tbuckley/cabot-search huggingface dataset:
Ambiguities in Comfort Care Discussions—Reply
Authors: Anne M. Kelemen, Hunter Groninger
Journal: JAMA Internal Medicine (2019)

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Platelet Protein Glycosylation in Immune Thrombocytopenia
Authors: Elena Monzón Manzano, Raul Justo Sanz, Stuart M Haslam, Leow Ke Xuan, Anne Dell, Teresa Álvarez-Roman, Mónica Martín, María Isabel Rivas Pollmar, Ihosvany Fernandez-Bello, Miguel A. Canales, Victor Jimenez-Yuste, Nora Butta
Journal: Blood (2018)
Abstract 18906: Combining Perindopril With a Calcium Channel Blocker and a Lipid Lowering Agent Significantly Decreases Mortality: A Subgroup Analysis of Europa
Authors: Michel Bertrand, Jean-Jacques Mourad
Journal: Circulation (2013)

Background: Management of patients with stable ischemic heart disease (IHD), in addition to heart rate control and antiplatelet therapy, relies on the administration of blood pressure lowering therapies and lipid normalization. However, the ACTION trial revealed that a strategy with a calcium channel blocker (CCB) and a lipid lowering therapy (LLT) alone, on top of conventional care, was not sufficient to provide further protection regarding cardiovascular events and death. Since a medical need remains for CCB, mainly in case of angina, we investigated if, as globally recommended by current guidelines for IHD patients, the addition of an ACE inhibitor would provide additional benefit in this specific population. Methods: The EUROPA trial evaluated the cardioprotective effect of perindopril in a low-risk population with coronary artery disease but no signs of heart failure for a mean follow-up of 4.2 years (75% of class I, 21% with class II, 3% Class III and 1% class IV angina status). The database was reanalyzed to compare the benefit of the addition of perindopril or placebo in patients receiving a CCB/LLT strategy at baseline and all along the trial (1056 patients). Results: Patients receiving perindopril on top of a CCB and a LLT displayed a significant 46% relative reduction of the primary endpoint (p=0.023), a composite of cardiovascular death, myocardial infarction and cardiac arrest, compared to those only having CCB/LLT. In addition, the triple combination allowed relative risk reductions of respectively 58% (p=0.027) and 71% (p=0.028) for all-cause and cardiovascular mortality. Non-significant decreases in myocardial infarction (28%) and heart failure (41%) seemed to support at least partly the positive impact on mortality. Conclusion: The addition of an ACE inhibitor to a CCB/LLT strategy clearly demonstrated a reduction of mortality in this post-hoc analysis of EUROPA and confirmed results previously obtained in high-risk hypertensive patients in the ASCOT study.
Disparities by province, age, and sex in site-specific cancer burden attributable to 23 potentially modifiable risk factors in China: a comparative risk assessment
Authors: Wanqing Chen, Changfa Xia, Rongshou Zheng, Maigeng Zhou, Chunqing Lin, Hongmei Zeng, Siwei Zhang, Lijun Wang, Zhixun Yang, Kexin Sun, He Li, Matthew D Brown, Farhad Islami, Freddie Bray, Ahmedin Jemal, Jie He
Journal: The Lancet Global Health (2019)

