tbuckley/cabot-search huggingface dataset:
PTH-015 A university hospital experience of upper GI bleeding in patients on novel oral anticoagulants
Authors: Adam McCulloch, Patrick McDowell, Sam Smith, Ralph Boulton
Journal: Endoscopy (2018)

<h3>Introduction</h3> The novel oral anticoagulants (NOACs), are increasingly favoured over conventional anticoagulants given their convenience and reduced drug interactions. Although NOACs have a favourable safety profile, the innate risk of haemorrhagic complications, including upper gastrointestinal bleeding (UGIB) is still a concern in high-risk patients. In light of this, we reviewed the outcomes of UGIB in patients on NOACs in our institution and compared them to patients not receiving any anticoagulation. <h3>Methods</h3> We identified inpatients on NOACs from a prospectively collected audit of 680 consecutive gastroscopies performed in 600 patients with UGIB between 1 August 2016 to 30 November 2017. <h3>Results</h3> (NOAC patients): 42 patients (avg age 76.8 years, range 36–91, 50% female) on NOACs underwent a gastroscopy for UGIB, 32 on Apixiban and 10 on Rivaroxaban. Nine (21.4%) were co-prescribed antiplatelet agents. Most common indications for anticoagulation were atrial fibrillation (78.6%) followed by thromboembolic disease (21.4%). 12 patients (28.6%) required endotherapy, with the most commonly encountered pathology being duodenal ulceration, followed by gastric ulceration. Four patients re-bled, all of whom underwent repeat gastroscopy where definitive haemostasis was achieved. Six patients (14.3%) died within 30 days of their gastroscopy (avg age 82.2 years, range 73–88), 3 as a direct result of an UGIB. All deaths occurred in patients with multiple comorbidities. Comparison to group without anticoagulation: Patients on NOACs were older (76.8 years vs 63.9 years, p-value 0.0001), hadslightly higher rebleed rates (9.5% vs 8.3%)and had a trend to higher UGIB related 30 day mortality rate (7.1% vs 2.4%). <h3>Conclusions</h3> A portion of patients on NOACs died as a direct consequence of GI bleeding. All deaths occurred in elderly patients with multiple comorbid illnesses emphasising the importance of robust patient selection in NOAC prescription. To date Dabigatran is the only NOAC with a licenced reversal agent, Idarucizumab. Until reversal agents are available for the other NOACs perhaps Dabigatran should be preferentially considered in high risk patients despite its limitations and bleeding risk.
A novel nomogram individually predicting disease‐specific survival after D2 gastrectomy for advanced gastric cancer
Authors: Wei Wang, Zhe Sun, Jing‐Yu Deng, Xiao‐Long Qi, Xing‐Yu Feng, Cheng Fang, Xing‐Hua Ma, Zhen‐Ning Wang, Han Liang, Hui‐Mian Xu, Zhi‐Wei Zhou
Journal: Cancer Communications (2018)

Abstract Background Few studies have shown nomograms that may predict disease‐specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long‐term DSS for AGC in Chinese patients. Methods A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat‐sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C‐index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets. Results The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C‐index, 0.82 vs. 0.74; P &lt; 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C‐index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P &lt; 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate. Conclusions The established nomogram was able to predict 3‐, 5‐, and 10‐year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.
New Business Models to Accelerate Innovation in Pediatric Oncology Therapeutics
Authors: Sonya Das, Raphaël Rousseau, Peter C. Adamson, Andrew W. Lo
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Few patient populations are as helpless and in need of advocacy as children with cancer. Pharmaceutical companies have historically faced significant financial disincentives to pursue pediatric oncology therapeutics, including low incidence, high costs of conducting pediatric trials, and a lack of funding for early-stage research. <h3>Observations</h3> Review of published studies of pediatric oncology research and the cost of drug development, as well as clinical trials of pediatric oncology therapeutics at ClinicalTrials.gov, identified 77 potential drug development projects to be included in a hypothetical portfolio. The returns of this portfolio were simulated so as to compute the financial returns and risk. Simulated business strategies include combining projects at different clinical phases of development, obtaining partial funding from philanthropic grants, and obtaining government guarantees to reduce risk. The purely private-sector portfolio exhibited expected returns ranging from −24.2% to 10.2%, depending on the model variables assumed. This finding suggests significant financial disincentives for pursuing pediatric oncology therapeutics and implies that financial support from the public and philanthropic sectors is essential. Phase diversification increases the likelihood of a successful drug and yielded expected returns of −5.3% to 50.1%. Standard philanthropic grants had a marginal association with expected returns, and government guarantees had a greater association by reducing downside exposure. An assessment of a proposed venture philanthropy fund demonstrated stronger performance than the purely private-sector–funded portfolio or those with traditional amounts of philanthropic support. <h3>Clinical Relevance</h3> A combination of financial and business strategies has the potential to maximize expected return while eliminating some downside risk—in certain cases enabling expected returns as high as 50.1%—that can overcome current financial disincentives and accelerate the development of pediatric oncology therapeutics.
Predicting Oncotype DX scores using clinicopathologic features: A report from the National Cancer Database.
Authors: Catherine Pesce, Kristine Kuchta, Beyza Erdogan, Chihsiung Wang, Katharine Yao, Mahmoud El-Tamer
Journal: Journal of Clinical Oncology (2018)

551 Background: The Oncotype DX recurrence score is used to predict the benefits of chemotherapy added to adjuvant hormone therapy in ER positive early-stage breast cancer. While its use has been validated and cost effectiveness has been established, its expense remains a concern in some health care systems and communities. Using clinical and pathologic features and the National Cancer Data Base (NCDB) we aim to predict patients with low or high Oncotype DX scores. Methods: From 2010-2014, 78,663 breast cancer patients with Oncotype DX scores were selected from the NCDB. Seven clinical and pathologic variables including age, ER, PR, histologic subtype, lymphovascular invasion (LVI), grade, and tumor size were used to predict high-risk ( > 30) or low-risk ( < 18) Oncotype DX scores using logistic regression. Data were split into training (70%) and testing (30%) sets for external validation. The predictive accuracy of the regression model was assessed using a Receiver Operator Characteristic (ROC) analysis. Model fit was analyzed by plotting the predicted probabilities against the actual probabilities. Nomograms were created for visualization of the high-risk and low-risk models using bootstrap estimation method of the model coefficients. Results: Estrogen receptor status, progesterone receptor status, and grade were the strongest predictors of both low-risk and high-risk Oncotype DX scores, followed by age, histology, tumor size, and LVI, yielding AUC of 0.70 for the low-risk model and 0.86 for the high-risk model. Conclusions: We have developed a model that can predict high-risk Oncotype DX scores with very good reliability. Such a tool may be useful in health care systems with limited resources. Model Coefficients of Strongest Predictors of High-Risk Oncotype DX Score Factors Coefficients ER negative 2.977 PR negative 2.095 Grade well differentiated 0.000 moderately differentiated 1.356 poorly differentiated 3.374 Tumor size < 10mm 0.000 10-20mm 0.264 20-30mm 0.584 30mm+ 0.78
SOLTI-1303 PATRICIA: A phase II study of palbociclib and trastuzumab (HR+ with or without letrozole) in trastuzumab‐pretreated, postmenopausal patients with HER2‐positive metastatic breast cancer.
Authors: Patricia Villagrasa, Aleix Prat, Mafalda Oliveira, Lorena De La Pena, Xavier Gonzalez, Javier Cortes, Sonia Pernas Simon, Jose Rios, Jordi Canes, Eva Ciruelos
Journal: Journal of Clinical Oncology (2018)

TPS1101 Background: Despite the high efficacy of anti HER2-agents, HER2-positive (HER2+) metastatic breast cancer (BC) remains incurable and in need of additional options. In this context, CDK4/6 inhibition combined with anti-HER2 therapy is currently being explored in phase II/III trials. Preclinical evidence from different HER2+ BC models have shown that CDK4/6 inhibition leads to deep cytostatic arrest and inhibition of its invasive properties, underlining the role of CDK4/6 in HER2 signaling. Moreover, Identification of the luminal subtype in HER2+/HR+ disease might be important since the median IC50 of palbociclib (P) in HER2+ BC cell lines falling into the luminal subtype is lower than in non-luminal HER2+ cell lines (47.5 vs. 300 nM). We have recently reported that PAM50 luminal subtype predicts progression‐free survival (PFS) in HER2+/HR+ advanced BC treated with P and trastuzumab (T) compared to non-luminal disease (10.37 vs. 3.53 months, p-value = 0.023). PATRICIA is a Simon 2‐Stage study to evaluate the efficacy of combining T plus P, +/- letrozole (L), assessed by PFS in heavily pretreated HER2+ patients. Methods: Postmenopausal HER2+ patients who had received 2‐4 prior lines of anti-HER2-based regimens are included in 3 cohorts: A: HR‐negative; B1: HR+, receiving both T and P; B2: HR+, receiving T, P and L. P is administered at 200 mg/day for 14 days of 21‐day cycles. T and L are administered at usual doses. The primary objective is to assess clinical efficacy measured as PFS at 6 months (PFS6). Assuming an increase of at least 20% in PFS6 by the addition of P +/‐ L to T, PFS6 should be ≥30% for a cohort to be successful and proceed to stage 2. Thus, it will be necessary to include 15 patients in each cohort in stage 1. In stage 2, each cohort may continue recruitment for up to 46 patients. Translational research for predictive biomarkers will be implemented. To date, 55 patients, 15 in A and 20 in each B cohort, have been included in 14 sites across Spain. The 1st stage efficacy analysis was performed for B cohorts, leading 2nd stage accrual began in September 2017. Cohort A stage 1 effectiveness analysis is intended for June 2018. Clinical trial information: NCT02448420.
Prenatal Vitamin D Supplementation to Improve Health in Offspring
Authors: Bo Chawes, Klaus Bønnelykke, Hans Bisgaard
Journal: JAMA Pediatrics (2018)

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Non–Small Cell Lung Cancer, Version 2.2013
Authors: David S. Ettinger, Wallace Akerley, Hossein Borghaei, Andrew C. Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Ramaswamy Govindan, Frederic W. Grannis, Stefan C. Grant, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Rudy P. Lackner, Inga T. Lennes, Billy W. Loo, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Mary C. Pinder-Schenck, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Douglas E. Wood, Stephen C. Yang, Kristina Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2013)

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.
Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection
Authors: Hana Velová, Maria W Gutowska-Ding, David W Burt, Michal Vinkler
Journal: Molecular Biology and Evolution (2018)

Toll-like receptors (TLRs) are key sensor molecules in vertebrates triggering initial phases of immune responses to pathogens. The avian TLR family typically consists of ten receptors, each adapted to distinct ligands. To understand the complex evolutionary history of each avian TLR, we analyzed all members of the TLR family in the whole genome assemblies and target sequence data of 63 bird species covering all major avian clades. Our results indicate that gene duplication events most probably occurred in TLR1 before synapsids diversified from sauropsids. Unlike mammals, ssRNA-recognizing TLR7 has duplicated independently in several avian taxa, while flagellin-sensing TLR5 has pseudogenized multiple times in bird phylogeny. Our analysis revealed stronger positive, diversifying selection acting in TLR5 and the three-domain TLRs (TLR10 [TLR1A], TLR1 [TLR1B], TLR2A, TLR2B, TLR4) that face the extracellular space and bind complex ligands than in single-domain TLR15 and endosomal TLRs (TLR3, TLR7, TLR21). In total, 84 out of 306 positively selected sites were predicted to harbor substitutions dramatically changing the amino acid physicochemical properties. Furthermore, 105 positively selected sites were located in the known functionally relevant TLR regions. We found evidence for convergent evolution acting between birds and mammals at 54 of these sites. Our comparative study provides a comprehensive insight into the evolution of avian TLR genetic variability. Besides describing the history of avian TLR gene gain and gene loss, we also identified candidate positions in the receptors that have been likely shaped by direct molecular host–pathogen coevolutionary interactions and most probably play key functional roles in birds.
Racial and Ethnic Differences in Presentation and Outcomes of Hepatocellular Carcinoma
Authors: Nicole E. Rich, Caitlin Hester, Mobolaji Odewole, Caitlin C. Murphy, Neehar D. Parikh, Jorge A. Marrero, Adam C. Yopp, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2018)
Deconstructive somatic cell nuclear transfer reveals novel regulatory T-cell subsets
Authors: Manching Ku, Eugene Ke, Mohsen Sabouri-Ghomi, Justin R. Abadejos, Brent Freeman, Amy Nham, Nathaniel Phillips, Kevin Y. Yang, Kathy O. Lui, Oktay Kirak
Journal: Journal of Allergy and Clinical Immunology (2018)
Substance Use Among American Indian Youths Today
Authors: Spero M. Manson
Journal: JAMA Network Open (2018)

The worldview of American Indians turns on the Seventh Generation Principle, namely that decisions-personal, corporate, governmental-by those who came before us affect today and that the decisions we make now in turn affect those who follow, stretching 7 generations in each direction.This is the basis for the often-heard phrase in everyday discourse among Native people that "our youth are our future" and why we place such special store in youths' health and well-being.They embody the continuity of the past, present, and future of our ways of life.As our children fare, so too we all fare.But mounting evidence chronicles the increasing peril of substance use among American Indian youths and fuels growing concern for the future of our youths and thus communities.
Implementation of a standardized approach to borderline resectable pancreatic cancer in a community oncology program.
Authors: Jonathan Scott Bleeker, Christopher Joseph Sumey, Steven Francis Powell, Preston D. Steen, Michael D. Keppen, Michele Lohr, Thavam C. Thambi-Pillai, Peter Kurniali, Miroslaw Mazurczak, Mark Mutuota Gitau, Miran Joel Blanchard, Ryan Kenneth Nowak, Steven McGraw, Robert Sticca, Daniel Tuvin, Gary Timmerman
Journal: Journal of Clinical Oncology (2018)

493 Background: Treatment paradigms for borderline resectable pancreatic cancer (BRPC) continue to evolve with increasing use of neoadjuvant chemotherapy (NAC) and chemoradiation (NACR). Variations in the definition of BRPC and in neoadjuvant approaches have made standardization of care for BRPC difficult. We report an effort to standardize management of BRPC throughout Sanford Health, a largely rural community oncology (CO) network in the Upper Midwest. Methods: Starting in February 2014, cases of PC without evidence of metastatic disease were categorized as BRPC if they met one or more of the following criteria: 1) abutment of superior mesenteric, common hepatic or celiac arteries with &lt; 180 o involvement 2) venous involvement deemed potentially reconstructable and/or 3) biopsy proven regional lymph node involvement. Patients with BRPC were treated with NAC followed by reimaging and surgery if resectable; if disease remained BRPC, patients underwent NACR and surgical re-evaluation. NAC was administered at 5 CO sites in the Sanford network; NACR and surgery were performed at 2 high volume centers. Results: Forty-three patients from 2/2014-4/2017 were diagnosed with BRPC. Median age of patients was 64 (range 39-83); 56% were male. 42/43 patients received NAC as initial therapy, with 1 receiving NACR due to patient preference. 90% of patients receiving NAC received mFOLFIRINOX (38/42), with FOLFIRI (1) and gemcitabine/nab-paclitaxel (3) also utilized. 11/42 (26%) patients had resectable disease after NAC and underwent surgery; 23 (55%) proceeded to NACR. Overall, 26/43 (61%) went to surgery with 18 (42%) able to undergo resection. Of those, 12/18 (67%) attained R0 resection and 10/18 (56%) were pathologic N0. Primary tumor location (head v. body/tail), age, pretreatment CA19-9, change in CA19-9 with treatment and NACR were not associated with a higher likelihood of resection. Conclusions: This report demonstrates the feasibility of implementing a standardized approach to BRPC across multiple CO sites over a wide geographic area. Adherance to protocol therapies was good and surgical outcomes are similar to many reported series; survival data is maturing and will be presented at the meeting.
Response to ‘Missing pebble in the mosaic of rheumatic diseases and mental health: younger does not always mean happier’ by Alunno <i>et al</i>
Authors: Imke Redeker, Falk Hoffmann, Johanna Callhoff, Hildrun Haibel, Joachim Sieper, Angela Zink, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2018)

In their letter ‘A missing pebble in the mosaic of rheumatic diseases and mental health: younger does not always mean happier’,1 Alunno et al commented on our recent publication2 and raised the issue of determinants of psychological well-being in different age groups of persons with axial spondyloarthritis (axSpA). We very much appreciate their interest in our study and valuable comments made and would like to address the raised issues here in more details.

In our study, we investigated determinants of psychological well-being in persons with axSpA using the five-item WHO Well-Being Index (WHO-5), a sensitive and specific screening tool for depression. We found that among 1736 persons with axSpA aged 18–79 years only 42% had a good well-being, whereas 28% had mild depressive symptoms and 31% even had moderate-to-severe depressive symptoms.2 In the linear regression model, we found a negative association between age and the odds of having moderate-to-severe depressive symptoms. Interestingly, a closer …