Nationwide Survey for Current Status of Laboratory Diagnosis of Clostridioides difficile Infection in Korea

Background@#The interest in Clostridioides difficile infection (CDI) has increased, and the choice of assays became wider since the first national survey in Korea on CDI diagnosis in 2015. We conducted a survey of the domestic CDI assays with more varied questions to understand the current situation in Korea. @*Methods@#In April 2018, about 50 questions on the current status of CDI assays and details on implementation and perceptions were written, and a survey questionnaire was administered to laboratory medicine specialists in 200 institutions. @*Results@#One-hundred and fifty institutions responded to the questionnaire, of which 90 (60.0%) including one commercial laboratory, performed CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and C. difficile culture, glutamate dehydrogenase assay, alone or in combination with other assays, were used in 75 (84.3%), 52 (58.4%), 35 (36.0%), and 23 (25.8%), respectively, and 65 (73.0%) institutions performed a combination of two or more assays. The sensitivity of toxin AB EIA was more negatively perceived, and that on specificity was more positively perceived. The perception of sensitivity and specificity of NAAT was mostly positive. Perception on the algorithm test projected it as useful but in need of countermeasures. Sixty-three (73.3%) institutions responded that they performed surveillance on CDI. @*Conclusion@#This study provides useful evidence on the current status of CDI laboratory diagnosis in Korea as well as on items that require improvement and is thought to aid in standardizing and improving the CDI laboratory diagnosis in Korea.

Outcomes and clinical relevance of stool multiplex bacterial polymerase chain reaction in patients with acute diarrhea: single center experience

Diagnostic stool multiplex polymerase chain reaction (PCR) testing has attracted considerable interest, because of its high sensitivity, short turnaround time, and ability to detect multiple organisms simultaneously. This study investigates the clinical usefulness of a stool multiplex bacterial PCR in patients with acute diarrhea. Methods: We retrospectively evaluated the stool multiplex bacterial PCR results, clinical parameters, and clinical courses of patients hospitalized because of acute diarrhea between August 2014 and November 2016. Results: A total of 725 patients (male, 372; mean age, 30.9 ± 29.3 years) underwent stool multiplex bacterial PCR. A total of 243 pathogens were detected in 226 patients. The detection rate of multiplex PCR testing was higher than that of stool culture (32.7% vs. 3.3%, p < 0.01). Severe symptoms of acute diarrhea (bloody diarrhea, frequent diarrhea) and prescribed empirical antibiotics were significantly more common in the positive multiplex PCR group (p = 0.02, p < 0.01, p < 0.01, respectively). However, mean durations of hospital stay were similar in the 2 groups according to the multiplex PCR results (p = 0.32). In addition, Campylobacter spp., which was the most commonly detected pathogen (97/243, 39.9%), was significantly associated with frequent diarrhea and prescribed empirical antibiotics (p < 0.01), but not with duration of hospital stay (p = 0.09). Conclusions: We concluded that stool multiplex bacterial PCR might be a useful tool for identifying bacterial etiology in patients with acute diarrhea, especially in those with Campylobacter spp. infection.

Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Streptococcus pneumoniae Isolates in Korea between 2014 and 2016

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.

Development of Statistical Software for the Korean Laboratory Accreditation Program Using R Language: LaboStats

BACKGROUND: In Korea, the Korean Laboratory Accreditation Program (KLAP) has set minimum standards for verification of clinical test performance. This verification process is time-consuming and labor-intensive when performed manually. We developed a free, statistical software program for KLAP, using the R language (R Foundation for Statistical Computing, Vienna, Austria). METHODS: We used CLSI guidelines for the algorithm. We built graphic user interfaces, including data input, with Embarcadero Delphi EX4 (Embarcadero Technologies, Inc., Texas, USA). The R Base Package and MCR Package for Method Comparison Regression were used to implement statistical and graphical procedures. RESULTS: Our program LaboStats has six modules: parallel test, linearity, method comparison, precision, reference interval, and cutoff. Data can be entered into the field either manually or by copying and pasting from an MS Excel worksheet. Users can print out precise reports. CONCLUSIONS: LaboStats can be useful for evaluating clinical test performance characteristics and preparing documents requested by KLAP.

