Reference intervals of cell population data parameters in Sysmex XN-Series and its patterns of changes from early adulthood to geriatric ages in South Korea.

INTRODUCTION: Cell population data (CPD) parameters may be putative biomarkers for the screening of various diseases including some infections and myelodysplastic syndrome. This study aimed to establish the age- and sex-specific reference intervals (RIs) for the CPD parameters in the Korean population. METHODS: The reference population for the RIs of CPD parameters comprised 124 856 subjects aged 20-99 years. CPD parameters were obtained from Sysmex XN-2000 (Kobe, Japan) datasets from 17 health promotion centers in 13 South Korean cities. We determined significant partitions for age and sex, and calculated RIs according to Clinical and Laboratory Standards Institute C28-A3 guidelines. RESULTS: The side scattered light intensity in the neutrophil area and the lymphocyte area did not require sex-related partitioning except in those over the age of 50, among whom the lower limit (LL) and upper limit (UL) were lower in females. However, the side scattered light distribution width in the lymphocyte area required age- and sex-related partitioning, in which LL and UL were higher in females. The LL and UL of the fluorescent light distribution width were higher in males in the neutrophil area and higher in females in the lymphocyte area, but age-related partitioning was not required. The forward scattered light intensity in the neutrophil area, lymphocyte area, and monocyte area did not require age-related partitioning in males. CONCLUSION: This study has determined comprehensive age- and sex-specific RIs for CPD parameters, which could help to prove the clinical significance of these parameters in the Sysmex XN-2000.

Establishment and validation of reference intervals for tumor markers (AFP, CEA, CA19-9, CA15-3, CA125, PSA, HE4, Cyfra 21-1, and ProGRP) in primary care centers in Korea: A cross-sectional retrospective study.

Background and Aims: The reference interval (RI) for a tumor marker may vary between populations, detection systems, and the methods used to obtain their values. The aims of this study were to establish age- and sex-specific RIs for the following nine common tumor markers and to validate the established RIs in Korean adults: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA15-3, CA125, Human epididymis protein 4 (HE4), total prostate specific antigen, cytokeratin fragment (Cyfra) 21-1, and progastrin-releasing peptide (ProGRP). Methods: This cross-sectional study consecutively selected 214,159 individuals (aged 18-98 years) who underwent health checkups at 16 health-promotion centers in 13 Korean cities. Finally, 62,752 examinees were used to establish the RIs after removing outliers. RIs were established using an indirect method according to the CLSI EP28-A3C guideline. The established RIs were validated by calculating the proportion of individuals outside each RI. Results: Sex-related differences were observed for AFP, CEA, CA19-9, Cyfra 21-1, and ProGRP (p < 0.05): AFP, CEA and Cyfra 21-1 were higher in males, and CA19-9 and proGRP were higher in females. Most of the tumor markers except CA15-3 and CA125 increased with age: CA125 decreased at ≥50 years of age (p < 0.05), while CA15-3 did not vary with age. Less than 5% of subjects were outside all RIs (the 2.5th and 97.5th percentiles) established in the present study. Meanwhile, less than 3% of the healthy reference subjects fell outside the current and manufacturers' RIs of all tumor markers except Cyfra 21-1. Conclusion: This study has determined age- and sex-specific RIs for nine common tumor markers in the healthy Korean population, which could be useful for clinicians making clinical decisions and assessments.

Nationwide seroprevalence of antibodies to SARS-CoV-2 in asymptomatic population in South Korea: a cross-sectional study.

