tbuckley/cabot-search huggingface dataset:
Histology could predict a “hot” or a “cold” gastric tumor?
Authors: Ina Valeria Zurlo, Antonia Strippoli, Maria Alessandra Calegari, Maurizio Martini, Alessandra Cocomazzi, Armando Orlandi, Alessandra Cassano, Emanuele Vita, Giovanna Garufi, Brunella Di Stefano, Cinzia Bagala, Emilio Bria, Carmelo Pozzo, Michele Basso
Journal: Journal of Clinical Oncology (2019)

44 Background: The emerging role of immunotherapy (IT) in cancer treatments has increased the research about tumor microenvironment (TME), tumor infiltrating lymphocytes (TILs) function and their TME regulation. Nowadays ongoing trial are showing conflicting preliminary data about the efficacy of IT in advanced gastric cancer (GC). Therefore, we performed this exploratory analysis to evaluate the correlation between histology, TILs density (reported as CD4/CD8 tissue ratio), neutrophil-lymphocytes ratio (NLR) and response outcome in GC patients who underwent cytotoxic neoadjuvant treatment (NAD). Methods: CD4+ and CD8+ expression was assessed by immunohistochemistry (IHC) in pre-NAD biopsies. NLR was calculated on baseline complete blood count. A cut-off value to define low or high NLR has been selected on 3.0, based on literature data. X 2 test was used to explore the correlation between histology, CD4/CD8 ratio, NLR and response. Results: We analyzed 10 diffuse and 10 intestinal GC histotypes. In the intestinal-type CD4/CD8 ratio was lower (ratio range 1:15 - 1:20) with a predominant count of CD8+ suggesting a hot and inflamed TME compared to the diffuse cohort (ratio range 1:3 -1:5) where both CD8+ and CD4+ density was lower (p=0.03). Baseline NLR was calculated in 18 out of 20 pts. All intestinal GCs showed a low NLR (&lt;3) while all diffuse GCs displayed a high cutoff (p=0.03). CD4/CD8 ratio resulted associated to histology (p=0.025) and response outcome (p=0.0003). NLR was statistically related to histology (p=0.03) and CD4/CD8 tissue ratio (p=0.03), confirming a different systemic inflammatory status and TME according to histology. Conclusions: Despite the small sample size, our exploratory analysis shows a possible correlation between histology, systemic inflammation and TME behavior (“hot” vs“cold”) described by NLR and TILs concentration (CD4/CD8 ratio) respectively and response to NAD. Intestinal-type seems to be a “hot” tumor whereas diffuse-type appears “cold”. Future clinical trial should analyze the impact of histology and TME features on IT efficacy and the appropriate strategy to convert “cold” tumor increasing TILs density.
Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease
Authors: Jeffrey T. Ha, Brendon L. Neuen, Lap P. Cheng, Min Jun, Tadashi Toyama, Martin P. Gallagher, Meg J. Jardine, Manish M. Sood, Amit X. Garg, Suetonia C. Palmer, Patrick B. Mark, David C. Wheeler, Vivekanand Jha, Ben Freedman, David W. Johnson, Vlado Perkovic, Sunil V. Badve
Journal: Annals of Internal Medicine (2019)

Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain.To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD).English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019).Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes.Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence.Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; low-certainty evidence).Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials.In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs.None. (PROSPERO: CRD42017079709).
Clinical Trial Evidence for the Real World
Authors: Joseph S. Ross, Ken Covinsky
Journal: JAMA Internal Medicine (2019)

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Nanotechnology based therapeutics for lung disease
Authors: Mohammad Doroudian, Ronan MacLoughlin, Fergus Poynton, Adriele Prina-Mello, Seamas C Donnelly
Journal: Thorax (2019)

