tbuckley/cabot-search huggingface dataset:
First-line PD(L)1 inhibitors for platinum-ineligible advanced urothelial carcinoma (aUC).
Authors: Archana Agarwal, Gregory Russell Pond, Ruby Gupta, Moshe Chaim Ornstein, Pedro C. Barata, Jorge A. Garcia, Alexandra Drakaki, Jae-Lyun Lee, Ravindran Kanesvaran, Mehmet Asim Bilen, Felipe R. Lorenzo, Petros Grivas, Syed A. Hussain, Catherine Curran, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

e16024 Background: FDA modified the label for 1st-line pembrolizumab or atezolizumab to PD-L1 high cisplatin-ineligible or platinum-ineligible aUC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD-(L)1 inhibitors for platinum-ineligible pts are unclear. We hypothesized that treatment response and outcomes are comparable to data reported in trials in the 1 st line setting of aUC, and conducted a retrospective study to test this hypothesis using data outside the clinical trial setting. Methods: We collected data from 8 institutions for aUC pts with locally advanced unresectable or metastatic UC. The following criteria were used to define pts platinum-ineligible while comorbidities, age and physician discretion were also allowed: Cr Cl &lt; 30 ml/min, ECOG PS 3, Cr Cl 30-59 ml/min and ECOG PS 2. Demographic &amp; clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was used to explore associations of baseline variables with response and outcomes. Results: Data were available for 79 pts. Pts received atezolizumab [n = 41], pembrolizumab [n = 28], nivolumab [n = 7] or durvalumab [n = 3]. Median age was 74 years (45-93). Reasons for platinum-ineligibility were: Cr Cl &lt; 30 ml/min (n = 26), ECOG PS 3 (n = 8), ECOG-PS 2 and Cr Cl &lt; 30-59ml/min (n = 14), elderly/co-morbidities (n = 17), and ‘unavailable’ (n = 14). Median OS was 45 weeks (CI 32-80) and ORR was 27.9%: Complete response in 4 pts [5.1%], partial response in 18 pts [22.8%], stable disease in 19 pts [24.1%], progressive disease in 34 pts [43 %]; data for 4 pts [5.1%] was unavailable for best response. Toxicity of any grade and Grade ≥3 was seen in 41.8% and 31.7% of pts, respectively. Hemoglobin (HR = 0.78, 95% CI 0.68 - 0.90, P = 0.001) and liver metastasis (HR = 1.13, 95% CI 0.51 - 2.53, P = 0.036) correlated with OS. Conclusions: The efficacy and toxicities of 1st-line PD-(L)1 inhibitors for platinum-ineligible pts outside clinical trials appear comparable to those reported in trials for unselected cisplatin-ineligible pts. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible pts with aUC warrant evaluation of novel safe and effective agents.
Evaluation of a multi-level, multi-parameter detection method for digestive system cancer diagnosis.
Authors: Yefan Zhang, Hong Zhao, Xinyu Bi, Zhen Huang, Jianqiang Cai, Xing Tang, Da Lou, Chris Chang Yu, Xue Dong Du
Journal: Journal of Clinical Oncology (2015)

e12578 Background: Despite efforts in recent years, major progress in cancer diagnosis remains to be elusive. Existing issues include inability to detect cancer early, relatively low sensitivity and specificity, side effects (for some imaging based technologies), and relatively high costs. In this work, an initial evaluation was carried out on diagnosis of two digestive cancer sites, hepatocellular carcinoma (HCC) and colorectal cancer, using a method named Cancer Differentiation Analysis technology (CDA) which measures both protein and cellular level information in blood in a single test. A performance comparison was made between CDA technology and traditional bio-marker method. Methods: Blood samples for HCC, colorectal cancer, and control groups were collected, and data were then taken with both bio-marker (serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA)) and CDA methods. Results: The measured CDA value showed significant statistical difference between the control (20 samples), HCC group (9 samples) and colorectal cancer （6 samples）with P < 0.01, In HCC group, CDA has a sensitivity of 77% (7 of 9) while AFP has a sensitivity of 33% (3 of 9) , and specificity was comparable. In colorectal cancer, CDA has a sensitivity of 83% (5 of 6) while CEA has a sensitivity of 33% (2 of 6) with comparable specificity. Given the limited sample size, more data will be collected to further confirm the initial results. Conclusions: Based on preliminary, limited data using the new multi-level, multi-parameter blood test method (CDA technology) for HCC and colorectal cancer diagnostics, sensitivity was improved over the traditional bio-marker technology. Keywords: digestive system cancer diagnosis, colorectal cancer
Abstract 12768: Right Ventricular Mechanical Dyssynchrony in Pulmonary Hypertension is Associated With Right Ventricular Performance and Pulmonary Hemodynamics
Authors: Sachiyo Igata, Nobuhiro Tahara, Atsuko Tahara, Akihiro Honda, Yoshikazu Nitta, Yoichi Sugiyama, Bekki Munehisa, Tomohisa Nakamura, Jun Kumanomido, Eita Kumagai, Yoshihiro Fukumoto
Journal: Circulation (2016)

