tbuckley/cabot-search huggingface dataset:
Global Estimate of Lung Cancer Mortality Attributable to Residential Radon
Authors: Janet Gaskin, Doug Coyle, Jeff Whyte, Daniel Krewksi
Journal: Environmental Health Perspectives (2018)

Background: Radon is the second most important cause of lung cancer, ranked by the World Health Organization as the fifth leading cause of mortality in 2010. An updated database of national radon exposures for 66 countries allows the global burden of lung cancer mortality attributable to radon to be estimated. Objective: Our goal was to estimate the global population attributable burden of lung cancer mortality in 2012 from residential radon. Methods: Estimates of the population attributable risk (PAR) of lung cancer mortality from radon were determined using the attributable fraction approach, using three models for excess relative risk of lung cancer from radon. Results: The estimates of the median PAR of lung cancer mortality from residential radon in 2012 for the 66 countries having representative national radon surveys were consistent, as 16.5%, 14.4%, and 13.6% for the exposure–age–concentration (EAC) model (BEIR VI), the Hunter model, and the Kreuzer model, respectively. The mean PAR using the EAC model ranged from 4.2% (95% CI: 0.9, 11.7) for Japan, to 29.3% (95% CI: 22.9, 35.7) for Armenia, with a median for the 66 countries of 16.5%. Radon-attributable lung cancer deaths for all 66 countries totaled 226,057 in 2012 and represent a median of 3.0% of total cancer deaths. Conclusions: Consistent findings between the three models used to estimate excess relative risks of lung cancer from radon, and between the attributable fraction methodology and the life table analysis, confirm that residential radon is responsible for a substantial proportion of lung cancer mortality worldwide. https://doi.org/10.1289/EHP2503
Chinese and Europeans with Acute Myeloid Leukemia Have Different Topologies of Mutations
Authors: Bin Yin, Xiaofeng Han, Hongyu Huang, Jiawei Yin, Min Zhang, Huikai Miao, Fan Zhang, Hong Liu, Hongchao Yin, Jiang Hu, Xuejun Hong, Yan Zeng, Depei Wu, Robert Peter Gale
Journal: Blood (2017)
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus–like inflammation
Authors: Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Y. Brodeur, April Deng, Karen Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein
Journal: Journal of Clinical Investigation (2018)

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet+, IFN-γ+, and FasL-expressing Th1 cells as well as autoantibody-producing B cells. Unexpectedly, contrary to what occurs in most models of SLE, they also developed skin lesions that are very similar to those of human cutaneous lupus erythematosus (CLE) as far as clinical appearance, histological changes, and gene expression. FasL was a key effector mechanism in the skin, as the transfer of FasL-deficient DO11gld T cells completely failed to elicit overt skin lesions. FasL was also upregulated in human CLE biopsies. Overall, our model provides a relevant system for exploring the pathophysiology of CLE as well as the negative regulatory role of TLR9.
Dilation or biodegradable stent placement for recurrent benign esophageal strictures: a randomized controlled trial
Authors: Daisy Walter, Maarten van den Berg, Meike Hirdes, Frank Vleggaar, Alessandro Repici, Pierre Deprez, Bartolomé Viedma, Laurence Lovat, Bas Weusten, Raf Bisschops, Rehan Haidry, Elisa Ferrara, Keith Sanborn, Erin O’Leary, Jeanin van Hooft, Peter Siersema
Journal: Endoscopy (2018)

Abstract Background Dilation is the standard of care for recurrent benign esophageal strictures (BES). Biodegradable stents may prolong the effect of dilation and reduce recurrences. Efficacy and safety of dilation and biodegradable stent placement early in the treatment algorithm of recurrent BES were compared. Methods This multicenter, randomized study enrolled patients with BES treated with previous dilations to ≥ 16 mm. The primary end point was number of repeat endoscopic dilations for recurrent stricture within 3 and 6 months. Secondary outcomes through 12 months included safety, time to first dilation for recurrent stricture, dysphagia, and level of activity. Results At 3 months, the biodegradable stent group (n = 32) underwent significantly fewer endoscopic dilations for recurrent stricture compared with the dilation group (n = 34; P &lt; 0.001). By 6 months, the groups were similar. The number of patients experiencing adverse events was similar between the groups. Two patients in the biodegradable stent group died after developing tracheoesophageal fistulas at 95 and 96 days post-placement; no deaths were attributed to the stent. Median time to first dilation of recurrent stricture for the biodegradable stent group was significantly longer (106 vs. 41.5 days; P = 0.003). Dysphagia scores improved for both groups. Patients in the biodegradable stent group had a significantly higher level of activity through 12 months (P &lt; 0.001). Conclusion Biodegradable stent placement is associated with temporary reduction in number of repeat dilations and prolonged time to recurrent dysphagia compared with dilation. Additional studies are needed to better define the exact role of biodegradable stent placement to treat recurrent BES.
Radial Artery as the Preferred Second Conduit for Coronary Bypass
Authors: Oz M. Shapira
Journal: New England Journal of Medicine (2018)

