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Background@#Rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) is a global coagulation test that guides evidence-based platelet transfusion in trauma patients. We evaluated ROTEM parameters for predicting mid-term (five days) platelet transfusion in trauma patients. @*Methods@#Maximum clot firmness and clot amplitudes after 5, 10, and 15 mins (A5, A10, and A15, respectively) of fibrin-specific ROTEM (FIBTEM) and extrinsically activated ROTEM (EXTEM) were retrospectively collected from 82 hospitalized, stable, non-bleeding trauma patients after successful initial resuscitation. Platelet-specific ROTEM (PLTEM) was calculated by subtracting FIBTEM from EXTEM. Platelet transfusions were reviewed for five days after ROTEM. @*Results@#The areas under the curve for FIBTEM, EXTEM, and PLTEM predicting platelet concentrate transfusion of > 12 U at mid-term were 0.915–0.923, 0.878–0.896, and 0.551–0.735, respectively. FIBTEM and EXTEM parameters were comparable to those of fibrinogen, fibrin/fibrinogen degradation products, D-dimer, and antithrombin III. Strong correlations (r > 0.7) were noted between platelet count and EXTEM (A5, A10, and A15) or PLTEM (A5), platelet function (per platelet count) and EXTEM (A10 and A15), and fibrinogen levels and all FIBTEM parameters. @*Conclusions@#FIBTEM and EXTEM can reliably predict mid-term platelet transfusion in trauma patients. FIBTEM, EXTEM, and PLTEM parameters correlate with conventional coagulation tests (platelets and fibrinogen).
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Background@#Appropriate platelet transfusion is essential for patient blood management and allocating limited healthcare resources. Therefore, this study evaluated the appropriateness of platelet transfusion in two tertiary hospitals. @*Methods@#At Chonnam National University Hospital (Hospital A) and Chonnam National University Hwasun Hospital (Hospital B), 1,470 platelet transfusions (299 and 1,171 cases at Hospitals A and B, respectively) during a single month were reviewed retrospectively using the Korean Transfusion Guidelines (5th edition). @*Results@#The most common indications were therapeutic transfusion to ensure hemostasis (54.8%) at Hospital A and to prevent spontaneous bleeding in patients with hematologic/oncologic diseases (65.8%) at Hospital B. Overall, 87.3% and 76.3% of transfusions were appropriate at Hospitals A and B, respectively. According to the different transfusion indications, the therapeutic transfusions were appropriate in more than 80% of cases in both hospitals.The appropriateness of prophylactic transfusions against spontaneous bleeding was 80.7% and 69.3%, respectively, and those before surgery or invasive procedures were 72.0% and 66.2%, respectively. Of the 38 and 278 inappropriate transfusions in Hospitals A and B, respectively (as determined by pre-transfusion platelet counts), most cases had platelet counts between 50 and 100×109 /L in Hospital A (23 cases) and between 20 and 50×109 /L in Hospital B (198 cases). @*Conclusion@#The two hospitals differed in terms of transfusion indications, appropriateness, and cases of inappropriateness. The indications and appropriateness of platelet transfusion should be reviewed in real practice on a hospital-by-hospital basis to improve transfusion management.
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Background/Aims@#We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. @*Methods@#A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). @*Results@#The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). @*Conclusions@#This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.
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Background@#In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. @*Methods@#A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. @*Results@#A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). @*Conclusion@#This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.
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Background@#In this study, we presented the national cancer statistics on the incidence of hematologic malignancies in the Republic of Korea (ROK) over a period of 20 years, from 1999 to 2018. @*Methods@#We obtained data on the incidence of hematologic malignancies using the Korean Statistical Information Service (KOSIS). For each hematologic malignancy, the number of cases, crude incidence rate, and age-standardized incidence rate were calculated, and the statistical trends were confirmed by Poisson regression and Joinpoint regression analysis. @*Results@#All the investigated hematologic malignancies showed a statistically significant increase in incidence over 20 years. The 20-year trend of the age-standardized incidence rate was as follows: non-Hodgkin lymphoma [average annual percent change (AAPC)=2.26%, P-trend ＜0.05], leukemia (AAPC=0.94%, P-trend ＜0.05), myeloid leukemia (AAPC=1.44%, P-trend ＜0.05), multiple myeloma (AAPC=3.05%, P-trend ＜0.05), myeloproliferative disorders (AAPC=9.87%, P-trend ＜0.05), myelodysplastic syndrome (AAPC=7.59%, P-trend ＜0.05), malignant immunoproliferative diseases (AAPC=11.82%, P-trend ＜0.05), lymphoid leukemia (AAPC=2.21%, P-trend ＜0.05), and Hodgkin lymphoma (AAPC=4.04%, P ＜0.05). @*Conclusion@#It was confirmed that the incidence of hematologic malignancies has increased significantly in the ROK over the past 20 years. This study can be used as foundational data source for future studies. In addition, it can aid in the necessary actions of predicting future incidences and establishing future healthcare policies.
