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Hmgb1 In Health And Disease, R. Kang, R. C. Chen, Q. H. Zhang, W. Hou, S. Wu, X. G. Fan, Z. W. Yan, X. F. Sun, H. C. Wang, D. L. Tang, +8 Additional Authors Jan 2014

Hmgb1 In Health And Disease, R. Kang, R. C. Chen, Q. H. Zhang, W. Hou, S. Wu, X. G. Fan, Z. W. Yan, X. F. Sun, H. C. Wang, D. L. Tang, +8 Additional Authors

Journal Articles

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed high-mobility group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG …

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Gender Differences In Acute And Chronic Pain In The Emergency Department: Results Of The 2014 Academic Emergency Medicine Consensus Conference Pain Section, P. I. Musey, S. D. Linnstaedt, T. F. Platts-Mills, J. R. Miner, A. V. Bortsov, D. C. Lee, C. S. Nam, R. G. Patel, R. B. Fillingim, S. A. Mclean, +12 Additional Authors Jan 2014

Gender Differences In Acute And Chronic Pain In The Emergency Department: Results Of The 2014 Academic Emergency Medicine Consensus Conference Pain Section, P. I. Musey, S. D. Linnstaedt, T. F. Platts-Mills, J. R. Miner, A. V. Bortsov, D. C. Lee, C. S. Nam, R. G. Patel, R. B. Fillingim, S. A. Mclean, +12 Additional Authors

Journal Articles

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine …

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No Man Is An Island: Living In A Disadvantaged Neighborhood Influences Chronic Pain Development After Motor Vehicle Collision, J. C. Ulirsch, M. A. Weaver, A. V. Bortsov, A. C. Soward, R. A. Swor, D. A. Peak, J. S. Jones, N. K. Rathlev, D. C. Lee, S. A. Mclean, +2 Additional Authors Jan 2014

No Man Is An Island: Living In A Disadvantaged Neighborhood Influences Chronic Pain Development After Motor Vehicle Collision, J. C. Ulirsch, M. A. Weaver, A. V. Bortsov, A. C. Soward, R. A. Swor, D. A. Peak, J. S. Jones, N. K. Rathlev, D. C. Lee, S. A. Mclean, +2 Additional Authors

Journal Articles

Living in a lower socioeconomic status neighborhood has been shown to alter stress system function and is associated with a number of adverse health outcomes, but its influence on musculoskeletal pain (MSP) outcomes after traumatic stress exposures such as motor vehicle collision (MVC) has not been assessed. We performed a multicenter, prospective study that enrolled 948 European-American individuals within 24 hours of MVC who were discharged home after emergency department evaluation. Follow-up evaluations were completed via telephone or Internet survey 6 weeks, 6 months, and 1 year after MVC on 91%, 89%, and 91% of participants, respectively. A robust aggregate …

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Targeting Hmgb1 In The Treatment Of Sepsis, H. C. Wang, M. F. Ward, A. E. Sama Jan 2014

Targeting Hmgb1 In The Treatment Of Sepsis, H. C. Wang, M. F. Ward, A. E. Sama

Journal Articles

Introduction: Sepsis refers to the host's deleterious and non-resolving systemic inflammatory response to microbial infections and represents the leading cause of death in the intensive care unit. The pathogenesis of sepsis is complex, but partly mediated by a newly identified alarmin molecule, the high mobility group box 1 (HMGB1). Areas covered: Here we review the evidence that support extracellular HMGB1 as a late mediator of experimental sepsis with a wider therapeutic window and discuss the therapeutic potential of HMGB1-neutralizing antibodies and small molecule inhibitors (herbal components) in experimental sepsis. Expert opinion: It will be important to evaluate the efficacy of …

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Pkm2 Regulates The Warburg Effect And Promotes Hmgb1 Release In Sepsis, L. C. Yang, M. Xie, M. H. Yang, Y. Yu, S. Zhu, M. T. Lotze, T. R. Billiar, H. C. Wang, L. Z. Cao, D. L. Tang, +2 Additional Authors Jan 2014

