tbuckley/cabot-search huggingface dataset:
Abstract P514: A Healthy Beverage Score and Risk of Chronic Kidney Disease Progression, Cardiovascular Disease, and All-Cause Mortality in the Chronic Renal Insufficiency Cohort
Authors: Emily Hu, Cheryl A Anderson, Morgan Grams, Lawrence J Appel, Josef Coresh, Deidra Crews, Jiang He, Haochang Shou, Katherine T Mills, Jonathon Taliercio, Madhumita Jena-Mohanty, Zeenat Bhat, Casey M Rebholz
Journal: Circulation (2020)

Background: The association between an overall healthy beverage pattern and chronic disease outcomes is unknown. We created the Healthy Beverage Score (HBS) to characterize the healthfulness of participants’ beverage profiles and examined its association with chronic kidney disease (CKD) progression, cardiovascular disease (CVD), and all-cause mortality among individuals with CKD. Methods: We conducted a prospective analysis of 2,275 participants aged 21-74 years with an estimated glomerular filtration rate (eGFR) between 20 and 70 mL/min/1.73 m 2 from the Chronic Renal Insufficiency Cohort. Diet was assessed using a 124-item food frequency questionnaire at visit 1 (2003-2008). The HBS (7-28) consisted of 7 components. Each component was scored 1-4 based on rank distribution by quartile. Participants were given more points for higher consumption of low-fat milk, coffee and tea, moderate consumption of alcohol, and lower consumption of 100% fruit juice, full-fat milk, artificially-sweetened beverages, and sugar-sweetened beverages. CKD progression, CVD, and all-cause mortality were ascertained through January 2018. We conducted multivariable Cox proportional hazards models. Results: There were 815 cases of CKD progression, 285 cases of CVD, and 725 deaths over a median of 7, 10, and 12 years of follow-up, respectively. Compared with participants in the lowest tertile of the HBS, participants in the highest tertile had a 27% lower risk of CKD progression (hazard ratio, HR: 0.73, 95% confidence interval, CI: 0.61-0.87) ( P -trend&lt;0.001) and 17% lower risk of all-cause mortality (HR: 0.83, 95% CI: 0.69-1.00) ( P -trend=0.05) after adjusting for covariates ( Table ). There was no significant association for CVD comparing tertile 3 with tertile 1 (HR: 0.93, 95% CI: 0.70-1.23) ( P -trend=0.70). Conclusions: A healthier beverage pattern was associated with lower risk of CKD progression and all-cause mortality. Beverage intake may be an important modifiable dietary target in managing outcomes for individuals with CKD.
Topoisomerase-II, c-erb B2, c-kit and bcl-2 expression in non-small cell lung cancer treated with docetaxel and gemcitabine based threapy
Authors: I. O. Kara, M. Erkisi, D. Gumurdulu, B. Sahin, H. Zeren
Journal: Journal of Clinical Oncology (2007)

18212 Background: This study was conducted to determine the expression of the topoisomeras-II, c-erb B2, c-kit and bcl-2 in patients with non-small cell lung cancer (NSCLC). Material-methods: These factors expression were identified by immunohistochemical method in 62 NSCLC patients pathologically verified on before therapy. Results: 3 patients were in stage-II, 10 in stage-IIIA, 21 in stage-IIIB and 28 in stage-IV. 14 patients had refused therapy, 12 were undergone to surgery alone and 36 recieved multimodality therapy. 27 patients recieved docetaxel-cisplatin therapy and 7 had recieved gemcitabine-cisplatin therapy. Of those docetaxel treated patients 14 received radiation therapy and others undewent surgery in combination therapy. In 31 patients topoisomerase-II was +2 (50%), +1 in 3 patients, +3 in 27 patients and in 1 patient the expression was negative. c-erb B2 was negative in 1, +1 in 2, +2 in 14 and +3 in 45 patients. bcl-2 was negative in 9, +1 in 16, +2 in 22 and +3 in 15 patients. c-kit was negative in 9, +1 in 26, +2 in 15 and +3 in 12 patients. Statistical analysis was done by SPSS- 14 software program. The disease stage, received therapies and the expression of the these proteins was correlated, median survival time and possible prognostic factors were identified. There were statistically significant between stage and patient status (P=0.000), either with therapy or no therapy (p=0.003), bcl-2 (p=0.09) and c-kit (p=0.022), respectively. There were statisticaly significant between stage and bcl-2 (p=0.023), bcl-2 and c-kit (p=0.001), respectively. At the end of the follow-up time, 38 (61.3%) patients were alive. The median survival was 37.2 months. There were not any prognostic values for topoisomerase-II (p=0.7), c-erb B2 (p=0.6), bcl-2 p=0.15) and c-kit (p=0.118) expression. Conclussion: In conclussion, we suggested that the treatment modality of patients with NSCLC should be combination therapy. The patients received docetaxel based therapy had long median survival time. In addition there was no prognosticeffect of the expression of the topoisomeras-II, c- erb B2, c-kit and bcl-2 in patients with non-small cell lung cancer (NSCLC). No significant financial relationships to disclose.
Age and body composition related-effects on the pharmacokinetic disposition of STEALTH liposomal CKD- 602 (S-CKD602) in patients with advanced solid tumors
Authors: W. Zamboni, L. J. Maruca, S. Strychor, B. A. Zamboni, S. Ramalingam, R. P. Edwards, D. M. Friedland, R. G. Stoller, C. P. Belani, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2007)

2528 Background: STEALTH liposomes (SL), which contain lipids conjugated to polyethylene glycol (PEG), prolong the circulation time of a drug in plasma, achieve high and extended drug exposure in tumor, and are eliminated via the reticuloendothelial system (RES). S- CKD602 is a SL formulation of CKD-602, a camptothecin analogue. CKD-602 released from S-CKD602 is eliminated by the kidney. There is significant interpatient variability in the pharmacokinetic (PK) disposition of S-CKD602. Thus, there is a need to identify factors associated with the PK variability. We hypothesize that older patients (pts) have a reduced capacity to eliminate SL agents due to age-related impairment of the RES and that body composition alters the disposition of SL. Methods: PK studies of S-CKD602 were performed in a phase I study of S-CKD602 at 0.1 to 2.5 mg/m 2 IV q 21 d in pts with solid tumors. Concentrations of encapsulated (E), released (R), and sum total (E + R) CKD-602 in plasma and CKD-602 in urine were measured by LC-MS/MS. Area under the plasma concentration versus time curve (AUC) was calculated and normalized by dose (AUC/dose). The ratio of total body weight to ideal body weight (TBW/IBW) was calculated as a measure of body composition. Results: Mean ± SD S-CKD602 sum total AUC/dose in pts &lt; 60 (n = 13) and = 60 (n = 17) years of age (yo) were 4.5 ± 5.0 and 11.2 ± 11.0 (μg/ml·h)/(mg/m 2 ), respectively (P&lt;0.05). Controlling for age, there was a statistically significant inverse relationship between TBW/IBW and S-CKD602 AUC/dose where low TBW/IBW was associated with high AUC/dose in both age groups (P&lt;0.05). The cumulative amount of CKD-602 recovered in the urine was 2.2-fold higher in pts &lt; 60 yo compared with = 60 yo. Conclusions: These data suggest that pts = 60 yo have a reduced clearance of S-CKD602 and reduced release of CKD-602 from S- CKD602 compared with pts &lt; 60 yo. In addition, pts &lt; 60 and = 60 yo with a lean body composition may have a reduced tissue distribution and an increased plasma exposure of S-CKD602. The clinical significance of these differences and the factors associated with them need to be evaluated for S-CKD602 and other liposomal and nanoparticle anticancer agents. No significant financial relationships to disclose.
Mutations in the V‐ATPase Assembly Factor VMA21 Cause a Congenital Disorder of Glycosylation With Autophagic Liver Disease
Authors: Magda Cannata Serio, Laurie A. Graham, Angel Ashikov, Lars Elmann Larsen, Kimiyo Raymond, Sharita Timal, Gwenn Le Meur, Margret Ryan, Elzbieta Czarnowska, Jos C. Jansen, Miao He, Can Ficicioglu, Pavel Pichurin, Linda Hasadsri, Berge Minassian, Alessandra Rugierri, Hannu Kalimo, W. Alfredo Ríos‐Ocampo, Christian Gilissen, Richard Rodenburg, Johan W. Jonker, Adriaan G. Holleboom, Eva Morava, Joris A. Veltman, Piotr Socha, Tom H. Stevens, Matias Simons, Dirk J. Lefeber
Journal: Hepatology (2020)

Vacuolar H+-ATP complex (V-ATPase) is a multisubunit protein complex required for acidification of intracellular compartments. At least five different factors are known to be essential for its assembly in the endoplasmic reticulum (ER). Genetic defects in four of these V-ATPase assembly factors show overlapping clinical features, including steatotic liver disease and mild hypercholesterolemia. An exception is the assembly factor vacuolar ATPase assembly integral membrane protein (VMA21), whose X-linked mutations lead to autophagic myopathy.Here, we report pathogenic variants in VMA21 in male patients with abnormal protein glycosylation that result in mild cholestasis, chronic elevation of aminotransferases, elevation of (low-density lipoprotein) cholesterol and steatosis in hepatocytes. We also show that the VMA21 variants lead to V-ATPase misassembly and dysfunction. As a consequence, lysosomal acidification and degradation of phagocytosed materials are impaired, causing lipid droplet (LD) accumulation in autolysosomes. Moreover, VMA21 deficiency triggers ER stress and sequestration of unesterified cholesterol in lysosomes, thereby activating the sterol response element-binding protein-mediated cholesterol synthesis pathways.Together, our data suggest that impaired lipophagy, ER stress, and increased cholesterol synthesis lead to LD accumulation and hepatic steatosis. V-ATPase assembly defects are thus a form of hereditary liver disease with implications for the pathogenesis of nonalcoholic fatty liver disease.
Sustainable Development Goals and the Future of Cardiovascular Health
Authors: William A. Zoghbi, Tony Duncan, Elliott Antman, Marcia Barbosa, Beatriz Champagne, Deborah Chen, Habib Gamra, John G. Harold, Staffan Josephson, Michel Komajda, Susanne Logstrup, Bongani M. Mayosi, Jeremiah Mwangi, Johanna Ralston, Ralph L. Sacco, K.H. Sim, Sidney C. Smith, Panos E. Vardas, David A. Wood
Journal: Journal of the American College of Cardiology (2014)
Abstract P519: Multivitamin Use And Arterial Stiffness In Older Women And Men
Authors: Chisa Matsumoto, Susanne Rautiainen, Elise Roche, JoAnn E Manson, Howard D Sesso
Journal: Circulation (2020)

Introduction: A multivitamin (MV) is the most commonly taken supplement in older U.S. adults. Arterial stiffness is an important intermediate marker of cardiovascular disease (CVD). However, few studies have examined the association of MV use and arterial stiffness. Hypothesis: Regular multivitamin use is associated with lower levels of arterial stiffness. Methods: A subcohort of participants enrolled in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a large scale randomized clinical trial testing a MV and a cocoa extract supplement on CVD and cancer, completed baseline measurement of arterial stiffness assessed by pulse wave velocity (PWV), augmentation index (AI), and central blood pressure (CBP). Frequency and duration of MV use was assessed via self-report questionnaire at baseline. The cross-sectional association of MV use and arterial stiffness was evaluated by multivariate linear regression with adjustment for conventional CVD risk factors. We also performed subgroup analyses to evaluate effect modification between MV use and sex, age, body mass index (BMI), and hypertension. Results: A total of 470 (229 women and 241 men) COSMOS participants were included in this study, with mean age 69.1±5.2 years, of whom 150 (32%) reported current MV use at baseline. Multivariate linear regression analysis revealed that current MV use (yes versus no) was significantly associated with lower PWV (β:-0.59±1.02, p=0.004) but not associated with other measures of arterial stiffness, including AI or CBP. There were also no consistent associations between frequency and duration of MV use with any of the measures of arterial stiffness. Also, there was no effect modification by sex, age, BMI, or hypertension on the association between MV use and arterial stiffness. Conclusions: MV use was associated with lower PWV in older subjects. Further results from the COSMOS trial on randomized MV supplementation and changes in arterial stiffness over 2 years will further elucidate the effects of MV on arterial stiffness.
Abstract MP48: Sex Difference, Circulating Short-chain Fatty Acids, Dietary Sodium Reduction in Untreated Hypertensives: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Haidong Zhu, Li Chen, Fengjun He, Ying Huang, Changqiong Wang, Gregory Harshfield, Yanbin Dong
Journal: Circulation (2020)

Introduction: Short-chain fatty acids (SCFAs) are products from the fermentative activity of gut bacteria and almost all circulating SCFAs are microbial in origin. Emerging evidence suggests that circulating SCFAs play a role in blood pressure (BP) control through the host receptors. Animal studies demonstrate that high salt diet modulates the gut microbiome and SCFAs. Moreover, gut microbiome contributes to sex differences in BP regulation. Hypothesis: We tested the hypothesis that the modest sodium reduction would alter circulating SCFAs among untreated hypertensives, and the changes in SCFAs would be associated with reduced blood pressure (BP) and improved cardiovascular phenotypes. Moreover, there would be sex differences in circulating SCFA response to sodium reduction. Methods: A total of 145 subjects (42% blacks, 19% Asian, 34% females) were included from a completed randomized, double-blind, placebo-controlled crossover trial of sodium restriction with slow sodium or placebo, each for 6 weeks. Targeted circulating SCFA profiling was performed in paired serum samples, which were collected at the end of each period, so as all outcome measures. Two-level mixed-effects linear regression models were used to assess the differences in SCFAs between sodium and placebo tablets while incorporating repeated measured data and controlling for age, sex and BMI as confounding variables. We further tested whether the changes in the SCFAs were associated with the changes in BPs, and cardiovascular phenotypes using mixed-effects models. Results: Sodium reduction increased all 8 SCFAs, among which the increases in 2-methylbutyrate, butyrate, hexanoate, isobutyrate, and valerate were statistically significant ( p &lt;0.05). The increased SCFAs were associated with decreased BP and improved capillary density. There were significant sex differences of SCFAs in response to sodium reduction ( p &lt;0.05). When stratified by sex, the increases in butyrate, hexanoate, isobutyrate, isovalerate, and valerate were significant only in women ( p &lt;0.05), but none were significantly changed in men ( p &gt;0.05). In women, increased isobutyrate, isovalerate, and 2-methylbutyrate were inversely associated with reduced BPs ( p &lt;0.05). Additionally, increased valerate was associated with decreased carotid-femoral pulse wave velocity (cf-PWV) ( p =0.04). Conclusions: Our results show that dietary sodium reduction increases SCFAs, suggesting that dietary sodium may influence the gut microbiome in humans given almost all SCFAs are microbial in origin. Moreover, increased circulating SCFAs are associated with decreased BPs, improved arterial compliance, and increased capillary density. The sex differences in SCFA response to dietary sodium reduction warrants further investigation.
Sunitinib as second-line treatment for advanced gastric cancer: preliminary results from a phase II study
Authors: Y. Bang, Y. Kang, W. Kang, N. Boku, H. Chung, S. Lanzalone, M. J. Lechuga, L. Sherman, R. Chao, A. Sobrero
Journal: Journal of Clinical Oncology (2007)

4603 Background: Sunitinib malate (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved internationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. We investigated the safety and activity of SU monotherapy in pts with previously-treated gastric cancer. Preliminary results from this open-label, multicenter, phase II study are reported. Methods: Eligibility criteria included measurable stage IV disease; 1 prior chemotherapy regimen; and ECOG PS =1. Pts took SU 50 mg/day for 4 wks followed by 2 wks off treatment in 6-wk cycles. A Simon 2-stage design was used with a target accrual of 38 pts in the first stage, expanding to 63 pts if =2 partial responses (PRs) were observed. The primary endpoint was RECIST-defined objective response rate. Secondary endpoints included duration of response and safety. Pharmacokinetic (PK) Ctrough parameters were also monitored. Results: As of Sept 15 2006, 38 evaluable pts (median age 56 years [range 29–78]; 2–3 metastatic sites [63%]; prior treatment with 5-FU ± platinum [P] [24%], capecitabine ± P [13%], TS-1 ± P [26%], other [37%]) have received a median of 2 SU cycles (range 1–3). Of 21 pts evaluable for efficacy, 1 PR has been confirmed and 8 pts had stable disease (SD), 4 with SD for =2 cycles. The most commonly reported AEs were typically grade 1/2 in severity and included stomatitis, skin discoloration, fatigue, anorexia, diarrhea, hand-foot syndrome (HFS), nausea and vomiting. Grade 3/4 toxicities included HFS (10.5%), fatigue (7.9%), anorexia (7.9%) and mucosal inflammation (5.3%). Grade 3/4 hematologic toxicities included neutropenia (29%), thrombocytopenia (29%) and anemia (11%). 7 pts experienced serious SU- related AEs requiring dose modifications in 3 pts and treatment discontinuation in 1 pt. Preliminary PK investigations indicate that concentrations seen in gastric pts are similar to those seen in other pts treated with SU. Conclusions: These initial findings show that SU is generally well tolerated and may have single-agent antitumor activity in pre-treated gastric cancer pts. Further trials with SU in combination with standard chemotherapy regimens are planned. No significant financial relationships to disclose.
What is the real impact of bone pain on survival of hormone-refractory prostate cancer (HRPC) patients treated with docetaxel?
Authors: S. Oudard, E. Banu, J. Medioni, D. Dionysopoulos, O. Cojocarasu, A. Banu
Journal: Journal of Clinical Oncology (2007)

5149 Background: Docetaxel is currently the standard of care for HRPC patients (pts). The moment of docetaxel initiation according to the presence or absence of the bone pain was less explored. Methods: Eligible HRPC pts were required to have a baseline bone pain evaluation using the rank-scores as follows: no pain or minimal pain (0), mild (1), moderate and severe pain (2), respectively. The main endpoint was to explore the overall survival (OS) impact of the bone pain (presence and intensity) using the Cox regression analysis, stratified by chemotherapy regimen. OS was calculated between start of chemotherapy and death or last follow-up for censored pts. Secondary endpoint was to evaluate the relationship between PSA doubling time (DT) and survival of pts with minimal or no pain. Results: Data of 145 consecutive HRPC pts treated in a single French center were analyzed. Chemotherapy was docetaxel (67%) or mitoxantrone-based. The median age was 68 years and 93% of pts had bone metastases, 55% with minimal or no pain at baseline. Median OS was 17.3 months (95% CI, 14.6–20) and 93% of pts died. There were OS differences between pain categories ( Table ). Pain intensity was significantly related with OS: hazard ratio=1.50 (95% CI, 1.20–1.88), P=0.0001 at the univariate analysis. Multivariate analysis adjusted by ECOG PS, hemoglobin and number of metastatic sites showed a 16% rise of the risk of death for pts with severe and mild pain. Pts with minimal or no pain at baseline have a different outcome depending of PSA DT (≥ 45 and &lt; 45 days): median OS 32.4 months (95% CI, 16.2–48.7) and 16.5 months (95% CI, 10–22.9), respectively. Conclusions: Our results suggest that HRPC pts with minimal or without bone pain can experience a better OS with docetaxel-based therapy. This motivates the use of docetaxel early, before bone pain apparition. The OS benefit was even higher for asymptomatic pts with a longer PSA DT. [Table: see text] No significant financial relationships to disclose.
Relevance of modified prognostic score for breast carcinoma on fine needle aspiration cytology in a resource-poor setting
Authors: S. A. Malami, S. M. Sahabi
Journal: Journal of Clinical Oncology (2007)

21177 Background: Breast cancer is the commonest malignancy in premenopausal Nigerian women in whom it is almost uniformly fatal probably due to lack of access to early diagnosis and treatment. To enhance the value of fine needle aspiration cytology, a rapid and comparatively new technique in our center, we sought to verify if it is also a cost-effective test to predict biological behavior in breast carcinoma. We developed a modified grading system to compare the cytologic features of the cases in our series with known prognostic factors (tumours size, histologic grade and axillary lymph node status) in subsequently excised tissues. Methods: Fine needle aspirates obtained in 42 patients diagnosed as ductal cell carcinoma not otherwise specified (NOS) at the UDUTH Hospital, Sokoto, Nigeria were investigated. The three cytologic features used were nuclear grade (score 1–3), cellular dyscohesion (score 1–3), and bare atypical nuclei (score 0, 1). A cytological score of 3 and below was considered a low score, and a score of 4–7 was considered a high score. We also categorized each patient according to the Nottingham Prognostic Index (NPI) into: good prognostic group (GPG), moderate prognostic group (MPG) and poor prognostic group (PPG). The cases in GPG and MPG were considered to belong to a more favourable category. Results of cytoprognostic scores were compared with the respective pathological information calculated by the NPI. Results: Eighteen of the 20 cases that had a cytologically high score were confirmed to be PPG while 2 correlated with MPG. Among the 22 cases that had cytologically low scores 14 cases were not correlated with favourable NPI index (belonged to PPG category) while the remaining 8 correlated well (MPG = 4 and GPG = 4). The overall accuracy for cytologic grading was 62% (26 out of 42 cases). Conclusion: Tumour typing on FNA material correlates with the NPI in the poor prognostic group. However, this modified cytoprognostic score seems to have doubtful promise as a prognostic factor in our group of patients with favourable NPI. The importance of each cytological feature used in this grading system will be determined by regression analysis in a larger sample size. No significant financial relationships to disclose.
Colorectal cancer: summary of NICE guidance
Authors: Nathan Bromham, Maija Kallioinen, Peter Hoskin, R Justin Davies
Journal: BMJ (2020)

### What you need to know Colorectal cancer (cancer of the colon, rectum, or bowel) is the fourth most common cancer in the UK, with over 42 000 new cases diagnosed each year.1 Survival rates have improved, with a five year survival rate of almost 60% now.2 This article summarises recent recommendations from the update of the National Institute for Health and Care Excellence (NICE) guideline for the diagnosis and management of colorectal cancer.3 The update focuses on the management of colorectal cancer, reflecting new research evidence in this area. ### What's new in this guidance