Nanomedicine is a multidisciplinary research field with an integration of traditional sciences such as chemistry, physics, biology and materials science. The application of nanomedicine for lung diseases as a relatively new area of interdisciplinary science has grown rapidly over the last 10 years. Promising research outcomes suggest that nanomedicine will revolutionise the practice of medicine, through the development of new approaches in therapeutic agent delivery, vaccine development and nanotechnology-based medical detections. Nano-based approaches in the diagnosis and treatment of lung diseases will, in the not too distant future, change the way we practise medicine. This review will focus on the current trends and developments in the clinical translation of nanomedicine for lung diseases, such as in the areas of lung cancer, cystic fibrosis, asthma, bacterial infections and COPD.
2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons
Authors: Craig T. January, L. Samuel Wann, Hugh Calkins, Lin Y. Chen, Joaquin E. Cigarroa, Joseph C. Cleveland, Patrick T. Ellinor, Michael D. Ezekowitz, Michael E. Field, Karen L. Furie, Paul A. Heidenreich, Katherine T. Murray, Julie B. Shea, Cynthia M. Tracy, Clyde W. Yancy
Journal: Circulation (2019)
Evidence of an Increase in Baseline Brachial Artery Lumen Diameter Independent of Body Mass Index (BMI) among Women with Polycystic Ovary Syndrome (PCOS)Compared to Age-Matched Control Women
Authors: Evelyn O. Talbott, Jeanne V. Zborowski, Kim Sutton-Tyrrell, David S. Guzick, Lewis H. Kuller
Journal: Circulation (2001)

P29 PCOS is a reproductive endocrine disorder, characterized by chronic anovulation, androgen excess, and insulin resistance, affecting approximately 5% of the female population. PCOS is associated with an increase in CHD risk factors, including LDL cholesterol,triglycerides, obesity,and hypertension. Endothelial dysfunction has been implicated in the development and progression of atherosclerosis and has been shown to be adversely affected in males with high free testosterone levels and in men and women with increased insulin resistance. We recruited 83 women with PCOS (42.3 ± 5.8 years) from our Pittsburgh cohort and 91 controls of similar age (43.4 ± 5.4 years) to evaluate endothelium-dependent vascular function using brachial artery ultrasonography. Women on hormone replacement or oral contraceptives were excluded from the analysis. The mean BMI ± SD was 31.7 ± 8.7 and 27.1 ± 6.4 kg/m 2 in cases and controls, respectively. The groups were also similar with respect to smoking status. No difference was observed in BMI-adjusted flow mediated vasodilation (FMD) between PCOS cases and controls (p=.630). However, baseline brachial lumen diameter (LD) was significantly higher among women with PCOS compared to controls (Mean ± SE = 3.30 ± .06 vs. 3.12 ± .05) after adjustment(p=.023). Further adjustment for LDLc, HDLc, triglycerides, systolic blood pressure (SBP), or insulin did not alter the PCOS-brachial lumen diameter association. Independently of case status and BMI, HDLc was significantly associated with baseline LD(p=.001); DBP was of borderline significance(p=.099). These findings suggested that PCOS may be associated with a compensatory enlargement of the arteries in response to accelerated arterial wall thickening and/or arterial stiffening. Further analyses within PCOS cases suggested that testosterone and insulin may mediate endothelial function (FMD). Future studies are needed to futher explore vascular changes and the implication for cardio- and cerebrovascular events in this high risk population.
Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study
Authors: Rob Pieters, Paola De Lorenzo, Philip Ancliffe, Luis Alberto Aversa, Benoit Brethon, Andrea Biondi, Myriam Campbell, Gabriele Escherich, Alina Ferster, Rebecca A Gardner, Rishi Sury Kotecha, Birgitte Lausen, Chi Kong Li, Franco Locatelli, Andishe Attarbaschi, Christina Peters, Jeffrey E. Rubnitz, Lewis B. Silverman, Jan Stary, Tomasz Szczepanski, Ajay Vora, Martin Schrappe, Maria Grazia Valsecchi
Journal: Journal of Clinical Oncology (2019)

Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value.Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE).A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response.Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.
Abstract 16958: Predictors of Atherosclerotic Cardiovascular Disease Risk in Subjects With Diabetes With and Without Cardiovascular Disease: The ACCORD Study
Authors: Nathan D Wong, Yanglu Zhao, Alain Bertoni, Patrick Hlavacek, Lisa Tarasenko, Cristina Masseria
Journal: Circulation (2017)

Background: Persons with diabetes (DM) are at substantial risk of atherosclerotic cardiovascular disease (ASCVD) events. Not well understood is the excess risk and predictors of subsequent ASCVD ev...
Autologous Hematopoietic Progenitor Cells Mobilization with Combination of Pegfilgrastim and Plerixafor: Efficacy and Cost Assessment
Authors: Luciano J. Costa, Racquel Innis-Shelton, Joscelyn Bowersock, Ayman Saad, Donna Salzman, Antonio Di Stasi, Nicole Watts, Lawrence S. Lamb
Journal: Blood (2017)
Abstract 12934: The Impact of Peripheral Artery Disease Assessed by Ankle-Brachial Index on Endothelial Dysfunction and Risk of In-Stent Restenosis After Percutaneous Coronary Intervention
Authors: Naohiro Komura, Kenichi Tsujita, Kenshi Yamanaga, Kenji Sakamoto, Satomi Iwashita, Sunao Kojima, Koichi Kaikita, Seiji Hokimoto, Kiyoshi Hibi, Teruyasu Sugano, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Circulation (2015)