Background: Right ventricular mechanical dyssynchrony (RVD) in pulmonary hypertension (PH) is prevalent and correlates with the extent of RV dysfunction and clinical worsening, but is not fully investigated. The aim of this study is to investigate clinical factors associated with RVD in patients with PH. Methods: The study involved 24 patients (23 females; mean age of 62.2±17.5) with pre-capillary PH diagnosed by right heart catheterization, without electrocardiographic intraventricular conduction delay. They underwent determination of blood chemistry, magnetic resonance imaging and echocardiography including 2-dimensional speckle tracking. RVD was evaluated by 2-dimensional speckle-tracking echocardiography calculating the coefficient of variance of the times to peak-systolic strain for the 4 mid-basal RV segments (RV-CV4). Results: Mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and RV-CV4 were 33.4±11.7 mmHg, 7.3±4.4 wood unit and 10.5±7.3,respectively. In univariate analyses, mPAP, PVR, RV-fractional area change (inversely), RV-ejection fraction (inversely) and uric acid were significant correlated with RV-CV4. Multivariate stepwise analysis revealed that uric acid was independently associated with RV-CV4 (R 2 =0.593). Conclusion: The present study demonstrated that high uric acid level was a sole independent associate of RV dyssynchrony in PH patients, suggesting a predictor of heart failure and mortality.
Racial differences in weight perception among breast cancer patients.
Authors: Jenny J Lin, Kezhen Fei, Rebeca Franco, Emily Gallagher, Derek Leroith, Nina A. Bickell
Journal: Journal of Clinical Oncology (2015)

e12623 Background: Black women are more likely than white women to be obese, and obesity is associated with worse breast cancer outcomes. Black women are more likely to be satisfied with their body size and may be less likely to try to lose weight. Weight perception, has not been studied as a potential mediator of racial disparities in women with breast cancer. We describe early findings of the association between weight perception and race among women with newly diagnosed breast cancer. Methods: We recruited 146 (82% white, 18% black) women with a new primary breast cancer at time of surgery and surveyed them about weight perception. We measured BMI at enrollment and classified women with BMI > 25 reporting they were “about the right weight” as under-perceivers. Chi-square tests assessed factors associated with under-perception of weight. We fit logistic regression models to evaluate the racial difference in under-perception controlling for other covariates. Results: Of 146 women with new breast cancer, 64% had stage 1, 32% stage 2 & 4% stage 3 at diagnosis. 58% of the women had a normal BMI (18.5-24.9kg/m2), 23% were overweight (BMI: 25-29.9 kg/m2) and 18% were obese. Black women were more likely to be overweight or obese (77% vs. 33%, p < .0001) and more likely to under-perceive their weight (15% vs. 6%) while whites were more likely to over-perceive of their weight (23% vs. 0%, p = 0.003). Women with less than college education were more likely to under-perceive their weight (21% vs. 5%, p = 0.02). In multivariate logistic regression models stratified by college education and controlling for age, blacks have higher rates of under-perceiving their weight compared to whites (RR = 7.47, 95% CI: 1.50-37.13), whereas among women with less education, there is no racial difference in under-perception of weight. Conclusions: As black women have higher rates of obesity and worse breast cancer outcomes, weight perception and the desire to change weight are critical modifiable factors that may contribute to racial disparities. Among black women, education is not associated with accurate weight perception. If weight loss can improve breast cancer outcomes, further work should elucidate how to change weight perception among high risk obese and black women.
Whole genome sequencing reveals that genetic conditions are frequent in intensively ill children
Authors: Courtney E. French, Isabelle Delon, Helen Dolling, Alba Sanchis-Juan, Olga Shamardina, Karyn Mégy, Stephen Abbs, Topun Austin, Sarah Bowdin, Ricardo G. Branco, Helen Firth, David H. Rowitch, F. Lucy Raymond
Journal: Intensive Care Medicine (2019)