Coronary-artery bypass grafting (CABG) remains one of the most effective methods of treatment for patients with coronary artery disease. Selection of the appropriate conduit for the bypass is key to achieving good short- and long-term procedural outcomes. The use of arterial grafts other than the left internal thoracic artery to the left anterior descending coronary artery for CABG remains very uncommon. In a recent report on nearly 1.5 million CABG procedures, the rates of use of both internal thoracic arteries and radial arteries for grafting in the United States were 4.9% and 6.5%, respectively.1 The fact that a multiple-arterial grafting . . .
Apoptotic cell induction of miR-10b in macrophages contributes to advanced atherosclerosis progression in ApoE−/− mice
Authors: Dongliang Wang, Wenting Wang, Weiqun Lin, Wenqi Yang, Peiwen Zhang, Ming Chen, Ding Ding, Chaoqun Liu, Jiakun Zheng, Wenhua Ling
Journal: Cardiovascular Research (2018)

We previously found that miR-10b inhibits cholesterol efflux from thioglycollate-elicited mouse peritoneal macrophages through repressing ATP binding cassette transporter (ABCA1). Herein, we deciphered the mechanism underlying macrophage miR-10b expression and the role of miR-10b in atherosclerosis.MiR-10b expression was increased in the arteries with advanced but not early atherosclerotic plaques of ApoE-/- mice. Free cholesterol-induced macrophage apoptotic cells (FC-AM) promoted miR-10b expression in mouse resident peritoneal macrophages (RPM) by up-regulation of Twist1/2 in a Mer receptor tyrosine kinase dependent manner. Surprisingly, antagomiR-10b de-repressed ABCA1 in RPM engulfing FC-AM but not in RPM alone or RPM-derived foam cells; systemic delivery of antagomiR-10b enhanced reverse cholesterol transport from RPM engulfing FC-AM but not from RPM or the foam cells in ApoE-/- mice. Mechanistically, RPM engulfing FC-AM possessed sufficient miR-10b functionally repressing ABCA1 expression, whereas RPM and foam cells had little miR-10b incompetently repressing ABCA1 expression. Notably, antagomiR-10b administration reduced advanced plaque size and also enhanced plaque stability in ApoE-/-mice, which were associated with increased plaque macrophage ABCA1 expression and reduced plaque apoptosis and inflammation. However, antagomiR-10b administration did not affect early atherosclerotic plaque formation in ApoE-/- mice.These data suggest that apoptotic cell induction of miR-10b in macrophages is important in advanced atherosclerosis progression.
Lymphovascular invasion and extranodal tumor extension as risk indicators of breast cancer-related lymphedema.
Authors: Nicola Fusco, Marco Invernizzi, Chiara Corti, Marianna Noale, Gianluca Lopez, Anna Michelotti, Luca Despini, Donatella Gambini
Journal: Journal of Clinical Oncology (2018)

e12609 Background: Breast cancer related lymphedema (BCRL) occurs in up to 54% of breast cancer (BC) patients after radiotherapy and/or surgery. This condition is a major contributor to women disability. To date, there are no validated predictive biomarkers, diagnostic tools, and curative treatments supported by strong evidence for these patients, which make BCRL an issue to be urgently addressed. Here, we provide an integrative characterization of a large series of women with node-positive (N+) BC and identified new bona fide predictors of BCRL occurrence. Methods: 332 surgically-treated N+ BCs were retrospectively collected (2-19 years of follow-up). Among them, 62 BCRL patients and 270 BCRL-negative patients were clustered in the study group and control group, respectively. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables, while the Wilcoxon rank-sum was employed for continuous variables. Factors associated with a hazard ratio of developing BCRL were assessed using a Cox proportional hazard regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm and concurrent obesity, dyslipidemia, and/or chronic infections. The number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group. Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival, particularly when considering the laterality of surgery. Patients with LVI and left side localization harbored 4-fold higher risk of BCRL. Right-arm metastases with ENE in patients subjected to axillary dissection increased the probability to develop BCRL compared to ENE-negative patients. Conclusions: The routinary evaluation of LVI and ENE either on pre-surgical (e.g. core biopsies), intra-surgical (e.g. intraoperative sentinel lymph nodes), or post-surgical (e.g. breast and axillary nodes excision) samples might represent the basis for a novel strategy in BCRL risk stratification.
PTH-076 Effect of increasing experience on outcomes of colorectal endoscopic resection in a large western series
Authors: Andrew Emmanuel, Shraddha Gulati, Margaret Burt, Bu Hayee, Amyn Haji
Journal: Endoscopy (2018)

