Associations Between Alcohol Consumption and Insulin Sensitivity and Cardiovascular Disease Risk FactorsThe Insulin Resistance and Atherosclerosis StudyOBJECTIVE -Light-to-moderate alcohol consumption has been associated with reduced cardiovascular disease (CVD) mortality, which may be explained by increased insulin sensitivity (S I ) and an improved lipoprotein and blood pressure profile. Prior research has shown improved S I with light-to-moderate alcohol intake even though somewhat imprecise measures of S I were used. RESEARCH DESIGN AND METHODS-Relationships between alcohol use and S I and CVD risk factors were assessed in a cross-sectional analysis of 1,196 white, African-American, and Hispanic men and women from the Insulin Resistance and Atherosclerosis Study (IRAS). Five categories of previous-year alcohol use (never, Ͻ0.5 drinks/day, 0.5-0.99 drinks/day, 1-2.99 drinks/day, and Ն3 drinks/day) and log S I ϩ 1 (frequently sampled intravenous glucose tolerance test with Bergman minimal model analysis), log fasting insulin, log triglycerides, HDL cholesterol, and systolic/diastolic blood pressure were examined using analysis of variance.RESULTS -Univariate analysis showed an inverse U-shaped relationship between S I and alcohol intake, with a peak at the 0.5-0.99 drinks/day category. A U-shaped relationship was observed between fasting insulin and the lipid and blood pressure measures. After adjustment for demographic (clinic, sex, ethnicity, age), lifestyle (smoking, dietary energy/fat intake, physical activity), and physical (BMI, waist circumference) variables, the alcohol/insulin association was attenuated, but the association with lipids and blood pressure remained for high-intake categories.CONCLUSIONS -These data suggest that the enhanced S I associated with light-to-moderate alcohol consumption may be a function solely of a BMI and central adiposity profile more favorable to higher S I .

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and implementation of risk-adapted therapy has been instrumental in the dramatic improvements in clinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of individual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions, notably ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing (RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as drivers in ALL, and identification of these new entities will contribute to refining ALL risk stratification. We used RNA-seq on 126 ALL patients from our clinical service to test the utility of including RNA-seq in standard-of-care diagnostic pipelines to detect gene rearrangements and IKZF1 deletions. RNA-seq identified 86% of rearrangements detected by standard-of-care diagnostics. KMT2A (MLL) rearrangements, although usually identified, were the most commonly missed by RNA-seq as a result of low expression. RNA-seq identified rearrangements that were not detected by standard-of-care testing in 9 patients. These were found in patients who were not classifiable using standard molecular assessment. We developed an approach to detect the most common IKZF1 deletion from RNA-seq data and validated this using an RQ-PCR assay. We applied an expression classifier to identify Philadelphia chromosome–like B-ALL patients. T-ALL proved a rich source of novel gene fusions, which have clinical implications or provide insights into disease biology. Our experience shows that RNA-seq can be implemented within an individual clinical service to enhance the current molecular diagnostic risk classification of ALL.

This pilot test effort focused on weight management strategies for individuals with type 2 diabetes living in rural, medically under-served communities. Randomly selected patients from the diabetes registry of a federally funded primary care practice in a rural community were randomized to one of two 8-week interventions: intensive lifestyle (reduced fat and calorie intake and increased activity) or intensive lifestyle plus ongoing formal evaluation for continuous quality improvement. Mean weight loss was 1.15 +/- 1.90 kg (96.4% African American, n = 23, p < 0.01) with no difference between groups. Among the 78% who lost weight, mean loss was 2.00 kg. Mean difference in pre- vs. postintervention fasting blood glucose was -24.23 mg/dL (n = 23, p < 0.05). In this rural, medically under-served community, the interventions were moderately successful in facilitating weight loss and improving fasting glucose concentration. For purposes of state-of-the-art weight management interventions with diabetics, the addition of formal evaluation did not result in improved outcomes.

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In a prospective, randomized, multicenter study, neoadjuvant chemotherapy (CT) with carboplatin and 5-fluorouracil (5-FU) followed by locoregional treatment (LRT) was compared with locoregional treatment alone in the treatment of patients with head and neck cancer. This study, which includes 324 patients, was conducted from January 1988 to July 1991. The aim of this study was to evaluate the impact of the carboplatin/5-FU regimen both on the incidence of mutilating surgery and on the survival rate. Chemotherapy consisted of three cycles of carboplatin 400 mg/m² day 1 and 5-FU 1 g/m² days 1-5, repeated every 3 weeks. Patients with a complete tumor response then received radiotherapy alone, instead of the treatment planned initially. Three hundred patients were analyzed: 79 had tumors of the oral cavity, 106 oropharyngeal tumors, and 115 pharyngolaryngeal tumors. One hundred fifty patients underwent CT+LRT; 150 patients had LRT alone. Grade 3 and 4 toxicity rates were minimal in the CT+LRT group; toxicity was mainly hematologic (24% neutropenia, 19% thrombocytopenia). There were 3 toxic deaths (2%), 2 due to septicemia and 1 due to cardiac toxicity. One hundred forty-three patients were evaluable for efficacy. The tumor objective response rate was 63% and complete response rate was 31% (35% for oropharyngeal, 34% for pharyngolaryngeal tumors, 22.5% for oral cavity tumors), which led to a 29% decrease in the rate of mutilating surgery. Conservative treatment was performed in 57% of patients in the CT+LRT group vs. 24% in the LRT group (p = 0.001). There was no significant difference between survival curves in the CT+LRT and LRT groups. At 4 years, overall survival rates were 56 and 46%; disease-free survival rates were 33 and 30% in the CT+LRT and the LRT groups, respectively. The survival rates were not significantly different in the two groups. The locoregional recurrence rates were 35% in the CT+LRT arm and 25% in the LRT arm (p = 0.04), with median follow-up of 25 months. The rates of secondary localization and distant metastasis were not significantly different in the two groups.