BackgroundUnderstanding disparities in the burden of cancer attributable to different risk factors is crucial to inform and improve cancer prevention and control. In this report, we estimate the site-specific population-attributable fractions (PAFs) for 23 potentially modifiable risk factors across all provinces in China.MethodsIn this comparative risk assessment study, we used 2014 cancer mortality data for adults from 978 county-level surveillance points in 31 provinces of mainland China. Risk-factor prevalence estimates were obtained from representative surveys. We used summary relative risks obtained from several recent large-scale pooled analyses or high-quality meta-analyses of studies in China. We calculated PAFs using multiple formulae incorporating exposure prevalence and relative risk data stratified by age, sex and province and then combined to create summary PAFs by sex, cancer site, and risk factors.FindingsAbout 1 036 004 cancer deaths (45·2% of all cancer deaths [95% CI 44·0–46·4]) in China in 2014 in adults aged 20 years or older were attributable to 23 evaluated risk factors. The PAF was higher in men (51·2% [95% CI 50·0–52·4]) than in women (34·9% [33·6–36·2]), with the leading risk factors being active smoking in men and low fruit intake in women. By province, the PAF in both sexes combined ranged from 35·2% in Shanghai to 52·9% in Heilongjiang, while the PAF varied from 40·9% in Shanghai to 56·4% in Guangdong among men and from 26·9% in Shanghai to 48·0% in Heilongjiang among women. The highest PAF among men was smoking in all 31 provinces, whereas among women it varied among low fruit intake (14 provinces), hepatitis B virus infection (seven provinces), smoking (six provinces), excess bodyweight (three provinces), and human papilloma virus infection (one province).InterpretationThe PAFs of cancers attributable to potentially modifiable risk factors vary substantially across provinces in China. Regional adoption of effective primary cancer prevention strategies has a vast potential to reduce the burden of cancer and disparities in China. Smoking, poor diet, and infection warrant particular policy attention as they contributed a large proportion to the total cancer burden.FundingNational Science and Technology Basic Research Special Foundation of China.
Heterotypic CAF-tumor spheroids promote early peritoneal metastasis of ovarian cancer
Authors: Qinglei Gao, Zongyuan Yang, Sen Xu, Xiaoting Li, Xin Yang, Ping Jin, Yi Liu, Xiaoshui Zhou, Taoran Zhang, Cheng Gong, Xiao Wei, Dan Liu, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Jianfeng Zhou, Kenjiro Sawada, Robert Fruscio, Thomas W. Grunt, Jörg Wischhusen, Víctor Manuel Vargas-Hernández, Bhavana Pothuri, Robert L. Coleman
Journal: The Journal of Experimental Medicine (2019)

High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5high (ITGA5high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor–stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation.
Abstract MP14: Proteinuria is Associated With a Greater Risk of Lower Limb Amputation in Patients With Peripheral Artery Disease
Authors: Jung-Im Shin, Morgan Grams, Josef Coresh, Alex Chang, Kunihiro Matsushita
Journal: Circulation (2018)

Introduction: Proteinuria is shown to be associated with increased risk of peripheral artery disease (PAD). However, its association with the risk of lower limb amputation in patients with PAD is unknown. Hypothesis: We hypothesized that proteinuria is associated with the risk of amputation in patients with PAD in a graded fashion. Methods: We identified 3,388 PAD patients with data on urine dipstick proteinuria within two years prior to PAD diagnosis between 1997 and 2017 in the Geisinger Health System (mean age 69.7 years, 44.8% female, 97.4% non-Hispanic White, 57.8% diabetic). We quantified the association of proteinuria with the risk of amputation using Cox proportional hazards models, adjusting for demographics, calendar year, estimated glomerular filtration rate, HbA1c, comorbidities including diabetic retinopathy/neuropathy, and medication use (antiplatelet drug, statin, and renin-angiotensin system inhibitor). Results: There were 55.2% with negative dipstick proteinuria, 11.1% trace, 14.1% with 1+, and 19.5% with ≥2+. A total of 245 patients underwent amputations over a median follow-up of 3.4 years. Incidence rate of amputation was 1.15 per 100 person-years for dipstick negative, 1.47 for trace, 2.11 for 1+, and 3.78 for ≥2+. This dose-response relationship remained similar even after accounting for potential confounders (p-trend=0.015), with particularly evident association for ≥2+ of dipstick (an adjusted hazard ratio of 1.52 [95% confidence interval: 1.08-2.17, p=0.017) (Figure). When we added proteinuria to other covariates, the risk discrimination slightly improved (Δc-statistic 0.007 [0.001-0.014]). Conclusions: Higher proteinuria was associated with a greater risk of lower limb amputation among patients with newly diagnosed PAD. Our results suggest the importance of considering proteinuria in risk assessment of limb loss in PAD patients.
Response to ‘Everything we see is a perspective, not the truth’ by Chattopadhyay <i>et al</i>
Authors: Anna Molto, Julie Sahuguet, Jacques Fechtenbaum, Adrien Etcheto, Clementina López-Medina, Pascal Richette, Maxime Dougados, Christian Roux, Karine Briot
Journal: Annals of the Rheumatic Diseases (2019)

