tbuckley/cabot-search huggingface dataset:
Abstract P415: Weight Variation and Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Authors: Mariana Sbaraini Da Silva, Mariana Lazo, Natalie R Daya, Olive Tang, Christie M Ballantyne, Chiadi E Ndumele, Elizabeth Selvin
Journal: Circulation (2020)

Introduction: Natriuretic peptides (NPs) are biochemical markers of cardiac function and NTproBNP strongly predicts heart failure. NPs also have a role in the adipose tissue, stimulating lipolysis, mitochondrial biogenesis and browning of adipocytes. Cross-sectional studies have demonstrated that diabetes and higher levels of adiposity are paradoxically associated with lower levels of BNP and NT-proBNP, suggesting that NPs may protect against metabolic dysregulation. Methods: We hypothesized that increases in NT-proBNP over time would be associated with decreases in weight and a lower risk of obesity in a community-based population. We analyzed data from 10,093 participants from the Atherosclerosis Risk in Communities (ARIC) Study with measurements of NT-proBNP at two time points 6-years apart (visit 2, 1990-92 and visit 4, 1996-98). Multivariable regression models were used, and sensitivity analysis excluding patients with heart failure was performed. Results: Mean age at baseline (1990-1992) was 57 years (SD 6), 57% were women and 78% were white. The prevalence of obesity increased from 28% to 35% in the 6-year follow up period. Higher baseline levels of NT-proBNP were associated with reduced risk of obesity after adjustment for other risk factors ( Table ). There was an inverse association between change in NT-proBNP levels between the visits and weight change ( Figure ). Results were similar after excluding cases of heart failure. Conclusions: We found inverse associations of NT-proBNP levels with weight change and incidence of obesity. Our results suggest that NPs or their pathways may be potential targets in the treatment of obesity. Nonetheless, the molecular networks involving the natriuretic system are complex and additional work, especially intervention studies, are needed to address the clinical relevance of this finding.
The value of combined modality therapy in elderly patients with stage III non-small cell lung cancer (NSCLC)
Authors: S. E. Schild, S. J. Mandrekar, A. Jatoi, W. L. McGinnis, P. J. Stella, R. L. Deming, J. R. Jett, Y. I. Garces, K. L. Allen, A. A. Adjei
Journal: Journal of Clinical Oncology (2007)

19503 Background: This study was performed to assess the value of combined modality therapy in elderly patients by comparing the differences in outcome of those who received radiotherapy (RT) alone or RT plus chemotherapy for stage III NSCLC. Methods: North Central Cancer Treatment Group (NCCTG) performed 2 recent phase III trials for stage III NSCLC. The first trial, 90–24–51, included 3 arms: once-daily radiotherapy (QDRT) alone, twice daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, 94–24- 52 included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients ≥65 years of age (elderly) who participated in these trials were included in this analysis. Results: Of the 166 elderly patients included in this analysis, 37 received RT alone and 129 received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared to 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank p=0.05). Patients who received RT plus chemotherapy experienced significantly greater severe (grade ≥3) toxicity than those who received RT alone (89.9% versus 32.4%, p &lt; 0.01). Conclusions: Elderly patients who participated in these trials appear to gain a survival advantage from RT and chemotherapy compared to RT alone. As is the case with younger patients, this benefit comes at the cost of additional toxicity. No significant financial relationships to disclose.
Abstract P290: The Association of Maternal Pre-pregnancy Weight With Childhood and Adolescent Blood Pressure and the Modifying Role of Vitamin D
Authors: Mingyu Zhang, Guoying Wang, Xiaobin Wang, Noel T Mueller
Journal: Circulation (2020)