OBJECTIVE: Asymptomatic active infection might be an important contributor to the COVID-19 outbreak. Serological tests can assess the extent of exposure and herd immunity to COVID-19 in general populations. This study aimed to estimate the nationwide seroprevalence of SARS-CoV-2 antibodies according to age, sex and clinical status in South Korea. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study randomly selected health examinees who underwent health check-up at 16 health promotion centres in 13 Korean cities across the country between late September and early December 2020. Residual serum samples were obtained from 4085 subjects (2014 men and 2071 women). Antibodies to SARS-CoV-2 were measured by electrochemiluminescence immunoassay using Elecsys Anti-SARS-CoV-2 (Roche Elecsys, Mannheim, Germany). PRIMARY AND SECONDARY OUTCOME MEASURES: Fisher's exact test was used to compare the seroprevalence according to sex, age group and region. The relative risks of being seropositive according to the characteristics of the study subjects were analysed using logistic regression analysis. RESULTS: The overall seroprevalence of anti-SARS-CoV-2 was 0.39% (95% CI=0.20% to 0.58%): 0.30% (95% CI=0.06% to 0.54%) for men and 0.48% (95% CI=0.18% to 0.78%) for women. The rate of anti-SARS-CoV-2 positivity varied significantly between different regions of Korea (p=0.003), but not with age group, sex, or the statuses of obesity, diabetes, hypertension or smoking. CONCLUSIONS: Most of the Korean population is still immunologically vulnerable to SARS-CoV-2, but the seroprevalence has increased relative to that found in studies performed prior to September 2020 in Korea.

Reference interval and the role of soluble suppression of tumorigenicity 2 (sST2) in subclinical cardiac dysfunction at health checkups.

BACKGROUND: Soluble ST2 (sST2) is known to predict adverse outcomes and death in individuals with established heart failure. However, the role of sST2 testing in the general population has not been established. The aims of this study were to determine the reference interval (RI) and the clinical utility of sST2 in subclinical cardiac dysfunction in general population. METHODS: This cross-sectional study consecutively selected 41,806 general subjects at health checkups who underwent echocardiography and sST2 testing at 16 health promotion centers in 13 Korean cities. The reference subjects were obtained among those with normal findings in echocardiography. Sex-specific RIs were established according to the CLSI C28-A3 guidelines. sST2 was measured using immunoassay with the Presage ST2 assay (Critical Diagnostics). RESULTS: In the general subjects, age, sex, BMI, systolic blood pressure, blood glucose, creatinine, liver function, and triglycerides were associated with the sST2 levels. The RI for sST2 was higher in males (≤49.6 ng/mL, 95% CI = 48.5-51.5) than in females (≤44.5 ng/mL, 95% CI = 43.5-45.6) and higher in subjects aged < 40 years than ≥ 40 years in both sexes. The sST2 levels were 29.1 ± 10.7 (mean ± SD) and 29.1 ± 14.4 ng/mL in the groups with normal cardiac function and subclinical cardiac dysfunction, respectively. The sST2 level was not associated with subclinical cardiac dysfunction (odd ratio = 1.002, P = .13). CONCLUSIONS: RIs obtained from a large and echocardiography-proven healthy community-based sample are presented. Subclinical cardiac dysfunction was associated with older age, male sex, and metabolic factors but not with the sST2 level.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BACKGROUND: Mild-to-moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase-to-platelet ratio (APRI) and the Fibrosis-4 index (FIB-4) in health checkups. METHODS: This cross-sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results. RESULTS: The median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34-0.61), 0.48 (0.38-0.68), 0.64 (0.43-1.03), and 1.01 (0.75-1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB-4 and APRI. CONCLUSION: Serum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

Subclinical Iron Deficiency in Non-Anemic Individuals: A Retrospective Analysis of Korean Health Examinees.