We would like to thank Chattopadhyay et al for their interest in our article presenting the low incident rate of vertebral fractures in an early axial spondyloarthritis (axSpA) population. We have read with interest their comments regarding the external validity of the data we are presenting.1 2 

We would like to highlight that the manuscripts the authors are referring to in their letter were focusing only in patients with either very long-standing disease (22.5 years in the Montala study3) or with radiographic involvement (ie, radiographic axSpA, also referred as ankylosing spondylitis) in …
Maternal and Newborn Vitamin D–Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes
Authors: German Tapia, Karl Mårild, Sandra R. Dahl, Nicolai A. Lund-Blix, Marte K. Viken, Benedicte A. Lie, Pål R. Njølstad, Geir Joner, Torild Skrivarhaug, Arieh S. Cohen, Ketil Størdal, Lars C. Stene
Journal: Diabetes Care (2019)

Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D-binding protein (DBP), vitamin D-associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D.From a cohort of >100,000 mother/child pairs, we analyzed 189 pairs where the child later developed T1D and 576 random control pairs. We measured 25(OH)D using liquid chromatography-tandem mass spectrometry, and DBP using polyclonal radioimmunoassay, in cord blood and maternal plasma samples collected at delivery and midpregnancy. We genotyped mother and child for variants in or near genes involved in vitamin D metabolism (GC, DHCR7, CYP2R1, CYP24A1, CYP27B1, and VDR). Logistic regression was used to estimate odds ratios (ORs) adjusted for potential confounders.Higher maternal DBP levels at delivery, but not in other samples, were associated with lower offspring T1D risk (OR 0.86 [95% CI 0.74-0.98] per μmol/L increase). Higher cord blood 25(OH)D levels were associated with lower T1D risk (OR = 0.87 [95% CI 0.77-0.98] per 10 nmol/L increase) in children carrying the VDR rs11568820 G/G genotype (Pinteraction = 0.01 between 25(OH)D level and rs11568820). We did not detect other gene-environment interactions.Higher maternal DBP level at delivery may decrease offspring T1D risk. Increased 25(OH)D levels at birth may decrease T1D risk, depending on VDR genotype. These findings should be replicated in other studies. Future studies of vitamin D and T1D should include VDR genotype and DBP levels.
GARP Dampens Cancer Immunity by Sustaining Function and Accumulation of Regulatory T Cells in the Colon
Authors: Mohammad Salem, Caroline Wallace, Maria Velegraki, Anqi Li, Ephraim Ansa-Addo, Alessandra Metelli, Hyunwoo Kwon, Brian Riesenberg, Bill Wu, Yongliang Zhang, Silvia Guglietta, Shaoli Sun, Bei Liu, Zihai Li
Journal: Cancer Research (2019)

