tbuckley/cabot-search huggingface dataset:
Abstract P352: Trend of Salt Consumption in Italy From 2008 to 2018: Preliminary Results of the Cuore Project
Authors: Chiara Donfrancesco, Cinzia Lo Noce, Ornella Russo, Daniela Minutoli, Anna Di Lonardo, Brigitta Buttari, Elisabetta Profumo, Daniela Galeone, Simona Giampaoli, Paolo Bellisario, Luigi Palmieri, Pasquale Strazzullo
Journal: Circulation (2020)

Introduction: The WHO Global Action Plan for the Prevention of Non-Communicable Diseases (NCDs) recommends a 30% relative reduction in mean population intake of salt/sodium. To this end, the Italian Ministry of Health (MoH) has strengthened prevention and health promotion through the “Gaining health: making healthy choices easy” Programme and the National Preventive Plan (NPP) 2014-2019, with the collaboration of the Interdisciplinary Working group for Salt Reduction in Italy (GIRCSI). Hypothesis: Agreements between the MoH and the associations of artisan bakers and food industry companies were signed since 2009 to reduce the salt content in bread and in other food products. Within the NPP, initiatives as local inter-sectors agreements and information activities for the population and training for food sector operators are implemented. In order to estimate the habitual salt intake and its trend in the general adult population, national surveys, funded by the MoH-CCM, are conducted within the CUORE Project. Methods: Baseline salt intake by the use of 24h urine collections was assessed in 2008-2012 from random samples of persons aged 35-79 years, resident in all Italian 20 Regions. A new survey is ongoing (2018-2019) involving random samples of persons aged 35-74 years, resident in 10 Regions. Urinary sodium excretion is assayed by a central lab at Federico II University of Naples, subjected to strict quality controls. Comparisons are made considering, for both periods, the seven regions examined up to now in the ongoing survey and the age range of 35-74 years. Results: Within the 2018-2019 survey, mean level of sodium chloride per day in 673 men and 709 women was 161 mmol (95% confidence interval: 156-166 mmol) and 122 mmol (119-126 mmol) respectively, whereas in the 2008-2012 survey the corresponding mean levels in 642 men and 627 women was 183 mmol (95% confidence interval: 178-189 mmol) and 140 mmol (135-144 mmol), respectively. A sodium chloride intake level within the WHO recommended upper level of 85 mmol (or 5 grams of salt) per day was detected in 9% (6-11%) of men and 24% (20-27%) of women examined in 2018-2019 vs 5% (3-6%) of men and 16% (13-19%) of women examined in 2008-2012. Conclusions: These preliminary data show that the average habitual sodium intake in Italy is still largely higher than recommended but a significant reduction seems to occur. These results fully justify and encourage the ongoing preventive initiatives for reduction of sodium intake and its monitoring in the population.
First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas
Authors: Ajay K. Gopal, Ronald Levy, Roch Houot, Sandip P. Patel, Leslie Popplewell, Caron Jacobson, Xinmeng J. Mu, Shibing Deng, Keith A. Ching, Ying Chen, Craig B. Davis, Bo Huang, Kolette D. Fly, Aron Thall, Adrian Woolfson, Nancy L. Bartlett
Journal: Clinical Cancer Research (2020)

