tbuckley/cabot-search huggingface dataset:
Review: Prophylactic antibiotics reduce exacerbations but do not improve quality of life in patients with COPD
Authors: Christine F. McDonald, Christopher J. Worsnop
Journal: Annals of Internal Medicine (2019)

ACP Journal Club19 February 2019Review: Prophylactic antibiotics reduce exacerbations but do not improve quality of life in patients with COPDChristine F. McDonald, MBBS, PhD, Christopher J. Worsnop, MBBSChristine F. McDonald, MBBS, PhDAustin Health, Heidelberg, Victoria, Australia (C.F.M., C.J.W.)Search for more papers by this author, Christopher J. Worsnop, MBBSAustin Health, Heidelberg, Victoria, Australia (C.F.M., C.J.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201902190-018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHerath SC, Normansell R, Maisey S, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2018;10:CD009764. https://pubmed.ncbi.nlm.nih.gov/30376188Clinical Impact RatingsGIM/FP/GP: Pulmonology: Reference1 Sethi S. Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon. Proc Am Thorac Soc. 2004;1:109-14. [PMID: 16113422] Google Scholar Author, Article, and Disclosure InformationAffiliations: Austin Health, Heidelberg, Victoria, Australia (C.F.M., C.J.W.)This article was published at Annals.org on 5 February 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 February 2019Volume 170, Issue 4Page: JC18KeywordsAdverse eventsAntibioticsChronic obstructive pulmonary diseaseMortalityNumber needed to treatQuality of lifeSerious adverse eventsSpirometryTachycardiaUpper respiratory tract infections ePublished: 19 February 2019 Issue Published: 19 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
KRAS mutation status to predict response in first-line capox and bevacizumab therapy for metastatic colorectal cancer.
Authors: You Yone, Mohammad Abdallah, Saad Sabih Tahir, Selim Cellek, Jufen Zhang, Yvonne Lester, Lauren Shillito, Jennifer Child, Lizzie Dawson, Bryan Singizi, Stephen Bustin
Journal: Journal of Clinical Oncology (2019)

536 Background: Capecitabine and Oxaliplatin (CAPOX) combined with the humanised anti-vascular endothelial growth factor Bevacizumab represents a standard first-line treatment for metastatic colorectal cancer (mCRC). However, the response rate is only approximately 50% and currently there is no biomarker to predict treatment response. This study aims to correlate KRAS status with response to CAPOX and Bevacizumab (CAPOX-Bev). Methods: Forty-five patients with mCRC were retrospectively screened between January 2012 and December 2015 at Broomfield Hospital, UK. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue samples (Qiagen FFPE tissue kit). Twelve types of mutations in Exons 2, 3 and 4 of the KRAS gene were analysed using a real-time quantitative polymerase chain reaction (qPCR) assay (EntroGen). Treatment response was assessed according to RECIST criteria version 1.1 by comparing pre-treatment and post-treatment radiological CT scans. The KRAS status was correlated with CT tumour response (responders: partial response and complete response; non-responders: progressive disease and stable disease). A Chi-square test was used to determine the correlation between KRAS status and tumour response. Results: 19/45 patients were KRAS wild type (WT, 42%) and 26 were KRAS mutant (MT, 58%). 8/19 (42%) KRAS WT patients were responders, compared to 3/26 (12%) KRAS MT patients. Conversely 11/19 (58%) of WT patients were non-responders, compared to 23/26 (88%) MT patients. The correlation of treatment response and KRAS status was statistically significant (p = 0.018), with a 31% difference in response rate between KRAS WT (42%) and KRAS MT (12%) groups. Conclusions: Within this pilot retrospective analysis, KRAS mutations demonstrated clinical value in identifying patients who are more likely to respond to first-line CAPOX-Bev in advanced colorectal cancer. This finding requires prospective evaluation within a large patient cohort powered to further detect potential differences in overall and progression free survival. [Table: see text]
Abstract 20004: Mineralocorticoid Receptor Antagonist Therapy Improves Vascular Function in Patients With Coronary Artery Disease
Authors: Maria Cybularz, Heike Langbein, Birgit Zatschler, Coy Brunssen, Andreas Deussen, Klaus Matschke, Henning Morawietz
Journal: Circulation (2017)

