Mol Diagn Ther
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Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. ⋯ Finally, homozygous and heterozygous carriers of CYP2C9 variant alleles require lower doses of phenytoin to reach therapeutic plasma concentrations, and are at increased risk of toxicity. New diagnostic techniques made safer and easier should allow quicker diagnosis of metabolic variations. Genotyping and phenotyping may therefore be considered where dosing guidelines according to CYP genotype have been published, and help identify the right molecule for the right patient.
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Calprotectin is potentially a more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase proteins such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because it directly reflects inflammation in the synovium and synovial fluid rather than systemic inflammatory activity. ⋯ Calprotectin levels strongly correlate with clinical and laboratory assessments of joint inflammation and also decrease in response to treatment, indicating that calprotectin is a promising marker for assessment and monitoring of disease activity in patients with RA. Investigations are required to further evaluate its diagnostic, prognostic, and therapeutic potential.
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Acute myocardial infarction (AMI) is the leading cause of death worldwide, with early diagnosis still being difficult. Promising new cardiac biomarkers such as troponins and creatine kinase (CK) isoforms are being studied and integrated into clinical practice for early diagnosis of AMI. ⋯ The introduction of novel high-sensitivity troponin assays has enabled more sensitive and timely diagnosis or exclusion of acute coronary syndromes. This review summarizes the available information on the potential of troponins and other cardiac markers in early diagnosis and prognosis of AMI, and provides perspectives on future diagnostic approaches to AMI.
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The reported association of the leptin receptor (LEPR) protein with hepatocellular carcinoma (HCC) carcinogenesis prompted us to evaluate whether genetic polymorphisms of the LEPR gene affect susceptibility to HCC and its clinicopathologic characteristics. ⋯ The Lys109Arg and Gln223Arg polymorphisms of the LEPR gene are associated with susceptibility to HCC but not with its clinicopathologic features. These polymorphisms may represent genetic markers for the risk of HCC in the context of chronic HBV infection.
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Acute kidney injury (AKI) represents a common disorder in hospitalized patients, and its incidence is rising at an alarming rate. Despite significant improvements in critical care and renal replacement therapies (RRT), the outcome of critically ill patients with AKI necessitating RRT remains unacceptably dismal. In current clinical practice, the diagnosis and severity classification of AKI is based on a rise in serum creatinine levels, which may occur 2-3 days after the initiating renal insult and delay potentially effective therapies that are limited to the early stage. ⋯ Indiscriminate use of various biomarkers may distract clinicians from adequate clinical evaluation, may result in worse instead of better patient outcomes, and may waste money. Future large randomized studies are necessary to demonstrate the association between biomarker levels and clinical outcomes, such as dialysis, clinical events, or death. It needs to be shown whether assignment to earlier treatment for AKI on the basis of generally accepted biomarker cut-off levels results in a reduction in mortality and an improvement in recovery of renal function.