In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20+ non-Hodgkin lymphomas (NHL).Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D).Sixty-seven patients received utomilumab (0.03-10.0 mg/kg every 4 weeks) and rituximab (375 mg/m2 weekly) in the dose-escalation groups or utomilumab (1.2 mg/kg every 4 weeks) plus rituximab in the dose-expansion cohort. No patient experienced dose-limiting toxicity. The MTD for utomilumab in combination with rituximab was not reached and estimated to be ≥10 mg/kg every 4 weeks. The majority of the utomilumab treatment-related adverse events (AE) were grade 1 to 2; the most common AE was fatigue (16.4%). The pharmacokinetics of utomilumab in combination with rituximab was linear in the 0.03 to 10 mg/kg dose range. A low incidence (1.5%) of treatment-induced antidrug antibodies against utomilumab was observed. The objective response rate was 21.2% (95% CI, 12.1%-33.0%) in all patients with NHL, including four complete and 10 partial responses. Analysis of paired biopsies from a relapsed/refractory FL patient with complete response showed increased T-cell infiltration and cytotoxic activity in tumors. Biomarker correlations with outcomes suggested that clinical benefit may be contingent on patient immune function.Utomilumab in combination with rituximab demonstrated clinical activity and a favorable safety profile in patients with CD20+ NHLs.
Intestinal OCTN2- and MCT1-targeted drug delivery to improve oral bioavailability
Authors: Gang Wang, Lichun Zhao, Qikun jiang, Yixin Sun, Dongyang Zhao, Mengchi Sun, Zhonggui He, Jin sun, Yang Wang
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs, thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery. In particular, intestinal carnitine/organic cation transporter 2 (OCTN2) and mono-carboxylate transporter protein 1 (MCT1) possess high transport capacities and complementary distributions. Therefore, we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review. First, basic information of the two transporters is reviewed, including their topological structures, characteristics and functions, expression and key features of their substrates. Furthermore, progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed, including improvements in the oral absorption of anti-inflammatory drugs, antiepileptic drugs and anticancer drugs. Finally, the potential of a dual transporter-targeting strategy is discussed.
Abstract 05: Race and Hospitalization for Cardiovascular Disease in Patients With Systemic Lupus Erythematosus
Authors: Meghan Angley, Tene T Lewis, Penelope P Howards, Sung Lim
Journal: Circulation (2020)

Background: Patients diagnosed with systemic lupus erythematosus (SLE) are at greater risk of cardiovascular disease (CVD) and death at earlier ages than the general population, with African Americans (AA) at risk at earlier ages than non-AAs. However, the association between race and recurrent hospitalizations for CVD, which are associated with mortality, has not been explored. Methods: The Georgia Lupus Registry (GLR) is a population-based registry of individuals with SLE in 2002-2004 in Atlanta, Georgia. Both incident and prevalent cases were enrolled, and we included all cases diagnosed beginning in 2000. The GLR was matched to Georgia inpatient hospital discharge records from 2000-2013. Using ICD-9-CM codes, we identified hospitalizations classified as having coronary heart disease, peripheral artery disease, cerebrovascular disease or heart failure. The Prentice-Williams-Peterson Model with a total time scale measured from diagnosis was used to examine recurrent time to event data. We truncated the number of hospitalizations at 3 to maintain stable modeling estimates. Patients were censored at the time of death or at the end of 2013. Models were adjusted for sex and age at diagnosis. Results: A total of 556 participants in the GLR (87% female, 73% AA) had a median age at SLE diagnosis of 38 years and 27% experienced at least 1 CVD hospitalization, while 17% experienced ≥ 2. Overall, AA race was associated with recurrent hospitalizations (adjusted hazard ratio [aHR]: 1.7, 95% confidence interval [CI]: 1.2, 2.3). In an event-specific stratified analysis, the association between AA race and the hazard of recurrence became even more pronounced in later events (Event 1 aHR: 1.2, 95% CI: 1.0, 1.5; Event 2 aHR: 1.5, 95% CI: 1.2, 2.2; Event 3 aHR: 1.9, 95% CI: 1.1, 3.2). Conclusions: African-Americans with SLE were more likely to experience recurrent hospitalizations for CVD than their non-AA counterparts, suggesting that AA individuals with SLE may be more vulnerable to CV complications of SLE. Figure 1. Survival curve for 1st event
Clear cell endometrial cancer patients have an increased risk of venous thrombotic events
Authors: L. Garrett, L. M. Lee, E. Oliva, N. Horowitz, L. Duska
Journal: Journal of Clinical Oncology (2007)