Introduction: Mineralocorticoid receptor antagonists (MRA) have a positive impact on the prognosis of patients with heart failure. The regulation of vascular function by MRA is less well-understood. Hypothesis: We hypothesized that MRA have a positive Impact on vascular function in patients with coronary artery disease. Methods: Therefore, we investigated the vascular function in internal mammary arteries of patients with coronary artery disease-with (n=15) or without (n=24) preoperative MRA therapy (spironolactone or eplerenone) undergoing coronary artery bypass grafting (CABG). Results: The patients did not differ in age, gender (males), body-mass index (BMI), ejection fraction, prevalence of diabetes, smoking status, LDL-cholesterol levels, and additional anti-hypertensive and statin therapy. In order to maintain a better endothelium-dependent and smooth muscle function all vessels were stored after surgery in a recently developed potassium-chloride and N-acetyl-histidine-enriched storage solution (TiP...
Preliminary Outcomes of Children and Young Adults with Acute Lymphoblastic Leukaemia and Down Syndrome (DS-ALL) on UKALL 2011. Reduction in Treatment-Related Mortality with De-Escalated Therapy
Authors: Sara Ghorashian, Sujith Samarasinghe, Amy A Kirkwood, Rachael Hough, Clare Rowntree, Sarah Lawson, Nicholas John Goulden, Emma Pond, Pamela R. Kearns, Anthony V. Moorman, John Moppett, Ajay Vora
Journal: Blood (2018)
Abstract P010: Mid-life Vitamin D Levels and Later Life Performance on Neuropsychological Testing: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Oluwaseun E Fashanu, Di Zhao, Andrea L Schneider, Andreea M Rawlings, Richey A Sharrett, Pamela L Lutsey, Rebecca F Gottesman, Alden L Gross, Eliseo Guallar, Alvaro Alonso, Thomas H Mosley, Erin D Michos
Journal: Circulation (2018)

Background: Prior cross-sectional studies among older adults have found associations between low vitamin D (vitD) levels and reduced cognitive performance but were unable to distinguish the temporal order between vitD and the onset of dementia. We examined the association between mid-life vitD levels, assessed by serum 25-hydroxyvitD, with later life performance on neuropsychological testing. Methods: We conducted a non-concurrent cross-sectional analysis of 5,887 white and black participants enrolled in the ARIC Neurocognitive Study. We included participants who had serum vitD concentrations measured at visit 2 (1990-1992; age range 47-69 years) and who had neuropsychological and functional testing at visit 5 (2011-2013; age range 67-91 years). Neuropsychological tests were grouped into memory, language, and executive function domains and were standardized. We categorized vitD using clinical cut points as deficient (&lt;20 ng/mL), intermediate (20-&lt;30 ng/mL), or sufficient (≥ 30 ng/mL). We used Poisson and linear regression models adjusted for demographic and socioeconomic factors to examine the associations between vitD with prevalent dementia and performance on neuropsychological testing. Results: In mid-life, the mean (SD) age of participants was 56 (5) years, 60% were female, and 22% black. Mean (SD) vitD was 24.6 (8.4) ng/mL; 30% had deficient, 46% intermediate, and 24% sufficient vitD levels. Compared to participants with sufficient vitD levels, the prevalence ratios (95% CI) of late-life dementia were 1.35 (0.99, 1.84) and 1.27 (0.90, 1.80) for participants with intermediate and deficient vitD levels, respectively. We found no significant association between mid-life vitD and late-life performance on neuropsychological testing ( Table ). Further adjustments for cardiovascular, genetic, and metabolic factors yielded similar results. Conclusion: In this cohort, mid-life serum vitD levels were not associated with prevalent dementia or with performance on neuropsychological testing 20 years later.
Discarding optimality: Throwing out the baby with the bathwater?
Authors: Patrick Simen, Fuat Balcı
Journal: Behavioral and Brain Sciences (2018)