Pkm2 Regulates The Warburg Effect And Promotes Hmgb1 Release In Sepsis, L. C. Yang, M. Xie, M. H. Yang, Y. Yu, S. Zhu, M. T. Lotze, T. R. Billiar, H. C. Wang, L. Z. Cao, D. L. Tang, +2 Additional Authors

Journal Articles

Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high-mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1 alpha (HIF1 alpha) and activates the HIF-1 alpha-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1 alpha and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate …

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Intraperitoneal Administration Of Fetuin-A Attenuates D-Galactosamine/Lipopolysaccharide-Induced Liver Failure In Mouse, P. Zhang, H. Shen, J. L. Huang, H. C. Wang, B. X. Zhang, R. R. Zhou, B. Y. Zhong, X. G. Fan Jan 2014

Intraperitoneal Administration Of Fetuin-A Attenuates D-Galactosamine/Lipopolysaccharide-Induced Liver Failure In Mouse, P. Zhang, H. Shen, J. L. Huang, H. C. Wang, B. X. Zhang, R. R. Zhou, B. Y. Zhong, X. G. Fan

Journal Articles

Fulminant hepatic failure (FHF) is a devastating syndrome, which sometimes results in death or liver transplantation, in which inflammation would aggravate the development of fetuin-A which would act as an anti-inflammatory factor and may be an available approach to attenuate FHF. The purpose of this study was to investigate the effects of fetuin-A on d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced liver failure in mice. A mouse model of FHF induced by d-GalN/LPS was established and fetuin-A was injected intraperitoneally prior to d-GalN/LPS treatment. At different time points after d-GalN/LPS intervention, serum TNF-alpha and IL-6 levels were measured by ELISA. Fetuin-A mRNA and protein expression …

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Clozapine-Induced Agranulocytosis Is Associated With Rare Hla-Dqb1 And Hla-B Alleles, J. I. Goldstein, L. F. Jarskog, C. Hilliard, A. Alfirevic, H. L. Huang, M. Lek, A. L. Holden, D. L. Kelly, A. K. Malhotra, P. F. Sullivan, +21 Additional Authors Jan 2014

Clozapine-Induced Agranulocytosis Is Associated With Rare Hla-Dqb1 And Hla-B Alleles, J. I. Goldstein, L. F. Jarskog, C. Hilliard, A. Alfirevic, H. L. Huang, M. Lek, A. L. Holden, D. L. Kelly, A. K. Malhotra, P. F. Sullivan, +21 Additional Authors

Journal Articles

Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genomewide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P = 4.7 x 10(-14), odds ratio …

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Schizophrenia Relapse After Stopping Olanzapine Treatment During Pregnancy: A Case Report, P. Ifteni, M. A. Moga, V. Burtea, C. U. Correll Jan 2014

Schizophrenia Relapse After Stopping Olanzapine Treatment During Pregnancy: A Case Report, P. Ifteni, M. A. Moga, V. Burtea, C. U. Correll

Journal Articles

Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnancy and thereafter. Relapses are more frequent when antipsychotics are discontinued. This paper describes the case of a 28-year old woman with schizophrenia who continued treatment with olanzapine during the first trimester. Olanzapine, a second-generation antipsychotic, was administered at a therapeutic dose from week 1 of gestation until week 13 when she reported the pregnancy to her psychiatrist. Despite the psychiatrist's recommendation to continue treatment, the patient stopped olanzapine at 20 weeks. She was hospitalized at week 36 for a schizophrenia relapse and was transferred to the …

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Molecular Genetic Evidence For Overlap Between General Cognitive Ability And Risk For Schizophrenia: A Report From The Cognitive Genomics Consortium (Cogent), T. Lencz, E. Knowles, G. Davies, S. Guha, D. C. Liewald, J. M. Starr, S. Djurovic, I. Melle, K. Sundet, A. Christoforou, I. Reinvang, S. Mukherjee, P. Derosse, A. Lundervold, V. M. Steen, M. John, T. Espeseth, K. Raikkonen, E. Widen, A. Palotie, J. G. Eriksson, I. Giegling, B. Konte, M. Ikeda, P. Roussos, S. Giakoumaki, K. E. Burdick, A. Payton, W. Ollier, M. Horan, G. Donohoe, D. Morris, A. Corvin, M. Gill, N. Pendleton, N. Iwata, A. Darvasi, P. Bitsios, D. Rujescu, J. Lahti, S. L. Hellard, M. C. Keller, O. A. Andreassen, I. J. Deary, D. C. Glahn, Anil Malhotra Jan 2014

Molecular Genetic Evidence For Overlap Between General Cognitive Ability And Risk For Schizophrenia: A Report From The Cognitive Genomics Consortium (Cogent), T. Lencz, E. Knowles, G. Davies, S. Guha, D. C. Liewald, J. M. Starr, S. Djurovic, I. Melle, K. Sundet, A. Christoforou, I. Reinvang, S. Mukherjee, P. Derosse, A. Lundervold, V. M. Steen, M. John, T. Espeseth, K. Raikkonen, E. Widen, A. Palotie, J. G. Eriksson, I. Giegling, B. Konte, M. Ikeda, P. Roussos, S. Giakoumaki, K. E. Burdick, A. Payton, W. Ollier, M. Horan, G. Donohoe, D. Morris, A. Corvin, M. Gill, N. Pendleton, N. Iwata, A. Darvasi, P. Bitsios, D. Rujescu, J. Lahti, S. L. Hellard, M. C. Keller, O. A. Andreassen, I. J. Deary, D. C. Glahn, Anil Malhotra

Journal Articles

It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of …

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The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith Jan 2014

The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith

Journal Articles

Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer's disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n = 16) was correlated with PET scans of cerebral glucose metabolism …

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Copy Number Variation In Obsessive-Compulsive Disorder And Tourette Syndrome: A Cross-Disorder Study, L. M. Mcgrath, D. M. Yu, C. Marshall, L. K. Davis, B. Thiruvahindrapuram, B. B. Li, C. Cappi, R. D. Bruun, Cathy Budman, J. M. Scharf, +112 Additional Authors Jan 2014

Copy Number Variation In Obsessive-Compulsive Disorder And Tourette Syndrome: A Cross-Disorder Study, L. M. Mcgrath, D. M. Yu, C. Marshall, L. K. Davis, B. Thiruvahindrapuram, B. B. Li, C. Cappi, R. D. Bruun, Cathy Budman, J. M. Scharf, +112 Additional Authors

Journal Articles

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (

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Biological Insights From 108 Schizophrenia-Associated Genetic Loci, S. Ripke, B. M. Neale, A. Corvin, J. T. R. Walters, K. H. Farh, T. Lencz, A. K. Malhotra, Consortium Psychiat Genomics, Conso Psychosis Endophenotypes Int, Consor Wellcome Trust Case-Control, +292 Additional Authors Jan 2014

Biological Insights From 108 Schizophrenia-Associated Genetic Loci, S. Ripke, B. M. Neale, A. Corvin, J. T. R. Walters, K. H. Farh, T. Lencz, A. K. Malhotra, Consortium Psychiat Genomics, Conso Psychosis Endophenotypes Int, Consor Wellcome Trust Case-Control, +292 Additional Authors

Journal Articles

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and …

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Default Mode Network Connectivity And Reciprocal Social Behavior In 22q11.2 Deletion Syndrome, M. J. Schreiner, K. H. Karlsgodt, L. Q. Uddin, C. Chow, E. Congdon, M. Jalbrzikowski, C. E. Bearden Jan 2014

Default Mode Network Connectivity And Reciprocal Social Behavior In 22q11.2 Deletion Syndrome, M. J. Schreiner, K. H. Karlsgodt, L. Q. Uddin, C. Chow, E. Congdon, M. Jalbrzikowski, C. E. Bearden

Journal Articles

22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and …

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Aggression In Schizophrenia And Its Relationship To Neural Circuitry Of Urgency, P. Szeszko Jan 2014

Aggression In Schizophrenia And Its Relationship To Neural Circuitry Of Urgency, P. Szeszko

Journal Articles

No abstract provided.

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Functional Development In Clinical High Risk Youth: Prediction Of Schizophrenia Versus Other Psychotic Disorders, S. I. Tarbox, J. Addington, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, D. O. Perkins, L. J. Seidman, M. T. Tsuang, E. F. Walker, S. W. Woods, +2 Additional Authors Jan 2014

Functional Development In Clinical High Risk Youth: Prediction Of Schizophrenia Versus Other Psychotic Disorders, S. I. Tarbox, J. Addington, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, D. O. Perkins, L. J. Seidman, M. T. Tsuang, E. F. Walker, S. W. Woods, +2 Additional Authors

Journal Articles

This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early …

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Stress Exposure And Sensitivity In The Clinical High-Risk Syndrome: Initial Findings From The North American Prodrome Longitudinal Study (Napls), H. D. Trotman, C. W. Holtzman, E. F. Walker, J. M. Addington, C. E. Bearden, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, R. K. Heinssen, T. H. Mcglashan, +5 Additional Authors Jan 2014

Stress Exposure And Sensitivity In The Clinical High-Risk Syndrome: Initial Findings From The North American Prodrome Longitudinal Study (Napls), H. D. Trotman, C. W. Holtzman, E. F. Walker, J. M. Addington, C. E. Bearden, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, R. K. Heinssen, T. H. Mcglashan, +5 Additional Authors

Journal Articles

There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with …

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Moderator Effects Of Working Memory On The Stability Of Adhd Symptoms By Dopamine Receptor Gene Polymorphisms During Development, J. Trampush, M. M. Jacobs, Y. L. Hurd, J. H. Newcorn, J. M. Halperin Jan 2014

Moderator Effects Of Working Memory On The Stability Of Adhd Symptoms By Dopamine Receptor Gene Polymorphisms During Development, J. Trampush, M. M. Jacobs, Y. L. Hurd, J. H. Newcorn, J. M. Halperin

Journal Articles

We tested the hypothesis that dopamine D1 and D2 receptor gene (DRD1 and DRD2, respectively) polymorphisms and the development of working memory skills can interact to influence symptom change over 10 years in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, we examined whether improvements in working memory maintenance and manipulation from childhood to early adulthood predicted the reduction of ADHD symptoms as a function of allelic variation in DRD1 and DRD2. Participants were 76 7-11-year-old children with ADHD who were genotyped and prospectively followed for almost 10 years. ADHD symptoms were rated using the Attention Problems scale on the Child Behavior …

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Rdocs Redux, D. R. Weinberger, T. Goldberg Jan 2014

Rdocs Redux, D. R. Weinberger, T. Goldberg

Journal Articles

No abstract provided.

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Effect Of Graft Choice On The Outcome Of Revision Anterior Cruciate Ligament Reconstruction In The Multicenter Acl Revision Study (Mars) Cohort, R. W. Wright, L. J. Huston, A. K. Haas, K. P. Spindler, S. K. Nwosu, C. R. Allen, A. F. Anderson, D. E. Cooper, E. B. Hershman, J. J. York, +83 Additional Authors Jan 2014

Effect Of Graft Choice On The Outcome Of Revision Anterior Cruciate Ligament Reconstruction In The Multicenter Acl Revision Study (Mars) Cohort, R. W. Wright, L. J. Huston, A. K. Haas, K. P. Spindler, S. K. Nwosu, C. R. Allen, A. F. Anderson, D. E. Cooper, E. B. Hershman, J. J. York, +83 Additional Authors

Journal Articles

Background: Most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome; however, graft choice for revision may be limited due to previously used grafts. Hypotheses: Autograft use would result in increased sports function, increased activity level, and decreased osteoarthritis symptoms (as measured by validated patient-reported outcome instruments). Autograft use would result in decreased graft failure and reoperation rate 2 years after revision ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons at 52 sites. Data collected …

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Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior For Patlak Model, R. Fang, K. Karlsson, T. Chen, P. C. Sanelli Jan 2014

Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior For Patlak Model, R. Fang, K. Karlsson, T. Chen, P. C. Sanelli

Journal Articles

Blood-brain barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- …

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White Matter Involvement In Chronic Musculoskeletal Pain, G. Lieberman, M. Shpaner, R. Watts, T. Andrews, C. G. Filippi, M. Davis, M. R. Naylor Jan 2014

White Matter Involvement In Chronic Musculoskeletal Pain, G. Lieberman, M. Shpaner, R. Watts, T. Andrews, C. G. Filippi, M. Davis, M. R. Naylor

Journal Articles

There is emerging evidence that chronic musculoskeletal pain is associated with anatomic and functional abnormalities in gray matter. However, little research has investigated the relationship between chronic musculoskeletal pain and white matter. In this study, we used whole-brain tract-based spatial statistics and region-of-interest analyses of diffusion tensor imaging data to demonstrate that patients with chronic musculoskeletal pain exhibit several abnormal metrics of white matter integrity compared with healthy controls. Chronic musculoskeletal pain was associated with lower fractional anisotropy in the splenium of the corpus callosum and the left cingulum adjacent to the hippocampus. Patients also had higher radial diffusivity in …

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Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation Ii: Rationale And Design Of The Orbit-Af Ii Registry, B. A. Steinberg, R. G. Blanco, D. Ollis, S. Kim, D. N. Holmes, P. R. Kowey, G. C. Fonarow, J. Ansell, B. Gersh, J. P. Piccini, +6 Additional Authors Jan 2014

Outcomes Registry For Better Informed Treatment Of Atrial Fibrillation Ii: Rationale And Design Of The Orbit-Af Ii Registry, B. A. Steinberg, R. G. Blanco, D. Ollis, S. Kim, D. N. Holmes, P. R. Kowey, G. C. Fonarow, J. Ansell, B. Gersh, J. P. Piccini, +6 Additional Authors

Journal Articles

Background Recent clinical trials have demonstrated the safety and efficacy of several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC. Methods/Design ORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to …

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Phase 2 Trial Of Cpx-351, A Fixed 5:1 Molar Ratio Of Cytarabine/Daunorubicin, Vs Cytarabine/Daunorubicin In Older Adults With Untreated Aml, J. E. Lancet, J. E. Cortes, D. E. Hogge, M. S. Tallman, T. J. Kovacsovics, L. E. Damon, R. Komrokji, S. R. Solomon, J. E. Kolitz, E. J. Feldman, +3 Additional Authors Jan 2014

Phase 2 Trial Of Cpx-351, A Fixed 5:1 Molar Ratio Of Cytarabine/Daunorubicin, Vs Cytarabine/Daunorubicin In Older Adults With Untreated Aml, J. E. Lancet, J. E. Cortes, D. E. Hogge, M. S. Tallman, T. J. Kovacsovics, L. E. Damon, R. Komrokji, S. R. Solomon, J. E. Kolitz, E. J. Feldman, +3 Additional Authors

Journal Articles

CPX-351 is a liposomal formulation of cytarabine: daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2: 1 to first-line CPX-351 or 713 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission 1 incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs …

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Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors Jan 2014

Prognostic And Biologic Significance Of Dnmt3b Expression In Older Patients With Cytogenetically Normal Primary Acute Myeloid Leukemia, C. Niederwieser, J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. K. Eisfeld, K. Maharry, P. Yan, J. E. Kolitz, C. D. Bloomfield, +17 Additional Authors

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DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall …

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Prognostic Gene Mutations And Distinct Gene- And Microrna-Expression Signatures In Acute Myeloid Leukemia With A Sole Trisomy 8, H. Becker, K. Maharry, K. Mrozek, S. Volinia, A. K. Eisfeld, M. D. Radmacher, J. Kohlschmidt, K. H. Metzeler, J. E. Kolitz, C. D. Bloomfield, +14 Additional Authors Jan 2014

Prognostic Gene Mutations And Distinct Gene- And Microrna-Expression Signatures In Acute Myeloid Leukemia With A Sole Trisomy 8, H. Becker, K. Maharry, K. Mrozek, S. Volinia, A. K. Eisfeld, M. D. Radmacher, J. Kohlschmidt, K. H. Metzeler, J. E. Kolitz, C. D. Bloomfield, +14 Additional Authors

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No abstract provided.

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Recombinant Interleukin-2 In Patients Aged Younger Than 60 Years With Acute Myeloid Leukemia In First Complete Remission, J. E. Kolitz, S. L. George, D. M. Benson, K. Maharry, G. Marcucci, R. Vij, B. L. Powell, S. L. Allen, D. J. Deangelo, Oncology Alliance Clinical Trials, +8 Additional Authors Jan 2014

Recombinant Interleukin-2 In Patients Aged Younger Than 60 Years With Acute Myeloid Leukemia In First Complete Remission, J. E. Kolitz, S. L. George, D. M. Benson, K. Maharry, G. Marcucci, R. Vij, B. L. Powell, S. L. Allen, D. J. Deangelo, Oncology Alliance Clinical Trials, +8 Additional Authors

Journal Articles

BACKGROUNDRecombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells. METHODSIn the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily …

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Treatment Of Lupus Nephritis With Abatacept, A. D. Askanase, M. Byron, L. L. Keyes-Elstein, P. C. Cagnoli, W. J. Mccune, W. W. Chatham, A. Davidson, B. Diamond, M. Mackay, R. Winchester, +24 Additional Authors Jan 2014

Treatment Of Lupus Nephritis With Abatacept, A. D. Askanase, M. Byron, L. L. Keyes-Elstein, P. C. Cagnoli, W. J. Mccune, W. W. Chatham, A. Davidson, B. Diamond, M. Mackay, R. Winchester, +24 Additional Authors

Journal Articles

Objective. To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce "clinical tolerance," defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. Methods. Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. …

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Use Of Methotrexate In Inflammatory Bowel Disease In 2014: A User's Guide, A. Swaminath, R. Taunk, G. Lawlor Jan 2014

Use Of Methotrexate In Inflammatory Bowel Disease In 2014: A User's Guide, A. Swaminath, R. Taunk, G. Lawlor

Journal Articles

Methotrexate has been used an immunomodulator in many autoimmune diseases, including inflammatory bowel disease. However, many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios: (1) steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti-TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD; (6) management of fistulizing disease in CD; and (7) as well as induction and maintenance of remission in ulcerative colitis. …

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Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors Jan 2014

Validation Of Zap-70 Methylation And Its Relative Significance In Predicting Outcome In Chronic Lymphocytic Leukemia, R. Claus, D. M. Lucas, A. S. Ruppert, K. E. Williams, D. Weng, K. Patterson, M. Zucknick, J. C. Barrientos, K. R. Rai, J. C. Byrd, +13 Additional Authors

Journal Articles

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL.

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Animal Models Of In Utero Exposure To A High Fat Diet: A Review, L. Williams, Y. Seki, P. M. Vuguin, M. J. Charron Jan 2014

Animal Models Of In Utero Exposure To A High Fat Diet: A Review, L. Williams, Y. Seki, P. M. Vuguin, M. J. Charron

Journal Articles

The incidence of metabolic disease, including type 2 diabetes and obesity, has increased to epidemic levels in recent years. A growing body of evidence suggests that the intrauterine environment plays a key role in the development of metabolic disease in offspring. Among other perturbations in early life, alteration in the provision of nutrients has profound and lasting effects on the long term health and well being of offspring. Rodent and non-human primate models provide a means to understand the underlying mechanisms of this programming effect. These different models demonstrate converging effects of a maternal high fat diet on insulin and …

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