OBJECTIVES: Non-anemic individuals may have undetected subclinical iron deficiency (SID). The aims of this study were to determine the prevalence of SID and identify the associated factors for SID. In addition, the screening performance of red blood cell (RBC) indices for SID in health check-ups was assessed. METHODS: This study was conducted with 16,485 non-anemic health examinees (3,567 males and 12,918 females) who underwent tests for iron variables (serum iron, total iron-binding capacity, ferritin, and iron saturation) at 16 health-promotion centers in 13 cities in Korea between January 2017 and June 2018. SID was defined as a decreased ferritin level (<24 µg/L in males and <15 µg/L in females) and either a decreased serum iron level (<44 µg/dL in males and <29 µg/dL in females) or a transferrin saturation of <20%. RESULTS: The prevalence rates of SID were 0.6 and 3.3% in males and females, respectively. In terms of age and sex, SID was most prevalent in males aged ≥70 years (7.8%) and females aged 15-49 years (7.6%). There were significant differences in the hemoglobin (Hb) level, white blood cell count, platelet count, mean corpuscular volume, mean corpuscular Hb (MCH), and RBC distribution width (RDW) between the SID and non-SID groups (p < 0.001). The factors associated with SID in males were older age (odds ratio, OR, 1.069, 95% confidence interval, CI, 1.03-1.109, p = 0.004), lower Hb (OR 0.58, 95% CI 0.345-0.976, p = 0.04), lower MCH (OR 0.433, 95% CI 0.298-0.629, p < 0.001), and higher RDW (OR 1.374, 95% CI 1.001-1.887, p = 0.049), while in females they were lower body mass index (BMI; OR 0.929, 95% CI 0.895-0.963, p < 0.001) and younger age (OR 0.954, 95% CI 0.945-0.963, p < 0.001), as well as lower Hb, lower MCH, and higher RDW. The AUC for the MCH (0.877, 95% CI 0.793-0.960 in males; 0.872, 95% CI 0.853-0.890 in females) indicates that the MCH at cut-offs of 29.2 and 29.3 pg are the best discriminators of SID in males and females, respectively (p < 0.001). CONCLUSIONS: Reproductive-age females with a lower BMI and elderly males are high-risk groups for SID. MCH is a reliable RBC index for the screening of SID. For the population with defined risk factors, including females with lower BMI and elderly males, screening for SID is needed to prevent the development of anemia.

Evaluation of the LC-1000 Flow Cytometry Screening System for Cervical Cancer Screening in Routine Health Checkups.

OBJECTIVE: This study evaluated the performance of a flow cytometry system (LC-1000) in screening cervical precancerous lesions at routine health checkups. STUDY DESIGN: In total, 928 health examinees were enrolled at 16 health promotion centers in 13 Korean cities between 2016 and 2017. All participants underwent liquid-based cervical cytology and flow cytometry testing to determine the cell proliferation index (CPIx). RESULTS: The positivity rate of the LC-1000 system increased with the severity of the cervical cytology findings (p for trend < 0.001). When low-grade squamous intraepithelial lesion (LSIL) or higher (including LSIL, high-grade squamous intraepithelial lesion [HSIL], and atypical squamous cells without excluding HSIL [ASC-H]) was defined as gold-standard positivity, the sensitivity, specificity, PPV, and NPV of LC-1000 were 75.3% (95% confidence interval [CI], 66.8-83.7), 58.5% (95% CI, 55.2-61.9), 18.1% (95% CI, 14.5-21.8), and 95.1% [95% CI, 93.2-97.0], respectively. The median CPIx increased significantly from normal cytology to HSIL (p < 0.001). The median CPIx was higher in high-risk human papillomavirus (HR-HPV)-positive cases than in HR-HPV-negative cases (0.23 vs. 0.17, p < 0.001), while it did not differ between HR-HPV-positive and HR-HPV-negative cases with normal cytology findings (0.16 vs. 0.16, p = 0.700). CONCLUSION: The LC-1000 system is potentially useful for screening cervical precancer and cancer, especially when excluding normal or ASC of undetermined significance cases in routinely screened populations.

Human Papillomavirus Genotype Distribution Among 18,815 Women in 13 Korean Cities and Relationship With Cervical Cytology Findings.

BACKGROUND: The prevalence and genotype distribution of Human papillomavirus (HPV) infection vary depending on geographical region and the immunity provided by vaccines. This study aimed to clarify the recent prevalence and genotype distribution of HPV according to age and cervical cytology findings in Korea. METHODS: This study included 18,815 health examinees that underwent cervical cytology and HPV genotyping tests at 16 centers of Korean Association of Health Promotion in 13 cities in Korea, between January 2014 and October 2015. HPV was genotyped by using multiplex PCR (Anyplex II HPV 28, Seegene, Korea), which detects 19 high-risk HPVs (HR-HPV) and nine low-risk HPVs (LR-HPV). RESULTS: Overall HPV prevalence was 27.8%, with 22.2% HR-HPV and 11.4% LR-HPV. The five most common carcinogens were HPV 52 (3.2%), 58 (2.7%), 16 (2.0%), 56 (1.9%), and 51 (1.8%). The five most common HR-HPVs in normal cytology samples were HPV 53, 68, 70, 52, and 58, while HPV 16, 52, 58, 33, and 31 were prevalent in high grade squamous intraepithelial lesions (HSIL). In atypical squamous cells of undetermined significance (ASCUS), the prevalence of HR-HPV varied with age; it was highest in those aged <30 yr, declining to a minimum at age 50-59 yr, and then increasing in older women (P<0.05). CONCLUSIONS: The prevalence and distribution of HR-HPV varied with age and cervical cytology findings. This information would be helpful in the development of cervical cancer prevention policies.