Introduction: The problem of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) remains unresolved. Patients with peripheral artery disease (PAD), defined as a decreased ankle brachial index (ABI), have high cardiovascular event rates and impaired endothelial function predicts future cardiovascular events. However, to our knowledge, no studies have assessed the relationship among ABI, endothelial dysfunction, and ISR after PCI. Hypothesis: We assessed the hypothesis that low ABI at PCI is associated with a high incidence of ISR. Methods: ABI and endothelial function were checked before PCI and at follow-up (F/U) angiography in 243 consecutive patients who had successful PCI. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertip using a RH-PAT device. Patients were categorized according to their ABI values (PAD: ABI≦0.9, borderline: 0.9&lt;ABI50% at F/U angiography assessed by quantitative coronary angiography. Results: Within the study population there were 27 PAD, 26 borderline, and 190 normal ABI at the index PCI. Among them, ISR was demonstrated in 68 patients (28%). As the PAD status become worse, patients were found to have significantly higher ISR rate (PAD: 52%, borderline: 35%, normal: 24%, p=0.02) and more impaired peripheral endothelial function assessed by RHI (PAD: 1.49±0.44, borderline: 1.77±0.41, normal: 1.97±0.52, p=0.0001). Furthermore, patients with ISR were found to have significantly lower ABI than those without ISR (1.05±0.15 vs. 1.11±0.13 p=0.004). By multivariate logistic regression analysis even after adjusting for other significant parameters in univariate analysis (BMS use, Calcium antagonist use, MLD post PCI, Total stent length, right coronary artery stenting, current smoking, HDL-Cholesterol, and ACS presentation), PAD proved to be the independent predictor of ISR (Odds ratio 3.32; 95% confidence interval; 1.29 to 8.54, p=0.01). Conclusions: In patients undergoing PCI, PAD is independently associated with a higher rate of subsequent ISR. Impaired endothelial dysfunction may contribute to this adverse outcome. These findings have important implications for the careful F/U of PAD patients undergoing PCI as ISR-prone patients.
The Role of APAL/ST8SIA6-AS1 lncRNA in PLK1 Activation and Mitotic Catastrophe of Tumor Cells
Authors: Man-Li Luo, Jingjing Li, Liping Shen, Junjun Chu, Qiannan Guo, Guorun Liang, Wei Wu, Jianing Chen, Rufu Chen, Erwei Song
Journal: JNCI Journal of the National Cancer Institute (2019)

Tumor growth can be addicted to vital oncogenes, but whether long noncoding RNAs (lncRNAs) are essential to cancer survival is largely uncharacterized.We retrieved Gene Expression Omnibus datasets to identify lncRNA overexpression in 257 cancers vs 196 normal tissues and analyzed the association of ST8SIA6-AS1 (termed Aurora A/Polo-like-kinase 1 [PLK1]-associated lncRNA, APAL) with the clinical outcomes of multiple types of cancer from public RNA sequencing and microarray datasets as well as from in-house cancer cohorts. Loss- and gain-of-function experiments were performed to explore the role of APAL in cancers in vitro and in vivo. RNA pulldown and RNA immunoprecipitation were used to investigate APAL-interacting proteins. All statistical tests were two-sided.APAL is overexpressed in multiple human cancers associated with poor clinical outcome of patients. APAL knockdown causes mitotic catastrophe and massive apoptosis in human breast, lung, and pancreatic cancer cells. Overexpressing APAL accelerates cancer cell cycle progression, promotes proliferation, and inhibits chemotherapy-induced apoptosis. Mechanism studies show that APAL links up PLK1 and Aurora A to enhance Aurora A-mediated PLK1 phosphorylation. Notably, targeting APAL inhibits the growth of breast and lung cancer xenografts in vivo (MCF-7 xenografts: mean tumor weight, control = 0.18 g [SD = 0.03] vs APAL locked nucleic acids = 0.07 g [SD = 0.02], P < .001, n = 8 mice per group; A549 xenografts: mean tumor weight control = 0.36 g [SD = 0.10] vs APAL locked nucleic acids = 0.10 g [SD = 0.04], P < .001, n = 9 mice per group) and the survival of patient-derived breast cancer organoids in three-dimensional cultures.Our data highlight the essential role of lncRNA in cancer cell survival and the potential of APAL as an attractive therapeutic target for a broad-spectrum of cancers.
Health Care Spending, Utilization, and Quality 8 Years into Global Payment
Authors: Zirui Song, Yunan Ji, Dana G. Safran, Michael E. Chernew
Journal: New England Journal of Medicine (2019)

