tbuckley/cabot-search huggingface dataset:
Abstract P261: Dietary Sodium, Potassium, and Blood Pressure in Normotensive Pregnant Women: The National Health and Nutrition Examination Survey
Authors: Abbi D Lane-Cordova, Lara R Scheider, William Tucker, James Cook, Sara Wilcox, Jihong Liu
Journal: Circulation (2019)

Dietary sodium, potassium, and the sodium-to-potassium ratio are linearly associated with blood pressure in non-pregnant adults in a dose-response manner. Earlier investigations suggested null or inverse associations of sodium and blood pressure during normotensive pregnancy, but this finding has not been confirmed in a large, racially diverse group while accounting for counteractive effects of dietary potassium. Our purpose was to determine associations of blood pressure with sodium, potassium and the sodium-to-potassium ratio in normotensive pregnant women. We used cross-sectional blood pressure measurements and dietary data from 984 normotensive pregnant women in multiple cycles of the National Health and Nutrition Examination Survey (mean age=27.6 ± 0.2 years). We used Kruskal-Wallis tests to determine differences in blood pressure across quartiles of sodium intake and linear regression to test for associations of sodium, potassium, and the sodium-to-potassium ratio with systolic and diastolic blood pressure. Adjustment variables included: age, race, education, marital status, body mass index, smoking, and month of pregnancy. Average duration of pregnancy was 5.6 ± 0.1 months with no difference between quartiles of sodium intake. There was no difference in unadjusted systolic or diastolic blood pressures across quartiles of sodium intake; Quartile 1: 106/56; Quartile 2: 106/55; Quartile 3: 107/57; Quartile 4: 107/56, p&gt;0.60 for all, and no difference in age and race-adjusted systolic or diastolic blood pressures across quartiles of dietary intake, Figure 1. In adjusted regression analyses, sodium ( b =0.16, 95%CI: -0.20, 0.52) and potassium ( b =0.18, 95%CI: -0.24, 0.60) intake and the sodium-to-potassium ratio ( b = -0.54, 95%CI: -1.55, 0.47) were not associated with systolic or diastolic blood pressure in normotensive pregnant women. Results were similar in analyses stratified by race/ethnicity. Blood pressure may be insensitive to sodium and potassium intake during normotensive pregnancy.
Double-blind, randomized, placebo-controlled trial of allergen-specific immunotherapy with the major allergen Alt a 1
Authors: Ana Isabel Tabar, Luis Prieto, Pilar Alba, Antonio Nieto, Mercedes Rodríguez, Miguel Torrecillas, Beatriz Huertas, Elisa Gómez, Francisco Javier Fernández, Miguel Blanca, David Rodríguez, Ricardo Palacios
Journal: Journal of Allergy and Clinical Immunology (2019)

There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata.We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata.We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 μg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria.There were significant reductions in the combined symptom and medication score for the 0.37-μg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported.Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG4 levels.
Abstract P230: Adherence to the MIND Diet is Associated with a Favorable Profile of Subclinical Cardiac Remodeling in the Framingham Offspring Cohort
Authors: Maura E Walker, Adrienne O’Donnell, Jayandra Himali, Debora Melo van Lent, Vanessa Xanthakis, Sudha Seshadri, Vasan Ramachandran
Journal: Circulation (2019)

Introduction: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is based on the central components of the Mediterranean and DASH diets and emphasizes foods that may provide a neuro-cognitive benefit. To date, no study has investigated adherence to the MIND diet and indices of cardiac remodeling. We hypothesized that adherence to the MIND diet may have a favorable impact on indices of cardiac remodeling. Methods: Multivariable linear regression related the MIND diet score to echocardiographic indices of cardiac remodeling in 2569 Framingham Offspring cohort participants (mean age, 67 years; 55% women). The MIND diet score contains 15 components, each with a maximum score of 1 (max score =15). We averaged MIND diet scores across 2-4 exam cycles. Primary and secondary echocardiographic measures are in Table 1 . Simple models (model 1) were adjusted for age, sex, and total energy intake, and additional models (model 2) were further adjusted for BMI, smoking, total/high-density lipoprotein cholesterol (TC-HDL) ratio, heart rate, diabetes, systolic blood pressure, and use of anti-hypertensive medication. Results: Participants had a mean (±SD) cumulative MIND diet score of 6.9 (± 1.7). The cumulative MIND diet score was significantly associated with favorable measures of E/e’, GLS, GCS, and MAPSE in model 1 ( Table 1 ). Associations between the MIND diet score and echocardiographic measures were attenuated and became non-significant in model 2 ( Table 1 ). A higher MIND diet score was associated with lower levels of several clinical risk factors including BMI (β±SE (p value): -0.01±0.002 (&lt;.0001)), TC-HDL ratio (-0.05±0.01 (0.0002)), heart rate (-0.83±0.12 (&lt;.0001)), with lower odds of diabetes (OR [95% CI]: 0.88 [0.82, 0.94]), and use of anti-hypertensive medication (0.94 [0.90, 0.99]). Conclusions: Favorable associations between cumulative adherence to the MIND diet and echocardiographic indices are likely mediated by the favorable impact of adherence to the MIND diet on clinical risk factors.
Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia
Authors: Jie Zhang, Jin Wei, Shan Jiang, Lan Xu, Lei Wang, Feng Cheng, Jacentha Buggs, Hermann Koepsell, Volker Vallon, Ruisheng Liu
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Although glomerular hyperfiltration is common in early diabetes and considered a risk factor for later diabetic nephropathy, the mechanisms underlying glomerular hyperfiltration have not been fully clarified. The authors identified a novel mechanism of acute hyperglycemia–induced hyperfiltration in which increases in luminal glucose at the macula densa upregulate the expression and activity of neuronal nitric oxide synthase 1 (NOS1) via sodium-glucose cotransporter 1 (SGLT1); this blunts the tubuloglomerular feedback (TGF) response and promotes glomerular hyperfiltration. This novel SGLT1-NOS1-TGF pathway mediates the glomerular hyperfiltration observed in response to acute hyperglycemia. These findings establish a critical role of macula densa NOS1 and SGLT1 as key determinants of, and potential therapeutic targets for, acute hyperglycemia–associated glomerular hyperfiltration, and possibly for diabetes as well. Background Glomerular hyperfiltration is common in early diabetes and is considered a risk factor for later diabetic nephropathy. We propose that sodium-glucose cotransporter 1 (SGLT1) senses increases in luminal glucose at the macula densa, enhancing generation of neuronal nitric oxide synthase 1 (NOS1)–dependent nitric oxide (NO) in the macula densa and blunting the tubuloglomerular feedback (TGF) response, thereby promoting the rise in GFR. Methods We used microperfusion, micropuncture, and renal clearance of FITC–inulin to examine the effects of tubular glucose on NO generation at the macula densa, TGF, and GFR in wild-type and macula densa–specific NOS1 knockout mice. Results Acute intravenous injection of glucose induced hyperglycemia and glucosuria with increased GFR in mice. We found that tubular glucose blunts the TGF response in vivo and in vitro and stimulates NO generation at the macula densa. We also showed that SGLT1 is expressed at the macula densa; in the presence of tubular glucose, SGLT1 inhibits TGF and NO generation, but this action is blocked when the SGLT1 inhibitor KGA-2727 is present. In addition, we demonstrated that glucose increases NOS1 expression and NOS1 phosphorylation at Ser1417 in mouse renal cortex and cultured human kidney tissue. In macula densa–specific NOS1 knockout mice, glucose had no effect on NO generation, TGF, and GFR. Conclusions We identified a novel mechanism of acute hyperglycemia–induced hyperfiltration wherein increases in luminal glucose at the macula densa upregulate the expression and activity of NOS1 via SGLT1, blunting the TGF response and promoting glomerular hyperfiltration.
Evaluation of hematology/oncology patient and physician expectations for integrative oncology in an ethnically diverse population.