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population: MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR <60 mL/min/1.73 m². RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m²) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings.

Reduction of urogenital schistosomiasis with an integrated control project in Sudan.

PURPOSE: Schistosomiasis remains a major public health concern in Sudan, particularly Schistosoma haematobium infection. This study presents the disease-reduction outcomes of an integrated control program for schistosomiasis in Al Jabalain locality of White Nile State, Sudan from 2009 through 2011. METHODS: The total population of the project sites was 482,902, and the major target group for intervention among them was 78,615 primary school students. For the cross-sectional study of the prevalence, urine and stool specimens were examined using the urine sedimentation method and the Kato cellophane thick smear method, respectively. To assess the impacts of health education for students and a drinking water supply facility at Al Hidaib village, questionnaire survey was done. RESULTS: The overall prevalence for S. haematobium and S. mansoni at baseline was 28.5% and 0.4%, respectively. At follow-up survey after 6-9 months post-treatment, the prevalence of S. haematobium infection was reduced to 13.5% (95% CI = 0.331-0.462). A higher reduction in prevalence was observed among girls, those with moderately infected status (around 20%), and residents in rural areas, than among boys, those with high prevalence (>40%), and residents in urban areas. After health education, increased awareness about schistosomiasis was checked by questionnaire survey. Also, a drinking water facility was constructed at Al Hidaib village, where infection rate was reduced more compared to that in a neighboring village within the same unit. However, we found no significant change in the prevalence of S. mansoni infection between baseline and follow-up survey (95% CI = 0.933-6.891). CONCLUSIONS: At the end of the project, the prevalence of S. haematobium infection was reduced by more than 50% in comparison with the baseline rate. Approximately 200,000 subjects had received either praziquantel therapy, health education, or supply of clean water. To consolidate the achievements of this project, the integrated intervention should be adapted continuously.

Prevalence, risk factors, and clinical manifestations of schistosomiasis among school children in the White Nile River basin, Sudan.

BACKGROUND: We investigated the prevalence, risk factors, and clinical manifestations of schistosomiasis in White Nile State, Sudan, to determine the local characteristics of schistosomiasis in the White Nile River basin. METHODS: Urine and stool samples were collected from 338 students (176 boys, 162 girls) at three primary schools and were examined using the urine filtration method and the Kato-Katz technique, respectively. Of the students, 200 were interviewed using a semi-structured questionnaire to assess water-contact patterns and health conditions related with urinary schistosomiasis. RESULTS: Of the 338 students, egg-positive rates for S. haematobium and S. mansoni were 45.0% and 5.9%, respectively, and 4.4% were mixed. The intensities of S. haematobium and S. mansoni infection were 1.091 ± 0.744 log EP10 (eggs per 10 mL of urine, mean ± SD = 57 ± 172 EP10) and 1.787 ± 0.844 log EPG (eggs per gram of stool, mean ± SD = 156 ± 176 EPG), respectively. The prevalence and intensity of S. haematobium infection differed significantly among the three schools, but not by gender or age. Urinary schistosomiasis was significantly associated with the frequencies of contaminated water contact, taking baths, swimming, and wading the stream; however, frequencies of these events were not significantly correlated with infection intensity. Self-reported hematuria and dysuria also correlated significantly with urinary schistosomiasis. CONCLUSIONS: The overall prevalence of schistosomiasis, especially urinary schistosomiasis, is high in the White Nile River basin, Sudan, and is closely associated with frequencies of water contact, taking baths, swimming, and wading the stream. We strongly recommend implementation of an integrated schistosomiasis control program in this area.

Prevalence of monoclonal gammopathy of undetermined significance in an elderly urban Korean population.

