Performance Evaluation of VITEK MS for the Identification of a Wide Spectrum of Clinically Relevant Filamentous Fungi Using a Korean Collection

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l’Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 Aspergillus (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed “no identification” or “multiple species identification” results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for Aspergillus, dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed “no identification” and “misidentification” results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification

Air and Environmental Contamination Caused by COVID-19 Patients: a MultiCenter Study

Background@#The purpose of this study was to determine the extent of air and surface contamination of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in four health care facilities with hospitalized coronavirus disease 2019 (COVID-19) patients. @*Methods@#We investigated air and environmental contamination in the rooms of eight COVID-19 patients in four hospitals. Some patients were in negative-pressure rooms, and others were not. None had undergone aerosol-generating procedures. On days 0, 3, 5, and 7 of hospitalization, the surfaces in the rooms and anterooms were swabbed, and air samples were collected 2 m from the patient and from the anterooms. @*Results@#All 52 air samples were negative for SARS-CoV-2 RNA. Widespread surface contamination of SARS-CoV-2 RNA was observed. In total, 89 of 320 (27%) environmental surface samples were positive for SARS-CoV-2 RNA. Surface contamination of SARSCoV-2 RNA was common in rooms without surface disinfection and in rooms sprayed with disinfectant twice a day. However, SARS-CoV-2 RNA was not detected in a room cleaned with disinfectant wipes on a regular basis. @*Conclusion@#Our data suggest that remote (> 2 m) airborne transmission of SARS-CoV-2 from hospitalized COVID-19 patients is uncommon when aerosol-generating procedures have not been performed. Surface contamination was widespread, except in a room routinely cleaned with disinfectant wipes.

Viral Load Kinetics of SARS-CoV-2Infection in Saliva in Korean Patients:a Prospective Multi-center Comparative Study

Background@#This study was performed to compare the viral load and kinetics of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in saliva with those in standard nasopharyngeal/oropharyngeal (NP/OP) swabs. @*Methods@#Fifteen patients with SARS-CoV-2 infection from four hospitals were prospectively enrolled and matched samples of nasopharyngeal/oropharyngeal swabs and saliva were collected at Day 1 of admission and every other day till consequently negative for two times. Real-time reverse transcription polymerase chain reaction (rRT-PCR) was performed to detect the envelope (E) and RNA-dependent RNA polymerase (RdRP) genes. @*Results@#The cycle threshold values of saliva were comparable to those of NP/OP swabs overall (P = 0.720, Mann–Whitney U test). However, the overall sensitivity of rRT-PCR using saliva was 64% (34/53), which is lower than the 77% (41/53) using NP/OP swabs. The sensitivity of rRT-PCR using saliva was especially lower in early stage of symptom onset (1–5 days; 8/15; 53%) and in patients who did not have sputum (12/22; 55%). @*Conclusion@#Saliva sample itself is not appropriate for initial diagnosis of coronavirus disease 2019 (COVID-19) to replace NP/OP swabs, especially for the person who does not produce sputum. COVID-19 cannot be excluded when the test using saliva is negative, and it is necessary to retest using NP/OP swabs.

Report on the External Quality Assessment Scheme of Serologic Tests for Syphilis in Korea (2016–2017)

The 2016–2017 surveys on the external quality assessment scheme for serologic tests for syphilis in Korea were conducted by the Korean Association of External Quality Assessment Service. Proficiency testing (PT) panels consisting of three pooled serum samples were shipped to 430 and 432 laboratories participating in the program in the 1st and 2nd trials of 2016 and 465 and 503 laboratories in the 1st and 2nd trials of 2017, respectively. The rates of returning results were 94.2% and 50.2% for non-treponemal and treponemal tests, respectively, in the 1st trial of 2016; 94.7% and 49.5% in the 2nd trial of 2016; 94.2% and 49.5% in the 1st trial of 2017; and 92.8% and 48.7% in the 2nd trial of 2017, respectively. The most commonly used methods for non-treponemal tests were rapid plasma reagin (RPR) card test, followed by RPR turbidoimmunoassay and venereal disease research laboratory tests. The most commonly used methods for treponemal tests were Treponema pallidum particle agglutination, followed by immunochromatographic assay, Treponema pallidum latex agglutination, chemiluminescence immunoassay, and fluorescent treponemal antibody-absorption. The accuracy rates of the 2017 PT for non-treponemal and treponemal tests were 92.5%–99.8% and 93.3%–100.0%, respectively, which were significantly lower compared to the 98.4%–100.0% and 97.0%–100.0% in 2016. A possible explanation for the lower accuracy rates in the 2017 PT survey is the matrix effect caused by pooling multiple individual serum samples. These data suggest that pooling of serum samples obtained from a small number of donors may help avoid the matrix effect affecting standard materials used for syphilis serology PT.