Authors: Damien Mikael Hansra, Jeremy Ramdial, Faheem Farooq, Jorge Antunez de Mayolo, Eugene Ahn, Ashwin Mehta
Journal: Journal of Clinical Oncology (2015)

6552 Background: Many integrative modalities are recommended in NCCN guidelines & evidence shows increased patient (pt) utilization.We aim to compare how integrative services are valued between hematology/oncology physicians (MD) & pts. Methods: Pts & MDs at an academic tertiary care medical center were enrolled to complete a survey. Demographics include: age, gender, race, & ethnicity. Clinical info include: cancer subtype & treating MD. Survey consisted of 7 questions assessing opinions on integrative care asking: “In addition to standard care, it is important to incorporate/provide” nutrition services, exercise therapy, spiritual/religious counseling, supplement/herbal advice, support groups, music therapy, or other complimentary medicine services (acupuncture, massage, relaxation therapy). Answers recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) & converted into 2 categories (1,2,3 = neutral/disagree vs. 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance between MD & pt responses. Results: 909 pts and 55 MDs enrolled from June 2013 to January 2015. Pt mean age 55, range 18-88 with 47% male & 53% female. 65% of pts were Hispanic vs. 35% not Hispanic. 81% white, 12% black/African American, 2% Asian/Pacific Islander, & 5% other. 15% of pts had hematologic disorders (93% malignant 7% benign) vs. 85% of pts had solid malignancies. Significance disparities were demonstrated: 82% of pts agree that nutritional advice is important vs. 67% of MDs, p = 0.01, exercise therapy (86% vs. 73%, p = 0.02), spiritual/religious (68% vs. 50%, p = 0.01), supplement/herbal therapies (85% vs. 56%, p < 0.0001), music (64% vs. 30%, p < 0.0001), &“other complementary services” (75% vs. 45%, p < 0.0001). Non statistical favoring of support groups by pts observed (71% vs. 68% respectively, p = 0.64). Conclusions: With with exception of support groups, pts value integrative modalities more than MDs. It is expected that increased availability & utilization of integrative oncology modalities at tertiary hospital sites could improve pt satisfaction, quality of life, & other clinical endpoints.
Targeting Sema3D in pancreatic cancer: A novel therapeutic strategy.
Authors: Adrian Murphy, Jennifer Kleponis, Agnieszka Rucki, Elizabeth M. Jaffee, Lei Zheng, Kelly Foley
Journal: Journal of Clinical Oncology (2015)

4129 Background: Pancreatic ductal adenocarcinoma (PDA) is known for its chemotherapy resistance and dismal survival rates. Little is known about the mechanisms of metastasis in PDA. We identified Annexin A2 (AnxA2), an essential mediator of metastasis using sera from patients with prolonged survival after GVAX treatment. AnxA2 regulates secretion of semaphorin3D (Sema3D) promoting invasion and metastasis of PDA cells. Sema3D and other axon guidance genes have been shown to be the cellular pathways most frequently altered in PDA. Methods: KPC mice, which spontaneously develop PDA, were generated with KRAS/P53 mutations. KPCA-/- mice were created by crossing AnxA2 knockouts with KPC mice. Cell lines were developed from primary tumors of these mice and gene expression profiling performed comparing KPC and KPCA-/- cells. Sema3D secretion was measured from KPC and KPCA-/- cells by ELISA. Anti-AnxA2 antibodies were used to see the effect of AnxA2 inhibition on Sema3D secretion. Sema3D knockdown KPC cells were used in a hemi-spleen model of liver metastasis to evaluate metastasis in vivo. Immunohistochemistry (IHC) was used to analyze Sema3D expression in resected human PDA tissue. Results: While PDA tumors spontaneously developed in both KPC and KPCA-/- mice, metastases were only seen in KPC (16/17) but not in KPCA-/- mice (0/23). Sema3D expression was down-regulated in KPCA-/- cells compared to KPC cells and Sema3D secretion was significantly lower from KPCA-/- cells (0.25 ng/ml) than KPC cells (17.5 ng/ml) (p = 0.01). Antibody blockade of AnxA2 suppressed Sema3D secretion in KPC cells suggesting its role in Sema3D secretion. Animals injected with KPC cells transfected with Sema3D-targeting shRNA had fewer metastases (5/13) and longer survival than mice injected with control (11/12) (p = 0.01). IHC on human PDA tumors showed that 15/20 patients with DFS < 1 year abundantly expressed Sema3D. Sema3D secretion can be measured in 96 well plates after 24 hours of incubation and this platform is optimized for drug testing. Conclusions: Sema3D secretion, which is regulated by AnxA2, is crucial for PDA metastasis. Targeting this pathway may lead to increased therapeutic options in PDA. We have established a platform to detect drugs that reduce Sema3D secretion.
