tbuckley/cabot-search huggingface dataset:
Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines
Authors: Annika Reintam Blaser, Joel Starkopf, Waleed Alhazzani, Mette M. Berger, Michael P. Casaer, Adam M. Deane, Sonja Fruhwald, Michael Hiesmayr, Carole Ichai, Stephan M. Jakob, Cecilia I. Loudet, Manu L. N. G. Malbrain, Juan C. Montejo González, Catherine Paugam-Burtz, Martijn Poeze, Jean-Charles Preiser, Pierre Singer, Arthur R.H. van Zanten, Jan De Waele, Julia Wendon, Jan Wernerman, Tony Whitehouse, Alexander Wilmer, Heleen M. Oudemans-van Straaten
Journal: Intensive Care Medicine (2017)

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.
Emotionally arousing context modulates the ERP correlates of neutral picture processing: An ERP test of the GANE model
Authors: Deborah Talmi, Gemma E. Barnacle
Journal: Behavioral and Brain Sciences (2016)

The time scale of the effects of emotional arousal on neutral information processing is crucial for the predictions of the glutamate amplifies noradrenergic effects (GANE) model. GANE suggests that when emotional and neutral stimuli are presented in a sequence, neutral information processing will change. We review the literature on event-related potentials, including our own data set, to test this prediction.
Long-Term Survival in Patients Receiving Conventional Therapy for Newly Diagnosed Multiple Myeloma; Results from United Kingdom Medical Research Council Trials 1980–1997.
Authors: Bradley M. Augustson, Gulnaz Begum, Gareth J. Morgan, J. Anthony Child, Nicola J. Barth, Janet A. Dunn, Mark T. Drayson
Journal: Blood (2004)
METB-02USING MAGNETIC RESONANCE SPECTROSCOPY TO TRACK DENDRITIC CELLS FOR VACCINE IMMUNOTHERAPY
Authors: Hassan Azari, Alexander L. Vlasak, Rolando Lovaton, Duane Mitchell, Maryam Rahman
Journal: Neuro-Oncology (2015)

INTRODUCTION: Recently, we demonstrated a strong correlation between the proportion of dendritic cell migration to lymph nodes and improved overall survival in GBM patients. Although we have utilized SPECT imaging, this modality is limited by the use of ionizing radiation and radionucleotides. Magnetic resonance imaging (MRI) is a feasible alternative and avoids patient radiation exposure and has additional benefit of providing clinically useful anatomic information in patients. Here we evaluate feasibility of labeling DCs with metabolites (e.g sarcosine) or (13)C to track them using spectroscopy. METHODS: DCs were generated from myeloid progenitors in normal or (13)C glucose supplemented medium. Mature DCs were loaded with sarcosine using electroporation and overnight incubation in sarcoine containing medium. Sarcosine assay was used to determine the amount of sarcosine per cell. A panel of DC antigen specific antibodies was used to evaluate DCs phenotype after loading with sarcosine or (13)C. Nuclear magnetic resonance (NMR) was used to determine DC metabolic signature, the sarcosine and (13)C content of the loaded DCs and also the metabolite spectral pattern of DC activated lymph nodes. RESULTS: Sarcosine and C13 glucose were well tolerated by the DCs without any change in expression of the maturation markers. Sarcosine assay showed that incubation of mature DCs in 6 and 20 mM sarcosine would lead to a concentration of 2 and 3pg/cell, respectively. NMR spectroscopy showed a unique sarcosine signature in intact mature DCs. It also confirmed (13)C incorporation in many metabolites. NMR spectral pattern in activated lymph nodes was correlated with number of cells harvested. CONCLUSION: Based on these results, sarcosine and C13 can be efficiently used to label DCs in culture and have the potential to distinguish and quantify labeled cells using NMR spectroscopy. Further investigations into using these labeling strategies to identify DCs using MR spectroscopy are under way.
Molecular Level of Minimal Residual Disease in Bone Marrow Before High-Dose Therapy and Autologous Stem Cell Transplantation Is a Prognostic Parameter in Patients with Multiple Myeloma.
Authors: Roland Fenk, Mark Korthals, Nina Sehnke, Ingmar Bruns, Akos Czibere, Fabian Zohren, Nancy Safaian, Ariane Dienst, Leilani Ruf, Frank Neumann, Rainer Haas, Ralf Kronenwett, Guido Kobbe
Journal: Blood (2007)
MNGO-11EARLY POSTOPERATIVE EMERGENCY DEPARTMENT PRESENTATION PREDICTS POOR LONG-TERM OUTCOMES IN PATIENTS SURGICALLY TREATED FOR MENINGIOMA
Authors: Arash Nayeri, Philip Brinson, Diana Douleh, Lola Chambless
Journal: Neuro-Oncology (2015)

