Gayoung Lim

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.

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.

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.

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.

Trends in Five-year Blood Cultures of Patients at a University Hospital (2003~2007)

Background: Blood culture is the definitive method for the diagnosis and treatment of bacteremia and fungemia. Analysis of blood cultures positive for pathogenic species and trends in antimicrobial susceptibility can help delineate appropriate and experimental treatment strategies. In this study, we investigated the incidence of pathogenic species and trends in antimicrobial susceptibility in blood cultures collected from 2003 to 2007 to help clinicians to determine the best methods of diagnosis and treatment. Changes between previously published analyses and this study were also investigated. Methods: Five-year blood culture results obtained at Kyung Hee University Hospital between 2003 and 2007 were analyzed to determine the bacterial and fungal species present and the antimicrobial susceptibility of the isolates. Antimicrobial susceptibility was tested by the broth microdilution method and the CLSI disk diffusion method. Results: Among the 66,437 blood cultures, 5,645 were positive. Of the positive blood cultures, 59.8% were positive for aerobic and facultative anaerobic gram-positive cocci. Coagulase-negative staphylococci (CoNS) were frequently isolated. The numbers of anaerobic species and fungi decreased over the years. Conclusion: CoNS were the microorganisms most commonly isolated from blood cultures at Kyung Hee University Hospital. The number of cultures positive for fungi was higher than that reported in previous studies, but the absolute isolation rate over five years decreased. Anaerobic species were much less frequently isolated than reported for other hospitals. (Korean J Clin Microbiol 2009;12:163-168)

Comparison of R-mix Virus Culture and Multiplex Reverse Transcriptase-PCR for the Rapid Detection of Respiratory Viruses

BACKGROUND Respiratory viral infections can become epidemic due to high contagiosity. Since there was no rapid diagnostic method for complete diagnosis in the past, diagnosis was solely made on the basis of clinical symptoms or the time of infection. With recent developments in rapid diagnostic methods like multiplex reverse transcriptase (RT)-PCR, R-mix virus culture, etc., early detection and effective treatment of respiratory viral infections is possible. Herein, we compared the efficiency of multiplex RT-PCR and the R-mix virus culture for the rapid detection of respiratory viruses. METHODS We used 96 nasopharyngeal swab specimens for culturing respiratory viruses using R-mix (Diagnostics Hybrids Inc., USA). Afterwards, multiplex RT-PCR was performed using specimens stored at -70 degrees C. RESULTS R-mix virus culture yielded positive results in 34 cases (35.4%) and multiplex RT-PCR in 73 cases (76.0%). Both methods yielded identical results in 51 cases (29 positive cases and 22 negative cases). Among 45 cases that showed different results, 40 showed negative results in R-mix virus culture and positive results in multiplex RT-PCR, and 1 showed positive result in R-mix virus culture and negative result in multiplex RT-PCR. Different viruses were detected in the remaining 4 cases by both the methods. CONCLUSIONS Multiplex RT-PCR provided faster results and had higher detection rates than R-mix virus culture. Further, unlike R-mix virus culture, multiplex RT-PCR can be used to identify new respiratory viruses. Therefore, multiplex RT-PCR is more useful than R-mix virus culture in the diagnosis of respiratory virus infection.

ABL1 gene deletion without BCR/ABL1 rearrangement in a young adolescent with precursor B-cell acute lymphoblastic leukemia: clinical study and literature review

Entire ABL1 gene deletion without BCR/ABL1 rearrangement is a rare phenomenon, with only four cases previously reported. Here we describe a fifth case of ABL1 deletion without BCR/ABL1 rearrangement in an adolescent patient with precursor B-cell lymphoblastic leukemia (B-ALL) and review the relevant literature. It is not clear how ABL1 deletion affects leukemogenesis; however, it is plausible that ABL1 deletion without BCR/ABL1 rearrangement is a rare but recurrent genetic abnormality in precursor B-ALL patients. Further studies are needed to evaluate the extent of the submicroscopic defects in chromosome 9 including ABL1 gene deletion, as well as treatment response and prognosis in long-term follow-up of such patients.

A rare case of microgranular acute promyelocytic leukemia associated with ider(17)(q10)t(15;17) in an old-age patient.

We present a rare case of microgranular variant acute promyelocytic leukemia (APL) associated with ider(17)(q10)t(15;17)(q22;q12) of an old-age patient. The initial chromosome study showed a 46,XX,del(6)(?q21q25),der(15)t(15;17)(q22;q12),ider(17)(q10)t(15;17)[10]/47,sl,+ider(17)(q10)t(15;17)[3]/46,XX[16]. FISH signals from a dual color dual fusion translocation PML-RARA probe were consistent with the results of conventional cytogenetics. Because of the rarity of ider(17)(q10)t(15;17) in microgranular APL, further studies on both gene dosage effect of this chromosomal abnormality and the influence of ider(17)(q10)t(15;17) on clinical features such as prognosis, survival, and treatment response of APL cases are recommended.

ABO discrepancy in an elderly patient with IgA kappa-type multiple myeloma

Dear Editor, Multiple myeloma, a hematologic malignancy characterized by the proliferation of a neoplastic plasma cell clone in the bone marrow, accounts for 10% of hematologic malignancies [1]. The common presenting features, such as anemia, bone pain, hypercalcemia, and increasing susceptibility to infections, are caused by the infiltration of plasma cells and changes in plasma protein [2]. Large amounts of monoclonal protein and a loss of functional antibody production can cause immunological dysfunction and distinct laboratory findings. In multiple myeloma, an ABO discrepancy can result from protein abnormalities causing rouleaux formation or pseudoagglutination in the blood group test [3]. Here, we report a novel case of ABO discrepancy in a patient with IgA kappatype multiple myeloma caused by the loss of isoagglutinin. A 78-year-old woman who had been suffering from multiple myeloma (IgA, kappa type) for 8 years was admitted for a scheduled chemotherapy. The total protein (9.6 g/dl) was elevated due to a large amount of IgA (4,430 mg/dl), whereas, the levels of uninvolved immunoglobulins were reduced (IgG, 236 mg/dl and IgM, <20 mg/dl). In the peripheral blood smear, rouleaux formation was prominent; moreover, her decreased hemoglobin level (4.5 g/ml) necessitated blood transfusion. On blood group testing, the cell type was B+; but anti-A was not detected in her serum. To confirm her blood type, the polymerase chain reaction with restriction fragment length polymorphism was performed and her genotype of ABO*B/O was revealed. She was transfused with five units of B+irradiation-filtered packed red cells without complication before initiating conventional-dose chemotherapy. ABO discrepancies can be caused by the loss of expected anti-A or anti-B isoagglutinins with agammaglobulinemia or hypogammaglobulinemia in primary and secondary immunodeficiencies [4–6]. In multiple myeloma, the levels of the uninvolved immunoglobulin isotypes are usually reduced, but an ABO discrepancy due to the loss of isoagglutinin in multiple myeloma is rarely reported. To the best of our knowledge, only a single study has reported on multiple myeloma with ABO discrepancies due to the loss of isoagglutinins (three cases) [7]. While the monoclonal chains in these cases were the IgG kappa, free lambda, and IgG lambda types, respectively, our patient had IgA kappatype monoclonality. A feature common to all of these cases was the severe loss of uninvolved IgM (Table 1). The isoagglutinins produced by blood group A or B patients consist predominantly of IgM molecules [8]. Therefore, the loss of IgM in these patients would be the reason why the Hwi-Joong Yoon and Tae Sung Park equally contributed to this work as corresponding authors.

Association between acute lymphoblastic leukemia (ALL) and der(8;9)(q10;q10): a novel case of double der(8;9) in Ph+ adult B cell ALL.

Dear Editor, Although whole-arm translocations (WATs) are relatively uncommon in hematologic malignancies, a few representative WATs are well known as a recurrent nonrandom genetic abnormality [1–3]. As far as we know, most of these dicentric WATs such as der(1;7)(q10;p10), der(1;15) (q10;q10), and der(1;18)(q10;q10) are associated with myeloid neoplasms as well as trisomy of chromosome 1q. However, WATs related to lymphoid malignancies are very sparse [3–5]. Because der(8;9)(q10;q10) has been rarely reported in the literature, detailed case reports have not been conducted until now. In this study, we present a novel acute lymphoblastic leukemia (ALL) case with double der (8;9)(q10;q10) in company with t(9;22) chromosome abnormalities, and also provide a brief review of the literature. A 49-year-old man was referred to our hospital in April 2010 because of persistent petechiae on both legs for 3 weeks. His initial complete blood count showed a hemoglobin level of 12.0 g/dL, a platelet count of 14,000/ μL and a white blood cell count of 185,800/μL with 2% neutrophil, 2% lymphocytes, and 96% blasts. A bone marrow study revealed a hypercellular marrow totally replaced by immature cells with condensed nuclear chromatin, distinct nucleoli, and scanty basophilic cytoplasm. In the flow cytometric analysis, the blasts were positive for CD10, CD19, CD22, CD34, and TdT, and negative for CD2, CD3, CD5, CD7, CD13, CD14, CD33, CD56, and myeloperoxidase. The chromosome study showed a 46,XY, der(8;9)(q10;q10),+der(8;9),t(9;22)(q34;q11.2) in 17 out of 20 metaphase cells analyzed (Fig. 1). A fluorescence in situ hybridization (FISH) study using a BCR/ABL1 probe (Abbott Molecular/Vysis, Des Plaines, IL) showed abnormal fusion signal patterns in 96.5% of the cells analyzed: nuc ish (ABL1)×4,(BCR)×3,(ABL1 con BCR×2)[386/ 400] (Fig. 1). Reverse transcriptase-polymerase chain reaction analysis for BCR/ABL1 rearrangement revealed minor (e1a2) type fusion transcript. Finally, he was diagnosed with B lymphoblastic leukemia with BCR/ABL1 rearrangement, and treated with vincristine, daunorubicin, and prednisolone (induction chemotherapy). Subsequently, imatinib mesylate was added to these regimens. His followup chromosome study and BCR/ABL1 FISH analysis (4 months later) revealed a normal karyotype and no fusion signals, respectively. He is now waiting for allogeneic hematopoietic stem cell transplantation. Seung Hwan Oh and Tae Sung Park equally contributed to this work as first authors. S. H. Oh : S. A. Song : J. Y. Lee :K. R. Jun :H. R. Kim (*) : J. N. Lee Department of Laboratory Medicine, Inje University College of Medicine, Gaegeum-dong, Busanjin-gu, Busan 614-735, South Korea e-mail: pk7146@hanmail.net