tbuckley/cabot-search huggingface dataset:
Abstract P294: Estimated Benefits and Risks of Lowering Sodium Intake With Potassium-based Salt Substitutes in China: a Modelling Study
Authors: Matti Marklund, Gitanjali Singh, Raquel C Greer, Frederick Cudhea, Kunihiro Matsushita, Renata Micha, Tammy Brady, Di Zhao, Liping Huang, Bruce Neal, Lawrence J Appel, Dariush Mozaffarian, Jason H Wu
Journal: Circulation (2019)

Introduction: Replacement of regular salt (NaCl) with potassium-based salt substitutes is a promising strategy to reduce blood pressure (BP) and prevent cardiovascular disease (CVD), especially in countries like China with high discretionary salt intake and low potassium intake. However, benefits of this strategy remain uncertain, and the risks of hyperkalemia and increased CVD mortality in persons with chronic kidney disease (CKD) are a concern. Hypothesis: In China, the estimated benefits of nationwide potassium-based salt substitution on CVD mortality will exceed potential risks. Methods: We used a comparative risk assessment framework to estimate potential benefits and risks of nationwide replacement of discretionary salt with potassium-based salt substitute (30±10% KCl) on CVD mortality in China. We incorporated existing data and corresponding uncertainties from randomized trials, the China National Survey of CKD, the Global Burden of Disease, and the CKD Prognosis Consortium ( Table ). We estimated averted CVD deaths from reduced BP subsequent to salt substitution in the adult population (benefits), and CVD deaths attributed to hyperkalemia from salt substitution in CKD patients (risks). Results: A nationwide implementation of potassium-based salt substitution in China, could prevent ~400,000 CVD deaths/year through BP lowering in the adult population, and increase ~10,000 CVD deaths/year through hyperkalemia among CKD patients (Table). For each additional death in CKD patients, around 40 CVD deaths could be averted in the adult population. Overall, the intervention could result in 369,258 (95% uncertainty interval: 160,702-576,680) net fewer deaths each year, corresponding to 9.4% (4.1-14.7) of annual CVD deaths in China. Conclusions: A nationwide potassium-based salt substitution in China could result in significant net benefits, preventing about 1 in 10 CVD deaths. Strategies to avoid potential hyperkalemic deaths among CKD patients could further improve the benefit:risk ratio.
Effect of polymorphism in one-carbon metabolism pathway on survival of gastric cancer patients in a large and comprehensive study.
Authors: Jinfei Chen, Zhi Xu, Dongying Gu, Tingting Zhao, Mingliang He
Journal: Journal of Clinical Oncology (2015)

e15091 Background: Although it has been shown that polymorphisms in one-carbon metabolism (OCM) pathway are associated with gastric cancer (GC), their interactions and contributions for patients’ survival are elusive. In this study, we investigated the effects of polymorphisms and their interactions on the survival of GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), Methionine synthase reductase (MTRR 66A > G), Methionine synthase (MTR 2756A > G), and Thymidylate synthase (TS 3’-UTR ins6 > del6, 5’-UTR 2R > 3R). Methods: We recruited 919 GC patients from 1998 to 2006. The Kaplan–Meier plots, Cox regression analyses and the log-rank tests were carried out in this study. Results: MTHFR 1298CC genotype showed protective effect (HR = 0.444, 95% CI = 0.210–0.940). MTRR 66 GA + GG genotypes decreased the risk of death (HR = 0.793, 95% CI = 0.651–0.967) in general, and in subgroups with more pronounced Diffuse type, greater depth of invasion (T2/T3/T4), higher level lymph node metastasis (N1/N2/N3), advanced TNM stages (II/III level) and 5-Fu treatment. However, the improved survival disappeared when GC patients simultaneously had MTR 2756 GA + GG genotypes (HR = 1.063, 95% CI = 0.750–1.507). Although MTRR 66GA genotype was not associated with the survival of GC patients, patients with simultaneous MTRR 66GA and MTR 2756AA genotypes exhibited significant risk reduction of death (HR = 0.773, 95% CI = 0.609–0.981). MTHFR 1298 CA + CC combined with TS 5-UTR 2R3R + 3R3R genotypes (HR = 0.536, 95% CI = 0.315–0.913) also increased patient survival rates. Conclusions: Our results suggest that the MTRR 66A > G and MTHFR 1298A > C polymorphisms may be useful prognostic biomarkers for GC patients.
Abstract 18102: Is There a Role for Intracoronary Fibrinolysis in the Primary PCI Era? A Randomized Trial of Intracoronary Tenecteplase versus Abciximab as Adjunctive Treatment in Acute Anterior Myocardial Infarction
Authors: Francisco J Morales-Ponce, Francisco J Lozano-Cid, Pedro Martínez-Romero, Pablo J González-Pérez, Juan A Sánchez-Brotons, Isabel Díaz-Torres, Juan C Rodriguez-Yáñez, Carmen Collado-Moreno, Sara Blasco-Turrión, Ivan Lobo-Torres, Eduardo Martínez-Morentín, Francisco J Camacho-Jurado, Marisol López-Sinoga, Clara P Bentolila Hachuel, Ana M Serrador-Frutos
Journal: Circulation (2017)

