization. CONCLUSIONS: Results from this meta-analysis suggest that yoga may be a useful therapy to manage bothersome vasomotor and psychological symptoms.

Use of mindfulness, meditation and relaxation to treat vasomotor symptoms.

Postmenopausal women with bothersome vasomotor symptoms (VMS) often seek alternatives to hormone-based treatment due to medication risks or personal preference. We sought to identify the effects of meditation, mindfulness, hypnosis and relaxation on VMS and health-related quality of life in perimenopausal and postmenopausal women. To do this, we conducted an umbrella review supplemented by new randomized, controlled trials (RCTs) published since the most recent good-quality systematic review for eligible interventions. We searched MEDLINE and the Cochrane Database of Systematic Reviews, PubMed, EMBASE, CINAHL and the Allied and Complementary Medicine Databases. We identified five systematic reviews and six new RCTs that met eligibility criteria. In a new meta-analysis examining four RCTs comparing paced respiration with a control group, we found that paced respiration is not associated with a statistically significant decrease in VMS frequency (standardized mean difference (SMD) 0.04, 95% confidence interval (CI) -0.73 to 0.82, I2 = 56.6%, three trials) or severity (SMD 0.06, 95% CI -0.69 to 0.80; I2 = 65.1%, three trials). There was not sufficient new information to conduct meta-analyses that examined the effect of mindfulness or hypnosis on our outcomes of interest. No effect on VMS or quality of life was found between various relaxation or mindfulness interventions.

Effect of the CT table strap on radiation exposure and image quality during cervical spine CT.

BACKGROUND AND PURPOSE: The CT table strap may impair shoulder lowering during cervical spine CT. The purpose of this investigation was to evaluate the effect of the CT table strap on radiation exposure and image quality during CT of the cervical spine. MATERIALS AND METHODS: Patients undergoing cervical spine CT were prospectively randomized to having the CT table strap placed around the torso and arms (control group) or around the torso only (intervention group). Radiation exposure, shoulder position, and image quality were evaluated. Potential confounders, including neck diameter and scan length, were also assessed. RESULTS: Fifty-eight patients were enrolled and randomized, and 51 subjects were included in the final study population. There was a 21% decrease in radiation exposure in the intervention group compared with the control group (mean dose-length product, 540 ± 152 versus 686 ± 200 mGy × cm, P = .005). Subjects in the intervention group achieved shoulder lowering of an average of >1 vertebral body lower than the control group (mean shoulder level, 7.7 ± 1.3 versus 6.5 ± 1.3, P = .001). Subjective image quality, determined by the lowest level of spinal cord visibility, was also better in the intervention group (mean cord visibility level, 6.9 ± 1.3 versus 5.9 ± 1.3, P = .006). No differences in neck diameter (P = .28) or scan length (P = .55) were observed between groups. CONCLUSIONS: The CT table strap inhibits shoulder lowering during CT of the cervical spine. Placement of the patient's arms outside the CT table strap results in decreased radiation exposure and increased image quality compared with patients whose arms are placed inside the strap.

Following unenhanced MRI assessment for local recurrence after surgical resection of mesenchymal soft tissue tumors, do additional gadolinium-enhanced images change reader confidence or diagnosis?

PURPOSE: Evaluate if gadolinium enhanced MR imaging (GeMRI) improves confidence, changes the final diagnosis, or improves accuracy in the assessment of musculoskeletal (MSK) tumor residual or recurrence following surgical resection. We also assess if different experience levels change the above results. METHODS AND MATERIALS: Initially, pre-contrast images were independently reviewed by two radiologists, one with 25 years of experience (R1) and one undergoing MSK specialty training (R2). Two questions were answered: (1) Mass present? and (2) Likelihood of malignancy? Subsequently, both pre-contrast and post-contrast images were independently reviewed. The same questions were again answered plus four others including if GeMRI changed mass characterization, better defined cystic versus solid, better defined tumor extent, or improved conspicuity. Lastly, the readers answered whether GeMRI changed confidence, and changed their final diagnosis. Histologic diagnoses were available in 43 cases, with the remaining 44 cases based upon clinical and/or imaging follow-up. RESULTS: GeMRI definitely improved confidence in 8/7 cases, and slightly improved confidence in 20/29 cases and changed the final diagnosis in 11/8 cases for R1 and R2 respectively. Positive and negative predictive values statistically improved for R2 (positive predictive value 36.4% versus 50%, p=0.02; negative predictive value 75.4% versus 79.1%, p=0.04) but not for R1. Reader concordance for malignancy improved with GeMRI (κ=0.44 pre-contrast and κ=0.71 post-contrast). CONCLUSION: GeMRI improved reader confidence, improved reader concordance and modestly improved accuracy for the less experienced reader. Where possible, GeMRI should be used in the assessment of MSK tumor residual or recurrence.

Intravascular radiation therapy after balloon angioplasty of narrowed femoropopliteal arteries to prevent restenosis: results of the PARIS feasibility clinical trial.

PURPOSE: To conduct a feasibility study to assess the feasibility, safety, and outcome of endoluminal gamma radiation therapy after balloon angioplasty of superficial femoral artery (SFA) lesions. MATERIALS AND METHODS: Forty patients with claudication were enrolled in the study and underwent percutaneous transluminal angioplasty (PTA) of SFA lesions with a mean lesion length of 9.8 cm +/- 3.0 and a mean reference vessel diameter of 5.2 mm +/- 3.1. After successful PTA, a segmented centering balloon catheter was positioned to cover the PTA site. The patients were then transported to the radiation oncology suite and treated with a microSelectron HDR afterloader with use of an Ir-192 source with a prescribed dose of 14 Gy, 2 mm into the vessel wall. Ankle-brachial index (ABI) and Rutherford score were evaluated at 1, 6, and 12 months after the procedure and angiographic follow-up was conducted at 6 months. RESULTS: Radiation was delivered successfully to 35 of 40 patients. There were no procedural complications. Exercise and rest ABI were higher at 1 year (0.72 +/- 0.26 and 0.89 +/- 0.18, respectively) compared to baseline (0.51 +/- 0.25 and 0.67 +/- 0.17, respectively). Maximum walking time on a treadmill increased from 3.41 min +/- 2.41 to 4.43 min +/- 2.49 at 30 days and was 4.04 min +/- 2.8 at 12 months. The angiographic binary restenosis rate at 6 months was 17.2% and the clinical restenosis rate at 12 months was 13.3%. There were no angiographic or clinical adverse events related to the radiation therapy. CONCLUSIONS: Intraarterial radiation after PTA of SFA lesions with use of high-dose rate gamma radiation is feasible and safe. The angiographic and clinical improvements are sustainable at 1 year and represent a potent antirestenotic therapy for the treatment of narrowed peripheral arteries.

Costs of revascularization over eight years in the randomized and eligible patients in the Emory Angioplasty versus Surgery Trial (EAST).

The Emory Angioplasty versus Surgery Trial (EAST) was a randomized trial that compared, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG) for multivessel coronary artery disease. We present the findings of the economic analysis of EAST through 8 years of follow-up and compare the cost and outcomes of patients randomized in EAST versus patients eligible but not randomized (registry patients). Charges were assessed from hospital UB82 and UB92 bills and professional charges from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were inflated to 1997 dollars. Costs were assessed for initial hospitalization and for cumulative costs of the initial hospitalization and additional revascularization procedures up to 8 years. Total 8-year costs were $46,548 for CABG and $44,491 for PTCA (p = 0.37). Cost of CABG in the eligible registry group showed a pattern similar to that for randomized patients, but total cost of PTCA was lower for registry patients than for randomized patients. Thus, the primary procedural costs of CABG are more than those for PTCA; this cost advantage, given the limits of measurement, is largely or even completely lost for randomized patients over the course of 8 years because of additional procedures after a first revascularization by PTCA.

Targeting patients undergoing angioplasty for thrombus inhibition: a cost-effectiveness and decision support model.

BACKGROUND: In recent clinical trials, glycoprotein IIb/IIIa blockers have demonstrated effectiveness in preventing adverse events after angioplasty in high-risk patients. However, uncertainty exists regarding the cost-effective selection of patients to receive antiplatelet therapy. METHODS AND RESULTS: All 4962 patients at Emory University Hospitals who underwent coronary intervention procedures (n=6062) from 1993 to 1995 were studied. Multivariate models to predict death and the composite of death, Q-wave and non-Q-wave myocardial infarction, and emergency additional revascularization were developed. Hospital costs and professional costs were determined. A cost-effectiveness analysis with therapy targeted to high-risk patients was performed. If patients with a >5% probability of events received antiplatelet therapy that reduced events by 24% and cost $1000, 40.1% of patients would receive therapy; complications would be reduced from 6.39% to 5.37%, and cost would increase $261 from $10343 to $10604, or $25504 per event prevented. The marginal cost per event prevented by moving from a 7% to a 5% probability of an event cutoff would be $57 799. CONCLUSIONS: For high-risk patients, there may be cost savings; for low-risk patients, therapy may not be cost effective; and for patients in the midrange (between 5% and 7% probability of an adverse event), events may be prevented at an acceptable level of cost.

Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST)

OBJECTIVES: To evaluate the long-term outcome of patients randomized to coronary bypass surgery or coronary angioplasty. BACKGROUND: The Emory Angioplasty versus Surgery Trial (EAST) is a single center randomized comparison of a strategy of initial coronary angioplasty (n = 198) or coronary bypass surgery (n = 194) for patients with multivessel coronary artery disease. The primary end point (death, myocardial infarction or a large ischemic defect at 3 years) was not different, and repeat revascularization was significantly greater in the angioplasty group. Subsequently, the National Heart, Lung and Blood Institute supported a five-year extension of the trial. METHODS: After the three year anniversary visit, annual questionnaires, telephone contact and examination of medical records were accomplished until death or the eight year anniversary in 100% of the patients surviving at 3 years. RESULTS: Survival at 8 years is 79.3% in the angioplasty group and 82.7% in the surgical group (p = 0.40). Patients with proximal left anterior descending stenosis and those with diabetes tended to have better late survival with surgical intervention although not reaching statistical significance. After the first 3 years, repeat interventions remained relatively equal for both treatment groups. CONCLUSIONS: Long-term survival is not significantly different between angioplasty and surgery, and late (three to eight year) revascularization procedures were infrequent. Patients without treated diabetes had similar survival in both groups.

Applying the resource-based relative value scale to the Emory angioplasty versus surgery trial.

The resource-based relative value scale developed for use in the Medicare fee schedule can also be very useful in profiling and comparing physicians' cardiovascular utilization across different medical activities. This article applies relative value units (RVUs) to data from the Emory Angioplasty versus Surgery Trial. The Emory Angioplasty versus Surgery Trial was a randomized clinical trial to determine the efficacy of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass surgery (CABG). All physician services in the clinical trial provided to 2 groups of patients--those undergoing CABG and those receiving PTCA-over the course of 4 years were assigned physician work RVUs (representing the intensity of physician work required) and total RVUs (representing both the intensity and practice costs). Physician charges were also compiled. These data were used to profile and compare physician services to the 2 groups of patients by type of service, distribution over time, and clinical department. Comparisons based on RVUs contrast sharply with differences based on charges. Mean physician charges, in 1996 dollars, were $27,158 for CABG patients and $21,491 for PTCA patients, a 26% difference (p <0.001). Physician work RVUs generated an 18.3% difference (p = <0.001). Using total RVUs, the difference between the 2 groups was 3.3% (p = 0.249). Resource-based relative value weights are a valuable tool for analyzing and comparing physicians' use of cardiovascular resource. The results suggest that conclusions about physician resource utilization based on physician charges should be carefully evaluated. When possible, physician work RVUs should be compiled and evaluated along with physician charges.

Prognostic value of thallium-201 single-photon emission computed tomography for patients with multivessel coronary artery disease after revascularization (the Emory Angioplasty versus Surgery Trial [EAST]).

The aim of this study was to investigate the relation between reversible thallium single-photon emission computed tomography (SPECT) myocardial perfusion defects at 1-year after revascularization and quantitative indexes in Emory Angioplasty versus Surgery Trial (EAST) and outcomes 3 years after revascularization in 336 patients. EAST was a randomized controlled trial assessing cardiac outcomes for angioplasty versus bypass surgery for patients with multivessel coronary artery disease. During this prospective trial, a substudy included the evaluation of the prognostic value of reversible defects on quantitative thallium SPECT. At 1-year after revascularization, 336 patients underwent SPECT thallium-201 stress myocardial perfusion and 3-hour delayed imaging. Subsequent events, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, myocardial infarction, and death, were recorded at 3 years. A stress-induced reversible thallium-201 defect was defined using a quantitative index of a reversibility score >30% and severity score >500. Reversible defects were observed more frequently in the percutaneous transluminal coronary angioplasty than in the coronary artery bypass graft surgery treatment groups (46% vs 27%, p <0.001). A total of 123 patients had stress-induced, reversible thallium defects and more events than patients with other perfusion results (freedom from all events was 81.3% vs 94% [p <0.001], and freedom from myocardial infarction and death 88.3% vs 95.5% [p = 0.031]). Quantitative thallium SPECT at 1 year after revascularization risk stratifies patients as to their likelihood of major cardiac outcomes.

Evaluating the exposure and disease relationship with adjustment for different types of exposure misclassification: a regression approach.

Misclassification of exposure can lead to biased results in the epidemiologic research. Available methods accounting for misclassification often require the use of a gold standard or assume non-differential misclassification of exposure. We present a regression approach which can detect and account for different types of misclassification when estimating the exposure and disease relationship. This approach uses two imperfect measures of a dichotomous exposure and does not require a gold standard. Standard statistical packages with a logistic regression module can be used for estimation of parameters through the EM algorithm process. Two examples are used to illustrate the methodology.

Economic impact of GPIIB/IIIA blockade after high-risk angioplasty: results from the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

OBJECTIVE: This study was conducted to assess the impact of GPIIb/IIIa blockade with tirofiban on costs during the initial hospitalization and at 30 days among patients undergoing high-risk coronary angioplasty. BACKGROUND: GPIIb/IIIa blockers are a new class of compounds that have been shown in clinical studies to prevent complications after high-risk angioplasty. METHODS: The RESTORE trial was a multinational, blinded placebo-controlled study of 2,197 patients randomized to tirofiban or placebo following coronary angioplasty. This economic assessment was a prospective substudy of the RESTORE trial, and included 1,920 patients enrolled in the U.S. Costs were estimated for the U.S. cohort based on their utilization of healthcare resources and on costs measured directly in 820 U.S. patients at 30 sites. RESULTS: There was a 36% difference in the rate of the composite event of death, myocardial infarction (MI) and revascularization at two days between tirofiban and placebo (8% vs. 12%, p = 0.002). This difference was attributed to a reduction in nonfatal MI, repeat angioplasty, coronary surgery and stent placement. These clinical benefits followed a similar trend at 30 days, with a 16% reduction in the composite event (p = 0.10). In-hospital cost, including professional and study drug costs, was $12,145 +/- 5,882 with placebo versus $12,230 +/- 5,527 with tirofiban (p = 0.75). The 30-day cost was $12,402 +/- 6,147 with placebo versus $12,446 +/- 5,814 with tirofiban (p = 0.87). CONCLUSIONS: Tirofiban has been shown to decrease in-hospital and possibly 30-day events after high-risk angioplasty. The beneficial clinical effects of tirofiban in high-risk patients can be achieved at no increased cost.

A comparison of the Charlson comorbidity index derived from medical record data and administrative billing data.

The objective of this article is to compare the Charlson comorbidity index derived from medical record data (Chart Index) with the same index derived from billing data (ICD-9 Index) to determine how well each predicted inpatient and 30-day mortality, length of stay, and complications among Medicare beneficiaries hospitalized for carotid endarterectomy. Economic and time constraints have increased the need for risk adjusters derived from administrative data, yet few studies have compared these measures with those derived from chart review. Using logistic regression, the Chart Index was found to be a significant predictor of inpatient mortality, 30-day mortality, length of stay, and complications, after controlling for age, gender, and neurologic and medical risk factors (P values = 0.004, 0.056, 0.0001, and 0.042, respectively). The ICD-9 Index approached significance as a predictor of the outcomes (P values = 0.092, 0.100, 0.093, and 0.080, respectively). The Chart Index was shown to be superior to the ICD-9 Index within this patient sample.

A regression model for multivariate random length data.

Multivariate random length data occur when we observe multiple measurements of a quantitative variable and the variable number of these measurements is also an observed outcome for each experimental unit. For example, for a patient with coronary artery disease, we may observe a number of lesions in that patient's coronary arteries, along with percentage of blockage of each lesion. Barnhart and Sampson first proposed the multiple population model to analyse multivariate random length data without covariates. This paper extends their approach to deal with multiple covariates. We propose a new multiple population regression model with covariates, and discuss the estimation issues. We analyse data from the TYPE II coronary intervention study to illustrate the methodology.

Prospective, randomized trial comparing blood and oxygenated crystalloid cardioplegia in reoperative coronary artery bypass grafting.

OBJECTIVES: Reoperative coronary artery bypass grafting presents unique challenges for myocardial preservation. The purpose of this study was to compare oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during reoperative coronary artery bypass grafting using transesophageal echocardiography to assess regional wall motion of the left ventricle before and after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative coronary artery bypass grafting were prospectively randomized to receive oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered with a combined antegrade-retrograde technique. Transgastric short axis views of the left ventricle were made with transesophageal echocardiography during the operation before cardiopulmonary bypass and immediately after cardiopulmonary bypass. Regional wall motion was graded by a blinded observer, and before cardiopulmonary bypass scores were compared with after cardiopulmonary bypass scores. RESULTS: No significant differences were found in the change in regional wall motion score from before cardiopulmonary bypass to after cardiopulmonary bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This study found blood and crystalloid cardioplegia to be equally efficacious for myocardial preservation during reoperative coronary artery bypass grafting.

Power considerations when a continuous outcome variable is dichotomized.

An investigator can compare two groups with respect to a continuous outcome variable, Y, by comparing the means of Y or by collapsing that variable into categories. For example, antihypertensive treatments can be compared on the basis of blood pressure measurements, or on the basis of the proportions of patients with blood pressure in prespecified ranges. This report is concerned with the loss of power when inherently continuous variables are dichotomized. The report will focus on the power loss when a normally distributed variable with a known, common variance in each of two groups is dichotomized. Power is shown to depend on the relationship between the means of the two groups and the cutoff point, and it varies from negligible to substantial. The results will be applied to data from the Lovastatin Restenosis Trial. Initially the trial considered a dichotomous outcome (proportion of patients with elevated percent diameter stenosis), but the endpoint was later changed to the mean percent diameter stenosis. The modification in the design of the trial was well justified because the power loss was considerable when comparing proportions.

Concomitant aortic and renal artery reconstruction in patients on an intensive antihypertensive medical regimen: long-term outcome.

A beneficial effect in blood pressure control is presumed for patients on an intensive preoperative antihypertensive regimen who undergo empiric renal revascularization. Nonetheless, a noticeable decline in surgical cure rates for hypertension has been recently observed in patients with generalized atherosclerosis. The outcome of patients on multiple preoperative antihypertensive agents who underwent combined aortic and renal artery reconstruction was reviewed. The study population comprised 43 patients who underwent concomitant renal artery and aortic reconstruction for atherosclerotic disease between 1983 and 1995 and who were taking two or more antihypertensive medications and had a serum creatinine of less than or equal to 1.7 mg/dL. Operative management included an aortic reconstruction with either unilateral (n = 22) or bilateral (n = 19) aortorenal bypass or renal endarterectomy (n = 2). Operative mortality was 4.7% (2 of 43). The estimated 5-yr probability of survival was 83% (95% C.I. 0.70, 0.99). Late follow-up data on blood pressure control were available for review in 32 patients at a median follow-up of 37 months. Hypertension was cured in 1 (3%) and improved in an additional 15 (47%) patients. The numbers of antihypertensive medications taken preoperatively (mean = 2.7) declined at late follow-up (mean = 1.6). Notably, the largest reduction was observed with beta blockers (p = 0.006), central sympatholytics (p = 0.041), and angiotensin converting enzyme (ACE) inhibitors (p = 0.052). The number of preoperative antihypertensive medications was not significantly related to survival or to blood pressure improvement. However, uncontrolled preoperative hypertension despite antihypertensive therapy was associated with a favorable blood pressure response to operation (p < 0.001). Patients on an intensive antihypertensive regimen can safely undergo concomitant renal artery and aortic reconstruction for the empiric management of hypertension. Poorly controlled preoperative hypertension in the presence of multiple antihypertensive agents is a favorable marker for improved postoperative blood pressure control.

Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer.

OBJECTIVES: Some patients with surgically resected stage I non-small-cell lung cancer eventually have metastatic disease. A histologic marker of metastatic potential and diminished survival for stage I non-small-cell lung cancer may distinguish this patient population. This study evaluates the degree of angiogenesis as a predictor of cancer-related death after operation for stage I non-small-cell lung cancer. METHODS: Demographic, surgical, and histopathologic data, including presence of vascular invasion, were reviewed for 106 patients with stage I non-small-cell lung cancer from 1985 through 1990. Visual quantitation of microvessels immunostained with factor VIII-related antigen and CD31 in 5 microm sections from the paraffin blocks of tissue defined rumor angiogenesis. RESULTS: Follow-up was 95.1% complete, mean 5.2 +/- 3.0 years. Lung cancer-related mortality rate was 24.4% at 5 years. Mean microvessel counts were 20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31. Univariate analysis revealed an FVIII count of at least 20 (p = 0.025) and blood vessel invasion (p = 0.017) to be significant predictors of disease-related death. After adjustment for other patient and tumor characteristics, multivariate Cox regression analysis found an FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (hazard ratio 3.7) to be significant independent correlates of lung cancer death (p = 0.018 and p = 0.011, respectively). CD31 quantitation did not predict survival on univariate or multivariate analyses and did not correlate strongly with FVIII quantitation (Spearman's rank correlation r = 0.19). CONCLUSIONS: This analysis reveals a significant association between tumor neovascularization and cancer-related mortality rate among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and metastatic potential, may define a subset of patients with stage I non-small-cell lung cancer who could benefit from adjuvant therapy after surgical resection.

Aggressive lipid lowering in postcoronary angioplasty patients with elevated cholesterol (the Lovastatin Restenosis Trial).

A substudy of the Lovastatin Restenosis Trial in patients with elevated cholesterol (>200 mg/dl) showed no evidence of an effect of aggressive lipid lowering on restenosis, confirming the results of the main trial.