tbuckley/cabot-search huggingface dataset:
Epidermal growth factor receptor intron 1 (CA)<sub>n</sub> dinucleotide repeat polymorphism and mutations associated with the responsiveness of molecular targeted therapy in lung cancer
Authors: J. Wang, S. Zhang, R. Lai
Journal: Journal of Clinical Oncology (2009)

e14595 Background: To explore EGFR gene intron 1 (CA) n repeat polymorphism and mutations associated with the responsiveness of molecular targeted therapy in lung cancer. Methods: Both observed groups consisted of 116 somatic specimens of lung cancer and controls consisted of 20 peripheral blood samples were analyzed by direct DNA sequencing of EGFR mutations at exons 18,19,21. Also (CA) n repeat polymorphisms in intron 1 of EGFR from 48 specimens were analyzed. 45 lung cancer patients were followed up. Results: EGFR mutations were found in 24 of 116 somatic specimens (20.69%). Response rate and disease control rate to EGFR TKIs was significantly higher in the patients with EGFR mutations (62.5% vs. 0)(P&lt;0.0l),(100% vs.44.4%) (P&lt;0.05)respectively than those without it in observed groups.In patients harboring EGFR mutations, disease control rate to patients treated with Iressa (100%) was significantly higher than those who never treated with it (40%)(P&lt;0.05). The frequency distribution of EGFR intron 1 (CA) n repeat in 48 specimens was 23(47.9%)low (CA) n repeat(CA≤16)and 25 (52.1%) high repeat(CA&gt;16). There was no significant difference in response rate and disease control rate of EGFR TKIs treatment between low and high (CA) n repeat numbers both in 16 patients with mutations and 18 patients without mutations in observed groups(P&gt;0.05). Conclusions: Somatic mutations of EGFR is a major determinant of EGFR TKIs response in lung cancer. There was no significant difference in response rate and disease control rate of EGFR TKIs treatment between low (CA) n repeat patients and high repeat ones under the consideration of the mutant factor. No significant financial relationships to disclose.
Neurocognitive outcomes after proton radiation for pediatric brain tumors.
Authors: M. B. Pulsifer, I. Delgado, N. Tarbell, K. Kuhlthau, S. M. MacDonald, T. I. Yock
Journal: Journal of Clinical Oncology (2010)

9508 Background: Radiation therapy is integral in treatment of pediatric brain tumors. However, conventional photon radiation is associated with long-term neurocognitive sequelae, including decrements in IQ and difficulties with attention, processing speed, and other executive skills. Proton radiation provides better targeting of tumors than conventional photon radiation, sparing surrounding healthy tissue. It is expected that radiation-related neurocognitive impairments would be lower after proton radiation relative to reports of photon radiation. We examined long-term neurocognitive outcomes of 56 patients with brain tumors treated with proton radiation at MGH. Methods: 184 patients with brain tumors received proton radiation and baseline (BL) neuropsychological testing starting in 9/02. Of these, 56 received follow-up testing two years from BL (M=2.12, SD=1.30). Results: 30 males (54%) and 26 females (46%) received proton radiation for treatment of medulloblastoma (50%), craniopharyngioma (16%), ependymoma (13%), and other (21%) tumors. Mean age was 8.23 years (SD=4.47) at BL (range: 1 to 19). Mean total radiation dose was 52.77 GyE (SD=4.14) and 71% received chemotherapy as part of treatment. Patients with follow-up testing did not differ in age at baseline or gender from those without follow-up. Performances at BL were average or slightly better in most areas, including IQ, receptive/expressive vocabularies, working memory, processing speed, manual dexterity, attention, reading, and arithmetic, with the exception of visuospatial organization and memory, where scores were below average (M=86.45, SD=16.66; M=84.41; SD=16.72, respectively). Comparison of pre- and post-treatment standard scores revealed no decline in nearly all areas assessed, with the exception of a significant decline in processing speed, t(38)=5.35, p<.05, and further reduction in visuospatial organization, t(22)=2.10, p<0.05. Declines were not related to histology, gender or age at BL. Conclusions: At 2-year follow-up after proton radiation, neurocognitive performances were stable, with no significant change seen in most areas assessed. Overall, results compare favorably to reports from photon radiation treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IBA, ProCure Corporation IBA, ProCure Corporation
Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity
Authors: Dariush Mozaffarian
Journal: Circulation (2016)

Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes mellitus. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not only blood lipids or obesity; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (eg, sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on the cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to date supports the cardiometabolic relevance of other popular priorities: eg, local, organic, grass-fed, farmed/wild, or non-genetically modified. Evidence-based personalized nutrition appears to depend more on nongenetic characteristics (eg, physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies targeting economic incentives, schools and workplaces, neighborhood environments, and the food system. Scientific advances provide crucial new insights on optimal targets and best practices to reduce the burdens of diet-related cardiometabolic diseases.
Abstract 12109: Depot-Specific Abnormalities in Adipose Tissue Insulin Signaling in a Porcine Model of Metabolic Syndrome
Authors: Gregory G Schwartz, J W Leitner, Li Lu, Shuyu Ye, Akshay Pendyal, Rocio Pereira, Cecilia C Wang, Jane E Reusch, Clifford R Greyson
Journal: Circulation (2014)

Background: The clinical metabolic syndrome (Met Syn) is associated with systemic insulin resistance and with increased mass and dysfunction of subcutaneous (SAT) and visceral adipose tissue. Accumulation and dysfunction of epicardial adipose tissue (EAT) have been associated with cardiovascular risk in Met Syn. We previously characterized a porcine dietary model of Met Syn that demonstrates defective insulin signaling in cardiac and skeletal muscle and arterial wall, and impaired cardiac tolerance to ischemia. We used this model in this study to assess effects of MetSyn on insulin signaling in SAT and EAT. Methods: Yucatan micropigs (n=16) were fed a diet enriched in saturated fat (coconut oil) and high fructose corn syrup for 6 months to induce obesity and MetSyn. Yucatan micropigs or domestic farm pigs fed standard low-fat chow served as lean controls (n=23). In each pig, SAT and EAT were sampled in the absence of exogenous insulin stimulation and/or 10 min after a saturating dose of insulin (10 U/kg, ...
Investigation of cognitive screening measures in patients with brain tumors: Diagnostic accuracy and correlation with quality of life
Authors: R. A. Olson, G. Iverson, M. Parkinson, H. Carolan, A. Ellwood, M. McKenzie
Journal: Journal of Clinical Oncology (2009)

e13000 Background: Brief cognitive screening measures are often selected by clinicians and researchers for brain tumor patients, primarily because of their ease of use. Currently, the Mini Mental State Examination (MMSE) is the most commonly chosen, despite a reported low sensitivity. The primary objective of this study was to compare the sensitivity of the MMSE with the Montreal Cognitive Assessment (MoCA). Methods: 44 patients with brain tumors were prospectively accrued and administered the MMSE and MoCA by blinded investigators, 75% of who completed a 4-hour “gold standard” neuropsychological assessment (NPA). Quality of life and community integration were measured with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Community Integration Questionnaire (CIQ), respectively. McNemar's test was used to compare sensitivity and specificity at pre-defined cutoff scores and receiver operating characteristic curve analyses were used to examine outcomes across all cutoffs. Correlations were assessed with Spearman's rank correlation coefficient. Results: 55% of patients met criteria for the DSM-IV diagnosis of Cognitive Disorder NOS on the NPA. Using pre-defined cutoffs, the MoCA was significantly more sensitive than the MMSE (55.5% versus 16.6%; p = 0.016), although specificity of the MoCA was poor (60.0%). MMSE scores below 27 were 100% specific; however, this applied to only three subjects. Furthermore, 39% of cognitively impaired subjects scored perfectly on MMSE. A MoCA cutoff of 22 had 28% sensitivity and 93% specificity, and a cutoff of 28 had 94% sensitivity and 20% specificity. The MoCA was correlated with both the FACT-Br (r = 0.319, p = 0.04) and CIQ (r = 0.427, p = 0.005), while MMSE scores did not correlate with either (p &gt; 0.2). Conclusions: The MoCA is more sensitive than the MMSE, though at no cutoff is it both sensitive and specific. Despite its limitations, the MoCA may offer cost saving in the oncology clinic as a cognitive screen: individuals with MoCA scores a) below 22 are likely cognitively impaired, b) above 27 are likely cognitively normal, and c) 22–27 would likely benefit most from NPA. Furthermore, the MoCA is better able to detect cognitive impairment that is related to functional limitations and quality of life. [Table: see text]
Effect of the GLP-1 Receptor Agonist Lixisenatide on Counterregulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes
Authors: Johan Farngren, Margaretha Persson, Bo Ahrén
Journal: Diabetes Care (2015)

