Woo-In Lee

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.

FISH-negative cryptic PML–RARA rearrangement detected by long-distance polymerase chain reaction and sequencing analyses: a case study and review of the literature

Although a normal karyotype according to conventional cytogenetic analysis in association with cryptic t(15;17) has been infrequently reported in cases of acute promyelocytic leukemia (APL), a fluorescence in situ hybridization (FISH)-negative cryptic PML-RARA rearrangement is even more rare, with only 12 such APL cases of FISH-negative cryptic PML-RARA rearrangements in the literature. Reported here is an additional clinical APL case with a FISH-negative cryptic PML-RARA rearrangement, confirmed by long-distance DNA polymerase chain reaction method. Discussion includes a relevant literature review of similar cases. DNA-PCR can be a useful tool for the analysis of complex and cryptic rearrangements.

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.

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.

The prevalence of "anti-HBc alone" and HBV DNA detection among anti-HBc alone in Korea.

The “anti‐HBc alone” is a frequent serological finding in clinical laboratories, making it difficult to determine whether the HBV infection has resolved. The objectives of this study were to investigate the prevalence of anti‐HBc alone and HBV DNA detection (occult HBV infection) among anti‐HBc alone, and to describe the demographic and clinical characteristics of anti‐HBc alone. A total of 17,677 sera referred from the Health Promotion Center (HPC group, 4,014 sera) as well as all the hospital clinical departments (Patient group, 13,663 sera) were tested for HBs Ag, anti‐HBc, and anti‐HBs. HBV DNA test using real‐time PCR was performed on 230 anti‐HBc alone. The prevalence of anti‐HBc alone was 8.9%, significantly higher in the Patient group than in the HPC group. The prevalence of anti‐HBc was higher in men than women and was increased with age. Very low levels of HBV DNA were found in only 4 (1.7%) out of 230 subjects with anti‐HBc alone. They were patients with conditions unrelated to chronic liver disease. Considering the high prevalence of anti‐HBc alone, the frequency of occult HBV infection among anti‐HBc alone was unexpectedly low. In addition, HBV viral load was low in these patients. Further studies are required to determine the clinical significance and infectivity of anti‐HBc alone, in conjunction with very low levels of HBV DNA and to standardize the detection methodology for both anti‐HBc alone and HBV DNA. J. Med. Virol. 82:1508–1514, 2010.

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.

[HLA-B27 subtypes in Korean patients with ankylosing spondylitis].

BACKGROUND HLA-B27 is strongly associated with ankylosing spondylitis (AS), and its subtypes differ in their ethnic distribution. Studies worldwide have shown that B*2701, B*2702, B*2704, B*2705, B*2707, B*2708, B*2714, B*2715, and B*2719 are AS-predisposing subtypes, whereas B*2706 and B*2709 are reported to be negatively associated with AS. The aim of this study was to investigate HLA-B27 polymorphism and clinical features according to subtypes in Korean patients with AS. METHODS Two hundred thirty samples from patients with impression of AS were analyzed by polymerase chain reaction using a sequence-specific primers (PCR-SSP) method. Pel-Freez SSP Unitray HLA-B*27 kit (Dynal Biotech, USA) including 16 primers was used to define HLA-B27 subtypes from B*2701 to B*2735. RESULTS Among 230 samples from patients with impression of AS, 171 were HLA-B27 positive, and among 160 patients diagnosed as AS, 154 (96.3%) were HLA-B27 positive, while 17 patients not diagnosed as AS were HLA-B27 positive. Among 154 HLA-B27 positive patients with AS, 142 (92.2%) were typed as B*2705 and 9 (5.8%) were typed as B*2704. Three cases (1.9%) could be interpreted only variously because of their HLA-B27 homogeneous alleles. Between B*2705 and B*2704, no specific HLA-B27 subtype appeared to contribute to AS susceptibility (P=0.60). Difference in clinical features between B*2705 and B*2704 could not be found in this study (P>0.05). CONCLUSIONS This study verified that HLA-B27 (96.3%) is strongly associated with AS and identified that the major subtypes of HLA-B27 positive patients with AS in Korea are B*2705 (92.2%) and B*2704 (5.8%).

Mean platelet volume and mean platelet volume/platelet count ratio in infective endocarditis

Abstract Infective endocarditis (IE), an infection of the endocardial surface, frequently leads to life-threatening complications, such as thromboembolism due to platelet activation. We investigated the mean platelet volume (MPV) in Korean patients with IE and the serial changes thereof, in comparison with other laboratory parameters. We analyzed 248 MPV results from 22 patients diagnosed with IE in our hospital between January 2011 and April 2012. MPV was measured with an Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown, NY) using EDTA-containing tubes. The mean MPV differed significantly between the patient and control groups, 8.74 vs. 7.96 fl, respectively. In addition, the platelet count and MPV/platelet count ratio were significantly decreased in the patient group. The total platelet mass and platelet size in IE might be increased. Further studies should examine more patients to verify the changes in the MPV and MPV/platelet count ratio in IE and assess in greater detail the relationship between MPV and thrombotic complications caused by platelet activation.

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

Acute myeloid leukemia associated with t(1;3)(p36;q21) and extreme thrombocytosis: a clinical study with literature review

We present an unusual case study on acute myeloid leukemia associated with t(1;3) and extreme thrombocytosis, along with a thorough review on relevant literature of t(1;3) cases (58 patients). On the basis of this study and literature review, thrombocytosis (>400,000/μL) is a relatively common finding in one third of patients with t(1;3), whereas increase of platelet count by more than 1,000,000/μL is an extremely rare phenomenon, even among patients with t(1;3). To our knowledge, this study is the only documented case that recorded more than 2,000,000/μL of extreme thrombocytosis in a de novo acute myeloid leukemia patient with t(1;3) at initial diagnosis. Because only a few patients with t(1;3) responded to conventional chemotherapy, more aggressive therapy such as stem-cell transplantation should be considered to improve patient survival in t(1;3) cases.