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1.  Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus Bloodstream Isolates from South Korean Patients 
We describe the genetic and microbiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates with agr dysfunction from a tertiary-care hospital in Korea. Of these, ST5-SCCmec type II-agr group II MRSA isolates, which are known to be prevalent in hospital-acquired infections in Korea, were the most abundant, because of the clonal spread of a specific agr-defective lineage. This finding suggests that the loss of agr function may confer a potential advantage in a hospital setting. Clonal spread of a specific defective-agr strain was not observed among community-associated MRSA or methicillin-susceptible S. aureus clones, regardless of community or hospital acquisition of infection. agr-defective clones, including ST5 and ST239 MRSA, were enriched for heteroresistant vancomycin-intermediate S. aureus.
doi:10.1128/AAC.01260-12
PMCID: PMC3591919  PMID: 23254438
2.  Treatment Duration for Uncomplicated Staphylococcus aureus Bacteremia To Prevent Relapse: Analysis of a Prospective Observational Cohort Study 
Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated Staphylococcus aureus bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. A prospective observational cohort study was performed in patients with SAB at a tertiary-care hospital in Korea between August 2008 and September 2010. All adult patients with SAB were prospectively enrolled and observed over a 12-week period. Uncomplicated SAB was defined as follows: negative results of follow-up blood cultures at 2 to 4 days, defervescence within 72 h of therapy, no evidence of metastatic infection, and catheter-related bloodstream infection or primary bacteremia without evidence of endocarditis on echocardiography. Of 483 patients with SAB, 111 met the study criteria for uncomplicated SAB. Fifty-three (47.7%) had methicillin-resistant SAB. When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73; P = 0.036). In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (P = 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.
doi:10.1128/AAC.01021-12
PMCID: PMC3591920  PMID: 23254436
3.  Changes in Osteoblastic Activity in Patient Who Received Bortezomib as Second Line Treatment for Plasma Cell Myeloma: A Prospective Multicenter Study 
BioMed Research International  2014;2014:245247.
We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.
doi:10.1155/2014/245247
PMCID: PMC4094867  PMID: 25050331
4.  R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma 
Blood research  2014;49(2):107-114.
Background
We investigated factors that influence outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab combined with the CHOP regimen (R-CHOP) followed by upfront autologous stem cell transplantation (Auto-SCT).
Methods
We retrospectively evaluated survival differences between subgroups based on the age-adjusted International Prognostic Index (aaIPI) and revised-IPI (R-IPI) at diagnosis, disease status, and positron emission tomographic/computerized tomographic (PET/CT) status at transplantation in 51 CD20-positive DLBCL patients treated with R-CHOP followed by upfront Auto-SCT.
Results
Patients had either stage I/II bulky disease (5.9%) or stage III/IV disease (94.1%). The median patient age at diagnosis was 47 years (range, 22-66 years); 53.3% and 26.7% had high-intermediate and high risks according to aaIPI, respectively. At the time of Auto-SCT, 72.5% and 27.5% experienced complete (CR) and partial remission (PR) after R-CHOP, respectively. The median time from diagnosis to Auto-SCT was 7.27 months (range, 3.4-13.4 months). The 5-year overall (OS) and progression-free survival (PFS) were 77.3% and 72.4%, respectively. The 5-year OS and PFS rates according to aaIPI, R-IPI, and PET/CT status did not differ between the subgroups. More importantly, the 5-year OS and PFS rates of the patients who achieved PR at the time of Auto-SCT were not inferior to those of the patients who achieved CR (P=0.223 and 0.292, respectively).
Conclusion
Survival was not influenced by the aaIPI and R-IPI at diagnosis, disease status, or PET/CT status at transplantation, suggesting that upfront Auto-SCT might overcome unfavorable outcomes attributed to PR after induction chemoimmunotherapy.
doi:10.5045/br.2014.49.2.107
PMCID: PMC4090331  PMID: 25025012
Diffuse large B-cell lymphoma; Hematopoietic stem cell transplantation; Autologous transplantation; Rituximab; Survival analysis
5.  Sternal Osteomyelitis Caused by Gordonia bronchialis after Open-Heart Surgery 
Infection & Chemotherapy  2014;46(2):110-114.