OBJECTIVE Counterregulatory responses are critical to prevent hypoglycemia in subjects with type 2 diabetes. This is particularly important in insulin-treated patients. This study explored the effect of the glucagon-like peptide 1 receptor agonist lixisenatide on the hormonal counterregulatory responses to insulin-induced hypoglycemia when added to basal insulin therapy in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 18 subjects with type 2 diabetes (11 males) with a mean age of 55 years, diabetes duration of 12 years, HbA1c level of 7.7%, fasting blood glucose (FBG) concentration of 9.7 mmol/L, and a BMI of 33 kg/m2, who were treated with basal insulin (mean duration 7 years, daily dose 39 units/day) and metformin (mean daily dose 2.1 g). Subjects received treatment with lixisenatide or placebo for 6 weeks in random order, with a 4-week washout period in between. After 6 weeks of treatment, subjects underwent a two-step hyperinsulinemic hypoglycemic clamp at 3.5 and 2.8 mmol/L. RESULTS After 6 weeks of treatment, HbA1c and FBG levels were lower after lixisenatide therapy than after placebo therapy. At the hypoglycemic level of 3.5 mmol/L, glucagon and epinephrine levels were significantly lower during lixisenatide treatment than during placebo treatment, whereas at 2.8 mmol/L glucagon and epinephrine levels did not differ between the subjects. Cortisol, pancreatic polypeptide, and norepinephrine levels did not differ significantly between the treatments. CONCLUSIONS Glucagon and epinephrine levels are reduced by lixisenatide at a concentration of 3.5 mmol/L, but their counterregulatory responses to deep hypoglycemia at a concentration of 2.8 mmol/L are sustained during treatment with lixisenatide in combination with basal insulin.
Quality of life assessment and depression screening in the gynecologic oncology clinic
Authors: B. E. Miller, E. Dunn, R. McQuellon
Journal: Journal of Clinical Oncology (2004)

5149 Background: It is difficult to assess a patient's quality of life (QOL) and mood status during a busy clinic, yet QOL can influence the decision to continue therapy, especially during palliation. The objective of this study was to determine how standardized tools for depression screening and QOL assessment could be integrated in a routine clinic visit. Method: Patients with gynecologic cancers completed a QOL assessment with a 100 mm LASA scale and the Karnofsky performance status prior to three consecutive clinic visits for chemotherapy. Before the 2nd and 3rd visit they also completed the Functional Assessment of Cancer Therapy (FACT-G) and Center for Epidemiologic-Depression (CES-D) scale. After each visit questions about patient satisfaction were answered on a 5 point Lickert scale and the physician completed the LASA scale and the Karnofsky performance status assessment. After the 3rd visit the physician viewed the FACT-G and CES-D results and discussed them with the patient. Descriptive statistics and t-test were used for evaluation. Results: 25 patients completed all three assessments, 22 were treated for recurrent disease. The mean LASA scale values as rated the patient at the first second and third clinic visit respectively were 68, 71 and 76; values determined by the physician were 73, 74 and 77; the most similar assessment by the patient and physician occurred after the third visit. The mean FACT-G score was 75 before the 2nd and 78 before the 3rd visit. The mean CES-D score was 19 before the 2nd and 17 before the 3rd visit. After the 2nd visit 18 patients felt that answering the questions made them more aware of their QOL; 20 patients reported feeling this way after the 3rd visit. Four patients did not like completing the questionnaires. Patients felt their needs were addressed with a score of 4.76 after the 1st and 4.96 after the 3rd visit (p=0.01); the score regarding patient satisfaction increased from 4.43 to 4.69 (p= 0.04). The average time needed for answering all questions was 9 minutes. Conclusion: It is possible to integrate quality of life assessment with the FACT-G and depression screening with the CES-D into a routine oncology clinic visit. No significant financial relationships to disclose.
Abstract 13558: Which Cutoff Value of Clinic BP Better Stratify Cardiovascular Risk in Patinets with Type 2 Diabetes ? - the J-HOP Study -
Authors: Kazuo Eguchi, Satoshi Hoshide, Shoichiro Nagasaka, Kazuomi Kario
Journal: Circulation (2014)

Introduction:  In the JNC-8 guideline, target clinic BP in type 2 diabetes (T2DM) was raised to 140/90mmHg based on recent clinical trials. However, there are still some opinions that the cutoff value of clinic BP 130/80mmHg might be better than 140/90.   Hypothesis:  We sought to clarify the hypothesis that different clinic BP cutoff values, 130/80mmHg or 140/90mmHg, could have different impact on cardiovascular risk stratification in patients with T2DM.   Methods:  We enrolled 4326 patients who have at least one cardiovascular risk factor, and performed clinic BP monitoring and measured urinary albumin creatinine ratio (UACR) as a surrogate marker of cardiovascular risk. Patients were stratified by 4 groups using SBP 140mmHg and DBP 90 mmHg: Group1, SBP>140,DBP>90; Group2, >140,≤90; Group3; ≤140,>90; Group4; ≤140≤90. Alternatively, SBP 130mmHg and DBP 80mmHg were also used as a cutoff value. Multivariable logistic regression analyses adjusting for age, sex, BMI, history of hypertension, and renal dysfunction were used for the likelihood of microalbuminuria (UACR ≧30mg/g·cr).   Results:  The mean age was 64.9±10.9 years; 47.0% were male; and 87.1% had hypertension. There were 1057 (24.5%) patients with T2DM, and they were analyzed in this study. In the cutoff value of SBP 140mmHg and DBP 90 mmHg, the odds ratio (OR) for microalbuminuria was 1.5 to 4 times in higher SBP and/or DBP groups ( Figure-left panel ). On the other hand, for the cutoff value of SBP 130mmHg and DBP 80 mmHg, OR was 1.6-1.7 in the group with SBP>130mmHg but the likelihood of microalbuminuria was similar between the Group 3 and 4. ( Figure-right panel ).   Conclusions:  In a large cohort sample of T2DM, the cutoff value of clinic BP would be better for 140/90 mmHg than 130/80mmHg with regard to the prediction of microalbuminuria.
Use of clodronate disodium for adjuvant treatment of oncological pain due to bone metastases of solid tumors among adults
Authors: R. Hegg, S. R. Graziani, N. A. Bossa, A. Aliano, G. Carboni
Journal: Journal of Clinical Oncology (2008)