Internal Quality Assurance Status of Stool Examination as Assessed by a Questionnaire in Korean Clinical Laboratories

This study aimed to survey the status of quality control (QC) assurance for stool examinations at clinical laboratories in Korea. We sent a questionnaire related to QC practices in stool examination by electronic mail to Korean clinical laboratories that performed stool examination. Overall, 20 of the 39 laboratories (51.3%) reported performing stool concentration methods, and 28 (71.8%) examined the slides using only saline. A large proportion (74.4%) of respondents did not check the internal QC because of the restriction of appropriate control materials. Only four laboratories (10.3%) checked the reactivity of the dye solution routinely. For appropriate external QC systems, QC slides (43.6%) were preferred, followed by QC materials (30.8%), virtual slides (17.9%), and a combination of the above options (7.7%). The most commonly observed parasites in stool samples at the clinical laboratories were Clonorchis sinensis (75%), followed by Endolimax nana, Enterobius vermicularis, and Entamoeba coli. The present study describes the difficulties in internal QC assessment due to the absence of standardized QC materials and systems. We hope the findings of this report will provide a foundation for a QC assessment program for stool examinations in the near future.

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.

Detection of Intestinal Parasites in Diarrhea Samples Using Various Diagnostic Methods and Evaluation of the Stability of In-house Quality Control Materials for Stool Examination

BACKGROUND: Because of a lack of quality control (QC) materials, stool examination has not been standardised. This study examined intestinal parasites in diarrhea specimens to manufacture and evaluate the performance stability of QC materials for stool examination. METHODS: This study examined diarrhea specimens submitted for stool culture. Microscopic examination was performed using the direct smear and formalin-ether concentration method (Military General Laboratory, MGL). Enzyme-linked immunosorbent assay (ELISA) kits (R-Biopharm AG, Germany) and xTAG Gastrointestinal Pathogen Panel (Luminex Corp., USA) were used for the three major protozoa: Cryptosporidium parvum, Giardia lamblia, and Entamoeba histolytica. Polymerase chain reaction (PCR) was performed for Dientamoeba fragilis and Blastocystis hominis. The QC materials for stool examination were generated using Diphyllobothrium nihonkaiense ova. The manufactured QC materials were evaluated under different storage conditions, with varying preservatives, temperatures, and storage times. RESULTS: From November 2015 to April 2016, 82 diarrhea specimens were collected and tested. All results from microscopy and ELISA were negative; C. parvum (n=2) and G. lamblia (n=1) were detected by xTAG, while D. fragilis (n=10) and B. hominis (n=2) were detected by PCR. High- and low-concentration QC materials were manufactured. Using the high-concentration QC material, ova were observed in all storage conditions using MGL. Using the low-concentration QC material, the ova were observed until 14 days, but not after 3 weeks. CONCLUSIONS: It should be considered for making QC materials for stool examinations that focus on D. fragilis and B. hominis frequently found in Korea and with the caution to the low-concentration of QC materials could be unstable.

Comparison of the Bruker Biotyper and VITEK MS Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Systems Using a Formic Acid Extraction Method to Identify Common and Uncommon Yeast Isolates

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and accurate identification of clinical yeast isolates. In-tube formic acid/acetonitrile (FA/ACN) extraction is recommended prior to the analysis with MALDI Biotyper, but the direct on-plate FA extraction is simpler. We compared the Biotyper with the VITEK MS for the identification of various clinically relevant yeast species, focusing on the use of the FA extraction method. METHODS: We analyzed 309 clinical isolates of 42 yeast species (four common Candida species, Cryptococcus neoformans, and 37 uncommon yeast species) using the Biotyper and VITEK MS systems. FA extraction was used initially for all isolates. If ‘no identification' result was obtained following the initial FA extraction, these samples were then retested by using FA (both systems, additive FA) or FA/ACN (Biotyper only, additive FA/ACN) extraction. These results were compared with those obtained by sequence-based identification. RESULTS: Both systems correctly identified all 158 isolates of the four common Candida species after the initial FA extraction. The Biotyper correctly identified 8.7%, 30.4%, and 100% of 23 C. neoformans isolates after performing initial FA, additive FA, and FA/ACN extractions, respectively, while VITEK MS identified all C. neoformans isolates after the initial FA extraction. Both systems had comparable identification rates of 37 uncommon yeast species (128 isolates), following the initial FA (Biotyper, 74.2%; VITEK MS, 73.4%) or additive FA (Biotyper, 82.0%; VITEK MS, 73.4%). CONCLUSIONS: The identification rate of most common and uncommon yeast isolates is comparable between simple FA extraction/Biotyper method and VITEK MS methods, but FA/ACN extraction is necessary for C. neoformans identification by Biotyper.

