tbuckley/cabot-search huggingface dataset:
Higher Adherence to Treatment With Low‐Molecular‐Weight‐Heparin Nadroparin Than Enoxaparin Because of Side Effects in Cancer‐Associated Venous Thromboembolism
Authors: Sake J. van der Wall, Frederikus A. Klok, Paul L. den Exter, Deisy Barrios, Raquel Morillo, Suzanne C. Cannegieter, David Jimenez, Menno V. Huisman
Journal: HemaSphere (2018)

Current guidelines recommend low-molecular-weight-heparins (LMWH) monotherapy for 3 to 6 months as first-line treatment for cancer-associated venous thromboembolism (VTE). In clinical practice, enoxaparin and nadroparin are common agents used. However, differences in therapy adherence between these LMWHs have never been reported. Therefore, our aim was to compare adherence to enoxaparin and nadroparin in patients with cancer-associated VTE. Consecutive patients with active cancer and objectively confirmed VTE, treated at a Dutch or a Spanish hospital, were followed during LMWH therapy with a maximum of 180 days. Cumulative incidences of discontinuation of both LMWHs were estimated and compared according to the Kaplan-Meier method, applying a competing risk analysis to correct for mortality. A total of 366 patients were analyzed during LMWH treatment, of whom 284 patients (78%) were treated with enoxaparin and 82 (22%) with nadroparin. The cumulative incidence of discontinuation of enoxaparin and nadroparin treatment because of side effects was 30% (95% confidence interval [CI] 24-36) and 8.8% (95% CI 1.1-15), respectively. Competing risk analysis revealed a higher number of patients discontinuing enoxaparin due to side effects (adjusted hazard ratio [HR]: 2.8; 95% CI 1.06-7.2). Pain at the injection site was the most common reason of discontinuation in patients using enoxaparin, occurring in 32 patients, while it occurred in 1 patient using nadroparin (adjusted HR: 4.0; 95% CI 0.52-31). This analysis reveals that enoxaparin was associated with a higher risk of discontinuation because of side effects compared to nadroparin. However, given the nature of the patient groups, these findings should be followed by future studies.
Validating critical analytical variables of a multiplexed gene expression assay measuring tumor inflammation designed to predict response to anti-PD1 therapy.
Authors: Simina Popa, Sarah Elizabeth Church, Irena Pekker, Naeem Dowidar, Amy Sullivan, Celine Ngouenet, Carl Schaper, Xing Ren, Patrick Danaher, Sean Ferree, Brett Wallden
Journal: Journal of Clinical Oncology (2018)

203 Background: The development and analytical performance of the Tumor Inflammation Signature (TIS) assay has been described previously. The TIS is an investigational use RNA expression assay on the nCounter Dx Analysis System, which is being evaluated as a patient enrichment biomarker for treatment with pembrolizumab single agent across multiple solid tumor types. Here we describe the analytical validation of the RNA input range and analytical precision starting from RNA isolated from formalin fixed paraffin embedded (FFPE) tissue blocks. Methods: Analytical validation of TIS assay performance across an RNA input range was performed using samples from 11 tumor types. The analytical precision between sites, instruments, reagent lots, and users was measured, using RNA samples isolated from FFPE tissue blocks. Results: The assay was validated across the specified RNA input range with ≥ 94% concordance at the minimum specified RNA input (50ng). The total standard deviation of the TIS score was &lt; 0.04 units across three sites with ≥98% concordance between sites. The 6 users across the three sites did not significantly contribute to the assay variability. There was 100% concordance in biomarker high/low categorization between multiple reagent lots and multiple instruments. Conclusions: The analytical performance of the NanoString TIS assay has been validated to give consistent results across the RNA input range and between site, instrument, assay user, and reagent kit lot. The assay is well suited for decentralized clinical testing and is currently under investigation as a biomarker to enrich for response to anti-PD1 therapy across multiple tumor types.
Surgeons are less satisfied with training than other doctors, GMC survey finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Surgeons are less satisfied with their training than doctors working in other specialties, a General Medical Council survey has found.

