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Clinical pathway diagnostic test

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https://www.readbyqxmd.com/read/28428191/the-role-of-minimal-residual-disease-testing-in-myeloma-treatment-selection-and-drug-development-current-value-and-future-applications
#1
Kenneth C Anderson, Daniel Auclair, Gary J Kelloff, Caroline C Sigman, Herve Avet-Loiseau, Ann T Farrell, Nicole J Gormley, Shaji K Kumar, Ola Landgren, Nikhil C Munshi, Michele Cavo, Faith E Davies, Alessandra Di Bacco, Jennifer S Dickey, Steven I Gutman, Howard R Higley, Mohamad A Hussein, J Milburn Jessup, Ilan R Kirsch, Richard F Little, Robert D Loberg, Jens G Lohr, Lata Mukundan, James L Omel, Trevor J Pugh, Gregory H Reaman, Michael D Robbins, A Kate Sasser, Nancy Valente, Elena Zamagni
Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10(-5)‒10(-6) cells...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28424823/-coma-in-the-emergency-room
#2
M Braun, C J Ploner, T Lindner, M Möckel, W U Schmidt
Coma of unknown origin (CUO) is a frequent unspecific emergency symptom associated with a high mortality. A fast diagnostic work-up is essential given the wide spectrum of underlying diagnoses that are made up of approximately 50% primary central nervous system (CNS) pathologies and approximately 50% extracerebral, almost exclusively internal medical causes. Despite the high mortality associated with this symptom, there are currently no generally accepted management guidelines for adult patients presenting with CUO...
April 19, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28400686/convergence-of-minds-for-better-patient-outcome-in-intensive-care-unit-infections
#3
Chand Wattal, Yash Javeri, Neeraj Goel, Debashish Dhar, Sonal Saxena, Sarman Singh, Jaswinder Kaur Oberoi, B K Rao, Purva Mathur, Vikas Manchanda, Vivek Nangia, Arti Kapil, Ashok Rattan, Supradip Ghosh, Omender Singh, Vinod Singh, Iqbal Kaur, Sanghamitra Datta, Sharmila Sen Gupta
BACKGROUND: There is emergence of resistance to the last-line antibiotics such as carbapenems in Intensive Care Units (ICUs), leaving little effective therapeutic options. Since there are no more newer antibiotics in the armamentarium in the near future, it has become imperative that we harness the interdisciplinary knowledge for the best clinical outcome of the patient. AIMS: The aim of the conference was to utilize the synergies between the clinical microbiologists and critical care specialists for better patient care and clinical outcome...
March 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28394042/metabolic-profiling-of-parkinson-s-disease-and-mild-cognitive-impairment
#4
Florence Burté, David Houghton, Hannah Lowes, Angela Pyle, Sarah Nesbitt, Alison Yarnall, Patrick Yu-Wai-Man, David J Burn, Mauro Santibanez-Koref, Gavin Hudson
BACKGROUND: Early diagnosis of Parkinson's disease and mild cognitive impairment is important to enable prompt treatment and improve patient welfare, yet no standard diagnostic test is available. Metabolomics is a powerful tool used to elucidate disease mechanisms and identify potential biomarkers. OBJECTIVES: The objective of this study was to use metabolic profiling to understand the pathoetiology of Parkinson's disease and to identify potential disease biomarkers...
April 10, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28388299/innovation-analysis-on-postgenomic-biomarkers-glycomics-for-chronic-diseases
#5
Eric Adua, Alyce Russell, Peter Roberts, Youxin Wang, Manshu Song, Wei Wang
Despite decades of investment in biomarker research, we still do not have robust and field-tested biomarkers for many chronic diseases so as to anticipate clinical outcomes and thus move toward personalized medicine. Biomarker innovations have tended to focus on genomics, but next-generation biomarkers from the nascent field of glycomics now offer fresh vistas for innovation in chronic disease biomarkers and systems diagnostics. Glycosylation, regarded as a complex enzymatic process where sugars (glycans) bind to proteins and lipids, affects many human biological functions, including cell signaling, adhesion, and motility...