Huge Abscess due to Mycobacterium Abscessus Infection after Breast Augmentation

Periprosthetic capsular contracture, implant rupture, and deflation are well-known delayed complications of augmentation mammaplasty. However, infection remains the most common cause of reoperation after breast implant surgery. We report the case of a nontuberculous mycobacterial infection with huge abscess formation after augmentation mammaplasty. A 29-year-old woman visited our clinic with enlarged breasts after undergoing breast augmentation at a local clinic 4 years ago. She had no pain and tenderness, except some hardness around the breast margin. Nine months after surgery, her breasts began to grow larger, but showed no other typical symptoms, which led the patient to neglect the enlargement. After exploring through an inframammary approach, a large amount of serous fluid leaked out on both sides and we identified a huge abscess in a pocket localized in the submuscular plane. During exploration, the infected implants, which contained a pus-like fluid with a foul odor, were completely drained. The specimen culture revealed growth of Mycobacterium abscessus, which is a rare cause of infections after breast augmentation. While the overall incidence of mycobacterial infections after breast augmentation is low, our case demonstrates that huge abscess and granuloma formation should be considered as a potential complication of breast surgery.

Clinical value of procalcitonin for suspected nosocomial bloodstream infection

BACKGROUND/AIMS@#Procalcitonin (PCT) may prove to be a useful marker to exclude or predict bloodstream infection (BSI). However, the ability of PCT levels to differentiate BSI from non-BSI episodes has not been evaluated in nosocomial BSI.@*METHODS@#We retrospectively reviewed the medical records of patients ≥ 18 years of age with suspected BSI that developed more than 48 hours after admission.@*RESULTS@#Of the 785 included patients, 105 (13.4%) had BSI episodes and 680 (86.6%) had non-BSI episodes. The median serum PCT level was elevated in patients with BSI as compared with those without BSI (0.65 ng/mL vs. 0.22 ng/mL, p = 0.001). The optimal PCT cut-off value of BSI was 0.27 ng/mL, with a corresponding sensitivity of 74.6% (95% confidence interval [CI], 66.4% to 81.7%) and a specificity of 56.5% (95% CI, 52.7% to 60.2%). The area under curve of PCT (0.692) was significantly larger than that of C-reactive protein (CRP; 0.526) or white blood cell (WBC) count (0.518). However, at the optimal cut-off value, PCT failed to predict BSI in 28 of 105 cases (26.7%). The PCT level was significantly higher in patients with an eGFR < 60 mL/min/1.73 m² than in those with an eGFR ≥ 60 mL/min/1.73 m² (0.68 vs. 0.17, p = 0.01).@*CONCLUSIONS@#PCT was more useful for predicting nosocomial BSI than CRP or WBC count. However, the diagnostic accuracy of predicting BSI remains inadequate. Thus, PCT is not recommended as a single diagnostic tool to avoid taking blood cultures in the nosocomial setting.

Central Nervous System Involvement in a Patient with Multiple Myeloma Manifesting as an Intraventricular Mass with Leptomeningeal Spread

Central nervous system involvement in multiple myeloma (CNS-MM) is a rare condition. Various manifestations of CNS-MM have been reported, including dural, parenchymal, and leptomeningeal involvement. Among them, leptomeningeal involvement is less common and intraventricular involvement is exceptional, with only one case reported in the literature. Herein, we report the first case of CNS-MM manifesting as an intraventricular mass with leptomeningeal involvement combined with perineural spread. We also describe characteristic computed tomography and magnetic resonance imaging findings of intraventricular multiple myeloma.

Clinical Outcomes of Hospital-Acquired Acute Cholecystitis in the Elderly / 대한췌담도학회지

BACKGROUND/AIM: Antimicrobials for nosocomial infections are generally chosen discriminately from community-acquired diseases from concerns for resistance to which the elderly are highly exposed. The elderly are affected frequently by acute cholecystitis (AC), for which appropriate antimicrobial therapy is particularly important. Also, cholecystectomy for elderly patients with co-morbidities is expectedly not as feasible as for uncomplicated young patients. Characteristics of hospital-acquired AC in the elderly patients were investigated in this study. METHODS: Records of patients over 65 years and older diagnosed with AC between March 2006 and February 2015 were reviewed retrospectively. Hospital-acquired AC was defined as development of AC in patients who were admitted for other disorders. Community-acquired AC was defined as presence of AC at the time of admission. Community-acquired AC group (CG) was used as a control group that was matched for age and sex with a ratio of 1:2. RESULTS: There were 40 patients in hospital-acquired AC group (HG) and 80 in CG. Demographics did not differ except higher prevalence of underlying illnesses in HG. Necessity to change initial antimicrobials for worsening conditions was more common in HG than in CG (20.0% vs. 2.5%, p < 0.01). Time to recovery was longer in HG (23.3 ± 5.6 days vs. 10.1 ± 0.7 days, p = 0.02). Rate of early cholecystectomy was lower (7.5% vs. 40.0%, p < 0.01) and that of open conversion was higher (20.0% vs. 6.3%, p = 0.02) in HG. CONCLUSIONS: For the elderly patients with hospital-acquired AC, antimicrobial and surgical management should be performed more meticulously since they showed distinct characteristics.

