Jin-Tae Suh

Utility of Procalcitonin as an Early Diagnostic Marker of Bacteremia in Patients with Acute Fever

Purpose Procalcitonin (PCT) is a current, frequently used marker for severe bacterial infection. The aim of this study was to assess the ability of PCT levels to differentiate bacteremic from nonbacteremic patients with fever. We assessed whether PCT level could be used to accurately rule out a diagnosis of bacteremia. Materials and Methods Serum samples and blood culture were obtained from patients with fever between August 2008 and April 2009. PCT was analyzed using a VIDAS® B.R.A.H.M.S PCT assay. We reviewed the final diagnosis and patient histories, including clinical presentation and antibiotic treatment. Results A total of 300 patients with fevers were enrolled in this study: 58 with bacteremia (positive blood culture) (group I); 137 with local infection (group II); 90 with other diseases (group III); and 15 with fevers of unknown origin (group IV). PCT levels were significantly higher in patients with bacteremia than in those with non-bacteremia (11.9 ± 25.1 and 2.5 ± 14.7 ng/mL, respectively, p < 0.001). The sensitivity and specificity were 74.2% and 70.1%, respectively, at a cut-off value of 0.5 ng/mL. A serum PCT level of < 0.4 ng/mL accurately rules out diagnosis of bacteremia. Conclusion In febrile patients, elevated PCT may help predict bacteremia; furthermore, low PCT levels were helpful for ruling out bacteremia as a diagnosis. Therefore, PCT assessment could help physicians limit the number of prescriptions for antibiotics.

Mean platelet volume/platelet count ratio in hepatocellular carcinoma

Mean platelet volume (MPV) has been actively investigated in liver disease such as steatosis, cirrhosis and hepatitis. Recently, MPV/platelet count (PC) ratio has been proposed as a predictor of long-term mortality after myocardial infarction. As PC is known to be decreased in various liver diseases such as cirrhosis, hepatosplenomegaly and malignancy, we planned to evaluate MPV/PC ratio in patients with hepatocellular carcinoma (HCC) in this study. Mean of MPV levels showed significant difference, which were 8.69 fl (range 6.7–12.2 fl) in patients group and 8.02 fl in control group (range 6.7–11.0 fl). In receiver operating characteristic (ROC) curve analysis, the MPV/PC ratio (fl/(109/l)) presented 74.5% of sensitivity and 96.5% of specificity at the criterion > 0.0491 (area under the curve (AUC) = 0.884), while MPV alone showed 57.4% of sensitivity and 81.4% of specificity at the criterion > 8.4 fl. Further studies should evaluate underlying pathogenic mechanisms of MPV/PC ratio difference and various possibilities of this ratio as an indicator of presence of a tumor in HCC.

Mean platelet volume in Korean patients with acute ischemic stroke: a gender difference.

Mean platelet volume (MPV) is the most commonly used measure of platelet size [1]. MPV is determined directly from the platelet distribution curve analysis in automated hematology analyzers and used as a surrogate marker of platelet production and function [2, 3]. We previously studied that MPV showed significant differences in Korean patients with hepatic diseases [4]. Recently, Ha et al. reported a very interesting article about stroke prediction with MPV. Some other recent studies have presented that elevated MPV is linked with hypertension, peripheral artery disease and stroke, all of which are related to atherosclerosis [1, 2, 5, 6]. It has been also reported that larger platelets are enzymatically and metabolically more active and thrombophilic than smaller ones, although it is still on a debate [5, 7]. Therefore, in this study, we planned to investigate this platelet index in Korean patients with acute ischemic stroke (AIS). The study included 166 patients with newly diagnosed with AIS and 8 individuals of transient ischemic attack (TIA) for patients group at Kyung Hee University Hospital, a tertiary teaching hospital in Seoul, Korea, between November 2010 and August 2011. For the control group, 311 subjects for medical check-ups were enrolled in our hospital, which were used as controls in the previous study [4]. Patients were diagnosed to AIS or TIA by physical examinations and radiologic findings. These clinical data were collected through a medical chart review. ANOVA followed by post hoc analysis were used to compare means in our study. Blood sampling was performed through venepuncture and MPV was measured using EDTA-containing tubes in Advia 2120 (Bayer Diagnostics, Tarrytown, NY, USA) within 2 h. The statistical analyses were performed with MedCalc v11.6 (MedCalc Software, Mariakerke, Belgium) and Excel 2007 (Microsoft Corporation, Redmond, WA). Statistical significance was set at p1⁄4 0.05. Mean age of patient group was 54.33 (14–84 year), and male to female ratio was 108:58. Mean of MPV levels was 7.92 fl (6.5–12.1 fl) in patient group and did not significantly increased in patient group than control group. However, there was a gender difference, which showed increased MPV levels in female AIS patients than male (Figure 1). Cemin et al. [7] also pointed out gender specificity that MPV is higher in female than in male with AMI. Therefore, the further study with more patients should be followed to assess the usefulness of MPV in AIS and investigate the meaning of gender difference of MPV in various atherosclerotic diseases. We previously reported that there was a gender difference in protein S activity of ischemic stroke patients [8]. Investigation of gender differences in various coagulationassociated laboratory tests must be followed in the near future.

Clinical usefulness of free light chain concentration as a tumor marker in multiple myeloma.

Monoclonal immunoglobulin, as a marker for monoclonal gammopathy, is evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). However, PEP and IFE are not satisfactory in sensitivity, objectivity, and facility. Recently, a highly sensitive, automated immunoassay for measurement of free light chain (FLC) concentrations in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. To explore the clinical usefulness of measurement of FLC concentrations, we measured the κ and λ FLC concentrations and calculated the κ/λ FLC ratios for three groups [multiple myeloma (MM), other diseases, and control] and compared the results of the FLC assay with the results of PEP or IFE. The concentrations of serum κ and λ FLCs and the κ/λ FLC ratios for the MM group and non-MM groups were distinct. In the MM group, some sera and urine samples had no evidence of M protein on PEP and IFE, but FLC assay showed abnormal concentrations of FLCs and abnormal κ/λ FLC ratios in most cases. As compared with the PEP, the κ/λ FLC ratio revealed higher sensitivity in all diagnostic ranges with different cutoff values. Particularly, when the cutoff value 2.0 for κ/λ FLC ratio was used, specificity and positive predictive value were largely improved than when the cutoff values 1.2 and 1.5 were used. These findings indicated that FLC assay enables to detect myeloma patients with very low M protein due to early stage or after therapy and to distinguish patients with monoclonal increase of FLC from patients with polyclonal increase of FLC due to other conditions, particularly using κ/λ FLC ratio 0.3–2.0 as a diagnostic range. Despite some technical limitations of the assay, the incorporation of κ/λ FLC ratios with FLC concentrations is useful in the detection of M protein, particularly with negative serum or urine IFE results, and differentiation of monoclonal gammopathies from patients with polyclonal increase in FLC due to other conditions.

Mean platelet volume in Korean patients with hepatic diseases.

Mean platelet volume (MPV) is a parameter generated by fully automated blood count analyzers as a part of routine complete blood count, and a useful platelet function index that can show platelet a...

Comparison of Diagnostic Performance of Three Real-Time PCR Kits for Detecting Mycobacterium Species

Purpose PCR is widely used for rapidly and accurately detecting Mycobacterium Species. The purpose of this study was to assess the diagnostic performance of three real-time PCR kits and evaluate the concordance with two older PCR methods. Materials and Methods Using 128 samples, the five PCR methods were assessed, including an in-house PCR protocol, the COBAS Amplicor MTB, the COBAS TaqMan MTB, the AdvanSure TB/NTM real-time PCR, and the Real-Q M. tuberculosis kit. The discrepant results were further examined by DNA sequencing and using the AdvanSure Mycobacteria Genotyping Chip for complete analysis. Results For Mycobacterium tuberculosis (MTB) detection, all five kits showed 100% matching results (positive; N = 11 and negative; N = 80). In non-tuberculous mycobacterium (NTM) discrimination, the AdvanSure yielded two true-positive outcomes from M. intracellulare and one false positive outcome, while the Real-Q resulted in one true-positive outcome and one false negative outcome for each case and another false negative result using the provided DNA samples. Conclusion Real-time PCR, yielded results that were comparable to those of the older PCR methods for detecting MTB. However, there were disagreements among the applied kits in regard to the sample test results for detecting NTM. Therefore, we recommend that additional confirmatory measures such as DNA sequencing should be implemented in such cases, and further research with using a larger numbers of samples is warranted to improve the detection of NTM.

Detection of t(3;5) and NPM1/MLF1 rearrangement in an elderly patient with acute myeloid leukemia: clinical and laboratory study with review of the literature.

We present a novel case of acute myeloid leukemia with an NPM1/MLF1 rearrangement in a 78-year-old Korean woman. The bone marrow chromosome study showed a complex karyotype: 46,XX,t(2;13) (q13;q32),der(3)t(3;5)(q25.1;q34),der(5)del(5)(?q31q34)t(3;5),inv(9)(p11q13)c,del(20)(q11.2)[13]/49,idem,+5,+8,+der(13)t(2;13)[7]. Multiplex gene rearrangement testing, cloning, and sequencing analyses revealed an NPM1/MLF1 fusion rearrangement between exon 6 of NPM1 (ENSG00000181163) and exon 2 of MLF1 (ENSG00000178053). Although t(3;5)(q25.1;q34) or the NPM1/MLF1 rearrangement has been reported mostly as a sole karyotypic abnormality in younger patients, it should also be considered in elderly patients with complex chromosomal abnormalities in acute myeloid leukemia or myelodysplastic syndrome.

Investigation of mutation distribution in DNA gyrase and topoisomerase IV genes in ciprofloxacin-non-susceptible Enterobacteriaceae isolated from blood cultures in a tertiary care university hospital in South Korea, 2005–2010

This study investigated the distribution of mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes and compared the distribution of these mutations with the distribution of plasmid-mediated quinolone resistance (PMQR) genes and extended-spectrum β-lactamase (ESBL) production in 101 ciprofloxacin-non-susceptible Enterobacteriaceae from blood culture isolates (80 Escherichia coli and 21 Klebsiella pneumoniae) isolated in Kyung Hee University Hospital, a tertiary care university hospital in Seoul, South Korea. Among the 101 isolates, 80 (79.2%) contained PMQR genes and 28 (27.7%) produced ESBL. Mutations in the gyrA and parC genes were observed more frequently than in the gyrB and parE genes as well as more frequently in E. coli than in K. pneumoniae isolates, even in the same ciprofloxacin minimum inhibitory concentration (MIC) range of the two species. In E. coli isolates, the distribution of the codon 529 mutation (Ile→Leu) in parE was increased with an increase in the ciprofloxacin MIC. An increase in high-level resistance to quinolones may occur with double mutations compared with a single mutation in gyrA as well as with additional mutations in parC. However, this finding could not be applied to ciprofloxacin-resistant K. pneumoniae. A higher level of quinolone resistance may be correlated with an additional mutation in parE, especially Ile529→Leu.

Combined Bacillus licheniformis and Bacillus subtilis infection in a patient with oesophageal perforation

Species of the genus Bacillus are a common laboratory contaminant, therefore, isolation of these organisms from blood cultures does not always indicate infection. In fact, except for Bacillus anthracis and Bacillus cereus, most species of the genus Bacillus are not considered human pathogens, especially in immunocompetent individuals. Here, we report an unusual presentation of bacteraemia and mediastinitis due to co-infection with Bacillus subtilis and Bacillus licheniformis, which were identified by 16S RNA gene sequencing, in a patient with an oesophageal perforation.

Mean platelet volume in pediatric chronic kidney diseases

To the editor Mean platelet volume (MPV) is the most commonly used measure of platelet size and a useful platelet function index that can show platelet activation and its production rate in bone marrow [1, 2]. MPV has been studied in various disease groups other than hematologic disease, and we have reported this platelet index in hepatic diseases and acute ischemic stroke [1, 2]. It has been suggested that high-grade systemic inflammatory diseases, such as rheumatoid arthritis, present with low levels of MPV [3]. However, there were some needs to evaluate MPV in low-grade or localized inflammatory diseases. Therefore, to investigate MPV in chronic localized inflammation such as glomerulonephritis, we planned to investigate MPV in Korean pediatric patients with chronic kidney diseases (CKD). This study was done at Kyung Hee University Hospital, a tertiary teaching hospital, between January 2011 and February 2012. The study included total 200 individuals for patients group, which were subdivided into 71 with IgA nephropathy (IgAN), 52 with mesangeal proliferative glomerulonephritis (MesPGN), and 77 with nephrotic syndrome (NS). The diagnosis and classification of CKD were based on renal biopsy results and clinical criteria. Since it was not easy to recruit normal pediatric patients from those who visited the pediatric department of our hospital, we had to compare MPVs with a disease control that had inflammatory signs in the upper respiratory tract (URT). Seventy pediatric patients with acute inflammatory symptoms in regions of URT were enrolled for age-matched disease controls (Table 1). Mean age of patient group was 11.64 (range 2–20 years), and male to female ratio was 75:125. Blood sampling was performed through venepuncture and MPV was measured using EDTA-containing tubes in Advia 2120 (Bayer Diagnostics, Tarrytown, NY, USA) within 2 hours. ANOVA followed by post-hoc analysis were used to compare means in our study. The statistical analyses were performed with MedCalc v11.6 (MedCalc Software, Mariakerke, Belgium) and Excel 2007 (Microsoft corporation, Redmond, WA). Statistical significance was set at p< 0.05. Based on the comparison of MPV between one disease control and three CKD groups, a significant difference was observed (Figure 1): MPV was markedly increased in IgAN and MesPGN than the other two groups (p1⁄4 0.01). Several cytokines, inflammatory mediators and growth factors may affect MPV, with subsequent production of larger and more reactive platelets [1, 3–6]. Because bone marrow might be exposed longer in chronic inflammation than acute conditions, inflammatory mediators have more time to make an impact upon platelet size. In this study, we were able to compare the change in MPVs between chronic and acute inflammation types by designating a patient group that showed acute inflammatory symptom and signs in the URT as the control group. Also, we confirmed whether there are meaningful differences in MPVs at IgAN and MesPGN that are known to show more frequent inflammatory findings such as cell proliferations, based on pathologic findings in renal biopsy. In such circumstances, MPV showed increased levels in IgAN and MesPGN than NS and acute diseases like upper respiratory infection. Therefore, we carefully suggest that the type, duration or degree of inflammation may affect the levels of MPV. However, we also note that there were some limitations to our study. First, subjects in the control