Introduction: High blood pressure (BP) is the leading modifiable risk factor of cardiovascular diseases. High maternal pre-pregnancy body mass index (BMI) may be one of earliest risk factors for high child BP, but evidence supporting this hypothesis is limited. Vitamin D was recently found to protect against elevated BP in childhood, yet no studies to our knowledge have examined if Vitamin D could be a modifiable target for mitigating the association of pre-pregnancy BMI and child BP. Methods: We analyzed longitudinal data of 719 mother-child pairs in the Boston Birth Cohort enrolled from 1998-2012 at the Boston Medical Center. We calculated child systolic BP (SBP) percentile according to a US reference and defined low Vitamin D as cord blood 25(OH)D concentration &lt;11 ng/mL. We examined the change in child SBP percentile per 5-kg/m 2 increment in pre-pregnancy BMI using linear regression models with GEE estimates. We adjusted for confounders (see Figure footnote) and assessed mediation by further adjusting for child BMI-z score. Results: Our analytic sample included 451 (63%) African American/Haitian mothers, 361 (50%) girls, and 304 (42%) children with low cord blood Vitamin D. A 5-kg/m 2 increment in maternal pre-pregnancy BMI was associated with a 1.99 (95% CI: 1.08, 2.90) percentile increase in child SBP (during childhood [3-12 years]: 1.85, 95% CI: 0.97, 2.73; during adolescence [13-18 years]: 4.22, 95% CI: 1.19, 7.25). Cord blood Vitamin D status modified the associations (P-interaction = 0.023) (Figure, Panel A). Results were attenuated in the mediation analysis, but the interaction remained significant (Figure, Panel B). Conclusion: Higher maternal pre-pregnancy BMI is associated with higher offspring BP in childhood and adolescence, and this association is partially mediated by child weight. The inter-generational association disappeared if mother-newborn cord blood had high Vitamin D. Optimizing maternal Vitamin D status during pregnancy may help prevent the inter-generational cycle of cardiovascular risk.
Full-waveform inversion imaging of the human brain
Authors: Lluís Guasch, Oscar Calderón Agudo, Meng-Xing Tang, Parashkev Nachev, Michael Warner
Journal: npj Digital Medicine (2020)

Magnetic resonance imaging and X-ray computed tomography provide the two principal methods available for imaging the brain at high spatial resolution, but these methods are not easily portable and cannot be applied safely to all patients. Ultrasound imaging is portable and universally safe, but existing modalities cannot image usefully inside the adult human skull. We use in silico simulations to demonstrate that full-waveform inversion, a computational technique originally developed in geophysics, is able to generate accurate three-dimensional images of the brain with sub-millimetre resolution. This approach overcomes the familiar problems of conventional ultrasound neuroimaging by using the following: transcranial ultrasound that is not obscured by strong reflections from the skull, low frequencies that are readily transmitted with good signal-to-noise ratio, an accurate wave equation that properly accounts for the physics of wave propagation, and adaptive waveform inversion that is able to create an accurate model of the skull that then compensates properly for wavefront distortion. Laboratory ultrasound data, using ex vivo human skulls and in vivo transcranial signals, demonstrate that our computational experiments mimic the penetration and signal-to-noise ratios expected in clinical applications. This form of non-invasive neuroimaging has the potential for the rapid diagnosis of stroke and head trauma, and for the provision of routine monitoring of a wide range of neurological conditions.
The effect of margin status on local recurrence following breast conservation and radiation therapy for DCIS
Authors: M. R. Kell, C. Dunne, C. Canning, M. Morrow
Journal: Journal of Clinical Oncology (2007)

