tbuckley/cabot-search huggingface dataset:
Hemolytic-Uremic Syndrome
Authors: Ellin Lieberman, Eva Heuser, George N. Donnell, Benjamin H. Landing, G. Denman Hammond
Journal: New England Journal of Medicine (1966)

IN 1955 Gasser and his associates1 introduced the term hemolytie-uremic syndrome to describe 5 children with a fatal disease characterized by acute renal failure, hemolytic anemia and thrombocytopenia. They considered that the severe renal disease distinguished the disorder in their patients from the disorder called thrombotic thrombocytopenic purpura by Moschcowitz2 and microangiopathy by Symmers.3 The coincidence of acute renal failure, hemolytic anemia and thrombocytopenia has subsequently been presented in the pediatric literature as the "hemolytic-uremic syndrome."4 5 6 7 8 9 Most authors have distinguished their patients from those with thrombotic thrombocytopenic purpura or necrosis of the renal cortex although the differential criteria often have . . .
Clinical and Patient-Centered Outcomes in Obese Patients With Type 2 Diabetes 3 Years After Randomization to Roux-en-Y Gastric Bypass Surgery Versus Intensive Lifestyle Management: The SLIMM-T2D Study
Authors: Donald C. Simonson, Florencia Halperin, Kathleen Foster, Ashley Vernon, Allison B. Goldfine
Journal: Diabetes Care (2018)

OBJECTIVE To compare the effect of Roux-en-Y gastric bypass (RYGB) surgery versus intensive medical diabetes and weight management (IMWM) on clinical and patient-reported outcomes in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively randomized 38 obese patients with type 2 diabetes (15 male and 23 female, with mean ± SD weight 104 ± 16 kg, BMI 36.3 ± 3.4 kg/m2, age 52 ± 6 years, and HbA1c 8.5 ± 1.3% [69 ± 14 mmol/mol]) to laparoscopic RYGB (n = 19) or IMWM (n = 19). Changes in weight, HbA1c, cardiovascular risk factors (UKPDS risk engine), and self-reported health status (the 36-Item Short-Form [SF-36] survey, Impact of Weight on Quality of Life [IWQOL] instrument, and Problem Areas in Diabetes Survey [PAID]) were assessed. RESULTS After 3 years, the RYGB group had greater weight loss (mean −24.9 kg [95% CI −29.5, −20.4] vs. −5.2 [−10.3, −0.2]; P &amp;lt; 0.001) and lowering of HbA1c (−1.79% [−2.38, −1.20] vs. −0.39% [−1.06, 0.28] [−19.6 mmol/mol {95% CI −26.0, −13.1} vs. −4.3 {−11.6, 3.1}]; P &amp;lt; 0.001) compared with the IMWM group. Changes in cardiometabolic risk for coronary heart disease and stroke were all more favorable in RYGB versus IMWM (P &amp;lt; 0.05 to P &amp;lt; 0.01). IWQOL improved more after RYGB (P &amp;lt; 0.001), primarily due to subscales of physical function, self-esteem, and work performance. SF-36 and PAID scores improved in both groups, with no difference between treatments. A structural equation model demonstrated that improvement in overall quality of life was more strongly associated with weight loss than with improved HbA1c and was manifest by greater improvements in IWQOL than with either SF-36 or PAID. CONCLUSIONS Three years after randomization to RYGB versus IMWM, surgery produced greater weight loss, lower HbA1c, reduced cardiovascular risk, and improvements in obesity-related quality of life in obese patients with type 2 diabetes.
Impact of Novel Low-Density Lipoprotein-Cholesterol Assessment on the Utility of Secondary Non-High-Density Lipoprotein-C and Apolipoprotein B Targets in Selected Worldwide Dyslipidemia Guidelines
Authors: Vasanth Sathiyakumar, Jihwan Park, Renato Quispe, Mohamed B. Elshazly, Erin D. Michos, Maciej Banach, Peter P. Toth, Seamus P. Whelton, Roger S. Blumenthal, Steven R. Jones, Seth S. Martin
Journal: Circulation (2018)

Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). After considering 2 LDL-C estimates that differ in accuracy, we examined: (1) how frequently non-HDL-C guideline targets could change management; and (2) the utility of apoB targets after meeting LDL-C and non-HDL-C targets.We analyzed 2518 adults representative of the US population from the 2011 to 2012 National Health and Nutrition Examination Survey and 126 092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features, including coronary artery disease, diabetes mellitus, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-C <70 and <100 mg/dL using Friedewald estimation (LDL-CF) and a novel, more accurate method (LDL-CN). Next, we examined those not meeting non-HDL-C (<100, <130 mg/dL) and apoB (<80, <100 mg/dL) guideline targets. In those meeting dual LDL-C and non-HDL-C targets (<70 and <100 mg/dL, respectively, or <100 and <130 mg/dL, respectively), we determined the proportion of individuals who did not meet guideline apoB targets (<80 or <100 mg/dL).A total of 7% to 9% and 31% to 36% of individuals had LDL-C <70 and <100 mg/dL, respectively. Among those with LDL-CF<70 mg/dL, 14% to 15% had non-HDL-C ≥100 mg/dL, and 7% to 8% had apoB ≥80 mg/dL. Among those with LDL-CF<100 mg/dL, 8% to 10% had non-HDL-C ≥130 mg/dL and 2% to 3% had apoB ≥100 mg/dL. In comparison, among those with LDL-CN<70 or 100 mg/dL, only ≈2% and ≈1% of individuals, respectively, had non-HDL-C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ≈0% to 3% of individuals with LDL-CN<70 mg/dL had non-HDL-C ≥100 mg/dL or apoB ≥80 mg/dL compared with 13% to 38% and 9% to 25%, respectively, in those with LDL-CF<70 mg/dL. With LDL-CF or LDL-CN<70 mg/dL and non-HDL-C <100 mg/dL, 0% to 1% had apoB ≥80 mg/dL. Among all dual LDL-CF or LDL-CN<100 mg/dL and non-HDL-C <130 mg/dL individuals, 0% to 0.4% had apoB ≥100 mg/dL. These findings were robust to sex, fasting status, and lipid-lowering therapy status.After more accurately estimating LDL-C, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary artery disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.
Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy
Authors: Feifei Liu, Xiaotong Yang, Meiyu Geng, Min Huang
Journal: Acta Pharmaceutica Sinica B (2018)

The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy.
PROGNOSTIC IMPACT OF MALNUTRITION AND FAT VOLUME IN MEN VERSUS WOMEN WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kazuya Tanabe, Kiyomi Kayama, Masatsugu Kawahira, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
Association of increased neutrophil-lymphocyte ratio after curative surgery with prognosis in patients with locally advanced esophagogastric adenocarcinoma.
Authors: Akihiro Suzuki, Keisuke Kubota, Aoi Fujikawa, Takashi Taketa, Hiroki Sunagawa, Seiji Ohigashi, Akihiro Kishida
Journal: Journal of Clinical Oncology (2018)

63 Background: The neutrophil-lymphocyte ratio (NLR) is associated with the inflammatory status of patients with some cancers. We hypothesize that increased NLR was associated with prognosis in patients with stage II/III esophagogastric adenocarcinoma. Methods: We retrospectively analyzed 220 patients with stage II/III gastric cancer who underwent curative resection with suitable lymphadenectomy at our hospital, between 2000 and 2014. All patients underwent baseline staging, including blood tests, computed tomography, and endoscopic biopsy. The relationship between NLR and clinical outcomes was analyzed by univariate and multivariate analyses. Results: Average age was 67.9 [95% confidence interval (CI); 43.8, 92.1] years, and majority of the patients were male. After surgery, 111 (50.5%) patients underwent adjuvant chemotherapy, most of all patients received S-1 according to Japanese treatment guideline. Median follow-up time was 74.8 (95% CI; 69.9, 79.7) months. The preoperative NLR was 3.2 (95% CI; -4.2, 10.6), whereas the postoperative NLR was 3.0 (95% CI; -6.9, 12.8). In univariate analyses, age, stage, preoperative NLR, baseline CA19-9 levels, postoperative white blood cell (WBC) count, postoperative hemoglobin levels, postoperative NLR, increased NLR after surgery and adjuvant chemotherapy were associated with overall survival (OS). In multivariate analyses, age ( p &lt; 0.001), stage ( p = 0.001), and increased NLR after surgery ( p = 0.048) were associated with OS. The prognosis of patients with increased NLR after surgery was observed to be worse than that of those with decreased NLR after surgery ( p = 0.001). Conclusions: Our findings indicated that increased NLR after curative resection was associated with poor OS in patients with locally advanced esophagogastric adenocarcinoma, suggesting that perioperative increased NLR was a potentially useful marker for individual therapy.
DOES LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN DIFFERENTIATE LOW-FLOW, LOW-GRADIENT SEVERE AORTIC STENOSIS PATIENTS IN ADDITION TO CONVENTIONAL CONTRACTILE RESERVE ASSESSMENT?
Authors: Tatsuya Miyoshi, Diego Medvedofsky, Kyle Buchanan, Toby Rogers, Linzhi Xu, Itsik Ben-Dor, Lowell Satler, Rebecca Torguson, Ron Waksman, Federico Asch
Journal: Journal of the American College of Cardiology (2018)
Paediatric immediate life support course
Authors: Rebecca Devaney
Journal: BMJ (2011)

This one day course run by the Resuscitation Council UK focuses on the immediate care of the seriously ill child and the initial resuscitation of infants and children who are in respiratory or cardiorespiratory arrest. It aims to give participants the knowledge and skills needed to become members of a paediatric resuscitation team.

The course is aimed at all healthcare staff who may be involved in providing clinical care in acute paediatrics, including junior doctors and nursing staff.

I did the course at the start of my paediatrics job as a foundation year 1 doctor at the Queen’s Medical Centre in Nottingham. It was held in the resuscitation department …
RELATIVE CONTRIBUTION OF AFTERLOAD AND INTERSTITIAL TISSUE FIBROSIS TO PRE-OPERATIVE LONGITUDINAL AND CIRCUMFERENTIAL FUNCTION IN PATIENTS WITH SEVERE AORTIC STENOSIS
Authors: Alisson Slimani, Julie Melchior, Clotilde Roy, Christophe De Mesteer, Amzulescu Mihaela, Sophie Pierard, Christophe Beauloye, David Vancraeynest, Anne-Catherine Pouleur, Agnes Pasquet, Bernhard Gerber, Jean-Louis Vanoverschelde
Journal: Journal of the American College of Cardiology (2018)
Abstract 17274: Temporal Changes in Myocardial Function after Transcatheter Aortic Valve Replacement for Aortic Stenosis with Speckle Tracking Echocardiography
Authors: Yasuharu Takeda, Satoshi Nakatani, Yasushi Sakata, Isamu Mizote, Kei Torikai, Kazuo Shimamura, Koichi Maeda, Toru Kuratani, Shinsuke Nanto, Yoshiki Sawa, Issei Komuro
Journal: Circulation (2012)

Objectives: Transcatheter aortic valve replacement (TAVR) offers a safer treatment solution for frail and elderly patients with severe aortic stenosis (AS) and significant comorbidities. Although T...
A Research Agenda for Malaria Eradication: Diagnoses and Diagnostics
Journal: PLoS Medicine (2011)

Many of malaria's signs and symptoms are indistinguishable from those of other febrile diseases. Detection of the presence of Plasmodium parasites is essential, therefore, to guide case management. Improved diagnostic tools are required to enable targeted treatment of infected individuals. In addition, field-ready diagnostic tools for mass screening and surveillance that can detect asymptomatic infections of very low parasite densities are needed to monitor transmission reduction and ensure elimination. Antibody-based tests for infection and novel methods based on biomarkers need further development and validation, as do methods for the detection and treatment of Plasmodium vivax. Current rapid diagnostic tests targeting P. vivax are generally less effective than those targeting Plasmodium falciparum. Moreover, because current drugs for radical cure may cause serious side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, more information is needed on the distribution of G6PD-deficiency variants as well as tests to identify at-risk individuals. Finally, in an environment of very low or absent malaria transmission, sustaining interest in elimination and maintaining resources will become increasingly important. Thus, research is required into the context in which malaria diagnostic tests are used, into diagnostics for other febrile diseases, and into the integration of these tests into health systems.
Foundation course in cardiology
Authors: Claire Brough
Journal: BMJ (2009)

The foundation course in cardiology is a three day comprehensive programme of the fundamentals in cardiac practice, delivered primarily by consultant cardiologists. Coverage ranges from assessing clinical trials and interacting with the cardiology industry, to practising transthoracic echocardiology and intra-aortic balloon pump insertion. Cardiology registrars in the early years of training and core medical trainees intending to pursue a career in cardiology. The course is delivered through a series of lectures, practical workshops, live patient case demonstrations, and interactive cases. Material presented during lectures is consolidated and applied directly to clinical practice through live demonstrations and hands on training. ### Lectures
London cuts trauma and orthopaedic surgery training posts for 2016
Authors: Abi Rimmer
Journal: BMJ (2016)

No training posts in trauma and orthopaedic surgery will be offered in London this year, Health Education England has said.

It said that, for the first time, there would be no new posts in London for specialty training year 3 (ST3) trauma and orthopaedics in 2016.

Mustafa Rashid, president of the British Orthopaedic Trainees Association, said that the decision had caused a great deal of distress among trainees who wished to train in the capital. “I have had around 30 trainees contact me, and they have …
Computed Tomography for Diagnosis and Classification of Bicuspid Aortic Valve Disease in Transcatheter Aortic Valve Replacement
Authors: Won-Keun Kim, Luise Gaede, Oliver Husser, Christoph Liebetrau, Matthias Renker, Andreas Rolf, Ulrich Fischer-Rasokat, Susanne Möllmann, Johannes Blumenstein, Eva Guenther, Arnaud Van Linden, Mani Arsalan, Mirko Doss, Sabrina Loders, Martin Arnold, Christian W. Hamm, Thomas Walther, Stephan Achenbach, Helge Möllmann
Journal: JACC. Cardiovascular imaging (2018)
Evolutionary Origins of Toll-like Receptor Signaling
Authors: Joseph J Brennan, Thomas D Gilmore
Journal: Molecular Biology and Evolution (2018)

Toll-like receptors (TLRs) are transmembrane pattern recognition receptors that are best known for their roles in innate immunity for the detection of and defense against microbial pathogens. However, TLRs also have roles in many nonimmune processes, most notably development. TLRs direct both immune and developmental programs by activation of downstream signaling pathways, often by activation of the NF-κB pathway. There are two primary TLR subtypes: 1) TLRs with multiple cysteine clusters in their ectodomain (mccTLRs) and 2) TLRs with a single cysteine cluster in their ectodomain (sccTLRs). For some time, it has been known that TLRs and the biological processes that they control are conserved in organisms from insects to mammals. However, genome and transcriptome sequencing has revealed that many basal metazoans also have TLRs and downstream NF-κB signaling components. In this review, we discuss what is known about the structure, biological function, and downstream signaling pathways of TLRs found in phyla from Porifera through Annelida. From these analyses, we hypothesize that mccTLRs emerged in the phylum Cnidaria, that sccTLRs evolved in the phylum Mollusca, and that TLRs have dual immune and developmental biological functions in organisms as ancient as cnidarians.
Association of microbiome and plasma cytokine dynamics to nivolumab response in metastatic renal cell carcinoma (mRCC).
Authors: Manuel C. Maia, Valeriy Poroyko, Haejung Won, Lorena Almeida, Paulo Gustavo Bergerot, Nazli Dizman, Joann Hsu, Jeremy Jones, Ravi Salgia, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

656 Background: Checkpoint inhibitors (CPI) represent a standard of care in mRCC. The relationship of the microbiome to benefit from CPIs has been suggested in clinical studies in melanoma (Wargo et al ASCO 2017). Here we provide updated evidence of association between microbiome composition, plasma cytokines and response to nivolumab in mRCC patients (pts). Methods: Stool and blood samples were prospectively collected from pts with mRCC at 3 time points relative to nivolumab treatment (baseline, week 4 and week 12) and used to assess gut microbiota composition in two different groups: responders (R; including complete/partial response and stable disease) and non-responders (P; primary progression). For stool analyses, microbial DNA was extracted, 16s rRNA gene tags (v4) were generated by PCR amplification and sequenced using MiSeq (Illumina). Sequence reads were processed by Mothur software, assembled in OTUs, taxonomically annotated and used to construct dissimilarity matrices. Differentially abundant taxa were determined by METASTATS and compared between R and P. We further interrogated whether plasma cytokine profile was influenced by specific bacterial species. Results: Of 20 pts, 16 were evaluable for response. In preliminary analyses, 25,304 OTUs were attributed to 165 genera from 8 phyla. PCoA analysis reveals that the first two principal coordinates can explain 49.2% of data set variation. Subsequent k-means clustering shows an almost complete separation of microbiota in R and P groups (p = 0.07). The analysis of microbiota membership in P and R groups revealed 2 differentially abundant taxonomic units present above 1% abundance. Namely, Roseburia spp and Faecalibacterium spp were significantly elevated in R as compared to P (p &lt; 0.05). Correlations between these bacteria and plasma cytokines will be presented at the meeting. Conclusions: Our results are the first to associate specific microbial genera to nivolumab response in mRCC, and this represents the first effort to combine analysis of the microbiome and serum cytokines. Manipulation of the stool microbiome as a means of modulating nivolumab response should be investigated.
A low microRNA-630 expression confers resistance to tyrosine kinase inhibitors in EGFR-mutated lung adenocarcinomas via miR-630/YAP1/ERK feedback loop
Authors: De-Wei Wu, Yao-Chen Wang, Lee Wang, Chih Yi Chen, Huei Lee
Journal: Theranostics (2018)

Purpose: MicroRNA-630 plays dual roles in apoptosis and drug resistance in human cancers.However, the role of miR-630 in resistance to tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma remains to be elucidated.Methods: Manipulation of miR-630 and its targeted gene YAP1 and/or combination of inhibitor treatments was performed to explore whether low miR-630 could confer TKI resistance due to de-targeting YAP1, and this could decrease proapoptotic protein Bad expression through the miR-630/YAP1/ERK feedback loop.A retrospective study was conducted to examine whether the expression of miR-630 and YAP1 could be associated with TKI therapeutic response in patients with lung adenocarcinoma.Results: Low miR-630 expression may confer TKI resistance via increased SP1 binding to the miR-630 promoter due to ERK activation by YAP1 de-targeting.Persistent activation of ERK signaling via the miR-630/YAP1/ERK feedback loop may be responsible for TKI resistance in EGFR-mutated cells.Moreover, a decrease in Bad expression by its phosphorylation at Serine 75 through ERK activation conferred low miR-630-mediated TKI resistance by modulating the apoptotic pathway.Xenographic tumors induced by miR-630-knockdown PC9 and PC9GR cells in nude mice were nearly suppressed by the combination of gefitinib with the YAP1 inhibitor verteporfin or an MEK/ERK inhibitor AZD6244.Patients with low miR-630 and high YAP1 expressing tumors had a higher prevalence of unfavorable responses to TKI therapy and poorer outcomes when compared with their counterparts.Conclusion: MiR-630 may be a potential biomarker for the prediction of TKI therapeutic response and outcome in patients with lung adenocarcinoma.
Plasma KRAS as a biomarker for pancreatic ductal adenocarcinoma (PDAC).
Authors: Benjamin A. Krantz, Dana Tsui, Maeve Aine Lowery, Marinela Capanu, Kenneth H. Yu, David Paul Kelsen, Erika Gedvilaite, Liguo Zhang, S Duygu Selcuklu, Daoqi You, Jennifer S Golia Pernicka, Richard K. G. Do, Christine A Iacobuzio-Donahue, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2018)

316 Background: PDAC needs validated diagnostic biomarkers for early detection and predictive markers for outcome. As 95% of PDACs harbor KRAS mutations (mKRAS), circulating tumor DNA (ctDNA) has potential utility in PDAC. We assessed the ability to detect and correlate mKRAS in a metastatic PDAC cohort from Memorial Sloan Kettering Cancer Center. Methods: 10 mL of whole blood was collected. cfDNA was extracted with QIAmp or QIAsymphony DNA extraction kits (Qiagen, Valencia, CA). Directed (KRAS G12D, G12R, G12V, Q61H) or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with Raindrop Plus (Raindance Technologies, Billerica, MA) or QX200 (BioRad, Hercules, CA) ddPCR systems. Number and size of liver, lung and lymph node metastases, peritoneal disease (mild, moderate, severe), ascites (trace, small, large) and bone mets (Y/N) were assessed by CT scan. Results: See table. 21 (55%) had detectable ctDNA (ctDNA(+)) with mean mutant allele fraction of 4.5% (0.015-36.8). ctDNA (+) vs (-) PFS and OS from collection were 6.9 and 8.4 months vs. 9.9 and 10.5 (p=0.89 for both). CA19-9, PFS and OS did not correlate with ctDNA tertile (p=0.15, 0.54 &amp; 0.50). On treatment and disease activity were not associated with ctDNA status (p= 0.20 &amp; 0.60). Number and size of liver mets were associated with ctDNA (+) (p=0.006 &amp; 0.007). Conclusions: ctDNA KRAS detection was measurable in metastatic disease with rates consistent with other PDAC reports. Median PFS, OS were lower in ctDNA (+) group but not statistically significant in this diverse cohort. Number and size of liver metastases were significantly higher in ctDNA (+). Future study should focus on practice changing applications with standardized collection, intra-patient comparisons and role of liver disease burden. We have initiated studies to evaluate plasma KRAS prior to and during treatment to address its value as a predictive assay and explore factors affecting ctDNA detection. [Table: see text]