Abstract Activated regulatory T (Treg) cells express the surface receptor glycoprotein-A repetitions predominant (GARP), which binds and activates latent TGFβ. How GARP modulates Treg function in inflammation and cancer remains unclear. Here we demonstrate that loss of GARP in Treg cells leads to spontaneous inflammation with highly activated CD4+ and CD8+ T cells and development of enteritis. Treg cells lacking GARP were unable to suppress pathogenic T-cell responses in multiple models of inflammation, including T-cell transfer colitis. GARP−/− Treg cells were significantly reduced in the gut and exhibited a reduction in CD103 expression, a colon-specific migratory marker. In the colitis-associated colon cancer model, GARP on Treg cells dampened immune surveillance, and mice with GARP−/− Treg cells exhibited improved antitumor immunity. Thus, GARP empowers the functionality of Treg cells and their tissue-specific accumulation, highlighting the importance of cell surface TGFβ in Treg function and GARP as a potential therapeutic target for colorectal cancer therapy. Significance: These findings uncover functions of membrane-bound TGFβ and GARP that tune the activity of Treg cells, highlighting a potential treatment strategy in autoimmune diseases and cancer.
American Heart Association/American College of Cardiology Foundation guide to warfarin therapy11The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be …
Authors: Jack Hirsh, Valentin Fuster, Jack Ansell, Jonathan L Halperin
Journal: Journal of the American College of Cardiology (2003)
Cervical cancer: deaths increase as HPV vaccine is underused, says WHO
Authors: Owen Dyer
Journal: BMJ (2019)

Potentially preventable cervical cancers will become an increasing health burden this century unless more people are immunised with one of the available vaccines against human papillomavirus (HPV), the World Health Organization’s International Agency for Research on Cancer has warned.

About 570 000 new cases of cervical cancer were diagnosed around the world in 2018, said the agency’s director, Elisabete Weiderpass, and more than 310 000 women died from the disease, making it the fourth deadliest cancer in women worldwide.

Most cervical cancers are caused by HPV infection, and most …
Ambulatory 5FU infusion pumps: Patient perceptions and quality of life.
Authors: Munaf Al-Kadhimi, Marisa E. Hill, Elita Fine, Matthew Eric Adess, Ari Polish, Lauren Allison Wiebe, Margaret Whalen, Eileen Van Pelt, Teresa Callahan, Cory Gustafson, Kathleen Collins, Robert de Wilton Marsh
Journal: Journal of Clinical Oncology (2019)

663 Background: Infusional-5-fluorouracil (inf-5FU), administered over 48 hours every 2 weeks, is frequently prescribed for the treatment of gastrointestinal cancers. A portable infusion device (ID) may be used for this purpose to enable treatment at home. At our institution, patients are educated by an oncology nurse as to what to expect, and how to function once they leave the infusion center. However, there is no formal process in place to report their experience and to record and analyze the results. The intended goal of this study was to accomplish this, such that the data could improve the education and experience of future patients. Methods: After verbal consent, a sequential cohort of patients, who had received 2 or more treatments with inf-5FU for gastrointestinal cancer, was invited to complete a de-identified paper questionnaire concerning their experience. Eleven specific questions suggested by the GI group were included, with an opportunity to add comments. The surveys were then collated and reviewed. Results: See table. Conclusions: While most patients felt well prepared by their medical team as to what to expect from the ID (93.1%), ≥ 25% had issues with bathing (73.6%), sleep (37.5%), exercising (30.6%), intimacy (26.4%), social interactions (25%) and anxiety (25%). These insights will be used to improve the education of future patients and a second assessment will follow. 72/72 patients approached over 6 months completed the survey with results below: [Table: see text]
No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study
Authors: Jing Dong, Puya Gharahkhani, Wong-Ho Chow, Marilie D. Gammon, Geoffrey Liu, Carlos Caldas, Anna H. Wu, Weimin Ye, Lynn Onstad, Lesley A. Anderson, Leslie Bernstein, Paul D. Pharoah, Harvey A. Risch, Douglas A. Corley, Rebecca C. Fitzgerald, Prasad G. Iyer, Brian J. Reid, Jesper Lagergren, Nicholas J. Shaheen, Thomas L. Vaughan, Stuart MacGregor, Sharon Love, Claire Palles, Ian Tomlinson, Ines Gockel, Andrea May, Christian Gerges, Mario Anders, Anne C. Böhmer, Jessica Becker, Nicole Kreuser, Rene Thieme, Tania Noder, Marino Venerito, Lothar Veits, Thomas Schmidt, Claudia Schmidt, Jakob R. Izbicki, Arnulf H. Hölscher, Hauke Lang, Dietmar Lorenz, Brigitte Schumacher, Rupert Mayershofer, Yogesh Vashist, Katja Ott, Michael Vieth, Josef Weismüller, Markus M. Nöthen, Susanne Moebus, Michael Knapp, Wilbert H.M. Peters, Horst Neuhaus, Thomas Rösch, Christian Ell, Janusz Jankowski, Johannes Schumacher, Rachel E. Neale, David C. Whiteman, Aaron P. Thrift
Journal: Clinical Gastroenterology and Hepatology (2019)
Evaluation of health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC): A prospective, multicenter, open-label, double-arm trial of trifluridine/tipiracil (FTD/TPI) versus best supportive care (BSC).
Authors: Meinolf Karthaus, Manfred Welslau, Jorge Riera-Knorrenschild, Albrecht Kretzschmar, Ursula Vehling-Kaiser, Rolf Mahlberg, Henning Pelz, Udo Lindig, Ludwig Fischer von Weikersthal, Volker Heinemann
Journal: Journal of Clinical Oncology (2019)