Introduction: There is lack of information about intracoronary (ic) fibrinolysis in the era of primary PCI. Our purpose was to compare the effects of ic administration of a fibrinolytic drug (tenec...
Abstract P417: Association of Breast Arterial Calcification Presence and Severity with Cognitive Function: The MINERVA Study
Authors: Carlos Iribarren, Meng Lu, Sabee Molloi, Gabriela Sanchez, Fatemeh Azamian-Bidgoli, Hyo-Min Cho, Huanjun Ding, Kristine Yaffe
Journal: Circulation (2019)

Mammographic Breast arterial calcification (BAC) may be a novel subclinical cardiovascular disease (CVD) risk marker. Since subclinical and clinical CVD are associated with cognitive impairment, we set out to investigate whether there is a relation between BAC presence/severity and cognitive function (CF). We used data from the M ult I eth N ic study of br E ast a R terial calcium gradation and cardio VA scular disease (MINERVA), a multiethnic cohort of women aged 60-79 at baseline (10/2012 and 2/2015) who were free of symptomatic CVD, all recruited at Kaiser Permanente of Northern California. The sample available for analyses with complete data on BAC, cognitive function and covariates was 3,919 (mean ± SD age=67 ± 4, 52% white, 18% Asian, 15% African-American and 12% Latina). A BAC continuous mass score (mg) was obtained using a validated densitometry method. BAC presence was BAC score &gt; 0 mg, and severe BAC was BAC score &gt; 20 mg. CF was dichotomized as Montreal Cognitive Assessment (MoCA) score &lt; 23 (first quartile) vs ≥ 23 (quartiles 2, 3 and 4). The unadjusted (Model 1) odds ratios (OR, 95% CI; p-value) of CF &lt; 23 vs. ≥ 23 associated with BAC &gt; 0 vs. BAC=0 was 1.15 (0.98-1.35; 0.08). However, adjustment for age, race and education (Model 2) abolished this association. Further adjustment for factors independently predicting CF (Model 3, with further inclusion of diabetes, HDL-C, CES depression score, breast feeding, multiple sclerosis and osteoarthitis) did not change the association. The unadjusted (Model 1) odds ratios (OR, 95% CI; p-value) of CF &lt; 23 vs. ≥ 23 associated with BAC &gt; 20 vs. BAC≤ 20 was 1.44 (1.02-2.01; 0.04). However, adjustment for age, race and education (Model 2) abolished this association and further adjustment for factors independently predicting CF did not alter the association. In conclusion, we found a statistically significant association between severe BAC and CF, but it was explained by covariation (confounding) by age, race and education, arguing that BAC may not play a role in cognitive impairment.
Reductionism in retreat
Authors: Denny Borsboom, Angélique O. J. Cramer, Annemarie Kalis
Journal: Behavioral and Brain Sciences (2019)

Abstract We address the commentaries on our target article in terms of four major themes. First, we note that virtually all commentators agree that mental disorders are not brain disorders in the common interpretation of these terms, and establish the consensus that explanatory reductionism is not a viable thesis. Second, we address criticisms to the effect that our article was misdirected or aimed at a straw man; we argue that this is unlikely, given the widespread communication of reductionist slogans in psychopathology research and society. Third, we tackle the question of whether intentionality, extended systems, and multiple realizability are as problematic as claimed in the target article, and we present a number of nuances and extensions with respect to our article. Fourth, we discuss the question of how the network approach should incorporate biological factors, given that wholesale reductionism is an unlikely option.
Abstract P148: Early Follow-Up Appointments for Congestive Heart Failure Admissions
Authors: Emily Schultz, Peter Sayegh, Akshai Bhandary
Journal: Circulation (2019)