We report the case of a deep sternal wound infection with sternal osteomyelitis caused by Gordonia bronchialis after open-heart surgery. The isolate was identified as a G. bronchialis by 16S rRNA and hsp65 gene sequencing, having initially been misidentified as a Rhodococcus by a commercial phenotypic identification system.
doi:10.3947/ic.2014.46.2.110
PMCID: PMC4091373  PMID: 25024874
Gordonia bronchialis; Wound infection; Osteomyelitis; 16S rRNA gene; hsp65
6.  Bevacizumab as a second- or later-line of treatment for metastatic colorectal cancer 
AIM: To determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS: All of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.
CONCLUSION: In patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.
doi:10.3748/wjg.v18.i10.1104
PMCID: PMC3296985  PMID: 22416186
Colorectal cancer; Metastasis; Bevacizumab; Efficacy; Second- or later-line
7.  Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients 
PLoS ONE  2014;9(5):e97346.
Background
The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit.
Methods
BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis.
Results
Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis.
Conclusions
Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.
doi:10.1371/journal.pone.0097346
PMCID: PMC4019586  PMID: 24824328
8.  Successful Chemotherapy Following Autologous Stem Cell Transplantation in Multiple Myeloma and Multi-organ Dysfunction with Infiltration of Eosinophils: A Case Report 
Eosinophils are derived from hematopoietic stem cells. Peripheral blood eosinophilia is defined as an absolute eosinophil count of ≥0.5×109/L. Eosinophilia is classified into primary or clonal eosinophilia, secondary eosinophilia, and idiopathic categories including idiopathic hypereosinophilic syndrome. Both hematopoietic and solid neoplasms may be associated with peripheral blood eosinophilia, but multiple myeloma is rarely associated with eosinophilia. We now report the case of a 31-year-old man with multiple myeloma associated with marked eosinophilia who developed multiple organ dysfunction with infiltration of eosinophils. He recovered after treatment with chemotherapy followed by autologous stem cell transplantation.
doi:10.4143/crt.2011.43.3.199
PMCID: PMC3192883  PMID: 22022299
Eosinophilia; Multiple myeloma; Autologous transplantation
9.  Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia 
PLoS ONE  2014;9(4):e95865.
Background
Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care.
Methods
From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture.
Results
A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321).
Conclusions
Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.
doi:10.1371/journal.pone.0095865
PMCID: PMC3994115  PMID: 24752070
10.  The Outcomes of Using Colistin for Treating Multidrug Resistant Acinetobacter Species Bloodstream Infections 
Journal of Korean Medical Science  2011;26(3):325-331.
Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with multidrug resistant (MDR) Acinetobacter species bloodstream infection and who were treated with or without colistin as part of their regimen. The colistin group was given colistin as part of therapy once colistin became available in 2006. The non-colistin group was derived from the patients who were treated with other antimicrobial regimens before 2006. Mortality within 30 days of the onset of bacteremia occurred for 11 of 31 patients in the colistin group and for 15 of 39 patients in the non-colistin group (35.5% vs 38.5%, respectively, P = 0.80). Renal dysfunction developed in 50.0% of the 20 evaluable patients in the colistin group, but in 28.6% of the 35 evaluable patients in the non-colistin group (P = 0.11). On multivariate analysis, only an Acute Physiological and Chronic Health Evaluation II score ≥ 21 was associated with mortality at 30 days. This result suggests that administering colistin, although it is the sole microbiologically appropriate agent, does not influence the 30 day mortality of patients with a MDR Acinetobacter spp. bloodstream infection.
doi:10.3346/jkms.2011.26.3.325
PMCID: PMC3051077  PMID: 21394298
Acinetobacter; Colistin; Bacteremia; Drug Resistance, Multiple
11.  Association of Mannose-Binding Lectin 2 Gene Polymorphisms with Persistent Staphylococcus aureus Bacteremia 
PLoS ONE  2014;9(3):e89139.