5597 Objective: To document the rate of clinically significant venous thromboembolism (VTE) in patients with clear cell carcinoma of the endometrium (CCC-E). Methods: Institutional review board (IRB) permission was obtained for retrospective record review. The pathology database at our institution located cases of CCCs over the time period 1994–2004. Controls with high grade endometrial cancers were matched for stage, age and date of diagnosis. All patients underwent surgical staging with gynecologic oncology staff surgeons and all patients received VTE prophylaxis peri-operatively. Records were reviewed and data were collected regarding patient age, tumor stage, body mass index, surgical procedure, adjuvant therapy, survival, and presence of VTE. All pathology was reviewed at the MGH. Results: Thirty-nine cases of CCC-E were identified. Complete clinical data were available for 29 cases. Age ranged from 38–85 (mean 64.6) years. 35% of patients had stage I tumors, 10% stage II, 27.5% stage III, and 27.5% had stage IV tumors. 58 age and stage matched controls were selected. The majority were grade 3 endometrioid cancers (50%) with the remainder being serous (35%), mixed histology (7%), carcinosarcoma (5%), and undifferentiated carcinoma (3%). The majority of the control patients had a higher BMI than the case patients. Overall there were 18 VTE events, 10 (34.5%) in those with CCC-E and 8 (13.8%) controls p = 0.046. A higher proportion of VTE occurred in those with stage III/IV disease (n=16) as compared to those with early stage (n =2) p =0.01. When considering the timing of VTE, the VTE observed in those with CCC-E occurred at presentation or with disease recurrence (8 vs 1) while nearly all VTE in the control group occurred in the postoperative period. (7 vs 2). This was statistically significant p =0.01 Conclusion: Patients with CCC-E are at increased risk of VTE compared to patients with other high- risk endometrial cancers. This is particularly true for those with advanced stage disease. Presentation with a VTE and postmenopausal bleeding should raise the suspicion for CCC-E. Likewise, in those with known CCC-E development of a VTE may be a harbinger of recurrence. Consideration should be given to extended prophylaxis in patients with CCC-E to prevent VTE. No significant financial relationships to disclose.
Inadequate Assessment of Patient–Ventilator Interaction Due to Suboptimal Diaphragm Electrical Activity Signal Filtering
Authors: Annemijn H. Jonkman, Lisanne H. Roesthuis, Esmée C. de Boer, Heder J. de Vries, Armand R. J. Girbes, Johannes G. van der Hoeven, Pieter R. Tuinman, Leo M. A. Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Abstract MP76: Assessing the Impact of the "Health Bucks" Program on Cardiovascular Disease in New York City: A Modeling Study
Authors: Heesun Eom, Stella S Yi, Daniel Bu, Rienna Russo, Brandon Bellows, Yiyi Zhang, Andrew E Moran, Yan Li
Journal: Circulation (2020)

Background: Low fruit and vegetable (FV) consumption is considered one of the leading causes of deteriorating health outcomes, and has been linked to obesity, diabetes, and cardiovascular disease. Yet, few adults in New York City (NYC) consume the daily recommended amounts. In order to address the need for fresh and affordable fruits and vegetables, the NYC Department of Health and Mental Hygiene has implemented the “Health Bucks” program, which provides low-income population with coupons that can be used to purchase fruits and vegetetabls. Previous studies have shown the impact of the Health Bucks program on fruit and vegetable consumption; however, it is unclear how the program would influence cardiovascular health and the associated health care costs in the long term. Objective: To estimate the health and economic impact of the Health Bucks program using a validated microsimulation model of cardiovascular disease (CVD) in NYC. Methods: We used the Simulations for Health Improvement and Equity (SHINE) CVD Model to estimate the impact of the Health Bucks program on lifetime CVD events and direct medical costs (2019 USD). We considered different program strengths by assuming the program can reduce the cost of fruits and vegetables by 20%, 30%, and 40%. Population characteristics were estimated based on data from the 2013-2014 NYC Health and Nutrition Examination Survey. CVD risk factor trajectories and risk of incident CVD events were derived from six pooled longitudinal US cohorts. Policy effects were derived from the literature. We run 1,000 simulations to account for uncertainties in the parameter. We discounted costs by 3% and reported health care costs in 2019 dollars. Results: A Health Bucks program that can reduce the cost of fruits and vegetables by 20%, 30%, and 40% would prevent 2,690 (95% CI: -14,793, 20,173), 27,386 (95% CI: 9,967, 44,805), and 50,014 (95% CI: 15,227, 50,014) coronary heart disease events, respectively, over the simulated lifetimes of the NYC population. The program would also prevent 47,469 (95% CI: 35,008, 59,931), 59,127 (95% CI: 46,676, 71,579), and 85,359 (95% CI: 72,902, 97,815) stroke events based on the price reduction level. The program would result in savings in health care costs, ranged from $937 million to $1.8 billion based on the price reduction level over the lifetime or from $19 million to $37 million annually. Conclusions: We projected that the Health Bucks program could prevent a significant number of CVD events among adults in NYC and yield substantial health care cost savings. Public health practitioners and policymakers may consider adopting this program in other locations.
Sunitinib versus interferon-alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC): Updated results and analysis of prognostic factors
Authors: R. J. Motzer, R. A. Figlin, T. E. Hutson, P. Tomczak, R. M. Bukowski, O. Rixe, G. A. Bjarnason, S. T. Kim, I. Chen, D. Michaelson
Journal: Journal of Clinical Oncology (2007)

