The Diagnostic Utility of the Point-of-Care CYP2C19 Genotyping Assay in Patients with Acute Coronary Syndrome Dosing Clopidogrel: Comparison with Platelet Function Test and SNP Genotyping.

BACKGROUND: Clopidogrel is a widely used antiplatelet agent for dual antiplatelet therapy and metabolized by CYP2C19. The polymorphism of CYP2C19 is associated with the therapeutic effect of clopidogrel. METHODS: A total of 119 patients diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) with drug-eluting stents was enrolled. Polymorphisms of CYP2C19 *2,*3,*17 were determined by the Spartan RX CYP2C19 and confirmed by SNP genotyping assay. Genotype was grouped as ultra-rapid metabolizer, extensive metabolizer, intermediate metabolizer, and poor metabolizer. The degree of platelet inhibition was assessed by the VerifyNow P2Y12 system (Accumetrics, USA). RESULTS: The CYP2C19 genotypes were distributed as 4 (3.3%) for UM, 39 (32.8%) for EM, 54 (45.4%) for IM, 22 (18.5%) for PM by evaluation with Spartan RX CYP2C19. The numbers of patients with the *1/*17, *1/*1, *1/*2, *1/*3, *3/*17, *2/*2, *2/*3, and *3/*3 genotype were 4 (3.3%), 39 (32.8%), 40 (33.6%), 13 (10.9%), 1 (0.9%), 11 (9.2%), 10 (8.4%), 1 (0.9%), respectively. The genotyping results between Spartan RX CYP2C19 and SNP genotyping assay showed discrepancy in 2 patients. The discrepancy appeared in *17 allele analysis in both patients as false-positive result. CONCLUSIONS: The false-positive *17 allele couldn't affect IM or PM group associated with thrombotic events, but it could affect UM group associated with bleeding events, which is relatively less investigated. Although the supplement of *17 allele detection should be accomplished, this novel point-of-care CYP2C19 genotyping instrument could determine the response to the clopidogrel and support the appropriate treatment of ACS patients.

Correlation between the CYP2C19 phenotype status and the results of three different platelet function tests in cardiovascular disease patients receiving antiplatelet therapy: an emphasis on newly introduced platelet function analyzer-200 P2Y test.

BACKGROUND: An association has been reported between CYP2C19 polymorphism and the altered antiplatelet activity of clopidogrel. We investigated this association using the newly introduced platelet function analyzer (PFA)-200 (INNOVANCE PFA-200 System; Siemens Healthcare, Germany) P2Y test. METHODS: Polymorphisms of CYP2C19*2, *3, *17 and the degree of inhibition of platelet function were determined in 83 patients. Three different platelet function tests were used to evaluate the degree of platelet inhibition and to check the association with genotype. RESULTS: The post-procedure PFA-200 values of extensive metabolizers (EM) patients (285.3±38.8) were higher than those of intermediate metabolizers (IM) and poor metabolizers (PM) patients (227.7±98.3 and 133.7±99.2, respectively; P=0.024). Light transmittance aggregometry (LTA) and the VerifyNow system showed that the post-procedure values for EM patients were lower than those of IM and PM patients (LTA: 24.4±15.7, 34.1±17.6, and 42.2±16.9, respectively, P<0.001; VerifyNow: 133.2±60.5, 171.5±42.6, and 218.7±59.3, respectively, P<0.001). The high residual platelet reactivity (HPR) rates were significantly different among the EM, IM, and PM groups using PFA-200 (PM:IM:EM=82.4:40.6:11.8, P<0.001). CONCLUSIONS: Approximately, 59.0% of Korean patients with cardiovascular disease receiving clopidogrel had CYP2C19 loss-of-function genotypes classified as IM or PM, and the frequency was similar to the data from Asian people. The PFA-200, LTA, and VerifyNow platelet function tests revealed evidence of a significant association between the efficacy of clopidogrel and CYP2C19 genotypes.