Objectives
Mannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.
Methods
We conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (≥7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.
Results
Patients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P = 0.019 and P = 0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83–196.37; P = 0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19–29.57; P = 0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12–63.39; P = 0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03–4.26; P = 0.040).
Conclusions
This is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.
doi:10.1371/journal.pone.0089139
PMCID: PMC3942407  PMID: 24595015
12.  Clinical Correlation between Brain Natriutetic Peptide and Anthracyclin-induced Cardiac Toxicity 
Purpose
Anthracycline can effectively treat hematologic malignancies, but has significant risk of cardiotoxicity. We measured the clinical correlation between brain natriuretic peptide (BNP) and anthracycline-induced cardiotoxicity.
Materials and Methods
Between March 2005 and March 2007, 86 patients with acute leukemia, malignant lymphoma, or multiple myeloma receiving systemic chemotherapy with anthracycline were enrolled in the Department of Hemato-oncology, Kosin University Gospel Hospital. We investigated the relationship between BNP level and cardiotoxicity through echocardiography, electrocardiography, BNP levels, and symptoms of heart failure at each chemotherapy cycle.
Results
Of the 86 participants (mean age, 48.5 years; range 20~65 years), cardiotoxicity developed in 21 patients (24.4%), with 2 patients showing arrhythmia only, 17 patients with transient aspects of heart failure, and 2 patients with chronic heart failure. Cardiotoxicity related to serum BNP level, age, cumulative dose of anthracycline, accompanying chronic disease, and elevated level of troponin-I. Heart failure was more common if BNP levels reached 100 pg/ml at least once.
Conclusions
The clinical correlation between BNP and cardiotoxicity was significant in patients with systemic anthracycline chemotherapy. A prospective clinical trial will be needed to identify the causal relationship between serum BNP level and cardiotoxicity.
doi:10.4143/crt.2008.40.3.121
PMCID: PMC2697468  PMID: 19688118
Hematologic neoplasms; Anthracycline; BNP; Cardiac toxicity
13.  Clinical Outcomes and Prognostic Factors of Empirical Antifungal Therapy with Itraconazole in the Patients with Hematological Malignancies: A Prospective Multicenter Observational Study in Korea 
Yonsei Medical Journal  2013;55(1):9-18.
Purpose
To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies.
Materials and Methods
Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled.
Results
The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ≥2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (≥4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity.
Conclusion
We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.
doi:10.3349/ymj.2014.55.1.9
PMCID: PMC3874917  PMID: 24339281
Hematological malignancy; prognosis; itraconazole; empirical antifungal therapy
14.  Success Rate and Risk Factors for Failure of Empirical Antifungal Therapy with Itraconazole in Patients with Hematological Malignancies: A Multicenter, Prospective, Open-Label, Observational Study in Korea 
We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
doi:10.3346/jkms.2014.29.1.61
PMCID: PMC3890478  PMID: 24431907
Hematological Malignancy; Itraconazole; Empirical Antifungal Therapy; Galactomannan Test
15.  Epstein-Barr Virus-Encoded BARF1 Promotes Proliferation of Gastric Carcinoma Cells through Regulation of NF-κB 
Journal of Virology  2013;87(19):10515-10523.