Population-based global payment gives health care providers a spending target for the care of a defined group of patients. We examined changes in spending, utilization, and quality through 8 years of the Alternative Quality Contract (AQC) of Blue Cross Blue Shield (BCBS) of Massachusetts, a population-based payment model that includes financial rewards and penalties (two-sided risk).Using a difference-in-differences method to analyze data from 2006 through 2016, we compared spending among enrollees whose physician organizations entered the AQC starting in 2009 with spending among privately insured enrollees in control states. We examined quantities of sentinel services using an analogous approach. We then compared process and outcome quality measures with averages in New England and the United States.During the 8-year post-intervention period from 2009 to 2016, the increase in the average annual medical spending on claims for the enrollees in organizations that entered the AQC in 2009 was $461 lower per enrollee than spending in the control states (P<0.001), an 11.7% relative savings on claims. Savings on claims were driven in the early years by lower prices and in the later years by lower utilization of services, including use of laboratory testing, certain imaging tests, and emergency department visits. Most quality measures of processes and outcomes improved more in the AQC cohorts than they did in New England and the nation in unadjusted analyses. Savings were generally larger among subpopulations that were enrolled longer. Enrollees of organizations that entered the AQC in 2010, 2011, and 2012 had medical claims savings of 11.9%, 6.9%, and 2.3%, respectively, by 2016. The savings for the 2012 cohort were statistically less precise than those for the other cohorts. In the later years of the initial AQC cohorts and across the years of the later-entry cohorts, the savings on claims exceeded incentive payments, which included quality bonuses and providers' share of the savings below spending targets.During the first 8 years after its introduction, the BCBS population-based payment model was associated with slower growth in medical spending on claims, resulting in savings that over time began to exceed incentive payments. Unadjusted measures of quality under this model were higher than or similar to average regional and national quality measures. (Funded by the National Institutes of Health.).
Hormone Replacement Therapy Acceptability to Nottingham Post-Menopausal Women with a Risk Factor for Osteoporosis
Authors: W A Wallace, V H Price, C A Elliot, M B A MacPherson, B W Scott
Journal: Journal of the Royal Society of Medicine (1990)

In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake.
DNA Methylation Markers for Breast Cancer Detection in the Developing World
Authors: Bradley M. Downs, Claudia Mercado-Rodriguez, Ashley Cimino-Mathews, Chuang Chen, Jing-Ping Yuan, Eunice Van Den Berg, Leslie M. Cope, Fernando Schmitt, Gary M. Tse, Syed Z. Ali, Danielle Meir-Levi, Rupali Sood, Juanjuan Li, Andrea L. Richardson, Marina B. Mosunjac, Monica Rizzo, Suzana Tulac, Kriszten J. Kocmond, Timothy de Guzman, Edwin W. Lai, Brian Rhees, Michael Bates, Antonio C. Wolff, Edward Gabrielson, Susan C. Harvey, Christopher B. Umbricht, Kala Visvanathan, Mary Jo Fackler, Saraswati Sukumar
Journal: Clinical Cancer Research (2019)

An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA).Experimental Design: Two case-control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection/training (N = 226) and testing (N = 246). Twenty-five methylated markers were assayed by Quantitative Multiplex-Methylation-Specific PCR (QM-MSP) to select and test a cancer-specific panel. Next, a pilot study was conducted on archival FNAs (49 benign, 24 invasive) from women with mammographically suspicious lesions using a newly developed, 5-hour, quantitative, automated cartridge system. We calculated sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) compared with histopathology for the marker panel.In the discovery cohort, 10 of 25 markers were selected that were highly methylated in breast cancer compared with benign tissues by QM-MSP. In the independent test cohort, this panel yielded an AUC of 0.937 (95% CI = 0.900-0.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI = 0.883-1.0) using the automated cartridge system.We developed and piloted a fast and accurate methylation marker-based automated cartridge system to detect breast cancer in FNA samples. This quick ancillary test has the potential to prioritize cancer over benign tissues for expedited pathologic evaluation in poorly resourced countries.