Research on the epidemiology of monoclonal gammopathy of undetermined significance (MGUS) is limited in Korea. The aim of this study was to determine the prevalence and characteristics of MGUS in an elderly urban Korean population. A random sample of 1118 Korean elders was selected from residents aged 65 years or older living in Seongnam, Korea 1 year from August 2005. We obtained plasma samples remaining after scheduled tests for the Korean Longitudinal Study on Health and Aging. The mean age of the study population was 72 years (range, 65-97 years). To screen for MGUS, immunofixation and free light-chain (FLC) assays were performed. Age-adjusted and gender-adjusted MGUS prevalence rates in 680 responders were estimated as 3.3% [95% confidence interval (CI) = 2.0-4.6%], and the estimated age-adjusted prevalence of MGUS was 4.3% in men (95% CI = 1.9-6.6%) and 2.6% in women (95% CI = 1.0-4.2%). Abnormal FLC ratios were detected in 10% of MGUS cases. Multivariate analysis of 945 participants revealed that significant risk factors for MGUS included advanced age, male sex, hyperproteinemia, increased erythrocyte sedimentation rate, and abnormal FLC ratio. MGUS is less prevalent among elderly Koreans (3.3%) than other races. This is the first study to estimate the prevalence of MGUS in the Korean elderly population. Our findings should be confirmed with additional studies analyzing follow-up samples from 2010.

Mutation analysis of the APC gene in unrelated Korean patients with FAP: four novel mutations with unusual phenotype.

Germline mutations within the adenomatous polyposis coli (APC) gene are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date more than 900 different APC germline mutations have been characterized worldwide demonstrating allelic heterogeneity. Here, we analyzed the APC gene in 23 DNA samples from unrelated Korean patients with the typical clinical symptoms of FAP by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. We identified 20 different APC sequence variants, including 9 truncating mutations, 1 missense mutation, 7 polymorphisms, and 3 intronic variants. Nine different truncating mutations, including four novel mutations (p.Leu180TyrfsX5, p.Gly567X, p.Ser1275PhefsX13, p.Leu1280CysfsX8), were detected. The most common mutation was a 5 bp deletion at codon 1,309 (p.Glu1309AspfsX4) as in Western studies. The next most common mutation was p.Ser1275PhefsX13 with a severe form of FAP with many extracolonic manifestations; this was a novel mutation identified in our study and may represent the second hot-spot mutation in a Korean population. Novel mutations are of particular interest because of the unusual phenotypic features shown by patients. In present study, we found new positions associated with thyroid cancer (codon 180) and desmoid tumor (codon 1,280), which have not been previously reported. The results of this molecular study have revealed the existence of novel pathogenic mutations in Korean patients with FAP. In addition to allowing phenotype-genotype correlations to be performed, these results are currently being used in genetic counseling and in patient care.

Concurrent p16 methylation pattern as an adverse prognostic factor in multiple myeloma: a methylation-specific polymerase chain reaction study using two different primer sets.

Disruption of cell cycle control genes, including p16, is known to contribute to the cancerogenesis of multiple myeloma (MM). We investigated the methylation status of p16 and its association with common cytogenetic changes, clinicolaboratory findings, and survival in MM. Methylation-specific polymerase chain reaction was performed in 99 newly diagnosed MM patients using two different sets of primers (p16M1 and p16M2). Four patterns of p16 promoter methylation were observed: (1) concurrent methylation of p16M1 and p16M2 (P1P2), 27.3%; (2) methylation of p16M1 alone (P1N2), 7.1%; (3) methylation of p16M2 alone (N1P2), 26.3%; and (4) no methylation (N1N2), 39.4%. Patients with p16P1P1 showed shorter survivals than those with the other methylation patterns (P1N2, N1P2, or N1N2; median survival, 12 vs. 43 months; P < 0.001), regardless of the treatment protocol. In a multivariate analysis, p16P1P2 was an independent prognostic factor of adverse outcome in MM. According to International Staging System (ISS), the study population could be divided into 21.2% (20/94) for stage I, 22.3% (21/94) for stage II, and 56.4% (53/94) for stage III (P = 0.003). ISS can divide patients into prognostic groups. Of note, in patients older than 60 years, ISS was not reflective of disease stage (P = 0.114). If p16P1P2 sets up as stage 4 of ISS, modified ISS could be a more reliable staging system irrespective of age in Korean MM patients (P = 0.003 and P = 0.004 in patients younger than 60 years and in patients older than 60 years, respectively). Our study suggests the potential use of p16 methylation status in predicting the outcome of MM patients and the applicability of demethylating agents in MM.