In Epstein-Barr virus (EBV)-infected gastric carcinoma, EBV-encoded BARF1 has been hypothesized to function as an oncogene. To evaluate cellular changes induced by BARF1, we isolated the full-length BARF1 gene from gastric carcinoma cells that were naturally infected with EBV and transfected BARF1 into EBV-negative gastric carcinoma cells. BARF1 protein was primarily secreted into culture supernatant and only marginally detectable within cells. Compared with gastric carcinoma cells containing empty vector, BARF1-expressing gastric carcinoma cells exhibited increased cell proliferation (P < 0.05). There were no significant differences in apoptosis, invasion, or migration between BARF1-expressing gastric carcinoma cells and empty vector-transfected cells. BARF1-expressing gastric carcinoma cells demonstrated increased nuclear expression of nuclear factor kappa B (NF-κB) RelA protein and increased NF-κB-dependent cyclin D1. The expression of p21WAF1 was diminished by BARF1 transfection and increased by NF-κB inhibition. Proliferation of naturally EBV-infected gastric carcinoma cells was suppressed by BARF1 small interfering RNA (siRNA) (P < 0.05). Immunohistochemical analysis of 120 human gastric carcinoma tissues demonstrated increased expression of cyclin D1 and reduced expression of p21WAF1 in EBV-positive samples versus EBV-negative gastric carcinomas (P < 0.05). In conclusion, the secreted BARF1 may stimulate proliferation of EBV-infected gastric carcinoma cells via upregulation of NF-κB/cyclin D1 and reduction of the cell cycle inhibitor p21WAF1, thereby facilitating EBV-induced cancer progression.
doi:10.1128/JVI.00955-13
PMCID: PMC3807382  PMID: 23824821
16.  Risk Factors for Mortality in Patients with Invasive Mucormycosis 
Infection & Chemotherapy  2013;45(3):292-298.
Background
Mucormycosis is an uncommon and life-threatening fungal infection. The clinical predictors of outcome were evaluated in patients with invasive mucormycosis.
Materials and Methods
We retrospectively reviewed histologically proven cases of invasive mucormycosis in our institution from 1996 to 2012.
Results
A total of 64 patients were analyzed. The median age was 59 years (interquartile range [IQR], 50-67), and 32 patients (50%) were male. The most common underlying diseases were diabetes mellitus (67%), hematologic malignancy (22%), and solid cancer (19%). The most common infection sites were the rhino-orbito-cerebral area (56%) and the lungs (31%). The 180-day all-cause mortality was 33%. Disseminated infection was associated with increased mortality (hazard ratio [HR]: 169.74, 95% confidence interval [CI]: 6.41 to 4492.64; P = 0.002). Pulmonary infection (HR: 0.08, 95% CI: 0.01 to 0.66; P = 0.02) and complete surgical removal of infected tissue (HR: 0.12, 95% CI: 0.02 to 0.64; P = 0.01) were associated with decreased mortality.
Conclusions
These results suggest that patients with mucormycosis had a lower risk of mortality if they developed a pulmonary infection, rather than a disseminated infection and with complete debridement of infected tissue.
doi:10.3947/ic.2013.45.3.292
PMCID: PMC3848522  PMID: 24396630
Risk factor; Mortality; Mucormycosis
17.  Efficacy of Oral Ribavirin in Hematologic Disease Patients with Paramyxovirus Infection: Analytic Strategy Using Propensity Scores 
Few antiviral agents are available for treating paramyxovirus infections, such as those involving respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV). We evaluated the effect of oral ribavirin on clinical outcomes of paramyxovirus infections in patients with hematological diseases. All adult patients with paramyxovirus were retrospectively reviewed over a 2-year period. Patients who received oral ribavirin were compared to those who received supportive care without ribavirin therapy. A propensity-matched case-control study and a logistic regression model with inverse probability of treatment weighting (IPTW) were performed to reduce the effect of selection bias in assignment for oral ribavirin therapy. A total of 145 patients, including 64 (44%) with PIV, 60 (41%) with RSV, and 21 (15%) with hMPV, were analyzed. Of these 145 patients, 114 (78%) received oral ribavirin and the remaining 31 (21%) constituted the nonribavirin group. Thirty-day mortality and underlying respiratory death rates were 31% (35/114) and 12% (14/114), respectively, for the oral ribavirin group versus 19% (6/31) and 16% (5/31), respectively, for the nonribavirin group (P = 0.21 and P = 0.56). In the case-control study, the 30-day mortality rate in the ribavirin group was 24% (5/21) versus 19% (4/21) in the nonribavirin group (P = 0.71). In addition, the logistic regression model with IPTW revealed no significant difference in 30-day mortality (adjusted hazard ratio of 1.3; 95% confidence interval [95% CI] of 0.3 to 5.8) between the two groups. Steroid use (adjusted odds ratio, 5.67; P = 0.01) and upper respiratory tract infection (adjusted odds ratio, 0.07; P = 0.001) was independently associated with mortality. Our data suggest that oral ribavirin therapy may not improve clinical outcomes in hematologic disease patients infected with paramyxovirus.
