Ischemia-modified albumin: a novel blood marker of endoscopic mucosal healing in inflammatory bowel disease

Background/Aims@#The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity. @*Methods@#A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn’s disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings. @*Results@#Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed. @*Conclusions@#IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.

Plasmacytoid dendritic cell neoplasms

Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN).MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

T-large granular lymphocytic leukemia

T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway.Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

Performance Validation of Three Scoring Systems for the Prediction of Thrombotic Microangiopathy Due to Severe ADAMTS13 Deficiency and the Response to Therapeutic Plasma Exchange: First Study in Korea

Background@#The BENTLEY score (B-S), French thrombotic microangiopathy (TMA) Reference Center score (FTMA-S), and PLASMIC score (PLASMIC-S) have been developed for TMA diagnostic prediction. We retrospectively validated their predictive performances in patients with severe (<10%) disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in terms of the risk of TMA and response to therapeutic plasma exchange (TPE). @*Methods@#The predictive performances of the three scoring systems were compared in 145 patients with suspected TMA who underwent ADAMTS13 activity tests between January 2014 and September 2022. The response to TPE and mortality in TMA-positive patients were compared after risk stratification, using the Mann–Whitney U and Fisher’s exact tests. @*Results@#The PLASMIC-S, FTMA-S, and B-S showed area under the curve values of 0.820, 0.636, and 0.513, respectively, for predicting TMA positivity in high-risk patients. The PLASMIC-S showed higher sensitivity (81.8%), negative predictive value (91.2%), positive predictive value (PPV; 66.7%), and accuracy (82.1%) than the FTMA-S (72.7%, 82.1%, 41.0%, and 60.0%, respectively) and B-S (4.6%, 70.2%, 50.0%, and 69.7%, respectively). The PLASMIC-S also showed higher specificity than the FTMA-S (82.2% vs. 54.5%). The modified PLASMIC-S, including lactate dehydrogenase/upper limit of normal ratios, increased the specificity, PPV, and accuracy to 97.0%, 92.3%, and 92.4%, respectively. In TMA-positive patients, high risk assessed by the PLASMIC-S predicted higher platelet recovery rates and less TPE sessions required for recovery than for those assessed at low-to-intermediate risk. @*Conclusions@#PLASMIC-S is the preferred scoring system for detecting patients with TMA positivity and for prognosis before confirmation of ADAMTS13 activity.

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

POEMS Syndrome: Bone Marrow, Laboratory, and Clinical Findings in 24 Korean Patients

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.

Bone marrow metastasis of small cell lung carcinoma with spontaneous tumor lysis syndrome without hepatic metastasis at diagnosis: first case report in Korea and review of literature

No abstract available.

High-grade nodal marginal zone lymphoma with diffuse bone marrow involvement and IgM-type monoclonal paraproteinemia: a case report and review of the literature

No abstract available.

Efficacy of a Novel Annular Closure Device after Lumbar Discectomy in Korean Patients: A 24-Month Follow-Up of a Randomized Controlled Trial

OBJECTIVE: Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH); however, up to 2–18% of patients with LDH have experienced recurrent disc herniation. The purpose of this study was to evaluate the efficacy of a novel annular closure device (ACD) for preventing LDH recurrence and re-operation compared with that of conventional lumbar discectomy (CLD). METHODS: In this prospective randomized controlled trial, we compared CLD with discectomy utilizing the Barricaid® (Intrinsic Therapeutics, Inc., Woburn, MA, USA) ACD. Primary radiologic outcomes included disc height, percentage of preoperative disc height maintained, and re-herniation rates. Additional clinical outcomes included visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and 12-item short-form health survey (SF-12) quality of life scores. Outcomes were measured at preoperation and at 1 week, 1, 3, 6, 12, and 24 months postoperation. RESULTS: Sixty patients (30 CLD, 30 ACD) were enrolled in this study. At 24-month follow-up, the disc height in the ACD group was significantly greater than that in the CLD group (11.4±1.5 vs. 10.2±1.2 mm, p=0.006). Re-herniation occurred in one patient in the ACD group versus six patients in the CLD group (χ²=4.04, p=0.044). Back and leg VAS scores, ODI scores, and SF-12 scores improved significantly in both groups compared with preoperative scores in the first 7 days following surgery and remained at significantly improved levels at a 24-month follow-up. However, no statistical difference was found between the two groups. CONCLUSION: Lumbar discectomy with the Barricaid® (Intrinsic Therapeutics, Inc.) ACD is more effective at maintaining disc height and preventing re-herniation compared with conventional discectomy. Our results suggest that adoption of ACD in lumbar discectomy can help improve the treatment outcome.