OBJECTIVES: Previous authors have identified a number of factors that predict morbidity, mortality, and recurrence in patients undergoing resection of a meningioma. We sought to study a novel potential prognostic indicator: early postoperative visit to the Emergency Department (ED). METHODS: We conducted a retrospective cohort study on 239 patients who underwent a meningioma resection at our institution between 2001-2013 with over three months of follow-up postoperatively. All postoperative entries in the medical record were reviewed to identify any ED visit within a 90-day postoperative period. Visits related to complaints other than neurologic or wound-related concerns were excluded. The relationships between ED presentation, tumor grade, and extent of surgical resection with future risk of operative recurrence and mortality were analyzed using Fisher's exact test. Variables associated with increased risks of mortality or operative recurrence in a univariate analysis were then included in the multivariate logistic regression model. RESULTS: 31% of all patients presented to the ED with a neurologic or wound-related complaint within 90 days of the operation. 68% of patients with confirmed mortality and 64% of patients who later developed an operative recurrence presented to the ED within 90 days of the original operation. Patients with a postoperative ED visit were found to be significantly more likely to die during the follow-up period (23.0% versus 4.85%, p < 0.0001) or develop an eventual operative recurrence (12.2% versus 3.0%, p = 0.0131). Postoperative ED presentation was found to be associated with a higher risk of mortality and operative recurrence independent of pathological tumor grade (p < 0.0001 and p = 0.0102 respectively). CONCLUSIONS: Presentation to the ED is associated with significantly higher rates of future operative recurrence and mortality in patients with recent meningioma resections. This poor prognostic relationship is independent of tumor pathological grade. Increased vigilance and follow-up may be warranted in such patients.
GRN163L, a Potent and Specific Inhibitor of Telomerase: Integrated Pharmacokinetic, Pharmacodynamic, and Safety Data Guides Design of Practical Treatment Regimens for Targeting Inhibitory Levels in Patients.
Authors: Robert J. Tressler, Allison C. Chin, Eric J. Feldman, Kanti R. Rai, Doug Kornbrust, Calvin B. Harley, Melissa A. Kelly Behrs, Laurence Elias
Journal: Blood (2006)
Analysis of Prognostic Factors for Survival in 75 Chinese Patients with Peripheral T-Cell Lymphoma (PTCL)
Authors: Yue Han, Jia Ruan, Qian Zhu, Xiaochen Chen, Shixiang Zhao, Wenjuan Zhang, Qian WANG, Zhengming Jin, Huiying Qiu, Aining Sun, Wu Depei
Journal: Blood (2012)
The Genotype of T-Cell Costimulatory Molecule Is Associated with Relapse Incidence In Patients with Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation
Authors: Haowen Xiao, Xiaoyu Lai, Yi Luo, Jimin Shi, Yamin Tan, Jingsong He, Wanzhuo Xie, Lifei Zhang, Yingjia Wang, Zhen Cai, Maofang Lin, Xiujin Ye, He Huang
Journal: Blood (2010)
Impact of Second-Generation Tyrosine Kinase Inhibitors As Second Line Treatment for Patients with Chronic Myeloid Leukemia,
Authors: J Valentin Garcia-Gutierrez, Pilar Herrera, Lorena L Abalo, Maria Dolores Rey, Maria Calbacho, Lourdes Ramos, Paloma Ramos, Carlos Montalban, Javier Lopez-Jimenez
Journal: Blood (2011)
Predictors of Survival in CLL: Multivariate Analyses Reveal Significant Correlation with IgVH Gene Mutation Status, Clinical Stage, and Cellular CD38 (but Not Zap-70) Expression.
Authors: Alicia D. Volkheimer, Marc C. Levesque, Bethany E. Beasley, Louis Diehl, Youwei Chen, Gina Vaccaro, Carlos DeCastro, David Rizzieri, Jon P. Gockerman, Joseph O. Moore, J. Brice Weinberg
Journal: Blood (2005)
The impact of high-intensity conditioning prior to allogeneic stem cell transplantation in patients with chemorefractory or relapsed T-cell lymphoma.
Authors: B. Glass, J. Hasenkamp, W. Jung, C. Wilhelm, G. Held, M. Nickelsen, M. Pfreundschuh, N. Schmitz, L. H. Truemper, G. Wulf
Journal: Journal of Clinical Oncology (2011)