Comparison of Automated Treponemal and Nontreponemal Test Algorithms as First-Line Syphilis Screening Assays

BACKGROUND: Automated Mediace Treponema pallidum latex agglutination (TPLA) and Mediace rapid plasma reagin (RPR) assays are used by many laboratories for syphilis diagnosis. This study compared the results of the traditional syphilis screening algorithm and a reverse algorithm using automated Mediace RPR or Mediace TPLA as first-line screening assays in subjects undergoing a health checkup. METHODS: Samples from 24,681 persons were included in this study. We routinely performed Mediace RPR and Mediace TPLA simultaneously. Results were analyzed according to both the traditional algorithm and reverse algorithm. Samples with discordant results on the reverse algorithm (e.g., positive Mediace TPLA, negative Mediace RPR) were tested with Treponema pallidum particle agglutination (TPPA). RESULTS: Among the 24,681 samples, 30 (0.1%) were found positive by traditional screening, and 190 (0.8%) by reverse screening. The identified syphilis rate and overall false-positive rate according to the traditional algorithm were lower than those according to the reverse algorithm (0.07% and 0.05% vs. 0.64% and 0.13%, respectively). A total of 173 discordant samples were tested with TPPA by using the reverse algorithm, of which 140 (80.9%) were TPPA positive. CONCLUSIONS: Despite the increased false-positive results in populations with a low prevalence of syphilis, the reverse algorithm detected 140 samples with treponemal antibody that went undetected by the traditional algorithm. The reverse algorithm using Mediace TPLA as a screening test is more sensitive for the detection of syphilis.

Anemia in Individuals over Age 80: Unattended Issue in Clinical Practice / 이화의대지

OBJECTIVES: To assess the current state of anemia evaluation in the elderly over 80 years of age. METHODS: Patients who were more than 80 years old and visited Dongguk University Ilsan Hospital from April 2005 to February 2014 were included. Statistical analysis were assessed using the logistic regression model. RESULTS: Total 548 patients, who had anemia according to WHO criteria, were identified. The median age was 85 years old (range, 82 to 99 years) and median hemoglobin level was 11.0 g/dL (range, 2.7 to 12.9 g/dL). Twenty-eight, 468, and 52 patients were classified as microcytic anemia, normocytic anemia, and macrocytic anemia, respectively. Among them, 397 patients (72.4%) did not undergo proper evaluation for the cause anemia i.e., 8 cases (28.5%) of microcytic anemia, 361 cases (77.1%) of normocytic anemia, and the 28 cases (53.84%) of 52 macrocytic anemia patients. The remaining 151 patients (27.6%) had completed the evaluation, and 24 patients (15.9%) were diagnosed as solid malignancies. In the assessment of iron deficiency anemia, hemoglobin levels, and age had no effect on whether or not to perform esophagogastroduodenoscopy. CONCLUSION: This finding showed that physicians often neglected anemia in individuals over 80 years of age. Though these patients have limited life expectancy, physicians should carefully discriminate the sub-population who will be benefit from adequate evaluation and treatment.

Unusual association of CD8+ T-cell lymphocytosis with invasive thymoma

No abstract available.

Respiratory Syncytial Virus Outbreak in the Basic Military Training Camp of the Republic of Korea Air Force / 예방의학회지

OBJECTIVES: An outbreak of acute febrile illness occurred in the Republic of Korea Air Force boot camp from May to July 2011. An epidemiological investigation of the causative agent, which was of a highly infective nature, was conducted. METHODS: Throat swabs were carried out and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed to identify possible causative factors. RESULTS: The mean age of patients who had febrile illness during the study period was 20.24 years. The multiplex RT-PCR assay identified respiratory syncytial virus (RSV) as the causative agent. The main symptoms were sore throat (76.0%), sputum (72.8%), cough (72.1%), tonsillar hypertrophy (67.9%), and rhinorrhea (55.9%). The mean temperature was 38.75degreesC and the attack rate among the recruits was 15.7% (588 out of 3750 recruits), while the mean duration of fever was 2.3 days. The prognosis was generally favorable with supportive care but recurrent fever occurred in 10.1% of the patients within a month. CONCLUSIONS: This is the first epidemiological study of an RSV outbreak that developed in a healthy young adult group. In the event of an outbreak of an acute febrile illness of a highly infective nature in facilities used by a young adult group, RSV should be considered among the possible causative agents.