<h3>Introduction</h3> Despite decades of experience in Japan, endoscopic mucosal resection (EMR) and particularly endoscopic submucosal dissection (ESD) for large colorectal lesions are relatively new techniques in western practice. It is well recognised in surgery that for new techniques, the relevance of early published studies can change rapidly as experience grows. Given the increasing use and experience in expert centres of endoscopic resection (ER), the relevance of initial published results of endoscopic resection in western centres may change. We determined the effect of increasing experience on resection strategies and outcomes in a large series of colorectal ERs at a tertiary referral centre. <h3>Methods</h3> We analysed all endoscopic resections of large (≥20 mm) colorectal lesions performed at a tertiary referral unit between January 2011 and December 2017. ERs were arbitrarily divided into 2 time periods (Period 1: January 2011 – December 2014 and Period 2: January 2015 – December 2017). Comparisons of outcomes of ER were made between these 2 time periods, including use of ESD, en bloc resection, successful initial ER, complications, perforations and recurrence detected at the first surveillance colonoscopy (3–6 months). <h3>Results</h3> Endoscopic resection was performed for 588 colorectal lesions (mean size 52.5 mm) during the study period (Period 1 n=264, Period 2 n=324) of which 578 (98.3%) were initially successful. Comparing Periods 1 and 2, there were no differences in overall complications (6.1% <i>vs</i> 4.6%, p=0.44) or perforations (3.0% vs 3.1%, p=0.97) and initial success of ER was similar (98.1% <i>vs</i> 98.5%, p=0.74). However, the use of ESD was far more common in Period 2 (p&lt;0.001) and en bloc resection was achieved more frequently in Period 2 (p=0.002). Recurrence detected at the first surveillance colonoscopy was significantly less frequent during Period 2 (5.6% <i>vs</i> 10.8%, p=0.05). <h3>Conclusion</h3> These data demonstrate the evolving nature of endoscopic resection practice in a western expert centre. The findings confirm that expert performed EMR is safe and effective, but refining and developing resection strategies with increasing experience, incorporating ESD more frequently, results in higher en bloc resection rates and probably improved initial adenoma clearance as demonstrated by less frequent recurrence at first surveillance. This underscores the importance of appropriate referral to expert centres that have developed the necessary expertise.
The hidden burden of anxiety and depression in ovarian cancer: A prospective study from diagnosis.
Authors: Penelope M Webb, Vanessa Beesley, Anna deFazio, Andreas Obermair, Peter T. Grant, Christina Nagle, Michael Friedlander
Journal: Journal of Clinical Oncology (2018)

155 Background: Women with ovarian cancer (OC) report high rates of anxiety (A) and depression (D), but most studies have used a cross-sectional design at a single time-point, not considered prior history and not included affected women who are symptom-free due to medication. Our goals were to quantify (i) the total burden of A and D among women with newly diagnosed OC; the proportions who (ii) experience symptoms only after their OC diagnosis and (iii) with persistent symptoms; and (iv) use of appropriate medication/services by those affected. Methods: The OPAL (Ovarian Cancer Prognosis &amp; Lifestyle) Study is a prospective study of Australian women diagnosed with OC from 2012-15 who agreed to complete questionnaires at baseline, 3, 6, 9, 12, 24, 36 &amp; 48 months after diagnosis. At baseline, they were asked if they had ever been diagnosed with A or D and if they took medication for this in the year before their OC diagnosis. At follow-up they completed the Hospital Anxiety and Depression Scale (HADS) and were asked about current medication use. Results: Of 893 women with data for ≥1 time point, 216 (24%) reported clinical levels (HADS &gt; 10) of anxiety (18%) and/or depression (15%) on at least one occasion during the first 3 years after diagnosis, with another 157 (18%) reporting use of anxiolytic or antidepressant medications. A further 167 (19%) reported subclinical (HADS 8-10) A or D. Of those with clinical levels of A/D and/or taking medication, 225 (60%) reported this at ≥3 time-points, 216 (58%) reported no prior history of A or D, and 271 (73%) reported no use of anxiolytic/antidepressant medication in the year before diagnosis. When women reported clinical levels of A or D, only 45% reported taking medication (37%) and/or seeing a psychiatrist or psychologist (19%). Conclusions: More than 40% of women with OC experienced clinical levels of A or D during treatment or the first 3 years of follow-up, for 25% this persisted. For 24% this was their first experience of distress and &gt; 50% of those affected did not receive appropriate medication or psychological support. The hidden burden of anxiety and depression in this population is much greater than previously reported but is amenable to effective intervention if recognized.
Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration
Authors: Willi Sauerbrei, Sheila E Taube, Lisa M McShane, Margaret M Cavenagh, Douglas G Altman
Journal: JNCI Journal of the National Cancer Institute (2018)

The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.
Nutrition services for men with prostate cancer: A health professional survey.
Authors: Kaity McLaughlin, Lindsay Hedden, Phil Pollock, Celestia S. Higano, Rachel A Murphy
Journal: Journal of Clinical Oncology (2018)

25 Background: Nutrition is a key part of prostate cancer (PC) survivorship for management of PC, treatment side effects, and overall health. The Prostate Cancer Supportive Care (PCSC) Program is one of only a few PC survivorship programs in Canada that provide nutrition support as part of standard care. A survey was conducted as part of a broader needs assessment to understand health care professionals’ (HCPs) perspectives on nutrition services for men with PC and inform nutrition programs. Methods: An online survey was administered to British Columbia (BC) HCPs caring for men with PC including urologists, radiation oncologists, medical oncologists, registered dietitians and researchers. We used purposive sampling to identify relevant HCPs. HCPs were asked about the importance of oncological nutrition services and how they should be delivered to men with PC. We summarized the percent agreement for each question and across professions then thematically analyzed qualitative data. Results: Of the 56 HCPs invited to participate in the survey, 38 (68%) responded. The majority (61%) agreed that men with PC require more nutritional support. HCPs indicated nutrition services should be offered multiple times throughout survivorship and facilitated through online resources, individual consultations with registered dietitians and consecutive group education sessions. Most (75%) urologists, radiation oncologists and medical oncologists responded that weight management should be the focus for nutrition services, whereas 90% of dietitians responded that nutrition for reducing the risk of PC progression should be the focus. The main themes that arose from the survey suggested that nutrition services should be available in different forms to facilitate individual needs and adapted based on cultural and community settings. Conclusions: HCPs confirm that there is an unmet need for nutrition services for men with PC in BC as existing services prioritize and offer services for cancer-related weight loss. Special consideration should be given to the focus of nutrition service provided, and when and how it is offered. These results will inform the development of additional resources for men with PC to support their nutritional needs.
The relative value of anti-Müllerian hormone to predict premature menopause in patients receiving adjuvant chemotherapy for breast cancer: Results from the OPTION trial.
Authors: Robert C. F. Leonard, Douglas Adamson, Gianfilippo Bertelli, Michelle McLinden, Nan Haiying, Joanna Dunlop, Janine Mansi, Robert Edward Coleman, Gerry Thomas, Richard Anderson
Journal: Journal of Clinical Oncology (2012)

1094 Background: The OPTION trial in premenopausal women tested the ovarian protection effect of goserelin (G) given randomly before and during adjuvant chemotherapy for breast cancer. Methods: Using standard chemotherapy, women were randomised in 2 strata, under 40 yrs and over 40 yrs at diagnosis. 227 patients were recruited by end December 2009. 173 met the criteria for 1 year follow-up for this analysis; 140 patients of these had provided adequate data on menstrual bleeding; 87 patients were aged under 40 and 53 patients were aged over 40 at the time of chemotherapy. Cessation of menstruation during chemotherapy was defined as at least two consecutive cycles with no menstrual bleeding since the previous cycle and no return of menstrual bleeding prior to the final cycle of chemotherapy. Of those patients who had ceased periods during chemotherapy, those with no further menstrual bleeding at 12 months follow up were deemed to be menopausal. Patients were randomised to receive G or no G at start of chemotherapy. Primary endpoint was recovery of menses at 12 months from start of chemotherapy. AMH was measured in 117 women pre-treatment, and at 1 year after starting chemotherapy. Results: There were no differences in pretreatment AMH between control and goserelin-treated groups, thus further analyses were performed on all women grouped together. AMH was lower following chemotherapy (0.40±0.65 vs 1.38±1.82ng/ml; mean±SD; P&lt;0.001)). Pre-treatment AMH was a significant predictor of post-treatment amenorrhoea (P=0.001). By multivariate logistic regression analysis with age and AMH, age remained significant (P=0.003) whereas AMH did not (P=0.07). Grouping pre-treatment and post-chemo AMH into quartiles showed that AMH became undetectable in 94% of women with lowest pre-treatment AMH vs 46.2% of women with the highest pretreatment AMH. We have previously demonstrated in a small cohort that pretreatment AMH can predict long-term (5 year) ovarian activity in women with breast cancer. Conclusions: The present data confirm the value of pretreatment AMH in assessing the likelihood of ongoing ovarian activity after chemotherapy for early breast cancer.