April 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28388234/variable-heavy-chain-domain-derived-from-a-cell-penetrating-anti-dna-monoclonal-antibody-for-the-intracellular-delivery-of-biomolecules
#6
Sun-Woo Im, Pavithra Pravinsagar, Sae-Ran Im, Young-Ju Jang
Targeting and modification of important intracellular proteins using efficient vehicles are invaluable in diagnostic and therapeutic fields. Cell-penetrating antibodies and their fragments can be utilized as vehicles for the delivery of modifiers into cells. In this study, we explored the applicability of variable heavy chain (VH) domain as delivery vehicles for mammalian cells. The characteristics of the recombinant VH domain produced from a cell-penetrating monoclonal anti-double stranded DNA antibody 2C10 were analyzed using flow cytometry, confocal microscopy, cell proliferation assay, and cell cycle analysis in various mammalian cell lines...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28379183/rapid-identification-of-pathogenic-variants-in-two-cases-of-charcot-marie-tooth-disease-by-gene-panel-sequencing
#7
Chi-Chun Ho, Shuk-Mui Tai, Edmond Chi-Nam Lee, Timothy Shin-Heng Mak, Timothy Kam-Tim Liu, Victor Wai-Lun Tang, Wing-Tat Poon
Charcot-Marie-Tooth disease (CMT) is a common inherited peripheral neuropathy affecting up to 1 in 1214 of the general population with more than 60 nuclear genes implicated in its pathogenesis. Traditional molecular diagnostic pathways based on relative prevalence and clinical phenotyping are limited by long turnaround time, population-specific prevalence of causative variants and inability to assess multiple co-existing variants. In this study, a CMT gene panel comprising 27 genes was used to uncover the pathogenic mutations in two index patients...
April 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28378453/lmplementation-of-the-prolyl-hydroxylase-inhibitor-roxadustat-fg-4592-and-its-main-metabolites-into-routine-doping-controls
#8
Daniel Eichner, Ryan M Van Wagoner, Mitch Brenner, James Chou, Scott Leigh, Lee R Wright, Lee A Flippin, Michael Martinelli, Oliver Krug, Wilhelm Schänzer, Mario Thevis
The utility of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors as therapeutic means for the treatment of patients suffering from anemia has been demonstrated for various different clinical settings. However, besides this intended use, HIF stabilizers can be the subject of misuse in amateur and elite sports due to their erythropoietic properties as recently proven by several cases of adverse analytical findings in doping control testing. Consequently, in order to allow for adequate and comprehensive test methods, knowledge about the drug candidates' metabolism and analytical options enabling appropriate detection windows in sports drug testing samples (i...
April 4, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28374029/prediction-of-luciferase-inhibitors-by-the-high-performance-miec-gbdt-approach-based-on-interaction-energetic-patterns
#9
Fu Chen, Huiyong Sun, Hui Liu, Dan Li, Youyong Li, Tingjun Hou
High-throughput screening (HTS) is widely applied in many fields ranging from drug discovery to clinical diagnostics and toxicity assessment. Firefly luciferase is commonly used as a reporter to monitor the effect of chemical compounds on the activity of a specific target or pathway in HTS. However, the false positive rate of luciferase-based HTS is relatively high because many artifacts or promiscuous compounds that have direct interaction with the luciferase reporter enzyme are usually identified as active compounds (hits)...
April 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28374027/the-reaction-mechanism-of-sarcosine-oxidase-elucidated-using-fmo-and-qm-mm-methods
#10
Yukihiro Abe, Mitsuo Shoji, Yoshiaki Nishiya, Hiroshi Aiba, Takahide Kishimoto, Kazuo Kitaura
Monomeric sarcosine oxidase (MSOX) is a flavoprotein that oxidizes sarcosine to the corresponding imine product and is widely used in clinical diagnostics to test renal function. In the past decade, several experimental studies have been performed to elucidate the underlying mechanism of this oxidation reaction. However, the details of the molecular mechanism remain unknown. In this study, we theoretically examined three possible reaction mechanisms, namely, the single-electron transfer, hydride-transfer, and polar mechanisms, using the fragment molecular orbital (FMO) and mixed quantum mechanics/molecular mechanics (QM/MM) methods...
April 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28370434/diagnostic-accuracy-of-confocal-microscopy-imaging-versus-punch-biopsy-for-diagnosing-and-subtyping-basal-cell-carcinoma
#11
D J Kadouch, M M Leeflang, Y S Elshot, C Longo, M Ulrich, A C van der Wal, A Wolkerstorfer, M W Bekkenk, M A de Rie
BACKGROUND: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM versus a punch biopsy in diagnosing and subtyping BCC is unknown. OBJECTIVE: To assess diagnostic accuracy of RCM versus punch biopsy for diagnosing and subtyping clinically suspected primary BCC. METHODS: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between February 3, 2015 and October 2, 2015...
April 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28364409/metabolomics-analysis-of-anaphylactoid-reaction-reveals-its-mechanism-in-a-rat-model
#12
Yubin Xu, Na Guo, Deqiang Dou, Xiaoku Ran, Chunyan Liu
BACKGROUND: Anaphylactoid reactions, accounting for more than 77% of all immune-mediated immediate hypersensitivity reactions, have become a serious threat to public health, but their effect mechanism is not clear and diagnostic tests are limited. Comprehensive metabolite analysis may reveal the anaphylactoid effect mechanism systematically and provide reference for future diagnostic purposes. METHODS: Plasma from Brown Norway rats given intravenous injection of saline, compound 48/80 (2...
April 1, 2017: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/28362927/understanding-the-pathophysiology-of-intracranial-aneurysm-the-ican-project
#13
Romain Bourcier, Stéphanie Chatel, Emmanuelle Bourcereau, Solène Jouan, Hervé Le Marec, Benjamin Daumas-Duport, Mathieu Sevin-Allouet, Benoit Guillon, Vincent Roualdes, Tanguy Riem, Bertrand Isidor, Pierre Lebranchu, Jérôme Connault, Thierry Le Tourneau, Alban Gaignard, Gervaise Loirand, Richard Redon, Hubert Desal
BACKGROUND: Understanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA. OBJECTIVE: To develop diagnostic and predictive tools for the risk of IA formation and rupture...
April 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28360039/how-i-treat-autoimmune-hemolytic-anemia
#14
Ronald S Go, Jeffrey L Winters, Neil E Kay
Autoimmune hemolytic anemia (AIHA) is an uncommon entity that presents diagnostic, prognostic and therapeutic dilemmas despite being a well-recognized entity for over 150 years. Because of significant differences in the rates of hemolysis as well as associated diseases and cause there is considerable clinical heterogeneity. In addition there is a lack of clinical trials required to refine and update standardized and evidence-based therapeutic approaches. To aid the clinician in AIHA management we present four vignettes that represent and highlight distinct clinical presentations with separate diagnostic and therapeutic pathways that we utilize in our clinical practice setting...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28341476/panel-based-clinical-genetic-testing-in-85-children-with-inherited-retinal-disease
#15
Rachel L Taylor, Neil R A Parry, Stephanie J Barton, Christopher Campbell, Claire M Delaney, Jamie M Ellingford, Georgina Hall, Claire Hardcastle, Jiten Morarji, Elisabeth J Nichol, Lindsi C Williams, Sofia Douzgou, Jill Clayton-Smith, Simon C Ramsden, Vinod Sharma, Susmito Biswas, I Chris Lloyd, Jane L Ashworth, Graeme C Black, Panagiotis I Sergouniotis
PURPOSE: To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). DESIGN: Single-center retrospective case series. PARTICIPANTS: Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. METHODS: Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate...
March 21, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28333917/a-clinical-utility-study-of-exome-sequencing-versus-conventional-genetic-testing-in-pediatric-neurology
#16
Lisenka E L M Vissers, Kirsten J M van Nimwegen, Jolanda H Schieving, Erik-Jan Kamsteeg, Tjitske Kleefstra, Helger G Yntema, Rolph Pfundt, Gert Jan van der Wilt, Lotte Krabbenborg, Han G Brunner, Simone van der Burg, Janneke Grutters, Joris A Veltman, Michèl A A P Willemsen
PURPOSE: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. METHODS: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin...
March 23, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28302091/development-of-a-test-that-measures-real-time-her2-signaling-function-in-live-breast-cancer-cell-lines-and-primary-cells
#17
Yao Huang, David J Burns, Benjamin E Rich, Ian A MacNeil, Abhijit Dandapat, Sajjad M Soltani, Samantha Myhre, Brian F Sullivan, Carol A Lange, Leo T Furcht, Lance G Laing
BACKGROUND: Approximately 18-20% of all human breast cancers have overexpressed human epidermal growth factor receptor 2 (HER2). Standard clinical practice is to treat only overexpressed HER2 (HER2+) cancers with targeted anti-HER2 therapies. However, recent analyses of clinical trial data have found evidence that HER2-targeted therapies may benefit a sub-group of breast cancer patients with non-overexpressed HER2. This suggests that measurement of other biological factors associated with HER2 cancer, such as HER2 signaling pathway activity, should be considered as an alternative means of identifying patients eligible for HER2 therapies...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28286901/the-effects-of-micrornas-on-glucocorticoid-responsiveness
#18
REVIEW
Huimin Wang, Xuxu Gou, Tang Jiang, Juan Ouyang
PURPOSE: Glucocorticoids (GCs) are of wide usage in the clinical treatment of lymphoblastic malignancies such as acute lymphoblastic leukemia. However, individually distinctive responsiveness to the GC therapy may attenuate their clinical efficacy, and more reliable predictor for GC resistance is still eagerly needed. Recent studies indicate that microRNAs (miRNAs), which demonstrate regulatory functions targeting mRNAs during the post-transcription, involved in the regulation of GCs sensitivity through several mechanisms, especially adjusting the magnitude of GC receptors (GRs), which mediates the cellular effects of GCs and plays a pivotal role in GCs sensitivity, inspiring that special miRNAs pattern could serve as the biomarkers to predict GC sensitivity and bring forth potential strategies for overcoming drug resistance...
March 12, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28284377/treatment-of-renal-fibrosis-turning-challenges-into-opportunities
#19
REVIEW
Barbara M Klinkhammer, Roel Goldschmeding, Jürgen Floege, Peter Boor
Current treatment modalities are not effective in halting the progression of most CKD. Renal fibrosis is a pathological process common to all CKD and thereby represents an excellent treatment target. A large number of molecular pathways involved in renal fibrosis were identified in preclinical studies, some of them being similar among different organs and some with available drugs in various phases of clinical testing. Yet only few clinical trials with antifibrotic drugs are being conducted in CKD patients...
March 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28279782/a-prospective-study-investigating-the-impact-of-multiparametric-mri-in-biopsy-na%C3%A3-ve-patients-with-clinically-suspected-prostate-cancer-the-prokomb-study
#20
Alexander D J Baur, Thomas Henkel, Manfred Johannsen, Thomas Speck, Lothar Weißbach, Bernd Hamm, Frank König
BACKGROUND: In patients with suspected prostate cancer (PCa) according to current guidelines systematic transrectal ultrasound (TRUS)-guided biopsy of the prostate is performed to verify or rule out PCa. However, TRUS-guided biopsy can result in underdetection of clinically significant cancers as well as diagnosis of clinically insignificant cancers. Multiparametric MRI (mpMRI) might improve the diagnostic pathway and help to avoid unnecessary biopsies. DESIGN AND METHODS: The PROKOMB (Prostata - Kooperatives MRT-Projekt Berlin) study is a prospective two-arm multicentre study designed to evaluate the potential role of mpMRI as a triage test before biopsy...
March 6, 2017: Contemporary Clinical Trials
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