Neutrophil-to-Lymphocyte Ratio Is Associated with Impaired Interferon-Gamma Release to Phytohemagglutinin.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been shown to predict adverse outcomes in several pathologic conditions. The majority of indeterminate interferon (IFN)-γ release assays were due to inadequate IFN-γ response to the phytohemagglutinin. We sought to study the value of NLR to predict an indeterminate result of QuantiFERON-TB Gold In-Tube (QFT-GIT) performed in routine laboratory practice. METHODS: Results from 2,773 QFT-GIT assays were analyzed. Data collection included demographic data, the level of IFN-γ to nil, mitogen, and TB antigen of QFT-GIT, total WBC, and a differential count. We calculated the absolute neutrophil count, lymphocyte count, and NLR. RESULTS: Of the total, 224 (8.1%) indeterminate results were observed. Twelve (1.8%) showed indeterminate results in the NLR range from 1.71 to 2.84, but 132 (19.2%) had indeterminate results in NLR ≥ 5.18 (p < 0.0001). The likelihood ratio for indeterminate results were 2.70 (95% CI, 2.36-3.08) in NLR ≥ 5.18 and 1.93 (95% CI, 1.64-2.27) in lymphocyte count ≤ 1050/µL. NLR and neutrophil count were independent predictors for indeterminate QFT-GIT result in multiple regression analysis. The IFN-γ response to PHA was negatively associated with NLR (r = -0.33, p < 0.001). CONCLUSION: We showed that the NLR is an independent predictor of indeterminate QFT-GIT result. Low frequency of indeterminate results in group with normal NLR may imply the importance of a balance between two cellular compartments in physiological and pathological conditions.

Clinical usefulness of serum cystatin C as a marker of renal function.

BACKGROUND: Accurate renal function measurements are important in the diagnosis and treatment of kidney diseases. In contrast to creatinine, the production of serum cystatin C has been extensively reported to be unaffected by body muscle mass, age, gender, and nutritional status. METHODS: Our study included 37 samples from diabetic chronic kidney disease (CKD) patients for whom serum creatinine tests had been requested and 40 samples from a healthy populations in Dong-A University Hospital between May 2010 and June 2010. The assay precision (i.e., the coefficient of variation) and the reference range of the serum cystatin C test were evaluated. We compared the estimated glomerular filtration rates (GFRs) based on cystatin C with those based on creatinine. Moreover, we investigated the influences of age, gender, weight, and muscle mass on serum creatinine and serum cystatin C. RESULTS: There was a positive correlation between GFR based on creatinine and that based on cystatin C (r=0.79, P<0.0001) among the diabetic CKD patients. Serum creatinine and cystatin C were significantly correlated with body weight and muscle mass, but the strengths of these correlations were greater for serum creatinine. The precision study revealed excellent results for both the high and low controls. The 95% reference interval of cystatin C in the healthy population was 0.371 to 1.236 mg/L. CONCLUSION: Based on these results, we conclude that, despite the strong correlation between serum creatinine and cystatin C, cystatin C is less affected by weight and muscle mass and might represent a better alternative for the assessment of renal function.

Platelet function tests: a review of progresses in clinical application.

The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics.

Diagnostic utility of multiprobe fluorescence in situ hybridization assay for detecting cytogenetic aberrations in acute leukemia.

BACKGROUND: Specific cytogenetic aberrations detected by conventional karyotyping or FISH play a major role in the diagnosis, prognosis, and treatment of patients with acute leukemia. The FISH technique enhances the capacity of conventional karyotyping to detect subtle chromosomal aberrations. Multiprobe FISH assay (Cytocell, UK) can hybridize multiple probes to a single slide, thereby increasing the detection rate of cytogenetic aberrations. This study aimed to evaluate multiprobe FISH in detecting cytogenetic abnormalities in acute leukemia. METHODS: Thirty newly diagnosed acute leukemia patients who attended the hematology clinic at Dong-A University Hospital from October 2008 to October 2012 were enrolled in the study. The multiprobe FISH results were compared with those of G-banding. RESULTS: Multiprobe FISH detected the chromosomal aberrations identified by G-banding, as well as additional aberrations in 6 of 30 (20.0%) cases, which included ETV6/RUNX1 translocation, p16 deletion, TP53 deletion, and IGH break-apart. CONCLUSIONS: The multiprobe FISH assay was a more sensitive and reliable technique compared with G-banding. It was also more cost-effective and yielded faster results.

Outbreak of pseudomonas oryzihabitans pseudobacteremia related to contaminated equipment in an emergency room of a tertiary hospital in Korea.

Pseudomonas oryzihabitans is frequently found in various sites within hospital settings, including sink drains and respiratory therapy equipment. Although it rarely causes human infections, P. oryzihabitans has recently been considered a potential nosocomial pathogen, especially in immunocompromised hosts. We report our experience of an outbreak of P. oryzihabitans pseudobacteremia, presumably due to faulty aseptic preparation of a saline gauze canister.

Significance of interferon-gamma response to mitogen in serial QuantiFERON-TB Gold In-Tube assay of routine laboratory practice.

BACKGROUND: Clinical data of serial interferon-γ release assay (IGRA) testing in routine laboratory practice are limited. IFN-γ response to mitogen is used as a positive control in IGRA. We assessed the association between IFN-γ response to nil, mitogen, tuberculosis (TB) mycobacterial antigens, and the variations from the results of the serial testing. METHOD: A total of 299 patients with serial QuantiFERON-TB Gold In-Tube (QFT-GIT) were enrolled. The medical records of patients were reviewed for demographic information, status of Mycobacterium tuberculosis infection, treatment of tuberculosis, and the quantitative response to nil, mitogen, and TB antigen. RESULTS: The initial QFT-GIT result was positive in 142 patients (47.5%), negative in 139 (46.5%), and indeterminate in 18 (6.0%). Of total, 79.6% showed concordant results in serial testing. The discordance in serial tests was significantly high in patients with a low mitogen response (≤ 3.93 IU/ml) (p<0.0001). Quantitative TB responses around the cut-off point in serial QFT-GIT were associated with an increased conversion and reversion rates (p = 0.01, p = 0.0005), respectively. CONCLUSION: Because IGRAs are dynamic assays, integrated interpretation of quantitative TB response with mitogen and nil response would be helpful in serial QFT-GIT. Recommendations for the interpretation of results of serial testing for active TB will be required.

A case of Clostridium difficile bacteremia in a patient with loop ileostomy.

Clostridium difficile, an anaerobic, spore-forming, gram-positive, rod-shaped bacterium, is the most common nosocomial pathogen causing pseudomembranous colitis. C. difficile is not intrinsically invasive and rarely infects extraintestinal sites. The bacterium, therefore, is not commonly detected in blood cultures. Here, we report a case of C. difficile bacteremia in a patient who had underwent loop ileostomy because of rectal obstruction following metastatic colon cancer originated from prostate cancer.

Effects of 60 Hz magnetic fields on teenagers and adults.

BACKGROUND: As use of electrical devices has increased, social concerns about the possible effects of 60 Hz electromagnetic fields on human health have increased. Accordingly, the number of people who complain of various symptoms such as headache and insomnia has risen. Many previous studies of the effects of extremely low frequency (ELF) magnetic field exposure on children have focused on the occurrence of childhood leukaemia and central nervous system cancers. However, very few provocation studies have examined the health effects of ELF magnetic fields on teenagers. METHODS: In this double-blind study, we simultaneously investigated physiological changes (heart rate, respiration rate, and heart rate variability), subjective symptoms, and magnetic field perception to determine the reliable effects of 60 Hz 12.5 µT magnetic fields on teenagers. Two volunteer groups of 30 adults and 30 teenagers were tested with exposure to sham and real magnetic fields for 32 min. RESULTS: ELF magnetic field exposure did not have any effects on the physiological parameters or eight subjective symptoms in either group. Neither group correctly perceived the magnetic fields. CONCLUSIONS: Physiological data were analysed, subjective symptoms surveyed, and the percentages of those who believed they were being exposed were measured. No effects were observed in adults or teenagers resulting from 32 min of 60 Hz 12.5 µT magnetic field exposure.

Urinary neutrophil gelatinase-associated lipocalin levels in comparison with glomerular filtration rate for evaluation of renal function in patients with diabetic chronic kidney disease.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. There is a growing body of evidence suggesting that NGAL is also a marker of kidney disease and severity in chronic kidney disease (CKD). We studied the utility of urinary NGAL in more accurately predicting renal function in patients with diabetic CKD. METHODS: We studied possible relationships between urinary NGAL, estimated glomerular filtration rate (eGFR), and proteinuria in diabetic CKD patients and in healthy populations. RESULTS: Urinary NGAL levels were significantly higher in CKD patients than in healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL, P=0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3] mL/min/1.73 m(2) vs. 85.6 [72 to 106.7] mL/min/1.73 m(2), P<0.0001). The urinary NGAL level showed a significant inverse correlation with GFR (r=-0.5634, P<0.0001). The correlation analyses between urinary protein level and urinary NGAL levels and GFR were as follows: urine protein and urinary NGAL (r=0.3009, P=0.0256), urine protein and GFR (r=-0.6245, P<0.0001), urine microalbumin and urinary NGAL (r=0.1794, P=0.2275), and urine microalbumin and GFR (r=-0.5190, P=0.0002). CONCLUSION: From these results, we concluded that urinary NGAL is a reliable marker of renal function in diabetic CKD patients. However, urinary NGAL did not provide more accurate information regarding renal function than GFR.

Origins of electromagnetic hypersensitivity to 60 Hz magnetic fields: A provocation study.

With increasing electrical device usage, social concerns about the possible effects of 60 Hz electromagnetic fields on human health have increased. The number of people with self-attributed electromagnetic hypersensitivity (EHS) who complain of various subjective symptoms such as headache and insomnia has also increased. However, it is unclear whether EHS results from physiological or other origins. In this double-blinded study, we simultaneously investigated physiological changes (heart rate, respiration rate, and heart rate variability), subjective symptoms, and perception of the magnetic field to assess origins of the subjective symptoms. Two volunteer groups of 15 self-reported EHS and 16 non-EHS individuals were tested with exposure to sham and real (60 Hz, 12.5 µT) magnetic fields for 30 min. Magnetic field exposure did not have any effects on physiological parameters or eight subjective symptoms in either group. There was also no evidence that the EHS group perceived the magnetic field better than the non-EHS group. In conclusion, the subjective symptoms did not result from the 60 Hz, 12.5 µT magnetic field exposures but from other non-physiological factors.

Comparison of survival predictions for rats with hemorrhagic shocks using an artificial neural network and support vector machine.

Hemorrhagic shock is the cause of one third of deaths resulting from injury in the world. Early diagnosis of hemorrhagic shock makes it possible for physicians to treat patients successfully. The objective of this study was to select an optimal survival prediction model using physiological parameters from rats during our hemorrhagic experiment. These physiological parameters were used for the training and testing of survival prediction models using an artificial neural network (ANN) and support vector machine (SVM). To avoid over-fitting, we chose the optimal survival prediction model according to performance measured by a 5-fold cross validation method. We selected an ANN with three hidden neurons and one hidden layer and an SVM with Gaussian kernel function as a trained survival prediction model. For the ANN model, the sensitivity, specificity, and accuracy of survival prediction were 97.8 ± 3.3 %, 96.3 ± 2.7 %, and 96.8 ± 1.7 %, respectively. For the SVM model, the sensitivity, specificity, and accuracy were 97.5 ± 2.9 %, 99.3 ± 1.1 %, and 98.5 ± 1.2 %, respectively. SVM was preferable to ANN for the survival prediction.

Physiological variables and subjective symptoms by 60 Hz magnetic field in EHS and non-EHS persons.

Electromagnetic hypersensitivity (EHS) is a set of claims of adverse medical symptoms self attributed by exposure to electromagnetic field. In this study, we simultaneously investigated both physiological changes (heart rate, respiration rate, and heart rate variability) and subjective symptoms to determine the origin of EHS. Two volunteer groups (15 self-reported EHS and 16 non-EHS participants) were tested under both sham and real exposure to 12.5 µT magnetic fields at 60 Hz that lasted a half an hour. The magnetic field exposure did not have any effect on physiological variables or subjective symptoms in either group. We conclude that the subjective symptoms did not result from exposure to 12.5 µT magnetic field at 60 Hz.