Recent progress in laboratory diagnosis of thalassemia and hemoglobinopathy: a study by the Korean Red Blood Cell Disorder Working Party of the Korean Society of Hematology

Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or β-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while β-thalassemias are associated with decreased synthesis of β-globin due to β-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or β-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.

Efficacy of a Novel Annular Closure Device after Lumbar Discectomy in Korean Patients: A 24-Month Follow-Up of a Randomized Controlled Trial

OBJECTIVE: Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH); however, up to 2–18% of patients with LDH have experienced recurrent disc herniation. The purpose of this study was to evaluate the efficacy of a novel annular closure device (ACD) for preventing LDH recurrence and re-operation compared with that of conventional lumbar discectomy (CLD).METHODS: In this prospective randomized controlled trial, we compared CLD with discectomy utilizing the Barricaid® (Intrinsic Therapeutics, Inc., Woburn, MA, USA) ACD. Primary radiologic outcomes included disc height, percentage of preoperative disc height maintained, and re-herniation rates. Additional clinical outcomes included visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and 12-item short-form health survey (SF-12) quality of life scores. Outcomes were measured at preoperation and at 1 week, 1, 3, 6, 12, and 24 months postoperation.RESULTS: Sixty patients (30 CLD, 30 ACD) were enrolled in this study. At 24-month follow-up, the disc height in the ACD group was significantly greater than that in the CLD group (11.4±1.5 vs. 10.2±1.2 mm, p=0.006). Re-herniation occurred in one patient in the ACD group versus six patients in the CLD group (χ²=4.04, p=0.044). Back and leg VAS scores, ODI scores, and SF-12 scores improved significantly in both groups compared with preoperative scores in the first 7 days following surgery and remained at significantly improved levels at a 24-month follow-up. However, no statistical difference was found between the two groups.CONCLUSION: Lumbar discectomy with the Barricaid® (Intrinsic Therapeutics, Inc.) ACD is more effective at maintaining disc height and preventing re-herniation compared with conventional discectomy. Our results suggest that adoption of ACD in lumbar discectomy can help improve the treatment outcome.

Biomechanical Analysis of Biodegradable Cervical Plates Developed for Anterior Cervical Discectomy and Fusion

STUDY DESIGN: In-vitro biomechanical investigation. PURPOSE: To evaluate the biomechanical effects of the degeneration of the biodegradable cervical plates developed for anterior cervical discectomy and fusion (ACDF) on fusion and adjacent levels. OVERVIEW OF LITERATURE: Biodegradable implants have been recently introduced for cervical spine surgery. However, their effectiveness and safety remains unclear. METHODS: A linear three-dimensional finite element (FE) model of the lower cervical spine, comprising the C4–C6 vertebrae was developed using computed tomography images of a 46-year-old woman. The model was validated by comparison with previous reports. Four models of ACDF were analyzed and compared: (1) a titanium plate and bone block (Tita), (2) strong biodegradable plate and bone block (PLA-4G) that represents the early state of the biodegradable plate with full strength, (3) weak biodegradable plate and bone block (PLA-1G) that represents the late state of the biodegradable plate with decreased strength, and (4) stand-alone bone block (Bloc). FE analysis was performed to investigate the relative motion and intervertebral disc stress at the surgical (C5–C6 segment) and adjacent (C4–C5 segment) levels. RESULTS: The Tita and PLA-4G models were superior to the other models in terms of higher segment stiffness, smaller relative motion, and lower bone stress at the surgical level. However, the maximal von Mises stress at the intervertebral disc at the adjacent level was significantly higher in the Tita and PLA-4G models than in the other models. The relative motion at the adjacent level was significantly lower in the PLA-1G and Bloc models than in the other models. CONCLUSIONS: The use of biodegradable plates will enhance spinal fusion in the initial stronger period and prevent adjacent segment degeneration in the later, weaker period.

Low-grade follicular lymphoma involvement of the bone marrow with a mixed paratrabecular, diffuse, and massive pattern expressing typical mantle cell lymphoma immunophenotype CD23−/FMC7+: a case report

No abstract available.

Hidden “Preleukemic Phase” of Chronic Myeloid Leukemia Presenting Without Leukocytosis in the Peripheral Blood Unrelated to Chemotherapy in a Patient Diagnosed With Diffuse Large B Cell Lymphoma

No abstract available.