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Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3Rmutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis.Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.
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Phospholipase C beta 2 (PLC-β2) regulates various essential functions in cell signaling, differentiation, growth, and mobility. We investigated the clinical implications of PLC-β2 protein expression in newly diagnosed normal karyotype acute myeloid leukemia (NKAML). The PLC-β2 expression status in bone marrow tissues obtained from 101 patients with NK-AML was determined using semiquantitative immunohistochemistry (IHC). IHC results were compared with those for known prognostic markers. Using a cutoff score for positivity of 7.0, the PLC-β2 overexpression group showed superior overall survival (OS) (72.6% vs. 26.5%; P = 0.016) and low hazard ratio (HR) (0.453; P = 0.019) compared with the PLC-β2 low-expression group. The PLC-β2 overexpression group showed no significant gain in event-free survival (50.6% vs. 43.0%, P =0.465) and HR (0.735; P =0.464).Among the known prognostic markers, only FLT3-ITD positivity was associated with a significantly low OS and high HR. In conclusion, PLC-β2 overexpression was associated with favorable OS in NK-AML patients. Our results suggest that PLC-β2 expression assessment using IHC allows prognosis prediction in NK-AML.
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Stool examination is the gold standard for the detection of intestinal parasites. We assessed the performance of a newly developed AVE-562 analyzer (AVE Science & Technology Co., Hunan, China) for the vision-based detection of eggs of Clonorchis sinensis—the most common intestinal parasite in Korea—in stool samples. In total, 30 stool samples with a high or low egg count or without eggs (as negative control samples) (N = 10 each) were prepared and analyzed. The performance of the AVE-562 analyzer was compared with that of the formalin-ether concentration (FEC) method. The overall correct identification rate of the AVE-562 analyzer based on FEC results was 66.6%. The sensitivity, specificity, positive predictive value, and negative predictive value of the AVE-562 analyzer for detecting C. sinensis eggs were 36.4%, 100.0%, 100.0%, and 73.1%, respectively. The average time required to run five tests simultaneously was 27 min using the AVE-562 analyzer and 58 min using the FEC method. Although the AVE-562 analyzer enables rapid and convenient stool examination, its sensitivity needs to be improved, particularly considering the prevalence of low-burden C. sinensis infection in Korea.
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The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l’Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 Aspergillus (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed “no identification” or “multiple species identification” results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for Aspergillus, dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed “no identification” and “misidentification” results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification
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Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.
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Background@#Prohibitin (PHB) regulates intracellular signal pathways, transcription, and cell cycles. Aberrant expression of the PHB gene is known to be related totumorigenesis, tumor progression, and chronic metabolic and inflammatory diseases. The present study aimed to develop a one-step quantitative reverse transcription PCR (RT-qPCR) kit for quantifying PHB mRNA levels and evaluate its performance in the laboratory. @*Methods@#TaqMan chemistry was used to develop the one-step PHB1 and PHB2 RT-qPCR kit. Normal peripheral blood cells from healthy individuals (N=20) and leukemia cells from patients initially diagnosed with acute myeloid leukemia (AML, N=20), chronic myeloid leukemia (CML, N=13), and acute lymphoid leukemia (ALL, N=7) were enrolled to evaluate the laboratory performance of the kit using commercially available total human RNA controls. @*Results@#The intra-assay and inter-assay precision of the kit developed in this study was less than 2%. The distribution of PHB1 mRNA expression of AML, CML, and ALL was 0.898-0.993 (median: 0.936), 0.817-0.976 (0.918), and 0.844-1.074 (0.973), respectively. The distribution of PHB2 mRNA expression of AML, CML, and ALL was 0.957-1.024 (median: 0.985), 0.988-1.047 (1.002), and 0.937-1.059 (1.004), respectively. The sensitivity, specificity, positive and negative predictive value, and test effectiveness of the developed PHB1 and PHB2 kit were greater than 50% for each parameter. @*Conclusions@#Our developed kit would be useful for diagnosing leukemia as well as detecting residual disease. Additionally, this kit could be used for monitoring and conducting molecular pathophysiological studies of obesity, metabolic, and inflammatory diseases.
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Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.
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Subject(s)
Humans , B-Lymphocytes , Blood Cell Count , Colorectal Neoplasms , Lymphocyte Subsets , LymphocytesABSTRACT
D antigens are clinically significant, and routine tests on the D antigen requires the inclusion of weak D testing, which is performed using indirect antihuman immunoglobulin methods. On the other hand, exact typing of the D type of an individual can be done more precisely with RHD genotyping, which is a useful tool in cases where the RHD gene is intact. The majority of weak-D or partial-D cases are from single nucleotide changes or hybridization of RHD and RHCE genes. Nevertheless, frameshift mutations can also result in weak or partial-D. The characteristics of a frameshift mutation is typically a change in protein product after a problematic mutation and early termination of transcription, leading into truncated protein products. This paper reports a D-variant case with RHD 711delC along with a review of the relevant literature. In addition, the results of software analysis are reported.