[A case of post-essential thrombocythemia myelofibrosis with severe osteosclerosis].

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. After many years, a few patients with ET may develop bone marrow (BM) fibrosis and rarely develop osteosclerosis. A 60-yr-old female was admitted due to severe left upper quadrant abdominal discomfort. She had been diagnosed as ET 19 yrs ago. On liver computed tomography severe splenomegaly was shown. Laboratory tests revealed WBC 24.3x10(9)/L, hemoglobin 13.4 g/dL, platelets 432x10(9)/L, lactate dehydrogenase 4,065 IU/L (reference range; 240-480). Blood smear demonstrated leukoerythroblastosis, teardrop cells, and giant and hypogranular platelets. BM study revealed inadequate aspirate due to dry tap. BM biopsy showed clusters of dysplastic megakaryocytes, grade 3 fibrosis, and severe osteosclerosis. Major/minor BCR-ABL1 rearrangement and JAK2 V617F mutation were not detected. Cytogenetic studies revealed normal karyotype. According to the 2008 WHO diagnostic criteria, the patient was diagnosed as having post-essential thrombocythemia myelofibrosis with severe osteosclerosis.

Homozygous deletion of CDKN2A (p16, p14) and CDKN2B (p15) genes is a poor prognostic factor in adult but not in childhood B-lineage acute lymphoblastic leukemia: a comparative deletion and hypermethylation study.

The biological behavior of childhood B-lineage acute lymphoblastic leukemia (B-ALL) is different from that of adults. We performed a comprehensive analysis of the deletion and the methylation profile of CDKN2A (hereafter identified separately as p16 and p14, for the different proteins encoded) and CDKN2B (hereafter p15) in 91 newly diagnosed B-ALL patients (61 children, 30 adults). The prognostic significance of the profiles of these genes and the association between alterations in these genes and known cytogenetic prognostic factors (BCR/ABL; ETV6/RUNX1, formerly TEL/AML1; MLL rearrangement; and ploidy changes of chromosomes) were also assessed. The prevalence of homozygous deletion, hemizygous deletion, and no deletion of the 9p21 region was 11.5%, 16.4%, and 72.1%, respectively, in children and 30.0%, 20.0%, and 50.0%, respectively, in adults; the higher incidence of homozygous deletion in adults was significant (P=0.029). Homozygous deletion was associated with poor overall survival in adults (P=0.019), but not in children. The incidence of promoter methylation of p16, p14, and p15 was 34.4%, 14.8%, and 34.4%, respectively, in children and 26.7%, 10.0%, and 40.0%, respectively, in adults, with no significant difference between the two groups. No significant association was observed between deletion and methylation or with known cytogenetic prognostic factors. The difference in incidence, distribution, and prognostic effect of homozygous deletion in children and adults may explain the prognostic disparity.

Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation.

Although platelet count is a good parameter for the diagnosis of disseminated intravascular coagulation (DIC), a single measurement of platelet is not enough to reflect the ongoing platelet consumption because of compensatory synthesis of circulating platelet number. Increased thrombopoiesis owing to peripheral destruction is expected in patients with DIC. Reticulated platelet, measured as immature platelet fraction (IPF), and plasma thrombopoietin (TPO) are markers of platelet production. We investigated the potential usefulness of circulating IPF and TPO in 222 patients suspected of having DIC. Both IPF and TPO levels were significantly increased in overt DIC patients and well correlated with DIC score. IPF also correlated with fibrin-related marker such as fibrinogen degradation product and D-dimer. Both IPF and TPO showed better mortality prediction than platelet count with the multivariate logistic regression and Kaplan-Meier survival analysis. These results suggest that IPF and TPO are new potential candidates to detect the severity of DIC and to predict DIC mortality.

Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement.

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (> or =10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels.