Cheryl Vigen

Unsuspected Pulmonary Emboli in Cancer Patients: Clinical Correlates and Relevance

PURPOSE Advances in computed tomography (CT) scanning have led to the detection of unsuspected pulmonary emboli (PE) on routine cancer staging scans. We hypothesized that these patients had signs or symptoms suggestive of PE that may have been overlooked by their health care providers. PATIENTS AND METHODS A retrospective chart review was performed on 59 patients found on routine cancer staging CT scans to have unsuspected PE. Information on patient demographics, malignancy characteristics, risk factors for venous thromboembolism (VTE), and symptoms was recorded. A retrospective case-control analysis was then performed using two age- and stage-matched control patients for each patient who had similar staging CT scans performed during the same period. RESULTS Fifty-two patients with unsuspected PE were identified. Forty-four percent had signs or symptoms commonly associated with PE; when fatigue was included, 75% were symptomatic. Ninety-two control patients were identified for 46 of the case patients. Patients with unsuspected PE were significantly more likely to have had a prior history of VTE (20% v 3%; P = .007). The patients with PE were significantly more likely than control patients to complain of fatigue (54% v 20%; P = .0002) and shortness of breath (22% v 8%; P = .02). There was no difference between the groups in administration of chemotherapy within 30 days, central venous catheter use, or erythropoietin therapy. CONCLUSION Seventy-five percent of patients found to have unsuspected PE on cancer staging CT scans were symptomatic. Fatigue and shortness of breath were significantly more common in patients with unsuspected PE than in control patients.

The effect of education and occupational complexity on rate of cognitive decline in Alzheimer's patients

We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimers disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset.

Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens.

Background:The effects of HIV infection, highly active antiretroviral therapy (HAART), and specific antiretroviral agents on lipoproteins in women are not well described. Methods:In a cross-sectional substudy of the Womens Interagency HIV Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed multivariate analyses of associations among fasting lipoprotein levels, HIV infection, and HAART. Results:Untreated HIV-positive women had lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TGs) but not lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and were the most likely to have unfavorable HDL-C by National Cholesterol Education Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV-infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL, respectively; P < 0.001 for all). Lamivudine, didanosine, nevirapine, and efavirenz were independently associated with higher HDL-C (P < 0.001 for all). Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C (P < 0.01 for all). Stavudine, abacavir, and all ritonavir-containing regimens were associated with higher TGs (P < 0.05 for all), and tenofovir was associated with lower TGs (P = 0.009). Conclusions:A dyslipidemic pattern was associated with HIV infection itself, was more severe in users of PI-containing HAART, but was not present in women taking non-PI HAART.

Autologous Hematopoietic Stem Cell Transplantation in 48 Patients With End-Stage Chronic Liver Diseases

The only presently viable treatment for end-stage liver disease is whole organ transplantation. However, there are insufficient livers available. The aim of the present study is to provide autologous bone marrow-derived stem cells as a potential therapeutic for patients with end-stage cirrhosis. This is a retrospective chart review of autologous stem cell treatment in 48 patients, 36 with chronic end-stage hepatitis C-induced liver disease and 12 with end-stage autoimmune liver disease. For all patients, granulocyte colony-stimulating factor was administered to mobilize their hematopoietic stem cells. Following leukapheresis, CD34+ stem cells were isolated, amplified, and partially differentiated in culture, then reinjected into each subject via their hepatic artery or portal vein. Treatment was generally well tolerated with the expected moderate but transient bone pain from G-CSF in less than half of the patients. Three patients had serious treatment-related complications, and only 20.8% of these end-stage liver disease patients died during 12 months of follow up. For all patients there was a statistically significant decrease in ascites. There was clinical and biochemical improvement in a large percentage of patients who received the transplantation. In the viral group, there were marked changes in albumin (p = 0.0003), bilirubin (p = 0.04), INR (p = 0.0003), and ALT levels (p = 0.02). In the autoimmune group, values also improved significantly for albumin (p = 0.001), bilirubin (p = 0.002), INR (p = .0005), and ALT levels (p = 0.003). These results suggest that autologous CD34+ stem cell transplantation may be safely administered and appears to offer some therapeutic benefit to patients with both viral and autoimmune-induced end-stage liver disease.

Metabolic Changes Associated With Second-Generation Antipsychotic Use in Alzheimer’s Disease Patients: The CATIE-AD Study

OBJECTIVE The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimers disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. METHOD The authors assessed 186 male and 235 female Alzheimers disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimers Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. RESULTS Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., > or = 7% of body weight) was seen among patients with antipsychotic use < or = 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and > 24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. CONCLUSION Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimers disease treated with second-generation antipsychotics should be monitored closely.

Occupational physical activity and risk of adenocarcinomas of the esophagus and stomach

Physical activity may have a role in many cancers, but little is known about its effect on esophageal and gastric adenocarcinoma risk. We investigated occupational physical activity and esophageal and gastric adenocarcinoma risk in a population‐based, case‐control study including 212 esophageal, 264 gastric cardia and 389 distal gastric cancer cases, and 1,330 controls in Los Angeles County. Lifetime occupational histories were obtained during in‐person interviews, and total lifetime occupational activity (Total Activity Index) was calculated using US Census job codes classified as sedentary, or moderately or highly physically active. Average Annual Activity Index was a per‐year Total Activity Index counterpart. Unconditional logistic regression was used to calculate odds ratios, 95% confidence intervals and trend tests adjusting for gender, race, age, birthplace, education, smoking, body mass index (BMI) and number of years worked. Esophageal adenocarcinoma risk tended to decrease with increasing Total Activity Index (OR = 0.67, 95% CI = 0.38,1.19 for highest versus lowest quartile), but neither gastric cardia nor distal gastric cancer was associated with the Total Activity Index. This inverse association held for esophageal adenocarcinoma (OR = 0.61, 95% CI = 0.38,0.99 for highest vs. lowest quartile) and modest associations were observed for gastric cardia (OR = 0.76, 95% CI = 0.49,1.18) and distal gastric cancer (OR = 0.77, 95% CI = 0.52,1.14) when based on Average Annual Activity Index before age 65 years. Analyses stratified by gender, race, age, BMI, education and years worked provided similar results. We found a modest protective effect of Total Activity Index on esophageal adenocarcinoma. Future studies with more complete information on occupational and recreational physical activity are needed to confirm and further investigate the suggested protective effect of physical activity on these tumor types.

Progressive prothrombotic state in women with advancing HIV disease.

Background: HIV-infected patients are at increased risk for venous thrombotic events (VTEs). We sought to determine if advancing stages of HIV were associated with coagulation abnormalities that could predispose to VTE. Methods: Functional protein S, factor VIII activity, and lupus anticoagulant were assayed in 144 participants of the Womens Interagency HIV Study. Women with conditions associated with VTE (cancer, pregnancy, hormone use, acute infection, cancer, and autoimmune disease) were excluded. Subjects included 34 women with history of clinical AIDS, 11 with immunologic AIDS (CD4 count, <200 cells/dL), 49 with asymptomatic HIV, and 50 HIV-negative comparators. Results: We found progressive decreases in protein S, when comparing HIV-negative women (median, 76%) to women with asymptomatic HIV (median, 67%), immunologic AIDS (median, 62%), or clinical AIDS (median, 46%; P < 0.0001). Similarly, advancing HIV was associated with stepwise increases in factor VIII, from a median of 116% in HIV-negative women to 149% in those with asymptomatic HIV, 196% in those with immunologic AIDS, and 211% in those with clinical AIDS (P < 0.0001). No subject had lupus anticoagulant. Conclusions: Advancing HIV is associated with progressive abnormalities of protein S and factor VIII; both of which are associated with increased risk for VTE, thus providing a biologic mechanism for the increased prevalence of VTE in HIV.

TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials

To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases) or CONFIRM-2, mRNA was isolated of microdissected formalin-fixed paraffin-embedded samples and quantitated using TaqMan-based technology. Existing TS and ERCC-1 cutoff levels were tested for their prognostic value in first-line and second-line therapy. TS expression was associated with overall survival (OS) in first-line, but not second-line therapy. ERCC-1 was associated with OS in patients treated with first-line and second-line FOLFOX4. In first-line FOLFOX4, combination of high TS and/or high ERCC-1 was associated with shorter OS. A correlation was observed between ERCC-1 expression and benefit from PTK/ZK+FOLFOX4 treatment. TS and ERCC-1 expression is associated with clinical outcome in mCRC. Baseline TS and ERCC-1 levels may allow the selection of patients who benefit from FOLFOX4 chemotherapy.

Diabetes and other comorbidities in breast cancer survival by race/ethnicity: The California Breast Cancer Survivorship Consortium (CBCSC)

Background: The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. Methods: We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer–specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Results: Risk of breast cancer–specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18–1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27–2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer–specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32–3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70–1.84; Pinteraction = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (Pinteraction = 0.09). Conclusion: These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction. Impact: Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome. Cancer Epidemiol Biomarkers Prev; 24(2); 361–8. ©2014 AACR.

Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PURPOSE To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. METHODS The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. RESULTS Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters-C/D, HVF, and IOP-substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). CONCLUSIONS No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs.