tbuckley/cabot-search huggingface dataset:
Optimization of Risk Stratification in Localized Prostate Cancer
Authors: Alicia Katherine Morgans
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 67-year-old retired engineering professor was found to have a prostate-specific antigen (PSA) level of 11 ng/mL on a screening test at his annual physical examination. A digital rectal examination revealed a nodule on the right side. He underwent a transrectal ultrasound-guided prostate biopsy that was notable for prostate adenocarcinoma, Gleason 3 + 4 = 7 (Gleason grade group 2; 30% Gleason 4 component) involving two cores (60% and 20% core involvement). A bone scan and pelvic computed tomography scan were negative for evidence of metastatic disease. (Should he undergo prostate magnetic resonance imaging? That seems rather common these days.) He was diagnosed with cT2b intermediate-risk localized prostate cancer (PCa) by National Comprehensive Cancer Network (NCCN) risk group and was seen in the multidisciplinary clinic to discuss management options (Table 1).
Abstract P284: Role of a Genetic Risk Score with Dietary Intake and Physical Activity in Relation to Metabolic Syndrome
Authors: Dale S Hardy, Tesfaye Mersha, Hongyan Xu, Susan Racette
Journal: Circulation (2016)

Background: Studies have found associations between genetic polymorphisms, food intake, physical activity, body mass index, and metabolic syndrome (METs). Objective: We hypothesized that a genetic risk score (GRS) with food intake and physical activity are influenced by mediational and interaction effects to increase METs among White and African American adults. Methods: We used the Atherosclerosis Risk In Communities (ARIC) study data at the third visit from 1996-1998. Data included 8,416 Whites and 2,061 African Americans aged 41-71y with 1,484 and 517 cases of METs, respectively. METs was defined according to the International Diabetes Federation criteria. Dietary data were obtained from the ARIC study food frequency questionnaire. The GRS was composed of eight single nucleotide polymorphisms involved in cardiovascular and lipid metabolism, known to have defects in protein binding and function. Mediational path analysis using linear-and-logistic regression was used to test simultaneous associations, and interaction using multivariate logistic regression tested relationships between the GRS, food intake, physical activity and METs. In mediational path analysis, Root Mean Square Error of Approximation, p&gt;0.05, Comparative Factor Index, p&gt;0.90, Tucker-Lewis Index, p&gt;0.90, and chi-square test, p&gt;0.05 were used to assess statistical significance. For interaction using logistic regression analysis, odds ratios (OR) and 95% confidence intervals with p&lt;0.05 were used to judge statistical significance. Results: In multivariate logistic regression, the GRS was associated with a 22% increased risk for METs among Whites (OR=1.22; 1.03-1.44), while this association was not significant in African Americans. After adjustment for Bonferonni correction for mass significance (p&lt;0.001), we found among Whites that energy-adjusted total fat, animal fat, caloric intake, sugar-sweetened drinks, red meat, fried foods, and processed meats were associated with higher risk for METs, while energy-adjusted total carbohydrates, crude fiber, dietary fiber, and cereal fiber had a protective association with METs. These results were similar in African Americans but did not meet Bonferonni significance. In mediational analysis, we observed insignificant mediational effects, but significant direct effects for the GRS to METs for physical activity (OR=1.164; p=0.047) and fish intake (OR=1.161; p=0.050) among Whites and for carbohydrate intake (OR=1.164; p=0.058) and drinks consumed (OR=4.445; p&lt;0.0000) among overweight/obese Whites. In interaction models, energy-adjusted carbohydrate, protein, animal fat, fructose, and sugary drinks interacted with the GRS to affect METs among Whites, but not African Americans. Conclusion: A GRS operates through interaction with dietary factors and physical activity rather than by their mediational effects on METs among White adults.
Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from trial BIG 1-98 comparing adjuvant endocrine therapy with tamoxifen versus letrozole
Authors: G Viale, A Giobbie-hurder, Mm Regan, As Coates, Mm Mastropasqua, P Dell'Orto, E Maiorano, G Macgrogan, S Braye, C Öhlschlegel, P Neven, Z Orosz, Wp Olszewski, F Knox, B Thürlimann, Kn Price, M Castiglione-gertsch, Rd Gelber, Ba Gusterson, A. Goldhirsch
Journal: Journal of Clinical Oncology (2008)
B cells as biomarkers: predicting immune checkpoint therapy adverse events
Authors: Shannon M. Liudahl, Lisa M. Coussens
Journal: Journal of Clinical Investigation (2018)

Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte–associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.
CCGs fail to declare pharma funding
Authors: Tom Moberly
Journal: BMJ (2018)

The BMJ GP commissioners in England are receiving tens of thousands of pounds from drug companies without declaring the funding in their public registers, an investigation by The BMJ has found. 1The BMJ worked with researchers from the University of Bath and Sweden's Lund University to examine payments from private companies and charities to clinical commissioning groups in 2015 and 2016.Using data collected through requests made under freedom of information legislation, they found more than a thousand payments that were not included in the CCGs' online registers of competing interests, gifts, sponsorship, and hospitality.
Abstract 19282: Safety and Utility of the CardioMEMs Device in Pulmonary Arterial Hypertension
Authors: Raymond Benza, Priscilla Correa-jaque, Veronica Franco, Mark Doyle, Jason A White, Greg Ginn, Robert biederman
Journal: Circulation (2016)

Introduction: Pulmonary arterial hypertension (PAH) remains fatal requiring better methods for outcome prediction. Although invasive hemodynamics are valuable prognostically, their routine use is i...
Primary Prevention With Statins in the Elderly
Authors: Martin Bødtker Mortensen, Erling Falk
Journal: Journal of the American College of Cardiology (2018)

The burden of atherosclerotic cardiovascular disease (ASCVD) in high-income countries is mostly borne by the elderly. With increasing life expectancy, clear guidance on sensible use of statin therapy to prevent a first and potentially devastating ASCVD event is critically important to ensure a healthy aging population. Since 2013, 5 major North American and European guidelines on statin use in primary prevention of ASCVD have been released by the American College of Cardiology/American Heart Association, the UK National Institute for Health and Care Excellence, the Canadian Cardiovascular Society, U.S. Preventive Services Task Force, and the European Society of Cardiology/European Atherosclerosis Society. Guidance on using statin therapy in primary ASCVD prevention in the growing elderly population (>65 years of age) differs markedly. The authors discuss the discrepant recommendations, place them into the context of available evidence, and identify circumstances in which uncertainty may hamper the appropriate use of statins in the elderly.
Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells
Authors: Jung Hwan Kim, John Podstawka, Yuefei Lou, Lu Li, Esther K. S. Lee, Maziar Divangahi, Björn Petri, Frank R. Jirik, Margaret M. Kelly, Bryan G. Yipp
Journal: Nature Immunology (2018)
Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules
Authors: Elizabeth J de Koster, Lioe-Fee de Geus-Oei, Olaf M Dekkers, Ilse van Engen-van Grunsven, Jaap Hamming, Eleonora P M Corssmit, Hans Morreau, Abbey Schepers, Jan Smit, Wim J G Oyen, Dennis Vriens
Journal: Endocrine Reviews (2018)

Abstract Indeterminate thyroid cytology (Bethesda III and IV) corresponds to follicular-patterned benign and malignant lesions, which are particularly difficult to differentiate on cytology alone. As ~25% of these nodules harbor malignancy, diagnostic hemithyroidectomy is still custom. However, advanced preoperative diagnostics are rapidly evolving. This review provides an overview of additional molecular and imaging diagnostics for indeterminate thyroid nodules in a preoperative clinical setting, including considerations regarding cost-effectiveness, availability, and feasibility of combining techniques. Addressed diagnostics include gene mutation analysis, microRNA, immunocytochemistry, ultrasonography, elastosonography, computed tomography, sestamibi scintigraphy, [18F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and diffusion-weighted magnetic resonance imaging. The best rule-out tests for malignancy were the Afirma® gene expression classifier and FDG-PET. The most accurate rule-in test was sole BRAF mutation analysis. No diagnostic had both near-perfect sensitivity and specificity, and estimated cost-effectiveness. Molecular techniques are rapidly advancing. However, given the currently available techniques, a multimodality stepwise approach likely offers the most accurate diagnosis, sequentially applying one sensitive rule-out test and one specific rule-in test. Geographical variations in cytology (e.g., Hürthle cell neoplasms) and tumor genetics strongly influence local test performance and clinical utility. Multidisciplinary collaboration and implementation studies can aid the local decision for one or more eligible diagnostics.
Excellent Outcome of Children with Down Syndrome (DS) and Acute Lymphoblastic Leukemia (ALL) Treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols 00-001 and 05-001
Authors: Uma H. Athale, Maneka Puligandla, Kristen E. Stevenson, Barbara L. Asselin, Luis A. Clavell, Peter D. Cole, Kara M. Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A. Schorin, Maria Luisa Sulis, Jennifer J.G. Welch, Marian H. Harris, Donna S. Neuberg, Stephen E. Sallan, Lewis B. Silverman
Journal: Blood (2016)
The Oral Proteasome Inhibitor Ixazomib, Alone and in Combination with Ibrutinib, Induces Lethality in Waldenstrom Macroglobulinemia Cells That Are Resistant to Ibrutinib
Authors: Aneel Paulus, Alak Manna, Sharoon Akhtar, Neeraj Kumar Singh, Ansu Kumar, Kabya Basu, Akshita Trivedi, Debapriya Majumdar, Taher Abbasi, Shireen Vali, Vivek Roy, Peter Martin, Morton Coleman, Anne J Novak, Stephen M Ansell, Sikander Ailawadhi, Asher A. Chanan-Khan
Journal: Blood (2017)
Urgent reversal of vitamin K antagonists
Authors: Beverley J Hunt, Marcel Levi
Journal: BMJ (2018)

### What you need to know

A 78 year old man is brought to the emergency department after collapsing. He is drowsy with signs of a left hemiparesis. Computed tomography of the brain shows an intracranial bleed. He has a history of atrial fibrillation, and he has been taking warfarin (INR target 2-3) for several years. His wife says he started a course of antibiotics for a chest infection a week before. His INR is 8. 

Warfarin is a vitamin K antagonist (fig 1) and a coumarin (more accurately 4-hydroxycoumarin) derivative. It is the most commonly used vitamin K antagonist in the world.1 The main uses for vitamin K antagonists are prevention of stroke in patients with atrial fibrillation, and prevention of thrombosis in those with previous venous thromboembolism or with mechanical heart valves. In some countries, other coumarins are used with a similar action but a shorter (acenocoumarol) or longer (phenprocoumon) half-life.



Fig 1 
Coagulation factors II (prothrombin), VII, IX, and X, and the physiological anticoagulant proteins C and S, undergo vitamin K-dependent post-translational carboxylation in the liver before secretion into plasma. This step activates the coagulation factors, giving them the ability to bind to calcium. During carboxylation, vitamin K is oxidised to its inactive form vitamin K epoxide, which is regenerated by the enzyme vitamin K epoxide reductase. Vitamin K antagonists act as competitive …
Abstract 11107: The ECG has a Low Diagnostic Yield in Active Individuals With Dilated Cardiomyopathy
Authors: Lynne Millar, Jess Webb, Harshil Dhutia, Emma Magavern, Rajay Narain, Aneil Malhotra, Ahmed Merghani, Rajan Sharma, Sanjay Sharma
Journal: Circulation (2015)

Introduction/Objective: Around 90% of patients with HCM have an abnormal ECG; however there is paucity of data on the ECG in DCM. Approximately 14% athletes show an LV cavity &gt;60mm and 1-2% reveal a borderline low LVEF which overlaps with DCM. The role of ECG in facilitating the differentiation between physiologic LV enlargement and DCM has not been investigated. We sought to ascertain the utility of the various ECG screening criteria in differentiating physiology from pathology in a cohort of individuals with LV dilatation. Methods: 89 individuals with a dilated LVEDD (43 asymptomatic athletes from cardiac screening (male=37, female=6) and 46 non-ischaemic DCM NYHA class I from a cardiomyopathy clinic (males=33, female=13) were included. Fourty (87%) of the DCM patients were on a beta-blocker. The 2010 ESC, ‘Seattle’ and the novel ‘Refined’ screening criteria were applied to the most recent ECG in both cohorts to assess whether ECG screening would have accurately raised suspicion of pathology. Results: Using the ESC criteria 11 DCM patients had a normal ECG and 6 had group 1 changes; therefore 40.0% of DCM patients would have been considered to have an ECG compatible with athletic training. Excluding sinus bradycardia, the most common group 1 change was early repolarisation. The sensitivity and specificity of the ESC criteria for detecting pathology in our cohort was 63.0% and 69.0% respectively. The sensitivity and specificity of the ‘Seattle’ criteria is 50% and 76.7%. The ‘Refined’ criteria was less sensitive at 41.3% but had a higher specificity of 79.2%. Conclusions: It is often assumed the ECG is abnormal in patients with a dilated cardiomyopathy. In our cohort 40% of the ECGs in our DCM patients would have not prompted further investigation if seen at pre-participation screening. This study demonstrates the ECG is not a particularly useful investigation in distinguishing physiological from pathological LV dilatation.
Abstract 19155: “Real World” Eligibility for Sacubitril/Valsartan in Unselected Heart Failure Patients: Data From the Swedish Heart Failure Registry
Authors: Joanne Simpson, Lina Benson, Pardeep S Jhund, Ulf Dahlström, John J McMurray, Lars H Lund
Journal: Circulation (2016)

Background: PARADIGM-HF demonstrated the benefits of sacubitril/valsartan (LCZ696) over enalapril in patients with heart failure and reduced ejection fraction (HFREF). How widely applicable sacubit...
Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer
Authors: Hongmei Nan
Journal: Cancer Research (2008)

4686  There is substantial variation in human pigmentation within and across populations. Melanin synthesized by melanocytes is the main contributor to human pigmentation. Lighter pigmentation is a risk factor for skin cancer. Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) were identified in pigmentation genes, very few SNPs were examined in relation to human pigmentary phenotypes. No studies were conducted for the risk of skin cancer except for the melanocortin 1 receptor (MC1R) gene. We evaluated the associations between 12 SNPs (including 8 non-synonymous SNPs) in 7 candidate pigmentation genes (TYR, OCA2, SLC24A5, SLC45A2, POMC, ASIP, and ATRN) involved in inducing the maturation from pheomelanine to eumelanine, and both pigmentary phenotypes (hair color, skin color, and tanning tendency) and skin cancer risk in a nested case-control study within the Nurses’ Health Study (NHS) among 219 melanoma cases, 286 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 873 common controls. Unconditional logistic regression and linear regression were used for data analysis. We found that the TYR Arg402Gln variant was significantly associated with skin color and tanning tendency (p-value  G was associated with melanoma risk (adjusted OR, 0.75; 95% CI, 0.60-0.95); the TYR Ser192Tyr was associated with SCC risk (adjusted OR, 1.23; 95% CI, 1.00-1.50); the OCA2 Arg419Gln was associated with BCC risk (adjusted OR, 1.50; 95% CI, 1.06-2.13); and the ASIP g.8818 A>G was associated with BCC risk (adjusted OR, 0.73; 95% CI, 0.53-1.00). These associations remained essentially the same after adjusting for pigmentary phenotypes. We observed an interaction between hair color and the TYR Ser192Tyr on SCC risk (p, interaction, 0.02). This study provides evidence for the contribution of pigmentation genetic variants to variation in human pigmentary phenotypes and development of skin cancer.
¿Es realmente la Incidencia de infección por Helicobacter pylori más frecuente en el servicio de Endoscopia? Experiencia en nuestro centro
Authors: A Esparza Nieva, C Echeverría Pérez, MDP Ortiz Lana, N Vergara Corres, A Cebrián García, R Irisarri Garde, EL Borobio Aguilar, M Polo Gil
Journal: Endoscopy (2017)

El Helicobacter pylori (H. pylori) es un microorganismo Gram negativo, con forma espiral, de crecimiento lento, con característica bioquímica de producir ureasa, que causa infecciones en el estómago. Se encuentra, aproximadamente, en dos tercios de la población mundial. Puede causar úlceras pépticas y cáncer de estómago. Es posible que se transmita por agua y alimentos contaminados, vía de transmisión persona-persona oral-oral o fecal-oral, pero los investigadores no están seguros. La adquisición se produce en mayor medida durante la infancia (países en vías de desarrollo vs. países desarrollados) se cree que el riesgo principal es el estado socioeconómico de la familia durante la infancia (cantidad de personas que comparten una vivienda, una cama y en ausencia de red de agua caliente.
Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer
Authors: Todd A. Pezzi, David L. Schwartz, Abdallah S. R. Mohamed, James W. Welsh, Ritsuko U. Komaki, Stephen M. Hahn, Boris Sepesi, Christopher M. Pezzi, Clifton D. Fuller, Stephen G. Chun
Journal: JAMA Oncology (2018)

Combined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States.To estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database.Analysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database.Utilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival.A total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit.Substantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.