Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Clinical application of a real-time polymerase chain reaction test for CYP2C19 genotyping based on genotype distribution in a healthy Korean population.

OBJECTIVE: With the recent reports of additional alleles of the CYP2C19 gene with decreased or no function, the clinical utility of real-time polymerase chain reaction (PCR)-based testing that detects only a small number of variant targets needs to be evaluated. METHOD: We retrospectively reviewed 7-year data for real-time PCR test records from a single hospital and analyzed CYP2C19 genotypes from publicly available whole-genome or whole-exome data from a healthy Korean population. RESULTS: Of the 2327 test results in this hospital, the *1 allele was most common (60.5%), followed by *2 (28.0%), *3 (10.1%), and *17 (1.4%). Among 5305 healthy Korean individuals, the frequencies of the *2, *3, and *17 alleles were 28.6%, 9.9%, and 1.0%, respectively, which were not statistically different from those of the hospital data (P = .4439, P = .6025, and P = .1142, respectively). Interestingly, the total frequency of additional nonfunctional alleles (*4, *6, *22, and *24) that could not be detected using real-time PCR was only 0.1%, with a total allele count of 8. CONCLUSION: Our study shows that the clinical utility of real-time PCR for CYP2C19 genotyping remains satisfactory. However, caution should be exercised because the test can miss patients with decreased CYP2C19 function.

Practical delta check limits for tumour markers in different clinical settings.

OBJECTIVES: Few studies have reported on delta checks for tumour markers, even though these markers are often evaluated serially. Therefore, this study aimed to establish a practical delta check limit in different clinical settings for five tumour markers: alpha-fetoprotein, cancer antigen 19-9, cancer antigen 125, carcinoembryonic antigen, and prostate-specific antigen. METHODS: Pairs of patients' results (current and previous) for five tumour markers between 2020 and 2021 were retrospectively collected from three university hospitals. The data were classified into three subgroups, namely: health check-up recipient (subgroup H), outpatient (subgroup O), and inpatient (subgroup I) clinics. The check limits of delta percent change (DPC), absolute DPC (absDPC), and reference change value (RCV) for each test were determined using the development set (the first 18 months, n=179,929) and then validated and simulated by applying the validation set (the last 6 months, n=66,332). RESULTS: The check limits of DPC and absDPC for most tests varied significantly among the subgroups. Likewise, the proportions of samples requiring further evaluation, calculated by excluding samples with both current and previous results within the reference intervals, were 0.2-2.9% (lower limit of DPC), 0.2-2.7% (upper limit of DPC), 0.3-5.6% (absDPC), and 0.8-35.3% (RCV99.9%). Furthermore, high negative predictive values >0.99 were observed in all subgroups in the in silico simulation. CONCLUSIONS: Using real-world data, we found that DPC was the most appropriate delta-check method for tumour markers. Moreover, Delta-check limits for tumour markers should be applied based on clinical settings.

Collaborative Study to Establish National Reference Standards for Anti-HIV-1 Antibody.

Background: National reference standards for anti-HIV-1 antibody are needed to evaluate the performance and maintain the quality control of anti-HIV-1 antibody assays. The aim of this study was to prepare a mixed-titer performance panel and assess its suitability as a national reference standard for anti-HIV-1 antibody according to stability, collaboration, and other studies. Methods: Nineteen serum samples from different HIV patients were obtained, along with 15 units of fresh frozen plasma samples with negative anti-HIV-1 antibody results. Ten anti-HIV-1 antibody-positive candidate standards and two negative candidate standards were prepared based on the reactivity in the Alinity i HIV Ag/Ab combo assay (Abbott Laboratories, Wiesbaden, Germany). A collaborative study was conducted across eight laboratories using five anti-HIV-1 antibody assays. Real-time and accelerated stability were evaluated to assess the long-term stability. Results: In the collaborative study, results of all five anti-HIV-1 antibody assays were positive for all 10 candidate standards prepared using HIV patient samples. The CV of each assay for every candidate standard was within 10%, except for one assay result. No real-time and accelerated stability change trend was observed at -70°C or -20°C, supporting that the reference standards were maintained in a stable state at -70°C for long-term storage. Conclusions: The overall results suggest that the 12 candidate standards could serve as national reference standards for anti-HIV-1 antibody.