5024 Background: In a randomized phase III trial of patients (pts) with mRCC, sunitinib demonstrated a significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to IFN-a as first-line therapy (Proc ASCO 2006;24:2s [Abstract LBA3]). We present the most recent data from this trial and an analysis of prognostic factors. Methods: Untreated pts with clear-cell mRCC were randomized 1:1 to receive either sunitinib (repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment) or IFN-a (9 MU given subcutaneously three times weekly). The primary endpoint was PFS. Results: A total of 750 pts were randomized: 375 to sunitinib, 375 to IFN-a. The median duration of treatment is 11 months (range: &lt;1–25) for sunitinib vs. 4 months (range: &lt;1–22) for IFN-a. The updated ORR by investigator assessment is 44% (95% CI: 39, 49) for sunitinib vs. 11% (95% CI: 8, 15) for IFN-a (p &lt;0.000001), including 4 complete responses for sunitinib and 2 for IFN-a. The median duration of response in the sunitinib group (n=165) is 12 months (95% CI: 10, 14) vs. 10 months (95% CI: 8, 17) in the IFN-a group (n=43). The median PFS is 11 months (95% CI: 10, 11) for sunitinib vs. 4 months (95% CI: 4, 5) for IFN-a. The median PFS for pts with 0 risk factors is 14 months (95% CI: 11, 16) for sunitinib vs. 8 months (95% CI: 7, 10) for IFN-a; 9 months (95% CI: 8, 11) vs. 4 months (95% CI: 4, 4), respectively, for pts with 1- 2 risk factors; 4 months (95% CI: 2, 10) vs. 1 month (95% CI: 1, 2), respectively, for pts with =3 risk factors. The sunitinib benefit in PFS extends across all MSKCC prognostic risk factor groups (HR=0.488; 95% CI: 0.406, 0.586). The baseline features that predict longer PFS (by investigator assessment) for the sunitinib group are hemoglobin =LLN (p=0.0043), corrected calcium =10 mg/dL (p=0.001), ECOG score of 0 (p=0.0005), number of metastatic sites 0 or 1 (p=0.0064), and time from diagnosis to treatment =1 yr (p=0.0002). Conclusions: Sunitinib is a reference standard for first-line treatment of mRCC, with significant improvement in PFS and ORR compared to IFN-a. The benefit of sunitinib extends across all subgroups of pts with mRCC. Previously defined MSKCC risk factors for mRCC predict longer PFS with sunitinib. No significant financial relationships to disclose.
MOLECULAR AND CLINICALLY DISTINCT PHENOTYPES IN HER2-OVEREXPRESSING BREAST CANCER (HER2 BC) CORRESPOND TO ESTROGEN RECEPTOR STATUS (ER) STATUS
Authors: S Loi, B Haibe-Kains, ND Brown, J Metallo, S Majjaj, C Desmedt, L Pusztai, M Piccart, FJ Esteva, C Sotiriou
Journal: Annals of Oncology (2010)
Conditioning of 3D Printed Nanoengineered Ionic–Covalent Entanglement Scaffolds with iP‐hMSCs Derived Matrix
Authors: Candice Sears, Eli Mondragon, Zachary I. Richards, Nick Sears, David Chimene, Eoin P. McNeill, Carl A. Gregory, Akhilesh K. Gaharwar, Roland Kaunas
Journal: Advanced Healthcare Materials (2020)

Abstract Additive manufacturing is a promising method for producing customized 3D bioactive constructs for regenerative medicine. Here, 3D printed highly osteogenic scaffolds using nanoengineered ionic–covalent entanglement ink (NICE) for bone tissue engineering are reported. This NICE ink consists of ionic–covalent entanglement reinforced with Laponite, a 2D nanosilicate (nSi) clay, allowing for the printing of anatomic‐sized constructs with high accuracy. The 3D printed structure is able to maintain high structural stability in physiological conditions without any significant swelling or deswelling. The presence of nSi imparts osteoinductive characteristics to the NICE scaffolds, which is further augmented by depositing pluripotent stem cell‐derived extracellular matrix (ECM) on the scaffolds. This is achieved by stimulating human induced pluripotent stem cell‐derived mesenchymal stem cells (iP‐hMSCs) with 2‐chloro‐5‐nitrobenzanilide, a PPARγ inhibitor that enhances Wnt pathway, resulting in the deposition of an ECM characterized by high levels of collagens VI and XII found in anabolic bone. The osteoinductive characteristics of these bioconditioned NICE (bNICE) scaffolds is demonstrated through osteogenic differentiation of bone marrow derived human mesenchymal stem cells. A significant increase in the expression of osteogenic gene markers as well as mineralized ECM are observed on bioconditioned NICE (bNICE) scaffolds compared to bare scaffolds (NICE). The bioconditioned 3D printed scaffolds provide a unique strategy to design personalized bone grafts for in situ bone regeneration.
Enhancement of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) sensitivity with anticancer agents in human cancer cells
Authors: Uhi Toh, Naoko Seki, Hideaki Yamana, Teruhiko Fujii, Kousuke Tayama, Kazuo Shirouzu
Journal: Cancer Research (2005)

3338  Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL/Apo2L) is one of the most promising biological agent in future anti-cancer therapy, which induces apoptosis in cancer cells by binding to death receptors DR4 and DR5. However, recent studies have shown several TRAIL resistant cancer cells in various organs, and that combination therapy with several chemotherapeutic agents can increase the efficacy of TRAIL in these resistant cells. In this study, we examined TRAIL sensitivity using MTS assay in the human esophageal cancer cell lines including KE3-KE10 which established in our laboratory, and also assessed TRAIL efficacy with EGFR tyrosine kinase inhibitor Gefitinib, and proteasome inhibitor Bortezomib as possible new approach of combination therapy. The relevant molecules of TRAIL-induced apoptosis signaling pathways including DR4/DR5, DcR2/DcR1, FlipL, caspases etc. were analyzed by Western blot. TRAIL sensitivity of esophageal cancer cell lines tested was varied. These was no significant relation between TRAIL sensitivity and DR4/DR5 expression level indicating that other molecular pathways would be involved in TRAIL resistant cells. Our studies demonstrate that Gefitinib and Bortezomib were useful for enhancement of TRAIL sensitivity in part of cell lines suggesting Akt and NFkB pathways as possible target of combining anti-cancer therapy.
A phase I dose escalation study of pharmacobiologically based scheduling of capecitabine and mitomycin C (MMC) in patients with gastrointestinal solid malignancies
Authors: M. E. Hill, A. Campbell, K. Kosuri, J. Thomas, M. Villalona, T. Bekaii-Saab
Journal: Journal of Clinical Oncology (2007)

15154 Background: A principal determinant of the therapeutic index of capecitabine-based treatment is the grade of thymidine phosphorylase(dThdPase) activity in malignant tissues. MMC, an agent that is active in gastrointestinal malignancies, produces significant upregulation of the dTHdPase starting 4–6 days after treatment and persisting for at least 10 days. On the basis of the time-dependency and transience of this upregulation, we performed a phase I study of capecitabine in combination with MMC. The aim was to determine the maximally tolerated dose of this combination. Methods: In this ongoing study, patients with advanced gastrointestinal solid malignancies received MMC on day 1 and capecitabine twice daily on days 8 and 21, every 4 weeks. The MMC dose was fixed at 6mg/m2, whereas capecitabine was escalated in successive patient cohorts. Patients were allowed to have had a maximum of 2 prior therapies for metastatic disease. The total cumulative dose of MMC was capped at 36 mg/m^2 to reduce the risk of cumulative toxicity. Results: So far 23 patients with a median age of 62 received capecitabine doses from 1000 to 2000 mg/m^2/d. The majority of the patients had at least 1 prior treatment (86%). Four patients were considered non-evaluable. No dose-limiting toxicities were observed as we reached our final dose level. Toxicities were generally mild with only 7 patients experiencing grade 3 toxicities and two experiencing grade 4 toxicities. The most common toxicities were fatigue (67%), nausea (43%), diarrhea (33%), and anemia (29%), and all toxicities were reversible. There were no objective responses; however, 32% of evaluable patients had prolonged stable disease (43% colorectal, 29% pancreas, 14% esophageal, and 14% gastric). Conclusions: Capecitabine in combination with MMC in the proposed schedule is well tolerated and has promising preliminary activity in various gastrointestinal malignancies. Recommended doses for phase II studies are capecitabine 1000 mg/m^2 twice daily and MMC 6 mg/m^2. This study is ongoing with 2 more patients being entered at the recommended phase II dose. No significant financial relationships to disclose.