Abstract P101: Menopause and its Related Endogenous Sex Hormone Alterations are Associated with Changes in Function and Subclasses of High-density Lipoprotein in Women at Midlife
Authors: Samar R El Khoudary, Patrick Hutchins, Karen A Matthews, Maria M Brooks, Trevor J Orchard, Jay W Heinecke
Journal: Circulation (2016)

Objective: Growing evidence challenges the cardioprotective effects of high-density lipoprotein-cholesterol (HDL-C) in postmenopausal women. HDL particle size and concentration are heterogeneous and HDL-C only measures the cholesterol content of all HDL particles. Therefore, HDL-C does not necessarily reflect HDL subclasses or functionality, which may be more important in predicting CVD risk. Our main objective was to characterize HDL subclasses and functional alterations over menopause and to evaluate their associations with changes in estradiol (E2) and follicle stimulating hormone (FSH), cardinal hormonal markers of menopause. Methods: Participants were drawn from the Study of Women’s Health Across the Nation (SWAN) at the Pittsburgh site. The women had stored blood specimens at two time points; one before and one after they reached menopause. HDL particle concentration and size using calibrated ion mobility analyses and HDL cholesterol efflux capacity (HDL-CEC) with radiolabeled J774 macrophages were measured at the two time points. None of the study participants were on lipid lowering medications or hormone therapy. Results: The study included 50 women (66% White and 34% Black), who were 47 (45, 49) years old (median (Q1, Q3)) and were either pre- (38%) or early peri-menopause (62%) at the first time point. At the second time point, all participants were postmenopausal with a median (Q1, Q3) time since their final menstrual period of 2.14 (1.55, 3.41) years. After menopause, women had significantly higher concentrations of total and large HDL particles, and smaller sizes of medium and small HDL particles (all P&lt;0.05), independent of race and change in age. HDL-CEC was significantly higher after menopause. Independent of age and race, larger declines in E2 were correlated with a more atherogenic changes (smaller increases in large HDL particles and larger increases in small HDL particles concentrations, P&lt;0.05). Additionally, greater rises in FSH were correlated with bigger reductions in sizes of large and medium HDL particles (P&lt;0.05). Conclusions: Within a median of 2.14 years of menopause, an improvement in HDL-CEC and significant alterations in HDL particle subclasses were observed. Whether patterns of these alterations change further in late postmenopause and how they relate to atherosclerotic risk are not known. The reported changes in HDL metrics over menopause warrant further evaluation of their potential risk on CVD after menopause.
Activity of RX-3117, an oral antimetabolite nucleoside, in subjects with advanced urothelial cancer: Preliminary results of a phase IIa study.
Authors: Nicholas Salgia, Sumanta K. Pal, Vincent Chung, Scott T. Tagawa, Joel Picus, Hani M. Babiker, Sumati Gupta, Raymond Couric Wadlow, Julie Poore, Christine Peterson, Ely Benaim
Journal: Journal of Clinical Oncology (2019)

455 Background: RX-3117 is an oral small molecule antimetabolite that is activated by uridine cytidine kinase 2 (UCK2) which is predominantly expressed in cancer cells. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Preliminary data from an analysis of a Phase 2a clinical study of RX3117 in advanced urothelial cancer is described. Methods: In the Phase 2a study designed to evaluate safety, tolerability and efficacy, subjects were treated with oral RX-3117 (700 mg) once-daily for 5 consecutive days on and 2 days off for 3 of 4 weeks or all 4 weeks in a 28-day cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic urothelial cancer, ECOG PS of 0 to 1, normal organ function (hepatic, renal and hematology) with no limit on the number of prior therapies. The primary Phase 2a endpoints are progression free survival (PFS) and/or objective clinical response with secondary endpoints of safety, TTP, DOR and ORR. Results: As of October 5, 2018; 33 subjects were treated (23 males and 10 females, median age 67.5 years); 29 subjects were evaluable having completed more than 1 cycle of therapy or discontinued due to a related adverse event. Twenty subjects had received 3 or more prior therapies; 30 received gemcitabine/cisplatin and 25 received a checkpoint inhibitor. The most common related adverse events were anemia (G1-2%, G2-3%, G3-3%), fatigue (G1-6%, G2-3%), neutropenia (G2-2%, G3-5%, G4-2%), diarrhea (G1-4%, G2-2%), and thrombocytopenia (G2-2%, G3-3%, G4-1%). One subject had a complete response after 4 cycles of therapy and continues therapy beyond 10 cycles; 5 subjects had PFS ranging from 133 to 315 days. Conclusions: RX-3117 appears to be safe and well-tolerated in chemotherapy and immunotherapy refractory advanced urothelial cancer with acceptable toxicities. Preliminary results show anti-tumor activity in heavily pre-treated patients. Clinical trial information: NCT02030067.
Abstract P098: The Relationship of Neighborhood Greenness to Heart Disease in 249,405 US Medicare Beneficiaries
Authors: Scott C Brown, Kefeng Wang, Joanna Lombard, Tatjana Rundek, Chuanhui Dong, Carolina Marinovic Gutierrez, Margaret M Byrne, Matthew Toro, Maria I Nardi, Jack Kardys, Li Yi, Jose Szapocznik
Journal: Circulation (2019)

Background: Nature exposures may be associated with reduced risk for heart disease. The present study examines the relationship between objective measures of neighborhood greenness (vegetative presence) and diagnoses of four forms of heart disease (acute myocardial infarction [AMI], ischemic heart disease, heart failure, and atrial fibrillation), in a large population-based sample of Medicare beneficiaries in Miami-Dade County, Florida. Methods: The sample included 249,405 Medicare beneficiaries ages 65 years and older whose location (ZIP+4) in Miami-Dade County, Florida, did not change from 2010 to 2011. Analyses examined relationships between greenness, measured by mean Normalized Difference Vegetation Index (NDVI) from satellite imagery at the Census block level, and four forms of heart disease in 2011. A series of hierarchical regression analyses, in a multi-level framework, assessed the relationship of greenness to each heart disease diagnosis, adjusting successively for individual sociodemographics and neighborhood median household income. A further final model adjusted for biological risk factors (diabetes, hypertension, and hyperlipidemia). Results: Higher greenness was generally associated with reduced risk of heart disease, in models adjusting for individual sociodemographics and neighborhood income: When compared to the lowest tertile of greenness, the highest tertile of greenness was associated with statistically significant (ps&lt;.01) reduced odds of AMI by 25% (OR=0.75; 95% CI: 0.63, 0.90), ischemic heart disease by 20% (OR=0.80; 95% CI: 0.77, 0.83), heart failure by 16% (OR=0.84; 95% CI: 0.80, 0.88), and a marginally significant reduced odds of atrial fibrillation by 6% (OR=0.94; 95% CI: 0.87, 1.00, p=.067). In addition, the highest tertile of greenness was associated with 19% reduced odds of any of the four forms of heart disease (OR=0.81; 95% CI: 0.78, 0.84) when compared to the lowest tertile of greenness, adjusting for individual sociodemographics and neighborhood income. These associations were attenuated in a final model which added biological risk factors, suggesting that cardiometabolic risk factors may at least partly mediate the observed relationships between greenness and heart disease. Conclusions: Even after adjusting for individual sociodemographics and neighborhood income, neighborhood greenness may be associated with reduced odds of heart disease, possibly as a result of increased time spent outdoors, physical activity, stress mitigation, and/or air pollution. Results suggest that strategies to reduce inequities in area greenness and improve public access to these areas may be a future means of reducing heart disease at the population level.