Subject(s)
Frameshift Mutation , Genotype , Hand , ImmunoglobulinsABSTRACT
In the original publication, the schedule of follow-up assessment was incorrect.
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BACKGROUND: Fluoranthene (FR) is a common environmental pollutant that exists in a complex mixture with other polycyclic aromatic hydrocarbons (PAHs). We identified biomarkers for monitoring FR exposure and investigated the rescue effect of FR-induced cellular toxicity via aryl hydrocarbon receptor (AHR) antagonist activity in bone marrow derived mesenchymal stem cells (BM-MSCs).METHODS: Morphological changes, viability, and rescue effects of an AHR antagonist (CH223191) were examined in BM-MSCs after exposure to FR. Cytotoxic effects were assayed using the tetrazolium-based colorimetric assay. Apoptosis was measured by annexin V and propidium iodide dye-based flowcytometry assay, mitochondrial membrane potential assay, and nuclear DNA fragmentation assay. Molecular signaling pathways of apoptosis and autophagy were investigated using immunoblotting. Proteomics were performed in order to reveal the spectra of cellular damage and identify biomarkers for FR exposure.RESULTS: Exposing BM-MSCs to FR (IC₅₀=50 µM) induced cell death and morphological changes, while the AHR antagonist showed rescue effects. Autophagy was activated and mitochondrial membrane potential was decreased. Proteomic analysis identified 48 deregulated proteins (26 upregulated and 22 downregulated). Among them, annexin A6, pyruvate kinase, UDP-glucose dehydrogenase, and phospholipase A2 could be potential biomarkers for FR exposure.CONCLUSION: The exposure of BM-MSCs to FR induced remarkable alterations in cellular biology and the proteome, allowing for identification of novel biomarkers for FR exposure. Furthermore, AHR antagonists might be able to prevent cellular damage due to FR exposure.
Subject(s)
Annexin A5 , Annexin A6 , Apoptosis , Autophagy , Biomarkers , Bone Marrow , Cell Death , DNA Fragmentation , Immunoblotting , Membrane Potential, Mitochondrial , Mesenchymal Stem Cells , Oxidoreductases , Phospholipases A2 , Polycyclic Aromatic Hydrocarbons , Propidium , Proteome , Proteomics , Pyruvate Kinase , Receptors, Aryl HydrocarbonABSTRACT
Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.
Subject(s)
Adult , Animals , Humans , Mice , Adenosine Triphosphate , Adult Stem Cells , Aging , Bone Marrow , Cell Respiration , Cytoplasm , Diet , Dietary Supplements , Hematologic Neoplasms , Hematopoiesis , Hematopoietic Stem Cells , Immune System , Incidence , Membrane Potentials , Mitochondria , Niacin , Niacinamide , Phenotype , Sirtuins , Stem Cells , Tryptophan , VitaminsABSTRACT
BACKGROUND: Few studies of high dose dexamethasone (HD-DXM) therapy in children with immune thrombocytopenic purpura (ITP) have been reported. The purpose of this study is to investigate efficacy and safety of repeated HD-DXM therapy as second-line treatment of ITP in childhood. METHODS: We retrospectively analyzed the medical records of patients < 18 years of age with primary ITP who received more than 2 cycles of HD-DXM therapy from May 2004 to January 2018. HD-DXM was given orally in 4-day pulses every 28 days as a 20–40 mg/1.73 m² daily dose. RESULTS: A total of 26 patients (male, 19; female, 7) were enrolled and their median age was 6 years (range, 1–15). All patients had received previous treatment for ITP. A median 6 cycles (range, 2–19) of HD-DXM was given. On the beginning of HD-DXM therapy, three patients satisfied the criteria for newly diagnosed ITP, 16 for persistent ITP and 7 for chronic ITP. Relapse-free survival (RFS) of responders (n=9) after the last HD-DXM cycle was estimated to be 38.1±17.2%, lasting for a median 9.1 months (range, 5.6–46.2). According to response after the 2nd cycle, RFS of responders (n=13) was significantly higher than non-responders (23.1±11.7% vs. 7.7%±7.4%, P=0.001). The most common adverse event was irritability (30.8%), followed by fatigue (19.2%). CONCLUSION: HD-DXM therapy in children was relatively tolerated and response after therapy was acceptable. More courses of HD-DXM may be feasible in responders after two cycles of HD-DXM.