More than 53 000 doctors in training completed the GMC’s national training survey. Overall, trainees recorded a satisfaction score of 81.2 out of 100, an increase from the 2013 score of 80.8.1

The GMC measured satisfaction by asking junior doctors about their post, including how they rated the …
Population attributable fraction
Authors: Mohammad Ali Mansournia, Douglas G Altman
Journal: BMJ (2018)

Much statistical analysis seeks to identify associations between exposures and outcomes. The population attributable fraction (PAF) is an epidemiologic measure widely used to assess the public health impact of exposures in populations. PAF is defined as the fraction of all cases of a particular disease or other adverse condition in a population that is attributable to a specific exposure; PAF equals (O − E)/O, where O and E refer to the observed number of cases and the expected number of cases under no exposure, respectively. The term “attributable” has a causal interpretation: PAF is the estimated fraction of all cases that would not have occurred if there had been no exposure.1 As an example, in early 1950,2 Doll derived O = 11189 and E = 1875 using the Doll and Hill case-control study of smoking and lung cancer deaths throughout England and Wales,3 so the smoking PAF for lung cancer deaths was (11189 − 1875)/11189 = 83%.

Using a cohort study, following Miettinen, we can estimate the PAF from …
Revalidation is unlikely to go ahead this year, BMA warns
Authors: Helen Jaques
Journal: BMJ (2012)

The BMA has questioned whether revalidation can be introduced at the end of this year as planned, because of lack of readiness among employers and of clarity on key issues such as remediation.

In a letter to the Department of Health the chairman of the BMA’s council, Hamish Meldrum, raises several “fundamental” issues that he says bring into question England’s readiness to implement revalidation this year.

For example, the government has …
WORSENING RENAL FUNCTION AFTER ACUTE TYPE B AORTIC DISSECTION
Authors: Ryosuke Murai, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Takeshi Maruo, Yasushi Fuku, Harumi Katoh, Tsuyoshi Gotoh, Takeshi Shimamoto, Tatsuhiko Komiya, Kazushige Kadota
Journal: Journal of the American College of Cardiology (2018)
GMC confirms it is ready for revalidation
Authors: Matthew Billingsley
Journal: BMJ (2012)

The General Medical Council has declared that “significant progress” means that it is ready to deliver revalidation from December 2012.

After an assessment of readiness by internal auditors, the regulator has confirmed that it has the systems, processes, and infrastructure in place across the UK to launch revalidation later this year.

Niall Dickson, the GMC’s chief executive, said, “Revalidation is on its …
Expression of B7-H3 (CD276) in surgically resected esophageal squamous cell carcinoma.
Authors: Yuta Maruki, Atsuo Takashima, Takahiro Miyamoto, Hidekazu Hirano, Hirokazu Shoji, Yoshitaka Honma, Satoru Iwasa, Natsuko Okita, Ken Kato, Shigeki Sekine, Kazuo Koyanagi, Hiroyuki Daiko, Shigehisa Kitano, Kazunori Aoki, Narikazu Boku
Journal: Journal of Clinical Oncology (2018)

70 Background: B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274), which has been reported to be expressed in many carcinomas and associated with poor prognosis. In this study, we explored the relationship between B7-H3 expression and clinical background and prognosis of esophageal squamous cell carcinoma (ESCC) patients treated with surgery alone. Methods: The subjects of this study was the ESCC patients who received curative surgery between January 2009 and December 2014 without prior treatment, excluding T4 and M1 disease. We evaluated tumor B7-H3 expression by immunohistochemistry, which was scored to 0 (absent) if &lt; 10% of cancer cells were stained, and 1 (weak), 2 (moderate), or 3 (strong) according to the intensity in stained cancer cells (&gt; 10%). The B7-H3 expression of score 2 and 3 was regarded as positive. We compared the clinical characteristics and prognosis between B7-H3 positive and negative patients using log rank test and Cox proportional hazards regression analysis for adjusting the backgrounds. Results: 33 (45%) of 74 patients were positive for expression of B7-H3. Between H7-H3 (+) and (-) groups, there were difference in pathological T stage (pT1/pT2/pT3: 9/0/24 vs. 23/4/14, p &lt; 0.01) and lymph vessel invasion (+/-: 7/26 vs. 17/24, p=0.08). There was no association between sex, age, N factor, and vascular invasion. B7-H3 (+) patients showed trend of poor recurrence free survival (RFS) and overall survival, not significant, (HR=1.41[95%CI:0.63-3.14] p=0.41 for RFS, HR=1.34[ 95%CI:0.52-3.48] p=0.55 for OS). However B7-H3 status was not a prognostic factor in multivariate analysis (HR=0.78[95% CI: 0.33-1.85] for RFS, HR=0.73 [ 95%CI:0.26-2.02] for OS). Conclusions: The expression ratio of B7-H3 was observed in 45% of the esophageal cancer, which was related with T stage and lymphatic vessel invasion but not with clinical outcomes such as RFS and OS.
Metabolomic Consequences of Genetic Inhibition of PCSK9 Compared With Statin Treatment
Authors: Eeva Sliz, Johannes Kettunen, Michael V. Holmes, Clare Oliver Williams, Charles Boachie, Qin Wang, Minna Männikkö, Sylvain Sebert, Robin Walters, Kuang Lin, Iona Y. Millwood, Robert Clarke, Liming Li, Naomi Rankin, Paul Welsh, Christian Delles, J. Wouter Jukema, Stella Trompet, Ian Ford, Markus Perola, Veikko Salomaa, Marjo-Riitta Järvelin, Zhengming Chen, Debbie A. Lawlor, Mika Ala-Korpela, John Danesh, George Davey Smith, Naveed Sattar, Adam Butterworth, Peter Würtz
Journal: Circulation (2018)

Background: Both statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower blood low-density lipoprotein cholesterol levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these 2 lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial. Methods: Two hundred twenty-eight circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5359 individuals (2659 on treatment) in the PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) trial at 6 months postrandomization. The corresponding metabolic measures were analyzed in 8 population cohorts (N=72 185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. Results: Scaled to an equivalent lowering of low-density lipoprotein cholesterol, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy ( R 2 =0.88). Alterations in lipoprotein lipid composition and fatty acid distribution were similar. However, discrepancies were observed for very-low-density lipoprotein lipid measures. For instance, genetic inhibition of PCSK9 had weaker effects on lowering of very-low-density lipoprotein cholesterol compared with statin therapy (54% versus 77% reduction, relative to the lowering effect on low-density lipoprotein cholesterol; P =2×10 -7 for heterogeneity). Genetic inhibition of PCSK9 showed no significant effects on amino acids, ketones, or a marker of inflammation (GlycA), whereas statin treatment weakly lowered GlycA levels. Conclusions: Genetic inhibition of PCSK9 had similar metabolic effects to statin therapy on detailed lipid and metabolite profiles. However, PCSK9 inhibitors are predicted to have weaker effects on very-low-density lipoprotein lipids compared with statins for an equivalent lowering of low-density lipoprotein cholesterol, which potentially translate into smaller reductions in cardiovascular disease risk.
Enrollment of esophago-gastric cancer patients in a clinical fast-track program and it’s affect on time to treatment and quality of life.
Authors: Atuhani S. Burnett, Jack Mouhanna, Jose Ramirez-Garcialuna, Emma Lee, Julie Breau, Mary Diovisalvi, Thierry Alcindor, Jamil Asselh, Marie Vanhuyse, Joanne Alfieri, Marc David, Carmen L. Mueller, Jonathan D. Spicer, Jonathan Cools-Lartigue, Lorenzo Ferri
Journal: Journal of Clinical Oncology (2018)