8040 Background: Patients with relapsed T-cell lymphoma carry a particularly dismal prognosis. Optimal therapeutic strategies are yet to be defined. However, emerging evidence suggests a pivotal role of allogeneic stem cell transplantation in this situation. Methods: Between 2003 and 2011, allogeneic peripheral blood stem cell transplantation (PBSCT) from matched related (MRD, n=23) and matched unrelated (MUD, n=33) donors had been provided to 66 consecutive patients with refractory or relapsed aggressive T-cell malignancies, comprising cases of peripheral T-cell lymphomas not otherwise specified (PTCL NOS, n= 23), PTCL AILT (n=12), anaplastic large cell lymphoma (ALCL, n= 11), T-lymphoblastic lymphoma (T-LBL, n=6), T-prolymphocyctic leukemia (T-PLL, n=7), CD4+/CD56+ blastic plasmacytoid DC neoplasm (DPCL, n=2), panniculitis like T-cell lymphoma (PLTCL, n=3), systemic progression of primary cutaneous T-cell lymphoma (CTCL, n=1) and NK/T-cell lymphoma (n=1). Preparatory therapy consisted of high intensity conditioning, mainly consisting of the FBC-12 regimen (fludarabine 125 mg/m2, busulfan 12 or 8 mg/kg, cyclophosphamide 120 mg/kg). Results: Transplantion related mortality at day 100 occurred in 19/66 (29%) patients (pts). After a median observation of 12 (range 1 to 86) months, 48% and 46% pts were alive and disease-free, respectively. Ten pts experiencing disease relapse after allogeneic stem cell transplantation received donor lymphocyte infusions, resulting in complete remission in 5 pts, partial remission in one pt and progressive disease in 4 pts. DLI was associated with GvHD in all pts, leading to GvHD-associated deaths in CR in two pts. Three pts with relapse after allogeneic SCT achieved long-term remissions (> 12 months) by DLI. Conclusions: We conclude that allogeneic PBSCT following high-intensity conditioning induces durable disease remission in significant proportions of patients with relapsed or refractory aggressive T-cell malignancies. Post transplantation DLI may contribute to disease control, albeit at risk of severe GvHD.
Patterns of second-line chemotherapy for metastatic prostate cancer in the United States.
Authors: Hongwei Wang, Laura Liao, Eliot Obi-Tabot, Robert Sands, Mathieu Rose, Quanwu Zhang
Journal: Journal of Clinical Oncology (2012)

e15193 Background: Patients with prostate cancer progressing from first-line (1L) docetaxel have limited approved treatment options available. Study is to evaluate patterns of second-line (2L) chemotherapy in a US managed care between 2004 and 2010. Methods: Patients with metastatic prostate cancer (mPC) and treated with docetaxel as 1L chemotherapy after July 1, 2004 were ascertained from the OptumInsight database. We evaluated type and timing of chemotherapy and relationships between patient characteristics, physician specialty, healthcare costs and geographic region, 6 months prior to 1L docetaxel and choice of 2L chemotherapy. Results: Patients (N=1,173) were on average 71 yrs old at onset of 1L docetaxel. During a mean follow-up period of 18 months, 38% of patients received 2L treatment. Out of the patients received 2L therapy, 32% received mitoxantrone (MITO), 24% with docetaxel rechallenge (RECH), 14% carboplatin (CARB), and 12% paclitaxel (PAC), plus 11% on Combo therapy. Examination of the 2L treatment groups showed that during the 6 months prior to 1L docetaxel, the RECH group (n=101) was older (73yrs), had fewer hospital admissions (12%), lower comorbidity burden [Charlson Comorbidity Index (CCI)=7.4], lower total healthcare costs ($10,083), and 78% seeing an oncologist; relative to MITO group (n=143) with 70 yrs, 16% hospital admissions, CCI of 7.5, total healthcare costs of $12,074, and 80% seeing an oncologist. The combo group (n=52) was 66 years old, with 19% hospital admissions, CCI of 8, total healthcare costs of $20,505, and 92% seeing an oncologist. Median time to MITO from the start of 1L docetaxel was 184 days, 309 days to RECH and 223 days to Combo therapy. Midwest (36%) and West (37%) were more frequently using MITO than Northeast (26%) and South (31%), while RECH was more frequently used in Northeast. Conclusions: Patients with mPC in US were most frequently treated with MITO or RECH as 2L chemotherapy after 1L docetaxel. MITO was also given sooner than RECH, hence a valid comparator for comparative effectiveness evaluation on new 2L therapy. Rechallenge with docetaxel increased with time and was given to patients with lower disease burden and healthcare costs than the MITO or Combo group.
Phase 2 Randomized Trial Comparing 6 Cycles of Standard RCHOP Chemotherapy Vs 6 Cycles of Brcap (bortezomib, rituximab, cyclophosphamide, adriamicine and prednisone) As First Line Treatment in Young Patients with Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL): Interim Analysis
Authors: Eva González-Barca, Estrella Carrillo, Carlos Grande, Alejandro Martín, Mónica Coronado, Santiago Montes-Moreno, Jaime Perez de Oteyza, Concepción Nicolas, Juan-Manuel Sancho, Luis Palomera, Javier Lopez, Armando Lopez-Guillermo, Francisco Javier Peñalver, José Ángel Hernández, Maria Jose Ramirez, Isidro Jarque, Joan Bargay, Mª José Rodríguez, Miguel Canales, Carmen Albo, Maite Encuentra, Dolores Caballero
Journal: Blood (2015)
Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake in Photodynamic Therapy
Authors: Christiane Bay, Catharina Margrethe Lerche, Bradford Ferrick, Peter Alshede Philipsen, Katrine Togsverd-Bo, Merete Haedersdal
Journal: JAMA Dermatology (2017)

Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT).To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence in normal skin.This intraindividual, randomized clinical trial was performed from November 28 to December 20, 2014, at Bispebjerg Hospital, Copenhagen, Denmark, among 12 healthy volunteers 18 years or older. Analysis was based on intention to treat. All participants completed the study protocol.Participants were each exposed to standardized skin preparation with curettage, microdermabrasion with abrasive pads, microneedling with dermarollers, ablative fractional laser (AFXL), non-AFXL, and no pretreatment, followed by 3 hours of methyl aminolevulinate hydrochloride incubation and subsequent red light illumination.The primary outcome measure was methyl aminolevulinate-induced PPIX fluorescence accumulation. Secondary outcome measures were PPIX photobleaching and clinical local skin reactions, supported by noninvasive reflectance measurements of percentage of skin redness, transepidermal water loss, and participant-assessed pain.Among the 12 healthy study participants (8 men; 4 women; mean [SD] age, 33 [15] years), histologic findings confirmed standardization of interventions with partial removal of the stratum corneum after curettage and microdermabrasion and similar vertical penetration depths for microneedling, AFXL, and non-AFXL (median, 125 μm). PPIX fluorescence reached highest intensities in skin pretreated with AFXL (median, 8661 arbitrary units [AU]) compared with microdermabrasion (median, 6731 AU), microneedling (median, 5609 AU), and curettage (median, 4765 AU) (P < .001), among which similar enhancement was shown. Comparatively lower fluorescence levels were demonstrated for skin pretreated with non-AFXL (median, 2898 AU), methyl aminolevulinate-treated controls (median, 2254 AU), and untreated controls (median, 239 AU) (P < .03). Increasing laser densities (2% vs 4% vs 6%) and the number of pretreatment passes (1, 2, and 3 passes) did not enhance PPIX fluorescence. Local skin reactions were most intensified in AFXL-pretreated skin and correlated with PPIX fluorescence and degree of PPIX photobleaching.Under standardized conditions, PPIX accumulation was most enhanced after AFXL pretreatment, followed by microdermabrasion, microneedling, and curettage. Increasing the number of pretreatment passes and laser densities did not further augment PPIX accumulation. These results may indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin.clinicaltrials.gov Identifier: NCT02372370.
Partitioning the heritability of coronary artery disease highlights the importance of immune-mediated processes and epigenetic sites associated with transcriptional activity
Authors: Majid Nikpay, Alexandre F.R. Stewart, Ruth McPherson
Journal: Cardiovascular Research (2017)