597 Background: There is no consensus on what constitutes an adequate surgical margin in patients receiving breast conserving surgery (BCS) and postoperative irradiation (RT) for ductal carcinoma in situ (DCIS). Inadequate margins may result in high local recurrence, and excessively large resections may lead to poor cosmetic outcome without oncological benefit. Methods: A comprehensive search for published trials which examined outcomes after adjuvant RT following BCS for DCIS was performed using medline and cross referencing available data. Reviews of each study were conducted, and data were extracted. Fixed and random effects methods were used to combine data. Primary outcomes were in breast tumour recurrence (IBTR) related to surgical margins. Results: Analysis of 3,606 patients from randomized trials confirms that patients with negative margins are significantly less likely to recur than those with positive margins after RT (RR 0.53, 95% CI= 0.42 to 0.66, p&lt;0.01). Combined data from randomized and non randomized trials, of 5,500 patients, demonstrates that where the margin status is close or unknown there is significant risk of IBTR compared to a negative margin (RR=1.68, 95% CI= 1.22–2.33, p&lt;0.01). When specific margin thresholds are examined a 2 mm margin is superior to less than 2 mm (OR=0.67, 95% CI 0.51 -0.89, p&lt;0.01), however we saw no significant difference in the rate of IBTR between a 2 mm margin and &gt;5 mm (OR=1.49, 95% CI 0.54 to 4.9, p&gt;0.05). Conclusions: Surgical margins negative for DCIS should be obtained following BCS for DCIS. A margin threshold of 2mm appears be as good as a larger margin when BCS for DCIS is combined with RT. No significant financial relationships to disclose.
Trends in Late Mortality Among Adolescent and Young Adult Cancer Survivors
Authors: Chelsea Anderson, Hazel B Nichols
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Over the past several decades, treatment of cancer in adolescents and young adults (AYAs) has evolved substantially, leading to steady improvements in estimated 5-year survival at diagnosis. However, the impact on late mortality in this population is largely unexamined. We investigated temporal trends in mortality among 5-year AYA cancer survivors. Methods The Surveillance, Epidemiology, and End Results database was used to identify AYAs (age 15–39 years) diagnosed with cancer during 1975–2011 who survived at least 5 years beyond diagnosis. Survival months were accrued from 5 years postdiagnosis until death or the end of 2016. Cumulative mortality from all causes, the primary cancer, other cancers, and noncancer or nonexternal causes (ie, excluding accidents, suicide, homicide) were estimated according to diagnosis era. Results Among 282 969 five-year AYA cancer survivors, 5-year mortality (ie, from 5 through 10 years postdiagnosis) from all-causes decreased from 8.3% (95% confidence interval = 8.0% to 8.6%) among those diagnosed in 1975–1984 to 5.4% (95% confidence interval = 5.3% to 5.6%) among those diagnosed in 2005–2011. This was largely explained by decreases in mortality from the primary cancer (6.8% to 4.2%) between these periods. However, for specific cancer types, including colorectal, bone, sarcomas, cervical/uterine, and bladder, cumulative mortality curves demonstrated little improvement in primary cancer mortality over time. Some reduction in late mortality from noncancer or nonexternal causes was apparent for Hodgkin lymphoma, leukemia, kidney cancer, head and neck cancers, and trachea, lung, and bronchus cancers. Conclusion Over the past four decades, all-cause and cancer-specific mortality have decreased among 5-year AYA cancer survivors overall, but several cancer types have not shared in these improvements.
Abstract MP17: Sedentary Behavior and Longitudinal Changes in Kidney Function in US Hispanics/Latinos: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Mary Hannan, Ana Ricardo, Jianwen Cai, Nora Franceschini, Robert Kaplan, David Marquez, Sylvia E Rosas, Neil Schneiderman, Daniela Sotres-Alvarez, Gregory A Talavera, Martha L DAVIGLUS, James Lash
Journal: Circulation (2020)

Introduction: Sedentary behavior increases cardiovascular risk due to detrimental effects on blood pressure, vascular function, and glucose metabolism. U.S. Hispanics/Latinos have a high prevalence of sedentary behavior and a large burden of chronic kidney disease (CKD). Therefore, we evaluated the association between sedentary behavior and changes in kidney function over time. Hypothesis: We assessed the hypothesis that higher sedentary time will be associated with increase in proteinuria, decrease in estimated glomerular filtration rate (eGFR), and incident CKD. Methods: We used data from the HCHS/SOL, a community-based cohort of self-identified Hispanic/Latino adults (18-74 years) from diverse backgrounds in the U.S. This study includes 11181 adults who underwent one-week accelerometry at Visit 1 (baseline, 2008-2011) and completed Visit 2 (2014-2017). Linear regression was used to assess the association of sedentary time with change in eGFR and urine albumin- to-creatinine ratio (ACR), and Poisson regression with robust variance was used to estimate the association with rate of incident CKD (defined as the composite of either the development of eGFR &lt;60ml/min/1.73m 2 and a decline in eGFR ≥1 ml/min per year, or ACR ≥30 mg/g), adjusted for covariates and time elapsed between visits. Results: At baseline, mean age was 42.2 years, 51.4% women, mean sedentary time was 11.8 hours, mean eGFR was 106.1mL/min, and median ACR 6.7mg/g. After a median follow-up of 5.9 years, the average decline in eGFR was 0.8ml/min/year and the average change in ACR was 0.3mg/g/year. In fully adjusted models, individuals with higher sedentary time experienced a greater decline eGFR from Visit 1 to Visit 2 (Table 1). Sedentary time was not significantly associated with change in ACR or incident CKD. Conclusion: Sedentary behavior may be associated with a decline in kidney function in U.S. Hispanics/Latinos, which may have important implications for prevention of kidney disease and associated cardiovascular risk in this population.
Abstract P219: The Vast Majority of People Who Eat “Gluten Free” for IBS, Celiac, or Autoimmune Disease Have Markers of Leaky Gut That Resolve When “Gluten Free” Foods Containing Lectins, Like Corn, Other Grains, Beans, and Nightshades are Removed From Their Diet
Authors: Steven R Gundry
Journal: Circulation (2020)

Initial evaluation of pts referred with Irritable Bowel Syndrome, Celiac, and/or autoimmune diseases includes Celiac HLA genetics, Celiac IgA and IgG markers, and autoimmune markers. Most patients are self described as eating a gluten free diet. Increasingly, and with more affordable tests being made available, we have started to use a battery of tests for leaky gut, wheat, corn, lectin, dairy, and egg proteins reactivity/sensitivity from Vibrant Wellness (San Carlos, Ca) called Zoomers. Leaky gut was determined by Anti-Zonulin IgG and IgA, Anti-Actin IgG and IgA; Wheat sensitivity panels included Transglutaminase, Wheat Germ Agglutinin, Gliadin, Glutenin, and Non-gluten wheat protein IgG and IgA panels. All corn proteins, including the wheat-corn epitope overlap and the GMO Cry proteins IgG and IgA, as well as IgG and IgA reactions to major lectins and aquaporins in beans, squash, spinach, nightshades, corn, and to protein components of dairy and eggs. We now report results on the first 50 patients, ages 7-76, M:F ratio 1:1, who, following these initial tests, started the lectin limited diet, The Plant Paradox. Results: 100% of pts were positive for leaky gut (50/50). Forty nine of 50 (98%) were reactive to more than one component of wheat, although only 35/50 (70%) where positive for HLA gluten genes. Seventy percent of pts (35/50) were sensitive to the corn-wheat cross reaction epitope, while 31/50 (62%) reacted to the GMO cry corn protein. Forty nine of 50 (98%) reacted to one or more bean lectins, while 38/50 (76%) reacted to one or more aquaporins in soy, spinach, corn, potatoes, bell peppers. While sensitivities to dairy and egg proteins did occur, they were rare compared to the above proteins. Retesting has been done in 11 of 50 pts, 2 to 9 months following the first test. Resolution of leaky gut occurred in 10/11 (91%), and reactivity to all wheat proteins as measured by IgG and IgA disappeared, indicating tolerance. We conclude that most patients following a gluten free diet still have leaky gut with both gluten and wheat antibodies, all of which resolve when a lectin free diet is followed.
Abstract 14815: A Minority of Patients With Cardiac Sarcoidosis Are Treated With Steroid-Sparing Immunosuppressants: Insights From the TriNetX Global Network Database
Authors: Brian K Mitchell, Huzaefah J Syed, Tamas Gal, Patrick Nana-Sinkam, F. Gerard Moeller, Kenneth A Ellenbogen, Antonio Abbate, Jordana Kron
Journal: Circulation (2019)

Introduction: Cardiac sarcoidosis (CS) is a granulomatous disease which can cause life-threatening arrhythmias and heart failure. Corticosteroids are the primary therapy, but their use is associate...
Abstract MP71: Socioeconomic Status, Guideline Directed Medical Therapy, and Prognosis in Heart Failure With Reduced Ejection Fraction: The Atherosclerosis Risk in Community (ARIC) Study
Authors: Lena Mathews, Ning Ding, Amira Collison, Yejin Mok, Jung-Im Shin, Deidra Crews, Wayne D Rosamond, Anna Kucharska-Newton, Patricia Chang, Chiadi E Ndumele, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2020)

Introduction: Current research suggests racial differences exist in the utilization of guideline directed medical therapy (GDMT) and prognosis in heart failure with reduced ejection fraction (HFrEF). Whether individual and community level socioeconomic status (SES) impacts prescription patterns of GDMT and prognosis in HFrEF has not been studied. Methods: We studied 669 ARIC participants with incident HFrEF (EF&lt;50%) (mean age 77.6 (SD 6.5) years; 39% black; 46% women) during 2005-2017 (median 1.8 years of follow-up). We assessed the proportion of patients on optimal GDMT (defined as ß-blockers [BB] and ACE inhibitors [ACEI] or angiotensin receptor blockers [ARB]) or adequate GDMT (one of either BB, ACEI/ARB, aldosterone antagonists [AA], or hydralazine and nitrates [H-ISDN]) at hospital discharge by individual SES (education and income), neighborhood SES (area deprivation index: ADI) and their combination (Table). We also examined the contribution of GDMT prescription to prognosis overall, and by SES. Subsequently, we quantified the association of SES with mortality and re-hospitalization for HFrEF. Results: The proportion of patients prescribed optimal and adequate GDMT was 54% and 81%, respectively. BB were most frequently prescribed (83%), followed by ACEI/ARB (61%), AA (11%), and H-ISDN (9%). Overall, BB were associated with lower mortality, while H-ISDN were associated with higher mortality, compared to their non-use counterparts. ACEI/ARB were associated with lower re-hospitalization, compared to non-users of ACEI/ARB. The prescription of GDMT and the effect of GDMT on prognosis did not significantly differ by SES. Despite that, lower SES was independently associated with higher risk of mortality and re-hospitalization (Table). Conclusions: Overall, optimal GDMT was low at discharge, but did not differ by SES. Despite that, there were significant differences in death and re-hospitalization by SES, suggesting a potential need for tailored approaches to HFrEF management for low SES individuals.
A phase I study combining high-dose (HD) topotecan (TPC) plus cyclophosphamide (CPM) with blood stem cells support in poor prognosis ovarian carcinoma (OC): The ITOV 01bis protocol
Authors: J. Lotz, P. Pautier, F. Selle, M. Fabbro, P. Viens, V. Ribrag, F. Lokiec, J. Gligorov, C. M. de Labareyre, C. Lhommé
Journal: Journal of Clinical Oncology (2007)

16061 Background: TPC and CPM-based CT may be proposed as 2nd-line chemotherapy (CT) after taxanes/platinum-compounds in refractory/relapsed OC. We have previously shown that the maximum tolerated dose (MTD) of TPC used as a single agent was 45 mg/m 2 in a 5-d administration schema (ITOV 01 protocol - Lotz et al, BMT 2006, 37: 669). Method: We decided herein to combine TPC at a dose ranging from 8 to 10 mg/m 2 /d x 5d (30’ daily perfusion) to a fixed HD CPM (60 mg/kg/d x 2d) until the MTD of TPC was reached. Three pts were to be treated at each planned dose level (8.0, 8.5, 9.0, 9.5, 10 mg/m 2 /d). Limiting toxicity was defined as one toxic death (excluding sepsis) or grade (G) 4 non-hematological toxicity. In this event, a further 3 pts were to be recruited at the same dose level. Mobilization to collect 3x10 6 CD34+/kg BW (6x10 6 if a 2 nd HD course using TPC alone was planned) was performed with CPM + filgrastim. Results: From 09/02 to 05/06, 26 pts (median age, 54, range: 21–64) were included (platinum-refractory/relapse - 15 pts, initial stage FIGO IV - 5 pts, residual disease at 2 nd -look - 6 pts). Three pts failed to be collected, one progressed before and one progressed after mobilization, so that 21 pts were able to complete their 1 st course. Six received a second cycle of HD TPC. One septicemia-related toxic death occurred at level 8 mg/m 2 /d. Median durations of G4 neutropenia &amp; thrombocytopenia observed during the first course of HDCT were 10 &amp; 9 d. No patients experienced G4 diarrhea. One pt experienced a G4 cutaneous toxicity at level 8.5 and 2/3 at level 9.5 mg/m 2 /d. MTD of TPC combined with CPM was consecutively set up at 9.0 mg/.m 2 /d x 5d. Pharmacokinetic data (Cmax, AUC) will be available. Conclusion: The MTD of TPC combined with CPM was set up at 9 mg/m 2 /d x 5d, i.e., 45 mg/m 2 . The forthcoming ITOV 04 protocol will combine HD TPC and Carboplatin (AUC 20) in patients whose relapse occurs between 6 and 12 months after platinum- based first-line CT. No significant financial relationships to disclose.