Increasing Burden of Nontuberculous Mycobacteria in Korea

No abstract available.

Performance Evaluation of Automated Clinical Chemistry Analyzer for Indocyanine Green (ICG) R15 Test

BACKGROUND: The conventional indocyanine green retention rate at 15 minutes (ICG R15) test is inefficient and inconvenient because it requires the use of a manual spectrophotometer and several samples per patient. This study aimed to establish the automation of the ICG R15 test using an automated clinical chemistry analyzer, and to evaluate the calculation of R15 with a small number of samples. METHODS: The performance of the AU5832 (Beckman Coulter, USA) for determining ICG concentration was evaluated in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines. The R15 results for 77 patients determined by spectrophotometry and AU5832 were compared. We evaluated the calculation of R15 with three samples, except for one sample in which the results had been obtained previously, at 5, 10, and 15 minutes after injection of ICG into the patients, and compared the results with those obtained with four samples. RESULTS: The automated ICG test using the AU5832 system showed proper performances according to CLSI. Although the difference in the R15 results between the two methods was within the 95% confidence interval, the R15 was adjusted by the regression equation because it was slightly lower according to the automated method compared with the manual method. The R15 with three samples (0, 5, and 15 minutes) showed the best correlation with conventional R15 with four samples (r2=0.996). Compared with the manual method, the R15 result using the AU5832 showed excellent agreement with four samples (kappa value 0.904) and with three samples (kappa value 0.880). CONCLUSIONS: The ICG R15 test using the AU5832 system is comparable with the conventional method in clinical use.

Clinical and Hematological Effects of Tocilizumab on Serum Hepcidin, Anemia Response and Disease Activity in Patients with Active Rheumatoid Arthritis

OBJECTIVE: The purpose of this study is to evaluate the clinical and hematological effects of tocilizumab in active rheumatoid arthritis (RA) patients. METHODS: Fourteen patients with active RA were enrolled in this study. The patients received tocilizumab 8 mg/kg intravenously every four weeks for 6 months. Disease activity, anemia-related factors including serum hepcidin-25, and hematological parameters were monitored at baseline and at 1, 3, and 6 months after the initiation of treatment. RESULTS: Significant reductions in tender joint count, swollen joint count, visual analogue scale, erythrocyte sedimentation rate (ESR), and C-reactive (CRP) protein plus reductions in a 28-joint disease activity score were observed within one month after the first tocilizumab treatment. These effects lasted throughout the six-month study period. In addition, significant improvements in anemia-related factors such as hepcidin-25, ferritin, iron, hemoglobin, red blood cell counts and mean corpuscular volume were observed during the treatment period. Hematological parameters were improved with reductions in counts for leukocytes, monocytes, neutrophils, and platelets. The lymphocyte counts and their subset numbers were unchanged. Changes in hepcidin levels showed significant correlation with changes in CRP, ESR, ferritin, hemoglobin and counts for red blood cells, leukocytes, and neutrophils during the treatment period. CONCLUSION: This study demonstrates that tocilizumab significantly and meaningfully reduces disease burden in patients with active RA. In addition, tocilizumab diminishes the levels of inflammatory anemia by inhibiting hepcidin production. These clinical data provide evidence of a favorable outcome from tocilizumab in RA.

Mucosal-associated Invariant T cells: A New Player in Innate Immunity

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that are restricted by the non-classical major histocompatibility complex class-1b molecule MR1. MAIT cells recognize riboflavin (vitamin B2) derivatives in a MR1-dependent manner. Following antigen recongnition, MAIT cells rapidly produce Th1/Th17 cytokines, such as interferon-gamma and interleukin-17, in an innate-like manner. MAIT cells maintain an activated phenotype throughout the course of an infection, secrete inflammatory cytokines, and have the potential to directly kill infected cells, thus, playing an important role in controlling the host response. In this review, we discuss current knowledge regarding the role of MAIT cells in infectious diseases, cancers, and autoimmune diseases.