doi:10.1128/AAC.01961-12
PMCID: PMC3553680  PMID: 23229488
18.  Clinical features and survival outcomes of patients with diffuse large B-cell lymphoma: analysis of web-based data from the Korean Lymphoma Working Party Registry 
Blood research  2013;48(2):115-120.
Background
This study aimed to survey the clinical spectrum of diffuse large B-cell lymphoma (DLBCL) in terms of epidemiology, pathologic subtypes, stage, and prognostic index as well as treatment outcomes.
Methods
In 2007-2008, 13 university hospitals evenly distributed in the Korean peninsula contributed to the online registry of DLBCL at www.lymphoma.or.kr and filed a total of 1,665 cases of DLBCL recorded since 1990.
Results
Our analysis showed a higher prevalence of DLBCL in male than in female individuals (M:F=958:707), and extranodal disease was more common than primary nodular disease (53% vs. 47%). Among the 1,544 patients who had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-CHOP (R-CHOP) therapy with or without radiation, 993 (63.9%) were alive, with 80% free of disease, 417 were dead (26.8%), with 13% free of disease, and 144 (9.3%) were lost to follow-up, with 23% free of disease. Age below 60 years, stage at diagnosis, international prognostic index (IPI) score regardless of age, and addition of rituximab to CHOP therapy in low- and low-intermediate-risk groups according to IPI scores significantly increased survival duration.
Conclusion
The epidemiology, clinical spectrum, and biological behavior of DLBCL in Korea are similar to those observed in Western countries, and the advent of rituximab improved survival.
doi:10.5045/br.2013.48.2.115
PMCID: PMC3698396  PMID: 23826580
Diffuse large B-cell lymphoma; Epidemiology; Survival; Rituximab; CHOP regimen
19.  No Recurrence of Pneumocystis jirovecii Pneumonia after Solid Organ Transplantation Regardless of Secondary Prophylaxis 
Antimicrobial Agents and Chemotherapy  2012;56(11):6041-6043.
There are no data on the efficacy of secondary prophylaxis against Pneumocystis pneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence of Pneumocystis pneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis pneumonia during the follow-up, regardless of secondary prophylaxis.
doi:10.1128/AAC.00998-12
PMCID: PMC3486611  PMID: 22948875
20.  Assessment of the Medial Dorsal Cutaneous, Dorsal Sural, and Medial Plantar Nerves in Impaired Glucose Tolerance and Diabetic Patients With Normal Sural and Superficial Peroneal Nerve Responses 
Diabetes Care  2012;35(4):834-839.
OBJECTIVE
This study evaluated the nerve conduction study (NCS) parameters of the most distal sensory nerves of the lower extremities—namely, the medial dorsal cutaneous (MDC), dorsal sural (DS), and medial plantar (MP) nerves—in diabetic (DM) and impaired glucose tolerance (IGT) patients who displayed normal findings on their routine NCSs.
RESEARCH DESIGN AND METHODS
Standard NCSs were performed on healthy control (HC), DM, and IGT groups (N = 147). The bilateral NCS parameters of the MDC, DS, and MP nerves were investigated. The Toronto Clinical Scoring System (TCSS) was assessed for the DM and IGT groups.
RESULTS
The mean TCSS scores of the IGT and DM groups were 2.5 ± 2.3 and 2.8 ± 2.2, respectively. No significant differences between the two groups were observed. After adjustment of age and BMI, the DM group showed significant NCS differences in DS and MDC nerves compared with the HC group (P < 0.05). These differences were also exhibited in the left DS of the IGT group (P = 0.0003). More advanced NCS findings were observed in the DM group. Bilateral abnormal NCS responses in these distal sensory nerves were found in 40 and 16% of DM and IGT patients, respectively.
CONCLUSIONS
These results showed that the simultaneous assessment of the most distal sensory nerves allowed the detection of early NCS changes in the IGT and DM groups, even when the routine NCS showed normal findings.
doi:10.2337/dc11-1001
PMCID: PMC3308311  PMID: 22100966
21.  Impact of Penicillin Nonsusceptibility on Clinical Outcomes of Patients with Nonmeningeal Streptococcus pneumoniae Bacteremia in the Era of the 2008 Clinical and Laboratory Standards Institute Penicillin Breakpoints 
To investigate the impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal Streptococcus pneumoniae bacteremia (SPB), a retrospective cohort study was performed. The characteristics of 39 patients with penicillin-nonsusceptible SPB (PNSPB) were compared to those of a group of age- and sex-matched patients (n = 78) with penicillin-susceptible SPB (PSSPB). Susceptibility to penicillin was redetermined by using the revised Clinical and Laboratory Standards Institute (CLSI) penicillin breakpoints in CLSI document M100-S18. Although the PNSPB group tended to have more serious initial manifestations than the PSSPB group, the two groups did not differ significantly in terms of their 30-day mortality rates (30.8% versus 23.1%; P = 0.37) or the duration of hospital stay (median number of days, 14 versus 12; P = 0.89). Broad-spectrum antimicrobial agents, such as extended-spectrum cephalosporins, vancomycin, and carbapenem, were frequently used in both the PNSPB and PSSPB groups. Multivariate analysis revealed that ceftriaxone nonsusceptibility (adjusted odds ratio [aOR] = 4.88; 95% confidence interval [CI] = 1.07 to 22.27; P = 0.041) was one of the independent risk factors for 30-day mortality. Thus, when the 2008 CLSI penicillin breakpoints are applied and the current clinical practice of using wide-spectrum empirical antimicrobial agents is pursued, fatal outcomes in patients with nonmeningeal SPB that can be attributed to penicillin nonsusceptibility are likely to be rare. Further studies that examine the clinical impact of ceftriaxone nonsusceptibility in nonmningeal SPB may be warranted.
doi:10.1128/AAC.00239-12
PMCID: PMC3421886  PMID: 22687517
22.  Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea 
Blood research  2013;48(1):31-34.
Background
Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL.
Methods
We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012.
Results
The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×109/L and 2.7 to 124.0 (median 54.5)×109/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 µg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%).
Conclusion
Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.
doi:10.5045/br.2013.48.1.31
PMCID: PMC3625006  PMID: 23589792
Acute promyelocytic leukemia; PML-RARA; Immunophenotyping; Cytogenetic analysis; All-trans retinoic acid
23.  Indeterminate T-SPOT.TB Test Results in Patients with Suspected Extrapulmonary Tuberculosis in Routine Clinical Practice 
Infection & Chemotherapy  2013;45(1):44-50.
Background
The two interferon-γ release assays such as QuantiFERON-TB Gold / In-Tube (QFT-TB) and T-SPOT.TB-are useful tools for the rapid diagnosis of tuberculosis (TB) but can yield indeterminate test results (ITRs). While some studies have identified risk factors for ITRs in the QFT-TB test, there have been few such studies for the T-SPOT.TB test. The aim of this study was to investigate the risk factors associated with ITRs in the T-SPOT.TB test.
Materials and Methods
From April 2008 to August 2010, all patients with suspected extrapulmonary tuberculosis (E-TB) were enrolled in a tertiary hospital in Korea. ITR was defined as < 20 spots in the positive control well or > 10 spots in the negative control well.
Results
Out of a total of 368 patients, 32 (8.7%, 95% CI, 6.0% to 11.7%) had ITRs in their T-SPOT.TB tests. The ITRs were due to a low mitogen response in 13 (40.6%) patients and to a high nil response in the other 19 (59.4%) patients. Statistical analysis revealed that old age, underlying diseases, immunosuppressive treatment, lymphopenia, and clinical manifestations of E-TB were not significantly associated with ITRs.
Conclusions
Indeterminate results in the T-SPOT.TB test are not affected by age, underlying disease, immunosuppressive treatment, lymphopenia, or clinical manifestations of E-TB, which are known risk factors for indeterminate results in the QFT-TB test.
doi:10.3947/ic.2013.45.1.44
PMCID: PMC3780939  PMID: 24265949
Tuberculosis; ELISPOT; Indeterminate response
24.  Early Response to Bortezomib Combined Chemotherapy Can Help Predict Survival in Patients with Multiple Myeloma Who Are Ineligible for Stem Cell Transplantation 
Novel agents to treat multiple myeloma (MM) have increased complete respone (CR) rates compared with conventional chemotherapy, and the quality of the response to treatment has been correlated with survival. The purpose of our study was to show how of early response to bortezomib combined chemotherapy influences survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. We assessed patient responses to at least four cycles of bortezomib using the International Myeloma Working Group response criteria. The endpoints were comparisons of progression free survival (PFS) and overall survival (OS) between early good response group (A group) and poor response group (B group). We retrospectively analyzed data from 129 patients registered by the Korean Multiple Myeloma Working Party, a nationwide registration of MM patients. The 3 yr PFS for the A and B groups was 55.6% and 18.4%, respectively (P < 0.001). The 3 yr OS for the A and B groups was 65.3% and 52.9%, respectively (P = 0.078). The early response to at least four cycle of bortezomib before next chemotherapy may help predict PFS in patients with MM who are ineligible stem cell transplantation.
doi:10.3346/jkms.2013.28.1.80
PMCID: PMC3546109  PMID: 23341716
Early Response; Multiple Myeloma; Bortezomib; Survival
25.  Impact of adequate empirical combination therapy on mortality from bacteremic Pseudomonas aeruginosa pneumonia 
BMC Infectious Diseases  2012;12:308.
Background
Pseudomonas aeruginosa has gained an increasing amount of attention in the treatment of patients with pneumonia. However, the benefit of empirical combination therapy for pneumonia remains unclear. We evaluated the effects of adequate empirical combination therapy and multidrug-resistance in bacteremic Pseudomonas pneumonia on the mortality.
Methods
A retrospective cohort study was performed at the 2,700-bed tertiary care university hospital. We reviewed the medical records of patients with bacteremic pneumonia between January 1997 and February 2011. Patients who received either inappropriate or appropriate empirical therapy were compared by using marginal structural model. Furthermore, we investigated the direct impact of combination therapy on clinical outcomes in patients with monomicrobial bacteremic pneumonia.
Results
Among 100 consecutive patients with bacteremic Pseudomonas pneumonia, 65 patients were classified in the adequate empirical therapy group, 32 of whom received monotherapy and 33 combination therapy. In the marginal structural model, only inadequate therapy was significantly associated with 28-day mortality (p = 0.02), and multidrug-resistance was not a significant risk factor.
To examine further the direct impact of combination therapy, we performed a subgroup analysis of the 65 patients who received adequate therapy. Multivariate logistic regression analysis identified absence of septic shock at the time of bacteremia (OR, 0.07; 95% CI, 0.01-0.49; p = 0.008), and adequate combination therapy (OR, 0.05; 95% CI, 0.01-0.34; p = 0.002) as variables independently associated with decreased all-cause 28-day mortality.
Conclusions
Our study suggests that adequate empirical combination therapy can decrease mortality in patients with bacteremic Pseudomonas pneumonia.
doi:10.1186/1471-2334-12-308
PMCID: PMC3519646  PMID: 23157735
Pseudomonas aeruginosa; Pneumonia; Combination treatment

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