180 Background: Esophago-gastric cancers are aggressive malignancies requiring numerous investigations to plan complex multi-modal therapy. The path from initial diagnosis to treatment can be associated with a long delay. This delay and complex patient trajectory may impact quality of life. Given the poor prognosis and highly symptomatic nature of upper GI cancer, a clear and timely access to treatment of crucial importance. We sought to determine the impact of a newly implemented streamlined and structure interdisciplinary pathway for newly diagnosed esophageal and gastric cancer on access times to treatment and quality of life (QoL). Methods: A streamlined pathway for patients referred to a high volume Upper GI Cancer clinic was generated with input from physicians, nutritionists, specialized nurses, and social workers. New diagnosis of esophageal or gastric cancer from 2014-16 were enrolled in this program and consenting patients completed serial QoL questionnaires (ESAS) at baseline, pre-treatment, 1 month post treatment. Dysphagia (DS) was quantified on a 5 point scale. Time intervals (days) were evaluated at various points between diagnosis and start of treatment (diagnosis, CT imaging, first visit with upper GI program, start of treatment). Data presented as median(IQR), * p &lt; 0.05. Results: Of the 251 patients with Upper GI cancer, 153 (61%) consented to participate including 140 esophageal/EGJ and 13 gastric cancer patients. Clinical stage distribution was 17.9% I, 30.7% II, 42.6% III, 8.7% IV. Of the 82 Esoph/EGJ patients with completed QoL questionnaires, 15 (18.3%) patients had severe dysphagia (DS = 3-4) and were prioritized for treatment. Patients with severe dysphagia had reduced time from index endoscopy to treatment (29 (16.3-39.3) vs 43 (32.8-68.0)days)* and first Upper GI clinic to treatment (15 (8.0-23.0) vs 25 (21.0-36.0)*. ESAS surveys showed increased QoL for both patients with and without dysphagia from baseline to pre-treatment indicating that simply entry into the streamlined program improved QoL. Conclusions: Structured interdisciplinary investigative and treatment programs for upper GI cancers can expedite time to treatment and improve QoL.
THE ROLE OF VENTRICULAR STROKE WORK AND VASCULAR IMPEDANCE IN DEFINING AORTIC STENOSIS
Authors: Eyal Ben-Assa, Jonathan Brown, Zahra Keshavarz-Motamed, Jose de la Torre Hernandez, Pinak Bipin Shah, Sammy Elmariah, Martin B. Leon, Elazer Edelman
Journal: Journal of the American College of Cardiology (2018)
Therapeutic effects of aerobic and resistance exercises for cancer survivors: a systematic review of meta-analyses of clinical trials
Authors: Joel T Fuller, Michael C Hartland, Luke T Maloney, Kade Davison
Journal: British Journal of Sports Medicine (2018)

Objective To systematically appraise and summarise meta-analyses investigating the effect of exercise compared with a control condition on health outcomes in cancer survivors. Design Umbrella review of intervention systematic reviews. Data sources Web of Science, Scopus, Cochrane Library, CINAHL and MEDLINE databases were searched using a predefined search strategy. Eligibility criteria Eligible meta-analyses compared health outcomes between cancer survivors participating in an exercise intervention and a control condition. Health outcomes were cardiovascular fitness, muscle strength, health-related quality of life, cancer-related fatigue and depression. Pooled effect estimates from each meta-analysis were quantified using standardised mean differences and considered trivial (&lt;0.20), small (0.20–0.49), moderate (0.50–0.79) and large (≥0.80). Findings were summarised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results There were 65 eligible articles that reported a total of 140 independent meta-analyses. 139/140 meta-analyses suggested a beneficial effect of exercise. The beneficial effect was statistically significant in 104 (75%) meta-analyses. Most effect sizes were moderate for cardiovascular fitness and muscle strength and small for cancer-related fatigue, health-related quality of life and depression. The quality of evidence was variable according to the GRADE scale, with most studies rated low or moderate quality. Median incidence of exercise-related adverse events was 3.5%. Conclusion Exercise likely has an important role in helping to manage physical function, mental health, general well-being and quality of life in people undergoing and recovering from cancer and side effects of treatment. PROSPERO registration number CRD42015020194 .
Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis
Authors: Chen Qu, Dandan Zheng, Sai Li, Yingjun Liu, Anna Lidofsky, Jacinta A. Holmes, Jianning Chen, Lu He, Lan Wei, Yadi Liao, Hui Yuan, Qimeng Jin, Zelong Lin, Qiaoting Hu, Yuchuan Jiang, Mengxian Tu, Xijun Chen, Weiming Li, Wenyu Lin, Bryan C. Fuchs, Raymond T. Chung, Jian Hong
Journal: Hepatology (2018)

Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, hepatitis B virus (HBV)‐infected, hepatitis C virus (HCV)‐infected and non‐alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively). A polymerase chain reaction (PCR) array was used to detect the changes in transcription factor (TF) expression in hepatic stellate cells (HSCs) with SYK knockdown. The effects of SYK antagonism on liver fibrogenesis were studied in LX‐2 cells, TWNT‐4 cells, primary human HSCs, and three progressive fibrosis/cirrhosis animal models, including a CCL 4 mouse model, and diethylnitrosamine (DEN) and bile duct ligation (BDL) rat models. We found that SYK protein in HSCs and hepatocytes correlated positively with liver fibrosis stage in human liver tissue. HBV or HCV infection significantly increased SYK and cytokine expression in hepatocytes. Increasing cytokine production further induced SYK expression and fibrosis‐related gene transcription in HSCs. Up‐regulated SYK in HSCs promoted HSC activation by increasing the expression of specific TFs related to activation of HSCs. SYK antagonism effectively suppressed liver fibrosis via inhibition of HSC activation, and decreased obstructive jaundice and reduced HCC development in animal models. Conclusion : SYK promotes liver fibrosis via activation of HSCs and is an attractive potential therapeutic target for liver fibrosis and prevention of HCC development. (H epatology 2018).
Incidence, predictors and prognostic significance of thromboembolic disease in patients with advanced <i>ALK</i>-rearranged non-small cell lung cancer
Authors: Jon Zugazagoitia, Mercedes Biosca, Julio Oliveira, María Eugenia Olmedo, Manuel Dómine, Ernest Nadal, José Carlos Ruffinelli, Nerea Muñoz, Ana María Luna, Berta Hernández, Maite Martínez, Iria Gallego, Eva Martínez de Castro, Carme Font, Virginia Calvo, Virginia Martínez-Marín, Jesús Corral, Esther Noguerón, Rebeca Mondéjar, Ignacio García Escobar, Carmen Salvador-Coloma, Óscar Juan, Manuel Sánchez Cánovas, Javier Valdivia, M. Pilar Ochoa, Rafael López Castro, Berta Obispo, Cristina Pangua, María Sereno, Lourdes Fernández Franco, Xabier Mielgo, Julia Calzas, Ana Blasco, Francisco Aparisi, Luis Chara, Juan Francisco Grau, Marta Soares, Ana Gómez, Victor Zenzola, Marcial García-Morillo, Diego Cacho, Asunción Díaz-Serrano, Carlos Aguado, Santiago Ponce-Aix, Jose Luis González-Larriba, Andrés J. Muñoz, David Lora, Luis Paz-Ares, Aránzazu Manzano
Journal: European Respiratory Journal (2018)

Thromboembolic disease is fairly common in patients with lung cancer [1–3]. This incidence seems to be higher in patients with lung adenocarcinomas [4], with approximately 15% of those with advanced stage disease developing venous thromboembolisms (VTE) during the whole course of their disease [5–7]. Pulmonary adenocarcinomas are a heterogeneous group of diseases that can be stratified according to the presence of major oncogenic driver alterations. Anaplastic lymphoma kinase ( ALK ) rearrangements are detected in approximately 4% of these cases [8]. Isolated reports have suggested that patients bearing ALK -rearranged tumours might have a higher than expected incidence of thromboembolisms [9, 10]. In the present study, we have analysed the incidence, predictors and prognostic significance of thromboembolic events in a large, multi-institutional and homogeneous cohort of advanced stage patients with ALK -rearranged lung cancers from Spain and Portugal. Our primary objective was to estimate the incidence of thromboembolic events and their association with overall survival in these patients. High incidence and prognostic relevance of thromboembolic disease in patients with ALK-rearranged NSCLCs <http://ow.ly/DEZr30j6kC8>
A Large Abdominal Mass in a Young Man
Authors: Yu Xi Terence Law, Lui Shiong Lee
Journal: JAMA Surgery (2018)

A man in his 30s presented with abdominal pain associated with unintentional weight loss in the preceding 6 months, large intraperitoneal and retroperitoneal masses, and elevated serum lactate dehydrogenase and β human chorionic gonadotrophin levels. What is your diagnosis?