Serial Determination of FLT3-ITD and NPM1 Mutations and Its Clinical Significance in Patients with MDS at Diagnosis and After Progression to AML with Myelodysplasia-related Changes

BACKGROUND: Accumulation of genetic aberrations in MDS is closely associated with progression to AML. FLT3-ITD is commonly found in AML and less frequently in MDS. FLT3-ITD in MDS is associated with a high risk of transformation to AML. Recently, significant interaction of NPM1 and FLT3-ITD was described in AML. This study was conducted to investigate the incidence and prognostic role of FLT3-ITD and NPM1 mutations (NPM1mt) on paired samples at diagnosis of MDS and AML. METHODS: Patients who were diagnosed as MDS transforming to AML were included. FLT3-ITD was detected by PCR, and NPM1mt was confirmed by direct sequencing after screening for NPM by immunohistochemistry. RESULTS: AML developed in 12.0% (43/357) of MDS patients. FLT3-ITD was detected in none of MDS and 14.7% (5/34) of AML. NPM1mt was detected in 2.4% (1/41) of MDS and 11.6% (5/43) of AML. One patient with type B NPM1mt at MDS transformed to type A NPM1mt at AML. FLT3-ITD positive AML showed a tendency of shorter survival and a significantly longer time to achieve complete remission than FLT3-ITD negative AML (P=0.007). Normal karyotype AML with FLT3-ITD showed shorter overall survival than that group of AML without FLT3-ITD (P=0.017). CONCLUSIONS: MDS patients acquired FLT3-ITD during AML transformation, and FLT3-ITD positive AML, especially that with normal karyotype, predicted a poor outcome. NPM1mt was identified in both MDS and AML. NPM1mt was rarely found in MDS patients, and mostly was acquired after AML transformation. Clonal evolution of NPM1mt subtype was found in one patient during acute transformation.

Evaluation of MicroScan and Phoenix System for Rapid Identification and Susceptibility Testing Using Direct Inoculation from Positive BACTEC Blood Culture Bottles / 대한진단검사의학회지

BACKGROUND: Procedures for rapid identification and susceptibility testing by direct inoculation (DI) from positive blood culture bottles into an automated system have not been standardized. This study was purposed to evaluate DI from BACTEC 9240 blood culture system (BD, USA) into MicroScan (Dade Behring, USA) or Phoenix (BD, USA). METHODS: From May to June 2006, bacterial pellets from positive aerobic bottles showing gram-positive cocci (GPC) or gram-negative rods (GNR) of single morphology were directly inoculated to MicroScan PosCombo1A and NegCombo32 and to Phoenix PMIC/ID-107 and NMIC/ID-53. In addition, the automated instruments were also inoculated from subcultures (standard inoculations, SI). Species identification and susceptibilities were compared between DI and SI and between MicroScan and Phoenix. RESULTS: A total of 108, 104, and 78 specimens were tested with MicroScan, Phoenix, and both, respectively. When DI and SI were matched, 94.8% of GPC were correctly identified with MicroScan, compared to 80.7% with Phoenix, and 93.9% of GNR were correctly identified with MicroScan, compared to 95.7% with Phoenix. DI with MicroScan and Phoenix showed correct susceptibilities in 94.6% of 1,150 and 96.5% of 660 tests (with very major error [VME] of 1.1% and 1.1%), respectively, among GPC and in 94.4% of 942 and 96.3% of 781 tests (with VME of 0.6% and 0%), respectively, of GNR. Correlation of identification/susceptibilities between MicroScan and Phoenix using DI were 81.8%/98.0% for Staphylococcus aureus and 100.0%/95.6% for Escherichia coli. CONCLUSIONS: DI warrants a reliable method for identification and susceptibility testing of both GPC and GNR in MicroScan, and those of only GNR in Phoenix.

Evaluation of the MicroScan NegCombo Panel Type 44 for Detection of Extended-Spectrum beta-Lactamase among Clinical Isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis / 대한진단검사의학회지

BACKGROUND: Accurate and rapid detection of extended-spectrum beta-lactamases (ESBLs) is important in guiding proper antimicrobial therapy for infected patients. We evaluated the performance of MicroScan NegCombo Type 44 panel (Dade Behring, USA), which was developed to confirm ESBL-producing Enterobacteriaceae using ceftazidime/clavulanate and cefotaxime/clavulanate. METHODS: From August 30 to September 20, 2007, 206 non-duplicate clinical isolates, including 106 Escherichia coli, 81 Klebsiella pneumoniae, 11 Klebsiella oxytoca, and 8 Proteus mirabilis were subcultured and tested with Type 32 and Type 44 panels. The results were compared with those of the CLSI phenotypic confirmatory test (CLSI-PCT) and disk approximation test (DAT). Isolates not susceptible to cefotetan or flagged as "Possible ESBL, unable to interpret confirm test (Possible ESBL)" on Type 44 panel were tested with boronic acid disks to confirm AmpC beta-lactamases (AmpC) production. RESULTS: Of the 206 isolates tested, 44 (21.4%) produced ESBL by CLSI-PCT or DAT, including 27 E. coli, 14 K. pneumoniae, 2 K. oxytoca, and 1 P. mirabilis. Thirty-eight isolates flagged as "Confirmed ESBL" on Type 44 panel were all confirmed as ESBL-producers. Of 14 K. pneumoniae flagged as "Possible ESBL", 6 were confirmed as ESBL and AmpC co-producers and 8 as AmpC-producers. CONCLUSIONS: Type 44 panel showed an excellent performance in detecting ESBL-producing E. coli, Klebsiella spp., and P. mirabilis. When flagged as "Confirmed ESBL", no other confirmatory test was necessary to report as ESBL; however, "Possible ESBL" required a differential test for AmpC production.

Performance Evaluation of Affinity Column Mediated Immunometric Assay for Tacrolimus / 대한진단검사의학회지

BACKGROUND: Therapeutic drug monitoring (TDM) of tacrolimus is essential because of narrow therapeutic range and poor correlation of dose to blood concentration. Affinity Column Mediated Immunometric Assay (ACMIA) does not require a pretreatment steps in measurement of tacrolimus. In this study, we evaluated the performance of tacrolimus assay using ACMIA (Dimension RxL Max, Dade Behring). METHODS: The imprecision, the linearity and the detection limits and the interferences by bilirubin and chyle, and correlation with hematocrit for tacrolimus by ACMIA were evaluated according to Clinical and Laboratory Standards Institute guidelines EP5-A2, EP6-A, EP17-A, EP9-A2, and EP7-A2. Method comparison studies with microparticle enzyme immunoassay (MEIA) (IMx Tacrolimus II, Abbott Laboratories) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Waters 2795 Quattromicro API, Micromass) were also performed. RESULTS: The total imprecision for low, middle and high level was 12.8%, 9.0% and 6.7%, respectively. The range of tacrolimus from 3.1 ng/mL to 35.4 ng/mL showed a clinically relevant linearity. The limit of detection and the functional sensitivity were 0.24 ng/mL and 0.72 ng/mL, respectively. Tacrolimus concentration measurement (Tac-CM) with ACMIA did not show significant interferences with bile and chyle and also did not show significant correlation with hematocrit. In comparison study for Tac-CM with MEIA and LC-MS/MS, Tac-CM with ACMIA showed a good correlation with MEIA (r=0.950) and LC-MS/MS (r=0.946). CONCLUSIONS: The imprecision, linearity, detection limits, interference and correlation of Tac-CM with ACMIA were suitable for clinical use. Tac-CM with ACMIA could reduce turn around time and help clinicians to manage transplant patients on immunosuppressant therapy.

A Case of Erythromycin-Resistant Ureaplasma urealyticum Meningitis in a Premature Infant / 대한진단검사의학회지

Ureaplasma urealyticum causes infection or colonization of female genital tracts associated with preterm delivery and infertility and the infection of the bloodstream, respiratory tract, and central nervous system in infants, especially in prematures. We report the first case of U. urealyticum meningitis in a premature infant in Korea. She was born with a birth weight of 1,481 gram at 32+3 weeks' gestation and hospitalized for a respiratory care in the NICU in November 2005. Endotracheal aspirates and urine cultures grew U. urealyticum at or = 10(4) CFU/mL of CSF. The patient had a marked CSF pleocytosis, low glucose and high protein content on the 13th hospital day. CSF cultures for ordinary bacteria, mycobacteria and fungi remained negative. U. urealyticum was resistant to erythromycin, tetracycline, ciprofloxacin and pristinamycin, but susceptible to doxycycline. Although she was treated with erythromycin for 30 days, the organism was still isolated four times from the CSF with fluctuation of C-reactive protein (CRP). After the addition of chloramphenicol, CSF cultures became negative in 3 days. However, CRP rose again with increased BUN at the 99th hospital day, and she died on the 103rd hospital day under the diagnosis of a clinical sepsis of unknown origin. In acute meningitis of prematures already colonized with U. urealyticum, ureaplasmal cultures and susceptibility test are warranted in Korea.

A Case of Effective Post-centrifugal Plasma Filtration for L-asparaginase-induced Severe Hyperlipidemia / 대한수혈학회지

Hyperlipidemia has been reported in children with acute lymphoblastic leukemiawho have been treated with L-asparaginase alone or in combination with a steroid. Hyperlipidemia caused by L-asparaginase is usuallyreversible after drug discontinuation, and is rarely associated with severe complications. However, the risk of acute pancreatitis is increased if there is a large increase in triglyceride levels. Prompt correction of hyperlipidemia should be considered to prevent this severe complication. We report a case of successful correction of L-asparaginase-associated severe relapsed hyperlipidemia using post-centrifugal plasma filtration (PCPF), a type of selective plasmapheresis. After 3 sessions of PCPF, the serum concentrations of lipids were markedly reduced. The serum concentration for triglyceridewas reduced to 475 mg/dL from 6,298 mg/dL, the total cholesterol level was reduced to 176 mg/dL from 946 mg/dL, and the level of low-density lipoprotein was reduced to 4 mg/dL from 403 mg/dL. One month later, as determined at the outpatient clinic, the lipid levels were normalized. PCPF was effective for clearing severely increased plasma lipids.

Proinflammatory Effects of High Mobility Group B1 (HMGB1) Versus LPS and the Mechanism of IL-8 Promoter Stimulation by HMGB1 / 결핵및호흡기질환

BACKGROUND: High mobility group box 1 (HMGB1) is a novel, late mediator of inflammation. This study compared the pro-inflammatory effects of LPS and HMGB1. The transcriptional factors that play an important role in mediating the HMGB1-induced stimulation of IL-8 were also evaluated. METHODS: RAW264.7 cells were stimulated with either LPS (100 ng/ml) or HMGB1 (500 ng/ml). The TNF-alpha, MIP-2 and IL-1beta levels in the supernatant were evaluated by ELISA at 0, 2, 4, 8, 12 and 24h after stimulation. An acute lung injury was induced by an injection of LPS (5 mg/kg) or HMGB1 (2.5 mg/kg) into the peritoneum of the Balb/c mice. The lung cytokines and MPO activity were measured at 4h (for LPS) or 24h (for HMGB1) after the injection. The transcriptional factor binding sites for NF-IL6, NF-kappaB and AP-1 in the IL-8 promoter region were artificially mutated. Each mutant was ligated with pIL-6luc and transfected into the RAW264.7 cells. One hour after stimulation with HMGB1 (500 ng/ml), the cell lysate was analyzed for the luciferase activity. RESULTS: The expression of MIP-2, which peaked at 8h with LPS stimulation, increased sequentially until 24h after HMGB1 stimulation. An intraperitoneal injection of HMGB1, which induced a minimal increased in IL-1beta expression, provoked the accumulation of neutrophils the lung. A mutation of AP-1 as well as NF-kappaB in the IL-8 promoter region resulted in a lower luciferase activity after HMGB1 stimulation. CONCLUSION: The proinflammatory effects of HMGB1, particularly on IL-8, are mediated by both NF-kappaB and AP-1.

A Case of Disseminated Infection Due to Scedosporium apiospermum in a Liver-transplantation Recipient / 대한진단검사의학회지

Scedosporium apiospermum, an anamorph of Pseudallescheria boydii, is a ubiquitous saprophytic mold. Now a day, S. apiospermum is an emerging pathogen related to a significant morbidity and high mortality in transplant recipients. For the first time in Korea, we report a case of disseminated infection caused by S. apiospermum after liver transplantation. A 47-year-old woman underwent living donor liver transplantataion for billiary cirrhosis. She was treated with cyclosporine A, methylprednisolone, and prophylactic antibiotics including amphotericin B. She was found to have developed pneumonia and brain abscess at postoperative day 9 and 17 by chest X-ray and brain CT, respectively. Cultures of endotracheal aspirates and aspirates of brain abscess yielded S. apiospermum. Despite of antifungal therapy with amphotericin B, voriconazole, and caspofungin and removal of mycotic aneurysm of the brain, the patient died on postoperative day 33.