With growing evidence that rare single gene disorders present in the neonatal period, there is a need for rapid, systematic, and comprehensive genomic diagnoses in ICUs to assist acute and long-term clinical decisions. This study aimed to identify genetic conditions in neonatal (NICU) and paediatric (PICU) intensive care populations.We performed trio whole genome sequence (WGS) analysis on a prospective cohort of families recruited in NICU and PICU at a single site in the UK. We developed a research pipeline in collaboration with the National Health Service to deliver validated pertinent pathogenic findings within 2-3 weeks of recruitment.A total of 195 families had whole genome analysis performed (567 samples) and 21% received a molecular diagnosis for the underlying genetic condition in the child. The phenotypic description of the child was a poor predictor of the gene identified in 90% of cases, arguing for gene agnostic testing in NICU/PICU. The diagnosis affected clinical management in more than 65% of cases (83% in neonates) including modification of treatments and care pathways and/or informing palliative care decisions. A 2-3 week turnaround was sufficient to impact most clinical decision-making.The use of WGS in intensively ill children is acceptable and trio analysis facilitates diagnoses. A gene agnostic approach was effective in identifying an underlying genetic condition, with phenotypes and symptomatology being primarily used for data interpretation rather than gene selection. WGS analysis has the potential to be a first-line diagnostic tool for a subset of intensively ill children.
Thyroid dysfunction and autoimmunity in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors as a potential clinical biomarker of response.
Authors: Francesco Atzori, Fabiana Pani, Germana Baghino, Silvia Cugudda, Roberta Mascia, Stefano Mariotti, Maria Teresa Ionta
Journal: Journal of Clinical Oncology (2015)

e15588 Background: A common adverse effect of tyrosine kinase inhibitors (TKIs) in metastatic renal cell carcinoma (mRCC) is hypothyroidism (HT), however the role of thyroid autoimmunity (TA) in the pathogenesis of HT related to TKIs has not systematically studied.The primary objective of this study is to evaluate prospectively the thyroid function (TF) and autoimmunity in patients (pts) with mRCC. Methods: 20 pts with mRCC, normal TF and no evidence of associated TA, were studied before and at monthly intervals after beginning TKIs: Pazopanib (P) in 1 pt, Sunitinib (S) in 14 pts replaced with Axitinib (A) after disease progression. S was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off, P daily oral dose of 800 mg and A daily oral dose of 10 mg. In all cases TSH, FT3, FT4, thyroid antibodies (TgAb and TPOAb), morphological evaluation with color doppler ultrasound were measured up to 12 months. Results: After 30-120 days of therapy 14 (70%) pts developed primary HT (TSH increased from 1.31±0.7 to 15.74±25.73 mUI/L, [normal range 0.4-4 mUI/L]). We observed in 6 hypothyroid pts de novo appearance of TPOAb (84-3000 IU/ml normal range 0-35 UI/l), who had the highest TSH values (25-114 mUI/ml). This was associated to a decrease of thyroid volume (12.5±11.6 ml to 6.2±4.2 ml [p < 0.001]) after 9 months of therapy in 19 (95%) pts significantly lower in TPOAb positive (2.1±1.33 ml) than in TPOAb negative pts (6.8±3.4 ml p < 0.001). Interestingly, we observed a markedly hypoechogenicity when compared to basal appearance which was more evident in TPOAb positive pts; as far as the vascularization is concerned, there was a trend to reduction parenchymal perfusion which did not reach the level of statistical significance. About two groups of pts cox regression analysis provided a hazard ratio for PFS of 0.59 (95% CI 0-45-0.76, p < 0.001). Conclusions: These data further confirm the thyroid inhibitory effect of TKIs. However, the novel appearance of TPOAb in a subgroup of pts with more severe HT, suggests that TKIs may also exacerbate TA, which could play a role as a potential biomarker of response to TKIs. Further prospective analyses are required to validate this finding.
First cardiovascular MRI study in individuals at risk of rheumatoid arthritis detects abnormal aortic stiffness suggesting an anti-citrullinated peptide antibody-mediated role for accelerated atherosclerosis
Authors: Graham Fent, Kulveer Mankia, Bara Erhayiem, Laura Hunt, Jacqueline Leong Nam, Lesley-Anne Bissell, James RJ Foley, Pei G Chew, Louise E Brown, John P Greenwood, Paul Emery, Sven Plein, Maya H Buch
Journal: Annals of the Rheumatic Diseases (2019)

Patients with rheumatoid arthritis (RA) are at greater risk of major cardiovascular (CV) events, predominantly due to accelerated atherosclerosis, underpinned by inflammation and RA disease factors and also heart failure.1 Overall, modest event rate has necessitated the use of surrogate CV abnormalities of increased CV risk including arterial stiffness. Increased arterial stiffness is well recognised in established RA,2 with early, similar reports using comprehensive and reliable cardiac MRI (CMRI) in our treatment-naive, early onset RA cohort.3 Autopsy, histopathological and clinical studies in general population and RA cohorts with and without CV disease (CVD) suggest citrullinated proteins as a mechanism for atherosclerosis, including presence of citrullination within the atherosclerotic plaque of subjects without RA.4 5 We hypothesised that individuals with circulating anti-cyclic citrullinated peptide (CCP) but no systemic inflammation (of RA typically associated with increased CV risk) also demonstrate …
Erratum. The virtual office visit for women with gestational diabetes mellitus. Diabetes Care 2017;40:e34—e35
Authors: David A. Sacks, Deborah Ling Grant, Mayra Macias, Xia Li, Jean M. Lawrence
Journal: Diabetes Care (2019)

Erratum.Impact of lifestyle and metformin interventions on the risk of progression to diabetes and regression to normal glucose
Abstract MP66: Body Mass Index Trajectories From Childhood to Adulthood: Evidence From the International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Verity Cleland, Jing Tian, Marie-Jeanne Buscot, Costan Magnussen, Lydia A Bazzano, Trudy L Burns, Stephen R Daniels, Terence Dwyer, David R Jacobs, Markus Juonala, Ronald J Prineas, Olli Raitakari, Alan R Sinaiko, Julia Steinberger, Elaine M Urbina, Jessica G Woo, Alison J Venn
Journal: Circulation (2019)

Background: Understanding body mass index (BMI) trajectories across the lifecourse may help identify risk of overweight or obesity and strategic points for preventive interventions. We describe BMI trajectories from childhood to adulthood in four population-based cohorts established in the 1970s-80s and their sociodemographic correlates. Methods: Data were from 12,086 participants (45% male) from four cohorts established in Australia, Finland and the US. Participants had ≥3 measures of height and weight, including ≥1 in childhood (6-18 years, mean 9.7 to 11.1 years at first visit) and ≥1 in adulthood (mean 40.0 to 50.9 years at last visit). Latent Class Growth Mixture Modelling estimated BMI trajectory groups. Correlates (age, gender, race, parental education) of BMI trajectories were identified with log multinomial regression. Results: Mean BMI ranged from 17.8-18.3 kg/m 2 at first visit and 26.4-30.2 kg/m 2 at last visit. Six BMI trajectories (Figure) were identified in three cohorts: persistently normal (48-57% of participants), improving from high (1-2%), progressing to overweight (30-39%), progressing to obese (1-8%), late onset obese (2-6%), and progressing to severe obesity (1-3%). One cohort had a seventh group: greatly improving (&lt;1%). Women were less likely to progress to overweight and more likely to progress to obese than men. Black participants were at greater risk of progressing to obesity, severe obesity and late onset obesity than white participants. Improving from high BMI was associated with being younger at first visit and lower parental education. Conclusion: Similar BMI trajectories were identified across cohorts, countries and time, despite different BMI distributions. Females and black Americans were most likely to be of high BMI at the end of follow-up. Few participants (≤2%) improved from high BMI. A better understanding of the factors that influence the highest and improving BMI trajectories may help identify risk reduction strategies.
Association between stromal/TGF-β/EMT gene expression signature and response to pembrolizumab monotherapy in cisplatin-ineligible patients with locally advanced (unresectable) or metastatic urothelial carcinoma.
Authors: Petros Grivas, Daniel E. Castellano, Peter H. O'Donnell, Razvan Cristescu, Tara L. Frenkl, Stephen Michael Keefe, Andrey Loboda, Sandra C. Souza, Hua Ma, Alex Snyder, Chunsheng Zhang, Andrew Albright, Jared Lunceford, Arjun Vasant Balar
Journal: Journal of Clinical Oncology (2019)

433 Background: PD-L1 immunohistochemistry and an 18-gene T cell–inflamed gene expression profile (GEP) are associated with response to anti–PD-1/PD-L1 therapy across tumor types, including urothelial carcinoma. A gene expression signature representing convergent biology related to stromal/EMT/TGF-β pathways was developed and prespecified for testing for association with pembrolizumab response in urothelial carcinoma patients treated on the KEYNOTE-052 trial (NCT02335424). Methods: KEYNOTE-052 was a single-arm phase 2 trial of pembrolizumab in cisplatin-ineligible patients with previously untreated, advanced urothelial carcinoma. Primary objective of this analysis was to assess the association between the Stromal/EMT/TGF-β signature and outcomes (best overall response [BOR], PFS, OS) as an independent biomarker and to understand its potential prognostic/predictive role beyond the T cell–inflamed GEP score or PD-L1 assessed using combined positive score (CPS). Cox regression models for PFS and OS and a logistic regression model for BOR evaluated associations between Stromal/EMT/TGF-β signature and outcomes adjusting for ECOG performance status (PS) and level of the GEP or CPS (1-sided P value). Results: RNA-Seq data from baseline tumor specimens were available for 187/370 patients on KEYNOTE-052. Lower Stromal/EMT/TGF-β score was associated with favorable BOR rate ( P &lt; 0.001), PFS ( P &lt; 0.001), and OS ( P = 0.002) after adjustment for ECOG PS and GEP (which remained significant at the 0.05 level in all cases). The patterns indicated a very consistent downward trend in the distribution of the Stromal/EMT/TGF-β score for responders versus nonresponders, regardless of GEP. In models that adjusted for both ECOG PS and PD-L1 CPS, the Stromal/EMT/TGF-β score remained significant (BOR rate, P = 0.002; PFS, P = 0.013; OS, P = 0.029). Conclusions: Higher Stromal/EMT/TGF-β signature was associated with resistance to pembrolizumab independently of GEP or PD-L1 in urothelial carcinoma patients on the KEYNOTE-052 trial. Clinical trial information: NCT02335424.
Heroin Smoking is Not Common in the United States—Reply
Authors: Vilakshan Alambyan, Ciro Ramos-Estebanez
Journal: JAMA Neurology (2019)

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Water Pipe (Hookah) Smoking and Cardiovascular Disease Risk: A Scientific Statement From the American Heart Association
Authors: Aruni Bhatnagar, Wasim Maziak, Thomas Eissenberg, Kenneth D. Ward, George Thurston, Brian A. King, Erin L. Sutfin, Caroline O. Cobb, Merlyn Griffiths, Larry B. Goldstein, Mary Rezk-Hanna
Journal: Circulation (2019)

Tobacco smoking with a water pipe or hookah is increasing globally. There are millions of water pipe tobacco smokers worldwide, and in the United States, water pipe use is more common among youth and young adults than among adults. The spread of water pipe tobacco smoking has been abetted by the marketing of flavored tobacco, a social media environment that promotes water pipe smoking, and misperceptions about the addictive potential and potential adverse health effects of this form of tobacco use. There is growing evidence that water pipe tobacco smoking affects heart rate, blood pressure regulation, baroreflex sensitivity, tissue oxygenation, and vascular function over the short term. Long-term water pipe use is associated with increased risk of coronary artery disease. Several harmful or potentially harmful substances present in cigarette smoke are also present in water pipe smoke, often at levels exceeding those found in cigarette smoke. Water pipe tobacco smokers have a higher risk of initiation of cigarette smoking than never smokers. Future studies that focus on the long-term adverse health effects of intermittent water pipe tobacco use are critical to strengthen the evidence base and to inform the regulation of water pipe products and use. The objectives of this statement are to describe the design and operation of water pipes and their use patterns, to identify harmful and potentially harmful constituents in water pipe smoke, to document the cardiovascular risks of water pipe use, to review current approaches to water pipe smoking cessation, and to offer guidance to healthcare providers for the identification and treatment of individuals who smoke tobacco using water pipes.