With the availability of genome-wide genotype data from GWAS studies, it is now possible to compute the genetic relatedness among individuals and estimate its contribution (SNP-based heritability) to phenotypic variance using Mixed-Linear-Models (MLMs). The estimated heritability can be partitioned according to biological features to gain insight into the genetic architecture of a disease. Here, we aimed to examine the genetic structure of coronary artery disease (CAD).We investigated the genetic structure of CAD using 3,163,082 autosomal genome-wide SNPs (MAF ≥ 0.01) and MLMs in a sample of genetically 'unrelated' 4535 cases and 2977 controls. We find that genome-wide SNPs explain 22% of liability to CAD (55% of narrow-sense heritability) and sex-differences in CAD is not due to common SNPs on autosomal chromosomes. Heritability was proportionally distributed across the allele frequency spectrum and notably enriched among genic SNPs. We identified a number of modules that are significantly associated with CAD including: Dendritic cells stimulation; Basigin interactions; and a Cancer module. Of note, genes involved in inflammation account for one-fifth of SNP-based heritability. Heritability-enrichment analysis showed significant enrichment in epigenetic sites associated with transcriptionally activity; namely, enhancers, H3K9ac/H3K27ac/H3K4me1/H3K4me3 histone modifications, and Fetal DNase I hypersensitivity sites whereas heritability was highly depleted in transcriptionally repressed regions.More individual SNP associations will be detected for CAD as sample size increases. The identified modules provide further biological insight for CAD and highlight the importance of immune-mediated processes in CAD pathogenesis. Finally, we showed that genetic liability to CAD is mainly attributed to epigenetic sites associated with transcriptional activity which encourage the design of custom sequencing/genotyping panels based on transcriptionally active regions.
Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arthritis
Authors: Jonathan J. Miner, Lindsey E. Cook, Jun P. Hong, Amber M. Smith, Justin M. Richner, Raeann M. Shimak, Alissa R. Young, Kristen Monte, Subhajit Poddar, James E. Crowe, Deborah J. Lenschow, Michael S. Diamond
Journal: Science Translational Medicine (2017)

Combination therapy with CTLA4-Ig and an antiviral human monoclonal antibody controls chikungunya virus arthritis in mice.
Trump’s immigration ban triggers call for boycott of US conferences
Authors: Michael McCarthy
Journal: BMJ (2017)

Nearly 6000 academics from across the world have signed a pledge1 to boycott conferences in the US to protest against president Donald Trump’s executive order2 banning citizens of seven Muslim majority countries from entering the US for 90 days.

The boycotters said that the order “institutionalizes racism, and fosters an environment in which people racialized as Muslim are vulnerable to ongoing and intensifying acts of violence and hatred.” Those affected include students and academics who will no longer be able to travel to US conferences. The boycotters said, “We question the intellectual integrity of these spaces and the dialogues they are designed to encourage while Muslim colleagues are explicitly excluded from them.”

Nadine …