20726 Background: Patients with bone metastases are a special group of patients with metastatic disease for whom the prognosis is better, with longer survival, but with a greater likelihood of intercurrences and complications. Methods: Between April 2004 and April 2007, we evaluated 54 patients (32 females and 22 males) of mean age 61.5 years (range: 35 to 81 years). The primary site of incidence of their neoplasia was breast cancer (24 patients), prostate cancer (10), non-small cell lung cancer (9), kidney cancer (3), malignant melanoma (2), neuroendocrine carcinoma (2), stomach cancer (2), cancer of the uterine cervix (1) and no primary site (1). The pain evaluation methodology consisted of using a numerical visual analog scale (VAS) on which a score of zero corresponded to absence of pain and ten to intense pain. We also evaluated the performance status (WHO), monitored the use of analgesics and tested renal function, serum calcium levels and hemoglobin levels every three cycles. We used disodium clodronate (Bonefos) 1,500 mg diluted in 500 ml of 0.9% physiological solution for two-hour adjuvant treatment sessions every 21 days, to treat pain due to bone metastases. Results: We evaluated 564 cycles of medication, with a mean of 11.75 cycles per patient (range: 2 to 47 cycles). The mean pain score at the start of the treatment was 6.8 (range: 2–8) and after six cycles it was 1.8 (range: 0–8). The patients were evaluated every month and notified every three months. Twenty-four patients were using radiotherapy for antialgic purposes at the start of the treatment and 11 patients were using concomitant palliative chemotherapy. There was a reduction in the use of analgesic medication (in the degree of analgesia according to WHO) among 35 patients (64%), thus: weak opioids as ordinary analgesics if necessary, among five patients; no use of simple analgesics in the event of pain, among 30 patients. Toxicity evaluation: One patient presented gastrointestinal toxicity with a condition of slight diarrhea. Conclusions: We concluded that the association of disodium clodronate with palliative oncological treatment such as radiotherapy and chemotherapy for bone metastases may be an effective alternative for controlling bone pain. No significant financial relationships to disclose.
Investigation of lifestyle risks exposure as response predictor of gefitinib in non-small cell lung cancer patients.
Authors: Y. Wang, H. Ying, X. S. Wang, Q. Shi, S. Chen
Journal: Journal of Clinical Oncology (2011)

e18070 Background: As smoking was significant negative predictor to EGFR-TKI treatment and act as risk for NSCLC too, our curiosity was evoked to do the pilot investigation on the relationship between life-style risk factor and gefitinib efficacy. Methods: Two hurndred seventy three patients with histological proven and clinical stage IIIB-IV NSCLC were investigated retrospectively. Based on clinical characteristics, they were divided into gefitinib sensitive or resistant groups. Self-designed questionnaire about tobacco exposure, occupational exposure, cooking Chinese food at home (CAH), living area (city or rural area) were obtained. Overall survival (OS) was calculated from the day of diagnosis for patient with advanced disease. To those who with completely resected disease with/or without adjuvant chemotherapy, OS was calculated from the day of recurrence determined. Results: The mean age was 60.97 ±12.10 years (27-86 years). The male: female is: 1.275:1 And 14.29% patients had squamous cell cancer. The percentage of patients with stage IIIa, IIIb and IV diseases were 15.38%, 25.27% and 43.96% respectively. In multivariate Logistic analysis, clinical features associated with negative response to gefitinib were male (odds ratio 0.20, p=0.000), smokers included SHS (odds ratio 0.22, p=0.000 ). Positive factors included non- squamous cell carcinoma (odds ratio 1.29, p=0.000), cooking at home (CAH; odds ratio 19.13, p=0.000). Living in rural area, chronic lung disease and occupational exposure were not significantly associated with gefitinib efficacy. The median overall survival of gefitinib sensitive and resistant groups were 26.32 month and 11.73 months respectively (p < 0.0001). Cox analysis showed that gefitinib sensitive is a mainly prognostic factor for longer survival (p=0.032). Conclusions: Gefitinib sensitive is a significantly prognostic factor for NSCLC patients. Cooking at home is a positive treatment predict factor for gefitinib. As small number of patients living in rural area, few patients with chronic lung disease or occupational exposure were included, the association of gefitinib treatment with these factors is still obscure.