Effect of Characterized Green Tea Extraction Methods and Formulations on Enzymatic Starch Hydrolysis and Intestinal Glucose Transport.

The purpose of the current study was to investigate the effect of various characterized green tea extracts (GTEs) according to extraction methods on enzymatic starch hydrolysis and intestinal glucose transport. Codigestion of wheat starch with water extract (WGT) or ethanol extract formulated with green tea polysaccharides and flavonols (CATEPLUS) produced 3.4-3.5 times higher resistant starch (RS) than wheat starch only. Its microstructures were changed to spherical shapes and smooth surfaces as shown by scanning electron microscopy (SEM) results. According to Fourier transform infrared (FT-IR) spectra, the absorption peak of O-H stretching was red-shifted in WGT or CATEPLUS. The results confirmed that hydrogen bonds were formed between starch granules and polysaccharides in WGT or CATEPLUS. Intestinal glucose transport subsequently measured after in vitro digestion was mostly suppressed in CATEPLUS. Gene expression of the glucose transporter protein, particularly SGLT1, was significantly inhibited by addition of CATEPLUS (p < 0.05). Results from the current study suggest that co-intake of green tea extracts formulated with green tea polysaccharides and flavonols could be a potentially useful means to delay blood glucose absorption when consuming starchy foods.

An Algorithmic Approach Is Superior to the 99th Percentile Upper Reference Limits of High Sensitivity Troponin as a Threshold for Safe Discharge from the Emergency Department.

Background and Objectives: High-sensitivity cardiac troponin I (hs-TnI) is an important indicator of acute myocardial infarction (AMI) among patients presenting with chest discomfort at the emergency department (ED). We aimed to determine a reliable hs-TnI cut-off by comparing various values for a baseline single measurement and an algorithmic approach. Materials and Methods: We retrospectively reviewed the hs-TnI values of patients who presented to our ED with chest discomfort between June 2019 and June 2020. We evaluated the diagnostic accuracy of AMI with the Beckman Coulter Access hs-TnI assay by comparing the 99th percentile upper reference limits (URLs) based on the manufacturer's claims, the newly designated URLs in the Korean population, and an algorithmic approach. Results: A total of 1296 patients who underwent hs-TnI testing in the ED were reviewed and 155 (12.0%) were diagnosed with AMI. With a single measurement, a baseline hs-TnI cut-off of 18.4 ng/L showed the best performance for the whole population with a sensitivity of 78.7%, specificity of 95.7%, negative predictive value (NPV) of 97.1%, and positive predictive value (PPV) of 71.3%. An algorithm using baseline and 2-3 h hs-TnI values showed an 100% sensitivity, 97.7% specificity, an NPV of 100%, and a PPV of 90.1%. This algorithm used a cut-off of <4 ng/L for a single measurement 3 h after symptom onset or an initial level of <5 ng/L and a change of <5 ng/L to rule a patient out, and a cut-off of ≥50 ng/L for a single measurement or a change of ≥20 ng/L to rule a patient in. Conclusions: The algorithmic approach using serial measurements could help differentiate AMI patients from patients who could be safely discharged from the ED, ensuring that patients were triaged accurately and did not undergo unnecessary testing. The cut-off values from previous studies in different countries were effective in the Korean population.

Usefulness of the prostate health index in predicting the presence and aggressiveness of prostate cancer among Korean men: a prospective observational study.

BACKGROUND: We aimed to evaluate the usefulness of the Beckman Coulter prostate health index (PHI) and to compare it with total prostate-specific antigen (PSA) levels and related derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in the Korean population. METHODS: A total of 140 men who underwent their first prostate biopsy for suspected PCa were included in this prospective observational study. The diagnostic performance of total PSA, free PSA, %free PSA, [-2] proPSA (p2PSA), %p2PSA, and PHI in detecting and predicting the aggressiveness of PCa was estimated using the receiver operating characteristic curve (ROC) and logistic multivariate regression analyses. RESULTS: Of 140 patients, PCa was detected in 63 (45%) of participants, and 48 (76.2%) of them had significant cancer with a Gleason score (GS) ≥ 7. In the whole group, the area under the curve (AUC) for ROC analysis of tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.63, 0.57, 0.69, 0.69, 0.72, and 0.76, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p = 0.005). For PCa with GS ≥ 7, the AUCs for tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.62, 0.58, 0.41, 0.79, 0.86, and 0.87, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p < 0.001). In the subgroup with tPSA 4-10 ng/mL, both %p2PSA and PHI were strong independent predictors for PCa (p = 0.007, p = 0.006) and significantly improved the predictive accuracy of a base multivariable model, including age, tPSA, fPSA and %fPSA, using multivariate logistic regression analysis. (p = 0.054, p = 0.048). Additionally, at a cutoff PHI value > 33.4, 22.9% (32/140) of biopsies could be avoided without missing any cases of aggressive cancer. CONCLUSIONS: This study shows that %p2PSA and PHI are superior to total PSA and %fPSA in predicting the presence and aggressiveness (GS ≥ 7) of PCa among Korean men. Using PHI, a significant proportion of unnecessary biopsies can be avoided.

Development and Application of Computerized Risk Registry and Management Tool Based on FMEA and FRACAS for Total Testing Process.

Background and Objectives: Risk management is considered an integral part of laboratory medicine to assure laboratory quality and patient safety. However, the concept of risk management is philosophical, so actually performing risk management in a clinical laboratory can be challenging. Therefore, we would like to develop a sustainable, practical system for continuous total laboratory risk management. Materials and Methods: This study was composed of two phases: the development phase in 2019 and the application phase in 2020. A concept flow diagram for the computerized risk registry and management tool (RRMT) was designed using the failure mode and effects analysis (FMEA) and the failure reporting, analysis, and corrective action system (FRACAS) methods. The failure stage was divided into six according to the testing sequence. We applied laboratory errors to this system over one year in 2020. The risk priority number (RPN) score was calculated by multiplying the severity of the failure mode, frequency (or probability) of occurrence, and detection difficulty. Results: 103 cases were reported to RRMT during one year. Among them, 32 cases (31.1%) were summarized using the FMEA method, and the remaining 71 cases (68.9%) were evaluated using the FRACAS method. There was no failure in the patient registration phase. Chemistry units accounted for the highest proportion of failure with 18 cases (17.5%), while urine test units accounted for the lowest portion of failure with two cases (1.9%). Conclusion: We developed and applied a practical computerized risk-management tool based on FMEA and FRACAS methods for the entire testing process. RRMT was useful to detect, evaluate, and report failures. This system might be a great example of a risk management system optimized for clinical laboratories.

Somatic Mosaicism of NF2 Gene Mutation with Constitutional NF1 Gene Mutation in Neurofibromatosis Type 2: a Case Report.

BACKGROUND: Neurofibromatosis (NF) is a genetic disorder, and neurofibromatosis types 1 and 2 have different genetic and clinical features. Herein, we present the clinical and genetic aspects of a patient carrying a constitutional NF1 gene mutation and whose neurocutaneous manifestations suggested a NF type 2 (NF2). METHODS: A 55-year-old woman presented with headache and deterioration of vision. Physical examination and radiologic findings revealed multiple subcutaneous nodules and multiple intracranial and spinal masses which were suspected to be NF2. RESULTS: Genomic DNA sequencing using a peripheral blood sample revealed a splicing mutation in the NF1 gene. Tumor resection and biopsy revealed intracranial meningiomas and paraspinal Schwannoma compatible with NF2. PCR-direct sequencing using tumor tissue samples showed pathogenic somatic mutation of the NF2 gene. CONCLUSIONS: We report a case of NF2 presenting with a pathogenic somatic mutation in the NF2 gene in a woman harboring a germline splicing mutation in the NF1 gene. This case emphasizes the importance of sequence analy¬sis by using tumor tissues and the need to elucidate the role of a NF1 splicing mutation.