Performance Evaluation of Five Different Disseminated Intravascular Coagulation (DIC) Diagnostic Criteria for Predicting Mortality in Patients with Complicated Sepsis

Disseminated intravascular coagulation (DIC) is a major complication in sepsis patients. We compared the performance of five DIC diagnostic criteria, focusing on the prediction of mortality. One hundred patients with severe sepsis or septic shock admitted to intensive care unit (ICU) were enrolled. Routine DIC laboratory tests were performed over the first 4 days after admission. The overall ICU and 28-day mortality in DIC patients diagnosed from five criteria (International Society on Thrombosis and Haemostasis [ISTH], the Japanese Association for Acute Medicine [JAAM], the revised JAAM [R-JAAM], the Japanese Ministry of Health and Welfare [JMHW] and the Korean Society on Thrombosis and Hemostasis [KSTH]) were compared. Both KSTH and JMHW criteria showed superior performance than ISTH, JAAM and R-JAAM criteria in the prediction of overall ICU mortality in DIC patients (odds ratio 3.828 and 5.181, P = 0.018 and 0.006, 95% confidence interval 1.256–11.667 and 1.622–16.554, respectively) when applied at day 1 after admission, and survival analysis demonstrated significant prognostic impact of KSTH and JMHW criteria on the prediction of 28-day mortality (P = 0.007 and 0.049, respectively) when applied at day 1 after admission. In conclusion, both KSTH and JMHW criteria would be more useful than other three criteria in predicting prognosis in DIC patients with severe sepsis or septic shock.

Acute Myeloid Leukemia With MLL Rearrangement and CD4+/CD56+ Expression can be Misdiagnosed as Blastic Plasmacytoid Dendritic Cell Neoplasm: Two Case Reports

No abstract available.

Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A

BACKGROUND: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. METHODS: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. RESULTS: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. CONCLUSIONS: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.

Establishment of Age- and Gender-Specific Reference Ranges for 36 Routine and 57 Cell Population Data Items in a New Automated Blood Cell Analyzer, Sysmex XN-2000

We established age- and gender-specific reference ranges for the 36 routine complete blood cell (CBC) and 57 cell population data (CPD) items in the Sysmex XN-2000 (Sysmex, Japan). In total, 280 peripheral blood samples were obtained from an equal number of healthy adults. Values for 36 routine items and 57 CPD items were obtained for each sample, and the results were categorized into six subgroups (N>39 in each subgroup) according to patient age (20-40, 41-60, and >60 yr) and gender (male and female), and compared with respect to age and gender differences. The majority of data items (22 of 36 routine CBC items and 44 of 57 CPD items) exhibited significant differences (P< or =0.05) in their results with respect to age or gender, and several red cell-, lymphocyte-, and platelet-related data tended to decrease in women or older adults. These results provide a basis for establishing age- and gender-specific reference ranges for routine and CPD items in Sysmex XN-2000. Furthermore, these reference ranges could be used to determine clinical significance for new items of Sysmex XN-2000 in further studies.

The first case of acute myeloid leukemia with solitary t(6;7)(p21.3;p22) passenger translocation that developed at relapse after allogeneic hematopoietic stem cell transplantation in a patient with a normal karyotype at the initial diagnosis

No abstract available.

In vitro characterization of human dental pulp stem cells isolated by three different methods

OBJECTIVES: In this study, we characterized human dental pulp cells (HDPCs) obtained by different culture methods to establish the most suitable methodology for dental tissue engineering and regenerative endodontic applications. MATERIALS AND METHODS: HDPCs were isolated by the outgrowth method (HDPCs-OG), the enzymatic digestion method (collagenase/dispase/trypsin, HDPCs-ED), or the combination of both methods (HDPCs-Combined). The expression of mesenchymal stem cell markers (CD105, CD90, and CD73) was investigated. In vitro differentiation capacities of HDPCs into adipogenic, osteogenic, and chondrogenic lineages were compared. Differentiation markers were analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. RESULTS: Our data indicated that whole HDPCs-ED, HPDCs-OG, and HDPCs-Combined could be differentiated into adipogenic, chrondrogenic, and osteogenic cell types. However, we found that the methods for isolating and culturing HDPCs influence the differentiation capacities of cells. HDPCs-OG and HDPCs-ED were preferably differentiated into adipogenic and osteogenic cells, respectively. Differentiation markers shown by RT-PCR and western blotting analysis were mostly upregulated in the treated groups compared with the control groups. CONCLUSIONS: Our findings confirmed that cell populations formed by two different culture methods and the combined culture method exhibited different properties. The results of this study could provide an insight into regenerative endodontic treatment using HDPCs.