Rahnev &amp; Denison (R&amp;D) argue against normative theories and in favor of a more descriptive "standard observer model" of perceptual decision making. We agree with the authors in many respects, but we argue that optimality (specifically, reward-rate maximization) has proved demonstrably useful as a hypothesis, contrary to the authors' claims.
NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018
Authors: Shaji K. Kumar, Natalie S. Callander, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jorge Castillo, Jason C. Chandler, Caitlin Costello, Matthew Faiman, Henry C. Fung, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Yubin Kang, Adetola Kassim, Michaela Liedtke, Ehsan Malek, Thomas Martin, Vishala T. Neppalli, James Omel, Noopur Raje, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Donna Weber, Joachim Yahalom, Rashmi Kumar, Dorothy A. Shead
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, evaluation, treatment, including supportive-care, and follow-up for patients with myeloma. These NCCN Guidelines Insights highlight the important updates/changes specific to the myeloma therapy options in the 2018 version of the NCCN Guidelines.
Estimating the Probability of Tolerating Each Challenge Dose of Peanut Protein at Exit Double-Blind, Placebo-Controlled Food Challenge: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial (PALISADE) of AR101
Authors: Warner Carr, Brian P. Vickery, Rezi Zawadzki, Noelle M. Griffin, Daniel C. Adelman, Edwin Kim
Journal: Journal of Allergy and Clinical Immunology (2019)
Early tumor shrinkage and depth of response as predictors of favorable treatment outcomes in patients with metastatic colorectal cancer treated with FOLFOX/FOLFIRI plus cetuximab.
Authors: S.P. Somashekhar, Amit Rauthan, Ashwin K Rajgopal, Rohit Kumar C
Journal: Journal of Clinical Oncology (2019)

631 Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line chemotherapy + anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer (mCRC). This association and the predictive accuracy of response measurements were investigated in the first-line setting for FOLFOX/FOLFIRI plus cetuximab. Methods: We performed a study of FOLFOX/FOLFIRI plus cetuximab as first-line treatment in Indian patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Cox regression models analysis investigated associations between ETS and overall survival (OS) and progression-free survival (PFS). Results: Sixty (78.9 %) of 76 patients had ETS, which was associated with prolonged PFS and OS. Both ETS and DoR were able to predict survival as accurately as RECIST response. Both ETS and DoR were associated with PFS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. In the study patients, the RR, median PFS, and OS were 68.4 %, 13.1 months, and 30.6 months, respectively. Median DpR was 52%. The DpR correlated with OS as well as PFS. FOLFOX plus cetuximab was active as a first-line, with no major toxicities. Conclusions: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus cetuximab. ETS is a promising and valuable end point for clinical trials’ design deserving further investigation.
EARLY Post-Transplant Events , Cost of Admission and Mortality, in Patients Undergoing Allogeneic Transplants from Identical Siblings, Unrelated Donors or Haploidentical Donors
Authors: Federica SORA, Patrizia Chiusolo, Luca Laurenti, Sabrina Giammarco, Francesco Autore, Idanna Innocenti, Simona Sica, Metafuni Elisabetta, Andrea Bacigalupo
Journal: Blood (2018)
Abstract MP049: Fermented vs. Non-fermented Dairy and Risk of Coronary Heart Disease in Men: the Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Timo Koskinen, Heli E Virtanen, Sari Voutilainen, Tomi-Pekka Tuomainen, Jaakko Mursu, Jyrki K Virtanen
Journal: Circulation (2017)

Introduction: Most of the recent dairy studies, including multiple meta-analyses, show either no relationship or an inverse association between total dairy intake and risk of cardiovascular diseases. Some of these studies have suggested that especially fermented rather than non-fermented dairy might provide benefits on cardiovascular health, but the data is inconclusive. Also, the average dairy intake has been modest in many study populations, which reduces the generalizability of the findings to populations with high dairy intake. Hypothesis: We assessed the hypothesis that fermented and non-fermented dairy products have distinct associations with the risk of coronary heart disease (CHD) in men from eastern Finland, a population with high intake of dairy products. Methods: A total of 1981 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study from eastern Finland, aged 42-60 years, with no CHD at baseline, were included. The consumption of foods was assessed with instructed 4-day food recording by household measures. Dairy products with fat content &lt;3.5% were considered low-fat. Multivariable Cox regression analyses included age, examination year, smoking, leisure-time physical activity, education, family history of CHD, and intakes of alcohol, energy, fiber, polyunsaturated fatty acids, and fruits, berries and vegetables. Fatal and non-fatal CHD events were ascertained from national registries, with no loss to follow-up. Results: The mean±SD intakes were 733±375 g/d for total, 187±218 g/d for fermented and 546±345 g/d for non-fermented dairy. Low-fat products comprised 87% (162±218 g/d) of the fermented and 43% (317±291 g/d) of the non-fermented dairy intake. During the mean follow-up of 20.1 years, 472 CHD events occurred. The multivariable-adjusted hazard ratio (95% CI) in the highest (&gt;280 g) vs. the lowest (&lt;26 g) quartile of total fermented dairy was 0.73 (0.56-0.95, P-trend=0.02) and in the highest (&gt;727 g) vs. the lowest (&lt;258 g) quartile of total non-fermented dairy 1.44 (1.06-1.94, P-trend=0.009). When low-fat and high-fat dairy were evaluated separately, only low-fat products were associated with the risk. The extreme-quartile hazard ratios (95% CIs) were 0.74 (0.57-0.96, P-trend=0.02) for low-fat fermented dairy and 1.47 (1.08-1.99, P-trend=0.02) for low-fat non-fermented dairy. Intakes of total dairy (extreme-quartile HR 1.03, 95% CI 0.74-1.42, P-trend=0.727), high-fat fermented dairy (HR 0.92, 95% CI 0.69-1.22, P-trend=0.32) or high-fat non-fermented dairy (HR 1.09, 95% CI 0.77-1.56, P-trend=0.44) were not associated with the risk of CHD. Conclusions: Our results suggest that low-fat fermented dairy products are associated with a lower risk of CHD, whereas low-fat non-fermented dairy products are associated with a higher risk in a population with high intake of dairy products.
Serum miR-626 and miR-5100 are Promising Prognosis Predictors for Oral Squamous Cell Carcinoma
Authors: Jianbo Shi, Xin Bao, Zengying Liu, Zhiyuan Zhang, Wantao Chen, Qin Xu
Journal: Theranostics (2019)

Although serum microRNAs (miRNAs) are currently being considered as promising noninvasive biomarkers for cancers, their role in the prognosis of oral squamous cell carcinoma (OSCC) has not been elucidated. Here we aimed to identify serum miRNA biomarkers that could be used as prognosis predictors of OSCC. Methods: A cohort of 260 serum miRNA samples was assessed in a three-step approach that included a screening stage, a training stage, and a testing stage. The correlation between prognosis of OSCC and the miRNAs expression was comprehensively analyzed. Results: A two-miRNA signature involving miR-626 and miR-5100 has been developed. Patients defined to be high-risk group by the two-miRNA signature had significantly shortened median survival time compared with the low-risk group. In multivariate analysis, this two-miRNA signature was independently predictive of survival, and achieved a superior predictive value compared with that of traditional clinicopathologic factors such as pathology grade as well as tumor and node metastasis (TNM) stage. An integrated prognostic model combining the TNM stage and miRNA signature displayed the highest prognostic performance (AUC value: 0.787, specificity: 0.884, sensitivity: 0.573) compared to the TNM stage-alone (AUC value: 0.630, specificity: 0.526, sensitivity: 0.733) or miRNA signature-alone model (AUC value: 0.771, specificity: 0.768, sensitivity: 0.773). In addition, we found that OSCC tumor cells not only expressed a high level of these two miRNAs, but also secreted certain miRNAs into the extracellular environment, suggesting these miRNAs may originate from tumor cells. Conclusion: In our study, we established a two-miRNA signature that was strongly and independently associated with prognosis in OSCC, and may serve as a promising prognosis predictor.
First detection of a Vssc allele V1016G conferring a high level of insecticide resistance in Aedes albopictus collected from Europe (Italy) and Asia (Vietnam), 2016: a new emerging threat to controlling arboviral diseases
Authors: Shinji Kasai, Beniamino Caputo, Takashi Tsunoda, Tran Chi Cuong, Yoshihide Maekawa, Sai Gek Lam-Phua, Verena Pichler, Kentaro Itokawa, Katsunori Murota, Osamu Komagata, Chigusa Yoshida, Han-Hsuan Chung, Romeo Bellini, Yoshio Tsuda, Hwa-Jen Teng, José Luiz de Lima Filho, Luiz Carlos Alves, Lee Ching Ng, Noboru Minakawa, Nguyen Thi Yen, Tran Vu Phong, Kyoko Sawabe, Takashi Tomita
Journal: Eurosurveillance (2019)

IntroductionAedes albopictus (Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission.AimTo determine insecticide resistance status and mechanisms in Ae. albopictus from different geographical regions.MethodsWe sampled 33 populations of Ae. albopictus from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel (Vssc) was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed.ResultsMost populations of Ae. albopictus tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance (kdr) allele V1016G in Vssc for the first time in Ae. albopictus. Two previously reported kdr alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S.ConclusionThe V1016G allele was detected in bothAsian and Italian Ae. albopictus populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in Ae. albopictus, particularly where this mosquito species is the main vector of arboviruses.
Effect of azithromycin on Chlamydia pneumoniae –mediated Interleukin-4 responses
Authors: Yitzchok M. Norowitz, Yvonne Huang, Jefffrey Loeffler, Elliot Klein, Natalie Banniettis, Manuel Penton, Margaret R. Hammerschlag, Helen G. Durkin, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz
Journal: Journal of Allergy and Clinical Immunology (2019)
hiPSCs in cardio-oncology: deciphering the genomics
Authors: Emily A Pinheiro, K Ashley Fetterman, Paul W Burridge
Journal: Cardiovascular Research (2019)

The genomic predisposition to oncology-drug-induced cardiovascular toxicity has been postulated for many decades. Only recently has it become possible to experimentally validate this hypothesis via the use of patient-specific human-induced pluripotent stem cells (hiPSCs) and suitably powered genome-wide association studies (GWAS). Identifying the individual single nucleotide polymorphisms (SNPs) responsible for the susceptibility to toxicity from a specific drug is a daunting task as this precludes the use of one of the most powerful tools in genomics: comparing phenotypes to close relatives, as these are highly unlikely to have been treated with the same drug. Great strides have been made through the use of candidate gene association studies (CGAS) and increasingly large GWAS studies, as well as in vivo whole-organism studies to further our mechanistic understanding of this toxicity. The hiPSC model is a powerful technology to build on this work and identify and validate causal variants in mechanistic pathways through directed genomic editing such as CRISPR. The causative variants identified through these studies can then be implemented clinically to identify those likely to experience cardiovascular toxicity and guide treatment options. Additionally, targets identified through hiPSC studies can inform future drug development. Through careful phenotypic characterization, identification of genomic variants that contribute to gene function and expression, and genomic editing to verify mechanistic pathways, hiPSC technology is a critical tool for drug discovery and the realization of precision medicine in cardio-oncology.