Performance of Norudia Glycated Albumin Assay on Multiple Analytical Platforms and Comparison to Lucica Assay.

BACKGROUND: The Norudia glycated albumin (GA) assay was evaluated for analytical performance and assay applicability on multiple analytical platforms. METHODS: The evaluation included precision, linearity, reference interval, and comparison with Lucica GA assay. A multicenter study was conducted to compare the results of Norudia GA assay on five kinds of widely used automated clinical chemistry analyzers. RESULTS: Within-laboratory imprecisions for GA% presented 1.3 - 3.3% and 0.8 - 2.6% for low- and high-level control materials, respectively, on different analyzers. GA assay was linear from 20.0 to 680.0 µmol/L of GA. The claimed reference range (12 - 16 GA%) was verified. Norudia GA showed a good GA% correlation with Lucica GA (correlation coefficient 0.999). GA% from each analyzer showed good correlation with the consensus mean of the results of five analyzers (correlation coefficient 0.997 - 0.999). CONCLUSIONS: The Norudia GA assay can successfully be implemented in all the tested platforms, with good GA% correlation.

Importance of Susceptibility Rate of 'the First' Isolate: Evidence of Real-World Data.

Background and objectives: For proper antimicrobial therapy, cumulative antibiograms should be representative of geographic region and be accurate. Clinical and Laboratory Standards Institute (CLSI) guidelines recommend that only the first isolates (FI) of a species per patient are used when reporting cumulative antibiograms. However, >50% of hospitals in the United States report antibiograms of all isolates. We compared antibiograms from the FI with those from total isolates (TI). Materials and Methods: Antimicrobial data of all isolates identified in the Microbiology unit of Ilsan Paik Hospital in 2019 were retrospectively acquired from the hospital information system. The susceptibility rates to antimicrobials of Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis were analyzed by FI and TI, respectively. Isolate counts and susceptibility rates of each species for the reported antimicrobials were compared. Results: The numbers of isolates by FI/TI were as follows: 1824/2692 E. coli, 480/1611 A. baumannii, and 662/1306 K. pneumoniae, and 407/953 P. aeruginosa for gram-negative bacteria and 649/1364 S. aureus, 211/313 E. faecium, and 323/394 E. faecalis for gram-positive bacteria. All antimicrobial agents showed higher susceptibility rates when calculated as FI than as TI in gram-negative bacteria except colistin: 3.7% for E. coli, 14.5% for A. baumannii, 8.3% for K. pneumoniae, and 7.9% for P. aeruginosa. In S. aureus, 8/11 antimicrobial agents revealed higher susceptibility rates for FI than for TI. E. faecalis and E. faecium showed lower susceptibility rates for 7/10 antimicrobial agents for FI than for TI. The oxacillin susceptibility rates of S. aureus were 36.6%/30.2% with FI/TI and vancomycin susceptibility rates for E. faecium were 54.1% and 49.5%, respectively. Conclusions: When comparing cumulative antibiograms by FI with TI using real-world data, there is a large gap for critical species requiring hospital infection control. Although FI calculation is difficult, antibiograms must be calculated as FI for proper preemptive antimicrobial therapy because FI provides proper antimicrobial susceptibility data.

Preanalytical Errors in the Central Laboratory of a University Hospital Based on the Analysis of Year-Round Data.

BACKGROUND: Preanalytical errors cause a decrease in the accuracy of clinical laboratory results. We analyzed preanalytical errors (preAEs) made in the clinical laboratory of a university hospital. METHODS: All samples received in a centralized laboratory from January 1, to December 31, 2018, were analyzed retrospectively. The categories of preAEs were improper request, incorrect labeling, improper collection/transport, inadequate sample volume, inappropriate container, hemolysis, and sample clotting. The rates of preAEs in these categories were calculated according to sample type, laboratory subunit, department, sampling place, sampling time, and patient age. RESULTS: Of 1,082,014 samples received and analyzed by the laboratory, 6,848 (0.63%) were classified as having preAEs. The most frequent categories of preAE were hemolysis (44.6%), sample clotting (30.8%), and inadequate volume (16.7%). The most frequent preAE category for whole-blood and serum/plasma was clotting and hemolysis, respectively. The most frequent preAE category in the blood bank, clinical chemistry, immunology, and test referral service laboratory subunits was hemolysis, in the hematology subunit it was sample clotting, and in the microbiology and urinalysis subunits it was inadequate sample volume. Surgical departments had a higher rate of preAEs than did non-surgical departments (p < 0.0001). Samples drawn in the sampling room showed the lowest frequencies of preAEs (0.01%). Samples drawn on general wards from 5 pm to 5 am, when duty nurses perform sampling, showed a preAE rate of 2.80%. The rate of preAEs increased with patient age. CONCLUSIONS: This analysis of preAEs is the most comprehensive to date. Our findings will promote the provision of high-quality laboratory services to clinicians and their patients.

Clinical Utility of HIV-1/2 Ab Immunochromatographic Assay as an Additive Test for HIV Screen-Positive Patients.

OBJECTIVE: Frequent false-positive results of current HIV screening occur due to its high sensitivity. These false-positives may delay subsequent clinical decision making. In this study, we aim to determine the usefulness of additional immunochromatographic assay (ICA) in hospitals using fourth-generation HIV-1/2 Ag/Ab assays followed by western blot (WB) confirmation. METHODS: Overall, 158,431 patients' sera were screened for HIV using a fourth-generation HIV-1/2 Ag/Ab assays (Elecsys HIV combiPT) from July 2011 to May 2019. All 401 ECLIA-positive sera were re-tested using an ICA kit (SD Bioline HIV1/2 3.0 ICA), followed by WB confirmation according to national policy. RESULTS: Sixty-five ECLIA-positive samples (65/401, 16.2%) were positive for ICA, 96.9% (63/65) of which were confirmed positive using WB. ICA results were negative in 83.8% (336/401) of ECLIA-positive samples, of which 98.5% (331/336) remained negative on WB. Five specimens (1.5%) from patients with symptoms consistent with acute HIV syndrome were false negatives on ICA. These false negatives were confirmed positive using a p24 antigen assay and nucleic acid test (NAT). CONCLUSIONS: ICA for anti-HIV Ab screen-positive specimens is helpful for earlier medical decision considering frequent false-positive results on screening. Nonetheless, ICA might be negative in acute HIV syndrome, necessitating p24 Ag assay or NAT with shorter window periods.

Real-time display of laboratory testing status improves satisfaction levels in an emergency department: A pilot study.

BACKGROUND: Clinicians need to know timelines of requested laboratory tests to provide effective patient management. We developed a real-time laboratory progress checking system and measured its effectiveness using appropriate indicators in an emergency room setting. METHODS: In our original in-house health information system display, blank spaces, which were generated for test results when tests were ordered, remained empty until the final results reported. We upgraded the laboratory reporting system to show real-time testing information. The stages included requests for test, label printing, sampling, laboratory receipts, performance of tests, verification of results, and interpretation of results and final report by laboratory physician. To assess the usefulness of the function, we measured the emergency department healthcare workers' satisfaction and compared the number of phone calls about test status before and after implementation. RESULTS: After the system upgrade, the healthcare workers' understanding of the testing process increased significantly as follows. More clinicians could estimate the time of final test results through the real-time testing status information (61.9% and 85.7%, P = .002), and respondents reported that the upgraded system was more convenient than the original system (41.3% and 22.2%, respectively, P = .022). The number of phone calls about the test status decreased after implementation of the upgrade; however, the difference was not statistically significant (before, 0.13% [63 calls/48 637 tests] and after, 0.09% [42/46 666]; P = .066). CONCLUSIONS: The real-time display of laboratory testing status increased understanding of testing process among healthcare workers in emergency room, which ultimately may increase the usefulness and efficiency of the laboratory service use.

Evaluation of the new Beckman Coulter Access hsTnI: 99th percentile upper reference limits according to age and sex in the Korean population.

BACKGROUND: Defining the 99th percentile upper reference limits (URL) of cardiac troponin I (cTnI) is critical because it is clinically important in determining myocardial injury, and is variable among reagents, age, sex, or races. The analytical performance of the new, high- sensitivity reagent Beckman Coulter Access hsTnI was evaluated, and its 99th percentile URL was determined in the Korean population. METHODS: Analytical performances of Access hsTnI assay were evaluated including imprecision and limit of measurements. To define the reference limits, 600 healthy subjects were included with similar proportions of sex and age groups. RESULTS: Beckman Coulter Access hsTnI assay presented a limit of blank, detection, and quantitation at 10% CV of 0.32 ng/L, 0.63 ng/L, and 6.1 ng/L, respectively, and 98.3% of the healthy population showed cTnI above the limit of detection. The 99th percentile URLs were 9.5 ng/L (90% CI 7.4-14.9), 7.8 ng/L (90% CI 5.5-19.2 ng/L), and 11.3 ng/L (90% CI 8.0-15.7 ng/L) in 600 healthy participants, 300 women and 300 men, respectively with imprecision less than 10% CV. The median values and 99th percentile URLs of hsTnI were higher in men and the age group ≥50 years than in women and the age group <50 years, respectively. CONCLUSIONS: Access hsTnI assay met the performance criteria of the IFCC for high-sensitivity cTnI assays. Their 99th percentile URLs in the Korean population were lower than the manufacturer's claims. cTnI values were significantly different among different sex and age groups.

Different parental origins of supernumerary X chromosomes in brothers with Klinefelter syndrome: A case report.

RATIONALE: Recurrence of Klinefelter syndrome (KS) in non-twin brothers is very rare. This study examined the inheritance pattern of supernumerary X chromosomes in non-twin brothers. PATIENT CONCERNS: A 16-year-old man presented with small-sized testicles. During his diagnostic work-up, his brother, in his late 20's, also complained of small testes and erectile dysfunction. DIAGNOSIS: Chromosome analysis in peripheral blood revealed non-mosaic 47,XXY karyotype in both brothers. Their mother showed a normal 46,XX karyotype. INTERVENTIONS: To examine the inheritance pattern of supernumerary X chromosomes, quantitative-fluorescence PCR was performed with small tandem repeat markers. It revealed that their supernumerary X chromosomes were inherited from different parents. OUTCOMES: After the diagnosis of KS, 2 brothers started to receive testosterone treatment. CONCLUSION: This case report is the first to report differences in the origins of supernumerary X chromosomes in brothers with KS and furthers the current understanding of the cytogenetic mechanisms in KS.

Hypoglycemic potential of whole green tea: water-soluble green tea polysaccharides combined with green tea extract delays digestibility and intestinal glucose transport of rice starch.

Green tea is being studied extensively for its postprandial hypoglycemic effect due to its abundant catechins. Along with catechins, water-soluble green tea polysaccharides are also currently gaining attention due to their natural hypoglycemic properties. The current study investigated the combinational effect of green tea extract (GTE) and crude green tea polysaccharides (CTP) in inhibiting glucose transport after digestion of rice starch, using an in vitro digestion model with a Caco-2 cell. Co-digestion of rice starch with GTE (16.09 ± 1.02 g L-1), CTP (16.83 ± 0.81 g L-1), or GTE + CTP (17.79 ± 0.80 g L-1) hydrolyzed less starch into glucose compared with the control (18.24 ± 0.45 g L-1). Glucose transport from digesta to the Caco-2 cell after 120 min incubation was significantly inhibited with GTE + CTP (53.26 ± 4.34%). Gene expression of intestinal glucose transporters, which included sodium-dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), was not altered by GTE, CTP or GTE + CTP, except for the GTE-mediated upregulation of GLUT2. It is concluded that GTE + CTP lowered digestibility of rice starch with glucose and also delayed glucose uptake to the intestinal epithelium. This finding suggests a potential for green tea polysaccharides as a natural postprandial hypoglycemic substance.

Kallmann syndrome with a Tyr113His PROKR2 mutation.

RATIONAL: Kallmann syndrome (KS) is a genetic gonadotropin-releasing hormone deficiency associated with hyposmia or anosmia and characterized by various modes of inheritance. PATIENT CONCERNS: A 16-year-old male did not reach puberty and was associated with hypogonadotropic hypogonadism and anosmia. His magnetic resonance imaging of brain revealed the absence of the olfactory bulb. DIAGNOSIS: His karyotype was 46 XY. Sanger sequencing of the KAL1 gene revealed no mutations. Diagnostic exome sequencing identified a prokineticin-receptor 2 (PROKR2) gene variant, c.337T > C (p.Tyr113His), previously reported to be a pathogenic mutation; we confirmed the presence of the mutation via Sanger sequencing of the coding exons of PROKR2. His apparently unaffected mother and sister, but not his father, were heterozygous for the PROKR2 Tyr113His mutation. LESSONS: This work advances our understanding of the role played by PROKR signaling and the mode of inheritance of the gene in patients with KS.

Evaluation of the Elecsys(®) Anti-HCV II assay for routine hepatitis C virus screening of different Asian Pacific populations and detection of early infection.

BACKGROUND: Early diagnosis of hepatitis C virus (HCV) infection is essential to allow appropriate treatment and prevent transmission. OBJECTIVES: To evaluate the Elecsys(®) Anti-HCV II assay as a routine screening assay in Asia using a large number of samples from different Asian Pacific populations and compare its performance with other HCV assays routinely used in the region. STUDY DESIGN: The sensitivity and specificity of the Elecsys(®) Anti-HCV II assay were determined using routine hospital samples and compared with at least one of the following comparator assays at nine independent centers: ARCHITECT™ Anti-HCV; Serodia(®)-HCV Particle Agglutination; Vitros(®) ECi Anti-HCV; Elecsys(®) Anti-HCV; ADVIA Centaur(®) HCV; InTec(®) HCV EIA; or Livzon(®) Anti-HCV. Commercially available seroconversion panels were used to assess sensitivity for early detection of infection. RESULTS: The Elecsys(®) Anti-HCV II assay was more sensitive in recognizing early infection and detected acute HCV infection earlier on average than the comparator assays for all six panels tested. 7,726 routine samples were tested and 322 identified as HCV positive. Elecsys(®) Anti-HCV II had a sensitivity of 100% and a specificity of 99.66%, both of which were comparable or superior to the results obtained for competitor assays, which ranged from 87.5-100% and 98.98-100%, respectively. CONCLUSIONS: The Elecsys(®) Anti-HCV II assay has the sensitivity and specificity to support its use as a routine screening method in the Asia Pacific region. Furthermore, this assay shortens the diagnostic window between infection and the detection of antibodies compared with established methods.

Single-nucleotide polymorphism PCR for the detection of Mycoplasma pneumoniae and determination of macrolide resistance in respiratory samples.

The aim of this study was to develop a single-nucleotide polymorphism (SNP) PCR assay to be performed directly on respiratory samples for the simultaneous detection of Mycoplasma pneumoniae and its 23S rRNA gene mutations, which are responsible for macrolide resistance. For multiplex SNP PCR, two outer primers for amplification of the 23S rRNA gene and two mutant-specific primers for the discrimination of single base changes were designed. A total of 73M. pneumoniae-positive samples and 100M. pneumoniae-negative samples were analyzed using this assay. By SNP PCR, we detected two mutations conferring high-level macrolide resistance in 22 samples (A2063G from 20 and A2064G from 2 samples); these results are identical to those produced by the 23S rRNA gene sequencing of M. pneumoniae-positive samples. Thus, this assay can be used as a practical method for the simultaneous detection of M. pneumoniae and mutations associated with macrolide resistance directly from respiratory samples.