Introduction: Congestive heart failure (CHF) admissions place a financial burden on patients and the healthcare system. The national direct medical costs of CHF have reached $20.9 billion and a CHF related hospitalization costs $14,631 per patient. Studies have demonstrated an association between early post-discharge follow up within 7 days and a reduction in readmission rates. Our study attempts to characterize the rates of follow up appointments in patients discharged from the medicine service in an urban academic hospital. Hypothesis: We hypothesized the rate of early follow-up appointments provided to patients with a diagnosis of an acute CHF exacerbation will be low. Methods: We performed a chart review of patients admitted to our institution from January 2016- February 2017 to the medicine service, including regular medicine floor and telemetry units, with a primary or secondary discharge diagnosis of acute systolic or diastolic heart failure. Discharge paperwork was reviewed for presence of an appointment with a primary care physician (PCP) or cardiologist scheduled within 7 days of discharge, including date and time of appointment. Patients discharged from the cardiology or other services and patients with dispositions of hospice or death were excluded. Results: Over a 13 month period, 63 patients were discharged from the medicine service with a primary or secondary diagnosis of CHF, twelve patients were excluded due to disposition. Among 51 patients, 15.7% (CI 95%, 0.07-0.286) were scheduled for follow-up appointment within 7 days of discharge with a PCP or cardiologist and 2 patients had appointments documented after 7 days. Therefore, 80.4% of patients (CI 95%, 0.695-0.913) did not have any scheduled follow up on their discharge summaries. Conclusion: In conclusion, the majority of CHF patients admitted to the medicine service of our institution are not provided appointments within 7 days of discharge. Data has shown that early follow up appointments are associated with reduced readmission rates. Lowering CHF readmissions are important for reducing medical complications and financial burden on patients and the healthcare system. Our future interventions will focus on increasing the number of patients with appropriate 7 day follow up with the aim to reduce readmissions and medical complications.
Drak, Drak, Goose: A New Signaling Axis in Glioblastoma
Authors: Justin D. Lathia
Journal: Cancer Research (2019)

Abstract While many molecular alterations in glioblastoma (GBM), the most common primary malignant brain tumor, have been defined, the intricate signaling networks associated with these alterations that represent actionable therapeutic targets are less well established. Chen and colleagues leverage a Drosophila GBM model to identify a conserved signaling axis downstream of the EGFR and PI3K that involves the death-associated protein kinase (Drak), a cytoplasmic serine/threonine kinase orthologous to the human kinase STK17A. Functional studies revealed that targeting this signaling axis attenuated mitosis and cytokinesis, providing a new pathway for therapeutic development in GBM. See related article by Chen et al., p. 1085
Predictors of prostate bed nodule on MRI in patients with rising PSA after radical prostatectomy.
Authors: Nicola Joseph Nasser, Victoria Chernyak, Shalom Kalnicki, Jonathan Klein
Journal: Journal of Clinical Oncology (2019)

122 Background: Radical prostatectomy (RP) is a common treatment modality for localized prostate cancer. Biochemical failure after RP is usually evaluated with whole body imaging to rule out metastatic disease and pelvic MRI to detect local recurrence in the prostate bed. We analyzed disease characteristics and demographic data of patients with rising PSA after RP to determine correlation with MRI-detected cancer recurrence. Methods: Using Clinical Looking Glass, an institutional data registry query tool, we identified all MRI scans performed at our institution between January 2013 and January 2018 to evaluate for the presence of prostate cancer after RP due to rising prostate specific antigen (PSA) levels. Using Chi-square testing, we analyzed PSA levels, pathologic disease characteristics, time from surgery to biochemical failure, and patient demographic characteristics as predictors of local recurrence detected by pelvic MRI. Results: We identified 64 patients who underwent MRI for rising PSA and had complete clinical and pathological data available. A prostate bed nodule compatible with local recurrence was found in 17 patients (27%). Thirty-six patients (56%) had no evidence of tumor in the prostate bed or pelvis. Eleven patients (17%) had a suspicious lesion which could represent scarring, retained seminal vesicle or recurrent cancer. Patient race was associated with likelihood of detecting a prostate nodule on MRI (p = 0.04) with African-American patients having 82% lower chance of MRI-detected tumor recurrence compared with White patients (p = 0.045). No other characteristic was significantly associated with MRI-detected recurrence including prostate cancer risk group, Gleason score, extra-capsular extension, positive surgical margin, seminal vesicle involvement, perineural invasion, lymphovascular invasion, and PSA level before MRI. Conclusions: African-American patients with biochemical failure after RP are less likely to have MRI-detectable recurrence in the prostate bed compared with white patients. This data may support a higher propensity toward microscopic metastatic disease at the time of biochemical failure in this population.
The impact of intraductal carcinoma of the prostate on the grade group system.
Authors: Masashi Kato, Akiyuki Yamamoto, Ryo Ishida, Tohru Kimura, Tomoyasu Sano, Momokazu Gotoh, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2019)

34 Background: The 2014 International Society of Urological Pathology (ISUP) and WHO 2016 classifications proposed a new grade group system for prostate cancer. Intraductal carcinoma of the prostate (IDC-P) is newly recognized on them and is reported to be strongly associated with high-grade and high-volume invasive prostate cancer. Although the presence of the IDC-P influences biochemical failure in radical prostatectomy patients, no data are available regarding the significance of IDC-P in integrating to the classification grade group system. The aim of this study is to enhance the utility of grade group system integrating into the presence of IDC-P. Methods: We retrospectively evaluated 1019 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. Data on age, PSA level at diagnosis, clinical T stage (cT), pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (range, 0.4–82 ng/ml). The median follow-up period was 82 (range, 0.7–148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, IDC-P positive rate increased correlated with upgrading. The grade group were as follows: Group 1 without IDC-P, 16.0% (n=163); Group 2 without IDC-P, 46.1% (n=470); Group 3 without IDC-P, 15.7% (n=160); Group 4 without IDC-P, 2.6% (n=27); and Group 5 without IDC-P, 4.1% (n=42); Group 2 with IDC-P, 2.9% (n=29); Group 345 with IDC-P, 12.6% [n=128; Group 3 (n=60); Group 4 (n=13); Group 5 (n=55)] Group 3, 4, and 5 with IDC-P showed a significantly worse prognosis than any other groups without IDC-P and Group 2 with IDC-P (p&lt;.0001). In a multivariate analysis, integrating IDC-P into ISUP Grade, PSA level at diagnosis, and surgical margin status significantly predicted the prognosis (P &lt; .0001). Conclusions: Integrating the presence of IDC-P into the grade group system will improve the accuracy of patients’ outcome prediction.
Receipt of systemic therapy in older versus younger patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Andrew W Hahn, Ben Haaland, Nityam Rathi, Nazli Dizman, Benjamin Louis Maughan, Sumanta K. Pal, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2019)

580 Background: More than half of pts diagnosed with mRCC are age 65 or older. However, older pts are often under-accrued/under-represented in clinical trials, partly due to concerns about their ability to tolerate systemic therapy (Rx). Given this, efficacy data from the registration trials may not apply to older pts. Herein, we investigate whether older patients with mRCC are less likely to receive various lines of systemic Rx than their younger counterparts. Methods: Clinical data was obtained from a prospectively maintained mRCC registry at the Huntsman Cancer Institute, University of Utah. Older pts were defined as ≥65 yrs at initiation of first-line systemic Rx for mRCC. Univariate analyses of the lines of systemic Rx received were performed using the Chi-squared test. Comparison of ordered categorical variables was made with the Wilcoxon rank sum test. Results: 264 pts who received first-line Rx for mRCC between 2004-2018 were included, and 108 of them were older pts. For older pts, median age at first-line Rx was 71.1 years and 78.7% had clear cell histology, whereas, the median age for younger pts was 53.4 years and 75.6% had clear cell histology. There was no difference in the baseline IMDC risk categories in older vs. younger pts (p = 0.907). A similar proportion of older and younger pts received at least two lines of systemic Rx (66.9% vs. 62.4%, p = 0.532). Furthermore, when analyzed across all lines of treatment, there was no difference in the number of systemic Rx between older and younger pts (p = 0.593). The median OS was similar in both groups: older 30 months (95% CI 21-44 months) vs. younger 34 months (95% CI 30-46 months) (p = 0.639). Conclusions: Older pts with mRCC receive a similar number of systemic Rx as their younger counterparts, and have similar survival outcomes. These findings can inform clinicians when selecting first and salvage-line treatment for older pts, and warrant proportionate accrual and representation of older pts in clinical trials.
Abstract P033: NT-proBNP as a Biomarker to Detect Salt Sensitivity
Authors: Otto A Sanchez, Paul E Drawz, Michelle Hanson, Renata Korczak, Daniel A Duprez, David R Jacobs, Lyn M Steffen
Journal: Circulation (2019)

Finding a biomarker to identify salt sensitive individuals would be an important step in the personalized management of hypertension. The natriuretic peptide, amino terminal pro-type B natriuretic peptide NT-proBNP, secreted by the heart in response to volume overload, is positively associated with incident hypertension. We hypothesized that when exposed to low salt diets, individuals with elevated NT-proBNP (≥ 100 pg/mL) will have a greater decrease in systolic blood pressure than those with NT-proBNP within the physiological range (40 - 90 pg/mL). Methods: Individuals with systolic/diastolic blood pressures greater than 120/85 mmHg and NT-proBNP values ≥ 40 pg/mL were included if they were not on blood pressure lowering medications and were free of cardiovascular or renal disease, diabetes, chronic obstructive pulmonary disease, pulmonary hypertension or any condition that would be associated with secondary causes of hypertension. Low salt diets consisted of meals containing total sodium 50 mmol/day. Meals were prepared at the Fairview University Hospital kitchen and provided to each participant for 10 days. Subjects were instructed to eat only the meals provided by the study. Sitting blood pressure, NT-proBNP, plasma glucose, sodium, creatinine and urinary sodium and creatinine were measured before and after 10 days on the low salt diet. Urinary creatinine and sodium was determined in 24-hour urine on day 10. Statistical analysis. Change (blood pressure after - blood pressure before low salt diet) in systolic blood pressure values were linearly regressed on log transformed NT-proBNP values. Results: 9 individuals (5 females) mean (SD) age 58.3 (8.1) years were classified into physiological 51.2 (7.8) pg/mL (n = 4) and an elevated 165.7 (84.5) pg/mL (n = 5) category of NT-proBNP. Systolic blood pressures was 127.9 (13.9) and 139.5 (9.6) mmHg for the physiological and elevated category of NT-proBNP, respectively, p = 0.18. Body mass index and plasma glucose, sodium and creatinine at baseline were also similar between the two groups. Following 10 days of low salt diet, systolic blood pressure decreased by a mean (SE) 16.9 (6.8) mmHg in those with elevated levels of NT-proBNP and by 10.9 (3.3) mmHg in those with physiological levels of NT-proBNP, p = 0.4. Baseline log NT-proBNP was inversely associated with change in systolic blood pressure r = - 0.60, p = 0.09. For log NT-proBNP values between 3.697 and 5.745 pg/mL, every log unit increase in NT-proBNP at baseline was associated with a mean (range) systolic blood pressure decrease of 10.4 (5 - 37.7) mmHg, p = 0.09. Conclusions: Results from a large-scale study are required to confirm the findings from this small pilot study that elevated values of NT-proBNP can predict who will have a decrease in systolic blood pressure in response to a low sodium diet.
Crafting Polymeric and Peptidic Hydrogels for Improved Wound Healing
Authors: David Stern, Honggang Cui
Journal: Advanced Healthcare Materials (2019)

Abstract Wound healing is a multifaceted biological process involving the replacement of damaged tissues and cellular structures, restoring the skin barrier's function, and maintaining internal homeostasis. Over the past two decades, numerous approaches are undertaken to improve the quality and healing rate of complex acute and chronic wounds, including synthetic and natural polymeric scaffolds, skin grafts, and supramolecular hydrogels. In this context, this review assesses the advantages and drawbacks of various types of supramolecular hydrogels including both polymeric and peptide‐based hydrogels for wound healing applications. The molecular design features of natural and synthetic polymers are examined, as well as therapeutic‐based and drug‐free peptide hydrogels, and the strategies for each system are analyzed to integrate key elements such as biocompatibility, bioactivity, stimuli‐responsiveness, site specificity, biodegradability, and clearance.