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Acute Cholecystitis

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play crucial roles in a variety of diseases, including autoimmunity, infectious diseases, and cancers. However, little is known about the roles of these invariant T cells in acute cholecystitis. The purposes of this study were to examine the levels of MAIT cells and NKT cells in patients with acute cholecystitis and to investigate potential relationships between clinical parameters and these cell levels. Thirty patients with pathologically proven acute cholecystitis and 47 age- and sex-matched healthy controls were enrolled. Disease grades were classified according to the revised Tokyo guidelines (TG13) for the severity assessment for acute cholecystitis. Levels of MAIT and NKT cells in peripheral blood were measured by flow cytometry. Circulating MAIT and NKT cell numbers were significantly lower in acute cholecystitis patients than in healthy controls, and these deficiencies in MAIT cells and NKT cell numbers were associated with aging in acute cholecystitis patients. Notably, a reduction in NKT cell numbers was found to be associated with severe TG13 grade, death, and high blood urea nitrogen levels. The study shows numerical deficiencies of circulating MAIT and NKT cells and age-related decline of these invariant T cells. In addition, NKT cell deficiency was associated with acute cholecystitis severity and outcome. These findings provide an information regarding the monitoring of these changes in circulating MAIT and NKT cell numbers during the course of acute cholecystitis and predicting prognosis.

Constitutional Chromosomal Abnormality Identified in a Sibling Donor After Bone Marrow Stem Cell Transplantation in a Pediatric Patient with Acute Megakaryoblastic Leukemia

No abstract available.

Comparison of AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR for Detection of Mycobacterium tuberculosis Complex in Routine Clinical Practice

The AdvanSure tuberculosis/non-tuberculous mycobacterium (TB/NTM) PCR (LG Life Science, Korea) and COBAS TaqMan Mycobacterium tuberculosis (MTB) PCR (Roche Diagnostics, USA) are commonly used in clinical microbiology laboratories. We aimed to evaluate these two commercial real-time PCR assays for detection of MTB in a large set of clinical samples over a two-year period. AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR were performed on 9,119 (75.2%) and 3,010 (24.8%) of 12,129 (9,728 respiratory and 2,401 non-respiratory) MTB specimens, with 361 (4.0%) and 102 (3.4%) acid-fast bacilli (AFB)-positive results, respectively. In MTB culture, 788 (6.5%) MTB and 514 (4.2%) NTM were identified. The total sensitivity and specificity of the AdvanSure assay were 67.8% (95% confidence interval [CI], 63.9-71.6) and 98.3% (95% CI, 98.0-98.6), while those of the COBAS TaqMan assay were 67.2% (95% CI, 60.0-73.8) and 98.4% (95% CI, 97.9-98.9), respectively. The sensitivities and specificities of the AdvanSure and COBAS TaqMan assays for AFB-positive and AFB-negative samples were comparable. Furthermore, the AdvanSure assay showed fewer invalid results compared with the COBAS TaqMan assay (5.0 vs. 20.4 invalid results/1,000 tests, P<0.001). AdvanSure assay represents a comparable yet more reliable method than COBAS TaqMan for the identification of mycobacteria in routine clinical microbiology.

Direct Measurement of Serum Immunoglobulin Heavy and Light Chain Pairs for Identification of Monoclonal Gammopathy and a Performance Comparison with Capillary Electrophoresis

BACKGROUND: Determination of monoclonal gammopathy through conventional protein electrophoresis is sometimes difficult because of the presence of large proteins such as haptoglobin and transferrin, which may obscure the results. Ambiguity in an electrophoresis band can give rise to confusion or difficulty in interpretation. The heavy chain/light chain assay (HLC assay) using Hevylite antibody (The Binding Site, UK) has recently been developed for the accurate measurement of monoclonal proteins. We compared the immunotyping (IT) profiles to the immunoglobulin (Ig) heavy/light chain measurements obtained using the HLC assay and observed the ratios between intact Ig kappa and lambda. METHODS: We collected 35 and 28 sera from patients with suspicious and definitive monoclonal protein, respectively. Then we performed serum protein electrophoresis (SPEP) and IT by Capillarys2 (Sebia, USA). Monoclonal protein production was investigated using Freelite antibody (The Binding Site) and specific Ig(G, A)kappa and Ig(G, A)lambda Hevylite antibodies. The results were analyzed using PASW 18.0 for Windows (IBM, USA). RESULTS: Direct measurement of Ig heavy/light chains showed discordant IT results for 12 (34.2%) of 35 patients' sera with suspicious SPEP pattern and identical IT results for 28 patients' sera with definitive monoclonal peak in the SPEP results. Overall, the results of the HLC assay and IT showed good agreement (kappa=0.718, P=0.000 by cross-tabulation Gamma, Kappa analysis). CONCLUSIONS: The results of direct measurement of serum Ig heavy chain/light chain pairs were comparable to those of IT and were helpful for determination of monoclonality in the case of ambiguous electrophoresis results. Measurement of the heavy chain/light chain pair ratio also allowed precise quantification of the monoclonal Igs with ambiguous electrophoresis patterns and identification or discrimination of clonality.

Comparison between V-Tubes and BD Vacutainer Tubes for Use in Laboratory Tests

BACKGROUND: Vacuum tubes are widely used in clinical laboratories for routine tests. We compared a newly developed V-tube (AB Medical, Korea) and BD tubes (BD, USA) in common clinical assays, i.e., hematological, chemical, and immunological tests. METHODS: In total, 100 volunteers comprising 79 patients and 21 healthy volunteers were recruited and peripheral blood samples were collected with 2 brands of EDTA tubes and serum-separating tubes (SSTs). EDTA-tube samples were evaluated using 16 routine hematological tests. The SST samples were analyzed for 32 routine chemical parameters and 3 thyroid hormones. The results were statistically analyzed using the paired t-test and Bland-Altman plot. In addition, the stability of each analyte in 2 brands of vacutainers was evaluated. The results of the hematological tests at t=0 hr were compared with those at t=72+/-2 hr, and the results of the chemical parameters and thyroid hormones at t=0 hr were compared with those at t=72+/-2 hr and t=168+/-2 hr for each tube. RESULTS: Paired t-test analysis revealed that the test results of 16 routine hematological parameters, 32 routine chemical parameters, and 3 thyroid hormones showed clinically allowable differences between the 2 brands of vacuum tubes (t=0 hr). The results obtained when using V-tubes showed a statistically significant correlation with those obtained when using BD tubes. The stability of each analyte was similar in both vacuum tubes. Except for 10 parameters (white blood cell count, mean corpuscular volume, basophils [%], mean corpuscular hemoglobin concentration, monocytes [%], phospholipid, sodium, potassium, chloride, and free T4), all parameters showed significant but clinically allowable differences with regard to storage duration. CONCLUSIONS: The newly developed V-tube vacutainers provide a suitable alternative to BD tubes in common clinical laboratories.

First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea / 전남의대학술지

It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases.

Gonadotropin-releasing Hormone Stimulation Test for Precocious Puberty / 대한진단검사의학회지

BACKGROUND: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard to identify central precocious puberty (CPP). This test requires multiple blood samples at different time points to measure gonadotropin levels, and is therefore expensive, time-consuming, and uncomfortable for patients. We aimed to simplify the GnRH stimulation test to require fewer blood samples. METHODS: A study of 166 girls with precocious puberty was undertaken. Blood samples were obtained at 0, 15, 30, 45, 60, 90, and 120 min after GnRH administration, and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated and ROC curves were constructed. RESULTS: One hundred and twenty-eight patients (77.1%) were diagnosed for CPP. Peak LH levels were achieved 30 min after GnRH stimulation in patients with CPP. Further, 98.4% of the 45-min samples were diagnostic for CPP, and the cumulative frequency of LH values of > or =5 IU/L was 100% at 45 min. Using this cut-off value for LH, the ROC curve for LH at 45 min showed the highest sensitivity (98.4%) and specificity (100%) in the diagnosis of CPP. CONCLUSIONS: Values of LH measured from a single blood sample obtained at 45 min in the GnRH stimulation test may be adequate for the diagnosis of CPP. Two samples, taken at 30 and 45 min after stimulation, were able to accurately diagnose CPP in 100% of the patients in this study.

First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea / 전남의대학술지

It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases.