Clinical features and outcomes of JAK2V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2V617F allele burden

Background@#JAK2mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2V617F allele burden is under investigation. @*Methods@#We retrospectively evaluated the impact of the JAK2V617F allele burden on clinical characteristics and outcomes of JAK2V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2V617F allele burden was measured using sequencing. @*Results@#Altogether, 127 patients with JAK2V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8-year OS based on the JAK2V617F allele burden was not significant. @*Conclusion@#The JAK2V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2V617F-positive PV and ET.

Therapeutic Plasma Exchange in Patients with Severe Fever with Thrombocytopenia Syndrome: A Single Institution Experience / 대한수혈학회지

Background@#Severe fever with thrombocytopenia syndrome (SFTS) is a novel infection caused by the tick-borne SFTS virus. More than 200 patients are reported every year in Korea, but there is no established treatment. In patients with SFTS, therapeutic plasma exchange (TPE) can be applied. @*Methods@#Clinical and laboratory characteristics of patients diagnosed with SFTS who underwent TPE were analyzed. The factors that can differentiate the prognosis between the patients who recovered after TPE and those who died were analyzed. @*Results@#Ten patients were diagnosed with SFTS and treated with TPE. The mean age was 70.8 (49–85) years, with three men and seven females. The laboratory findings showed a decrease in white blood cell (WBC) count, platelet count, and serum albumin and an increase in AST, ALT, LDH, and CK levels. Patients performed an average of three (2∼4) TPE procedures at intervals of 1∼2 days, three of whom died. Compared to the results at admission, the WBC counts increased after TPE, and the platelet counts remained unchanged. The AST, LDH, and CK levels decreased by 2∼6 fold in the recovered patients and increased in those who died. Among them, the change in LDH was statistically significant between the two groups (P=0.0227). @*Conclusion@#TPE has been used as an adjuvant treatment in SFTS patients who do not have a definitive treatment to date. Additional studies, including small-scale studies such as this study, will be needed to establish the timing, interval, and predictive factors of the effect of TPE.

Therapeutic Plasma Exchange in Patients with Severe Fever with Thrombocytopenia Syndrome: A Single Institution Experience / 대한수혈학회지

Background@#Severe fever with thrombocytopenia syndrome (SFTS) is a novel infection caused by the tick-borne SFTS virus. More than 200 patients are reported every year in Korea, but there is no established treatment. In patients with SFTS, therapeutic plasma exchange (TPE) can be applied. @*Methods@#Clinical and laboratory characteristics of patients diagnosed with SFTS who underwent TPE were analyzed. The factors that can differentiate the prognosis between the patients who recovered after TPE and those who died were analyzed. @*Results@#Ten patients were diagnosed with SFTS and treated with TPE. The mean age was 70.8 (49–85) years, with three men and seven females. The laboratory findings showed a decrease in white blood cell (WBC) count, platelet count, and serum albumin and an increase in AST, ALT, LDH, and CK levels. Patients performed an average of three (2∼4) TPE procedures at intervals of 1∼2 days, three of whom died. Compared to the results at admission, the WBC counts increased after TPE, and the platelet counts remained unchanged. The AST, LDH, and CK levels decreased by 2∼6 fold in the recovered patients and increased in those who died. Among them, the change in LDH was statistically significant between the two groups (P=0.0227). @*Conclusion@#TPE has been used as an adjuvant treatment in SFTS patients who do not have a definitive treatment to date. Additional studies, including small-scale studies such as this study, will be needed to establish the timing, interval, and predictive factors of the effect of TPE.

Risk Factors for Adverse Events of Therapeutic Plasma Exchange Assessed in a Single Center Study / 대한수혈학회지

BACKGROUND: Therapeutic plasma exchange (TPE) is used to remove pathologic substances involved in various disease etiologies. The use of TPE is increasing steadily in a variety of disease. This study analyzed the incidence, type and severity of adverse events (AE) according to the initial TPE of each patient in a single center. The risk factors for AE of TPE were also elucidated. METHODS: The medical and laboratory records of patients, who received TPE from January 2014 to December 2018, were reviewed retrospectively. The signs or symptoms during and after TPE were analyzed. RESULTS: TPE sessions were performed on 95 patients. The mean age was 53.3 years and men comprised 63.2%. The most common indication for TPE was desensitization for ABO-incompatible liver transplantation (ABO-i LT) (N=56, 58.9%). A total of 27 patients (28.4%) experienced AE during the initial TPE. The types of AE were allergic reactions (N=14, 14.7%), anaphylactic reaction (N=3, 11.1%), hypotension (N=5, 5.3%), hypocalcemic reaction (N=4, 4.2%), and febrile nonhemolytic reaction (N=1, 1.1%). The severities of AE were evaluated as mild in eight procedures (8.4 %), moderate in seventeen (17.9 %), and severe in two (2.1 %). Multivariable logistic regression analysis showed that the desensitization for ABO-i LT (odds ratio (OR), 2.08; 95% CI, 1.03~4.22) and the amount of FFP (OR, 1.07; 95% CI, 1.01~1.09) were associated with a higher incidence of AE. CONCLUSION: TPE can be performed under careful patient monitoring to provide prompt intervention, particularly in patients with desensitization of ABO-i LT using FFP.

Annual Report of the Korean Association of External Quality Assessment Service on Urinalysis and Fecal Occult Blood Testing (2018)

In 2018, external quality assessment trials for urinalysis and fecal occult blood (FOB) were performed using 1,590 participants. Urine chemistry tests were performed thrice while urine sediment and FOB tests twice. Urine chemistry tests comprised of pH, protein, glucose, ketone body, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity analyses. The results of urine chemistry and specific gravity tests showed accuracy rates >95%, except for the pH test. The accuracy rate of urine sediments was low, especially for atypical calcium oxalate crystal and red blood cell cast. In the FOB quality test, reagents showed accuracy rates >90%, except for SD and GC Genedia FOB reagents. In the FOB quantitative test, Alfresa NS-Plus C instrument showed falsely high values in the FOB negative specimens.

Acute Monoblastic Leukemia with t(11;17)(q23;q21): Fusion of the KMT2A(MLL) and MLLT6(AF17) Genes

The KMT2A (formerly MLL) gene is associated with at least 10% of all cases of acute leukemia. More than 80 translocation partner genes of KMT2A have been discovered to date, six of which have been identified on the long arm of chromosome 17. Among these, the MLLT6 (formerly AF17) gene is located at 17q12 and fuses with the KMT2A gene in rare cases of acute leukemia. We report here a case of AML with a KMT2A/MLLT6 fusion that was confirmed using molecular genetic methods. According to a literature review, this is the first reported case of AML with a KMT2A/MLLT6 fusion in Korea.

The First Case of Otitis in Korea Caused by Brevibacterium otitidis

Brevibacterium spp. are gram-positive rods that are considered to be strictly nonpathogenic, and a very few cases of their infection in humans have been reported. In this study, we report a case of otitis caused by Brevibacterium otitidis. A 53-year-old woman, who visited the hospital, complained of symptoms, such as otorrhea from both ears, ear fullness, tinnitus, and hearing impairment, for several months. Ear discharge was cultured on blood agar for pathogen identification. Bacteria from the isolated colony were initially identified as Actinomyces odontolyticus by VITEK 2 (bioMerieux, France), whereas VITEK® MS (bioMerieux, France) identified them as Brevibacterium luteolum. Subsequently, bacteria from the isolated colony were confirmed as B. otitidis by 16S rRNA sequencing. Antimicrobial susceptibility testing confirmed their sensitivity to vancomycin and linezolid and resistance to clindamycin and penicillin. To our knowledge, this is the first reported case of otitis caused by B. otitidis in Korea.

Annual Report on the External Quality Assessment Scheme for Urinalysis and Fecal Occult Blood Testing in Korea (2017)

In 2017, external quality assessment trials for urinalysis and fecal occult blood (FOB) were performed with 1,544 participants. Urine chemistry tests were performed three times and urine sediment and FOB tests were evaluated 2 times. Urine chemistry tests consisted of pH, protein, glucose, ketone, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity analyses. The results of the urine chemistry and specific gravity tests showed accuracy rates >95%. The accuracy rate of urine sediments was low, especially for fat droplets and atypical uric acid crystals. In the FOB quality test, all reagents showed accuracy rates >82%, which suggested the persistent improvement of false-positive reactions. In the FOB quantitative test, discrepant results depending on the instrument used were observed. To compensate for the result differences caused by the amounts of stool samples, the results should be reported using another unit (µg/g of stool).

Incidence of Adverse Transfusion Reactions from an Institutional Hemovigilance System: A Single Center Study / 대한수혈학회지

BACKGROUND: A hemovigilance system is essential to detect and analyze adverse transfusion reactions to various blood components. A blood bank physician has the role of discriminating the adverse transfusion reactions based on the hemovigilance criteria. This study investigated the incidence of adverse transfusion reactions per transfused case and the incidence of adverse transfusion reactions according to the various blood components in recipients. METHODS: From January 2016 to February 2017, 38,689 blood component units were transfused into 3,768 patients. A total of 11,170 transfused cases were reported. The patients’ signs or symptoms were monitored and reported by nurses using an electronic reporting system. A blood bank physician classified the adverse transfusion reactions according to the Korean hemovigilance reporting definitions. RESULTS: The frequency of all transfusion-related events was 469 according to the nursing record. Out of 469 events, 175 (37.3%) were classified as adverse transfusion reactions. The incidence of a febrile nonhemolytic transfusion reaction according to the blood component was highest for red blood cells (1.3%), followed by a platelets (0.8%) and fresh frozen plasma (0.3%). The incidence of allergic reactions was 1.0% (platelets), 0.8% (fresh frozen plasma), and 0.3% (red blood cells). The incidence of febrile nonhemolytic transfusion reactions was lowered significantly by leukocyte-reduction. CONCLUSION: The incidence of adverse transfusion reactions was 37.3% of the transfusion-related events. Therefore, close monitoring by the blood bank physician is essential for safe transfusion. The use of leukocyte-reduced blood components could reduce the incidence of febrile nonhemolytic transfusion reactions.

Abnormal Urinalysis Results Caused by Interfering Substances

BACKGROUND: To understand causes of abnormal reaction for the urinalysis, we analyze the interfering substances of clinical urine samples. We focused the effect of urinary vitamin C and fluorescein sodium to the urine chemistry especially glucose, hemoglobin, and leukocyte esterase. METHODS: Incidence of urinary vitamin C was determined for patients and people underwent a medical check–up. We decided dipstick results of glucose, hemoglobin, and leukocyte esterase as false negative based on urine sediment and serum glucose results. Dipstick urinalysis was tested by URiSCAN Pro III with URiSCAN 11 strip (YD Diagnostics, Korea). Urine sediments tests were performed by manual microscopic analysis or Sysmex UF–1000i (Sysmex Co., Japan). RESULTS: The incidence of vitamin C was 20.4% for all subjects. The positive rate of the medical check-up group (34.6%) was higher than others. When vitamin C was detected in clinical urine samples, 42.3%, 10.6%, and 8.2% were defined as false negative for glucose, hemoglobin, and leukocyte esterase dipstick tests, respectively. Fluorescein sodium also interfered on the results of hemoglobin and leukocyte esterase of the dipstick reagents. CONCLUSIONS: Vitamin C was frequently found in the clinical urine samples, and its incidence was higher in the people who underwent medical check-up. The urinary vitamin C and fluorescein sodium can cause interferences in urine dipstick results. Thus, it is expected that present study will give useful information to predict false negative rates of urine dipstick tests by vitamin C and fluorescein sodium.

Annual Report on the External Quality Assessment Scheme for Urinalysis and Faecal Occult Blood Testing in Korea (2016)

In 2016, external quality assessment trials for urinalysis and faecal occult blood (FOB) were performed with 1,487 participants in Korea. Urine chemistry and FOB tests were performed three and two times, respectively, whereas urine sediment was evaluated once using photography. Urine chemistry tests consisted of pH, protein, glucose, ketone, bilirubin, blood, urobilinogen, and nitrite levels; leukocyte count; specific gravity. The results of the urine chemistry and specific gravity tests showed accuracy rates of >95%. The accuracy rate of urine sediments was low, especially that for transitional epithelial cells and atypical crystals. In the FOB quality test, all reagents showed accuracy rates of >90%, which suggested the improvement of false-positive reaction. In the FOB quantitative test, discrepant results depending on the instrument used was observed. To compensate for the result differences caused by the stool samples, the results should be reported using another unit (µg/g of stool).

Quality Improvement of Urinalysis Results Based on Automatic Sediment Urinalysis and Urine Strip Results

BACKGROUND: Microscopic examinations are usually performed to confirm urine sediments in samples flagged in automated urinalysis. The aim of this study was to analyze the review rates and the difference in urinalysis results according to review rules. METHODS: A total of 1,408 urine samples submitted for health screening were collected. The urine chemistry test and urine sediment test were performed using EikenUS 3100 (Eiken Chemical Co. Ltd., Japan) and Sysmex UF-1000i (Sysmex Co., Japan), respectively. We assessed the rate of agreement between the 2 analyses and the kappa values for white blood cells (WBCs) and red blood cells (RBCs). Microscopic examinations were performed for all cases of discordant results between the urine strip and automated sediment analysis, some cases of concordant results, and cases of albuminuria. RESULTS: The review rate was 14.3%. Microscopic examinations were additionally performed on 77 samples (77/1,207, 6.4%) including 29 and 56 samples flagged for WBCs and RBCs, respectively. Based on the results of microscopic examination, the false-positive and the false-negative results of the urine chemistry test and automatic sediment analysis were corrected. Among concordant results between two methods, a clinically significant number of false-negatives were identified (6 results of WBC detection [6/125, 4.8%] and 4 of RBC detection [4/145, 2.8%]). Among the 22 unflagged cases of albuminuria, pathologic casts were detected in 21 cases (21/22, 95.5%). CONCLUSIONS: Microscopic examination based on the combined results of the two analyses improved the quality of the test.

Native Valve Endocarditis due to Corynebacterium striatum confirmed by 16S Ribosomal RNA Sequencing: A Case Report and Literature Review / 감염과화학요법

Corynebacterium species are non-fermentous Gram-positive bacilli that are normal flora of human skin and mucous membranes and are commonly isolated in clinical specimens. Non-diphtheriae Corynebacterium are regarded as contaminants when found in blood culture. Currently, Corynebacterium striatum is considered one of the emerging nosocomial agents implicated in endocarditis and serious infections. We report a case of native-valve infective endocarditis caused by C. striatum, which was misidentified by automated identification system but identified accurately by 16S ribosomal RNA sequencing, in a 55-year-old male patient. The patient had two mobile vegetations on his mitral valve, both of which had high embolic risk. Through surgical valve replacement and an antibiotic regimen, the patient recovered completely. In unusual clinical scenarios, C. striatum should not be simply dismissed as a contaminant when isolated from clinical specimens. The possibility of C. striatum infection should be considered even in an immunocompetent patient, and we suggest a genotypic assay, such as 16S rRNA sequencing, to confirm species identity.

Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

Annual Report on the External Quality Assessment Scheme for Urinalysis and Faecal Occult Blood Testing in Korea (2015)

In Korea, external quality assessment trials for urinalysis and faecal occult blood (FOB) were performed for 1,250 participants. Urine chemistry and FOB tests were evaluated three times, whereas urine sediment by photography was evaluated twice. Urine chemistry tests consisted those for pH, protein, glucose, ketone, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity. The results of the urine chemistry and specific gravity tests showed accuracy rates >95%. In the FOB quality test, all reagents showed false-positive results. These reagents showed positive results in stool specimens containing >11 ng/mL haemoglobin. In the FOB quantitative test, the results were significantly different, based on the instrument used for the measurements. The average accuracy rate of urine sediments was 90.8%, whereas those for renal epithelial cells and cholesterol crystals were 83%.

Myeloid Sarcoma of Peritoneum in Acute Myeloid Leukemia Patient with Inversion of Chromosome 16 / 대한내과학회지

Myeloid sarcoma is an extramedullary myeloid neoplasm that usually involves the skin, soft tissues, and lymph nodes. Myeloid sarcoma is found in 2.5-9.1% of acute myeloid leukemia patients, usually those with t (8;21), while inv (16) is rarely associated with myeloid sarcoma. Consequently, little is known of the characteristics and incidence of inv (16) in myeloid sarcoma. Myeloid sarcoma in acute myeloid leukemia patients with inv (16) is most often found in the abdominal lesions; the intestinal tract is involved most commonly, in the form of a mass. Here, we report an unusual myeloid sarcoma presenting as peritoneal carcinomatosis in acute myeloid leukemia with inv (16) that appeared to be ascites.

MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B4 receptor BLT2. Our results suggest that TLR4-MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activation of the transcription factor nuclear factor (NF)-kappaB function downstream of BLT2 in this response. These results suggest that a TLR4-MyD88-BLT2-Nox1-ROS-NF-kappaB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages.

Evaluation of CD3+CD4-CD8- (Double-negative) T Cells in Bronchoalveolar Lavage Fluid: an Effective Tool for Pulmonary Disease Diagnosis

BACKGROUND: Cellular analysis of bronchoalveolar lavage fluid (BALF) is a useful diagnostic tool for interstitial lung diseases (ILDs). The lymphocytes in BALF consist of CD3+CD4+ T cells (T4), CD3+CD8+ T cells (T8), and a few B cells. However, sometimes, an increased number of CD3+CD4-CD8- T cells (double-negative T cells, DNTs) are noted in BALF. It is known that DNTs in the blood are associated with immunoregulation and autoimmune diseases. However, there are only few studies on DNTs in BALF. We evaluated the DNTs in BALF in patients with pulmonary diseases. METHODS: Immunophenotyping results of the BALF obtained from 122 pulmonary disease patients over an 8-yr period were reviewed. T-lymphocyte subsets (T4, T8, and DNT) and inflammatory markers were analyzed for each group of clinical diagnosis. T-lymphocyte percentage of more than 15% of the total cells was defined as BALF lymphocytosis, and DNT percentage of more than 5% of T lymphocytes was defined as high DNT. RESULTS: The most frequent diseases found in the patients were pneumonia (31.6%), autoimmune-related ILDs (18.0%), hypersensitivity pneumonitis (10.7%), and organizing pneumonia (10.7%). However, the occurrence of autoimmune-related ILDs was significantly high (40%) in patients with lymphocytosis and high DNT (P=0.002). All lung cancer patients showed lymphocytosis with high DNT. In addition, CD3-signal intensities of DNTs were significantly higher than those of other T-lymphocyte subtypes (P=0.003). CONCLUSION: The number of DNTs in BALF was increased in patients with autoimmune-related ILDs and lung cancer. High DNTs in BALF are useful as supportive diagnostic tools for autoimmune-related ILDs.

Annual Report on External Quality Assessment Scheme for Urinalysis and Faecal Occult Blood Testing in Korea (2014)

In 2014, external quality assessment trials for urinalysis and faecal occult blood (FOB) were performed of 1,270 participants. Urine chemistry and FOB tests were evaluated three times, while urine sediment examination by photography was evaluated one time. Urine chemistry tests consisted of pH, protein, glucose, ketone, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity (SG). The urine chemistry test results showed accuracy rates >95%, while those of the SG test by using a refractometer had accuracy rates <95%. In the FOB quality test, the Bio Focus reagent (BIO FOCUS Co., Korea) disclosed low positive rates (87%). The result of the FOB quantity test showed different values according to the instruments used, and the Kyowa instrument (Kyowa Chemical Industry Co., Japan) revealed the lowest values. In a urinary sediment examination, it is necessary to increase the frequency of the quality assessment trials due to low accuracy rates.

The Relationship between ABO Blood Group Phenotypes and Seroprevalence of Infectious Disease in Korea / 대한수혈학회지

BACKGROUND: The distribution of ABO and Rhesus D (RhD) blood group antigens differs according to race and region. Previous studies have reported that blood group type was associated with not only transfusion-related diseases but also various diseases, such as malignancy and infectious disease. However, true relationship of blood groups and many diseases remained controversial. The aim of this study was to determine whether ABO and RhD blood groups are correlated with several infectious diseases. METHODS: From January 2003 to December 2012, we retrospectively reviewed results for HBsAg, HCV Ab, HIV Ab, VDRL, HAV IgM, CMV IgM, EBV VCA IgM, and Clostridium difficile toxin A and B (CD toxin). We also reviewed ABO and RhD results of these patients. Data were analyzed using chi-square test and binary logistic regression test. Odds ratio and 95% confidence intervals were determined. RESULTS: A total of 109,898 medical records of ABO and HBsAg results were reviewed. Blood group type-A was more prone to have positive results with HBsAg, while blood group type-O was less affected (odds ratio 1.086, P=0.003, odds ratio 0.935, P=0.029, respectively). With 3,171 records of CD toxin, blood group type-O was more affected (odds ratio 1.247, P=0.027). The relationship of the other serologic results and blood groups was not statistically significant. CONCLUSION: Seroprevalence of HBsAg and CD toxin showed an association with blood group type. Blood group type-A had higher HBsAg seroprevalence than the other group. Blood group type-O was more prone to have CD toxin.