TPS726 Background: The RECOURSE trial in pts with refractory mCRC showed improvement in OS (7.1 vs 5.3 mo, p &lt; 0.001), but had no formal assessment of QoL. Thus, the TALLISUR trial is designed to investigate the HRQoL in pts treated with FTD/TPI and those who are treated with BSC alone on patient´s request while being suitable for treatment (Tx) with FTD/TPI prospectively. This novel design of a double-arm trial with BSC as appropriate comparative Tx is addressing assessment requirements (i.e. data on survival, morbidity and QoL) for the German Federal Joint Committee (GBA). Methods: Pts who have been previously treated with, or are not candidates for available Ctx including 5-FU, oxaliplatin, irinotecan, anti-VEGF-, and anti EGFR-agents with adequate organ functions independent from their ECOG status. Tx is FTD/TPI 35 mg/m 2 d 1-5 and 8-12 qw d 28 or BSC. Efficacy is documented by PFS (clinical or radiological), OS and an exploratory analysis of RR while safety includes type, incidence and severity of FTD/TPI-related AEs. QoL will be assessed by means of the EORTC QLQ-C30 and EQ-5D-5L questionnaires for one year, close safety observation and/or FU phase. The primary endpoint (EP) is the rate of responders with unchanged or improved HRQoL. Major exclusion criteria include other tumor therapy as Rtx, and intestinal obstruction. Response will be defined as an improvement or stabilization compared to the baseline score of the global health status/QoL scale. Response is calculated as mean of the score of the EORTC QLQ-C30, global health status/QoL scale at all scheduled time points of QoL analysis in the time interval from d -2 before start of Cycle 2 until the end of Tx/close observation compared to the baseline score of the global health status /QoL scale. A RR of 45%±10% is assessed as appropriate in pts with ≥2 cycles FTD/TPI. A total of 195 pts are needed to answer the question with a 2-sided type I error of 5%. The strategy will be regarded successful if the lower boundary of the CI for the RR is ≥35%. TALLISUR started 09/2017 (EudraCT-No 2017-000292-83) and has recruited 160 mCRC pts in total (17th Sep 2018). Clinical trial information: 2017-000292-83.
Creating novel translation inhibitors to target pro-survival proteins in chronic lymphocytic leukemia
Authors: Rong Chen, Mingzhao Zhu, Rajan R. Chaudhari, Omar Robles, Yuling Chen, Wesley Skillern, Qun Qin, William G. Wierda, Shuxing Zhang, Kenneth G. Hull, Daniel Romo, William Plunkett
Journal: Leukemia (2019)