Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.

Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.

Light chain (AL) amyloidosis is a disease in which malignant plasma cell clones affect multiple organs including the heart and kidney. The mechanism for organ function deterioration in AL amyloidosis differs from multiple myeloma. Thus, not all agents used to treat multiple myeloma shows similar efficacy in AL amyloidosis. In AL amyloidosis, both hematologic and organ responses after treatment are important to improve the clinical outcome. Especially, improving heart function is one of the key aspects in the treatment of AL amyloidosis. With recent advances in the understanding of the pathophysiologic mechanism of AL amyloidosis, novel treatment methods are under active trial. In this article, I have reviewed the advances in pathophysiology, diagnosis, risk stratification, and treatment of AL amyloidosis.

Vocal cord dysfunction (VCD), a condition that frequently mimics or confounds asthma, is characterized by a paradoxical adduction of the vocal cords on inspiration. The apposition of the vocal cords produces airflow obstruction sufficient to cause wheezing, chest tightness, shortness of breath, and cough. Misdiagnosis as asthma has led to inappropriate treatment, most notably with high-dose corticosteroids. Herein we report two cases of VCD who presented with chronic cough and episodic breathlessness, respectively. Flow-volume loops on spirometry were abnormal, with evidence of variable extrathoracic airway obstruction, manifested as flat or truncated inspiratory loops. Laryngoscopy or bronchoscopy demonstrated paradoxical adduction with posterior "chinking" of the vocal cords on inspiration. One case also had asthma and depressive illness. After the diagnosis of VCD, the clinical manifestations resolved with speech therapy and/or psychotherapy. VCD should be suspected in patients with asthma-like symptoms. An early diagnosis avoids unnecessary aggressive management.
Adrenal Cortex Hormones ; Airway Obstruction ; Asthma ; Bronchoscopy ; Cough ; Diagnosis ; Diagnostic Errors ; Dyspnea ; Early Diagnosis ; Humans ; Laryngoscopy ; Psychotherapy ; Respiratory Sounds ; Speech Therapy ; Spirometry ; Thorax ; Vocal Cord Dysfunction* ; Vocal Cords*

BACKGROUND: Several investigators have demonstrated a considerable disagreement between FEV1 and PEFR to assess the severity of airflow obstruction. The purpose of this study was to examine whether the discrepancy between the two measurements affects the assessment in the severity of acute asthma. METHODS: Thirty-five consecutive asthma patients measured both FEV1 and PEFR at 0, 1hr, 1, 3, 5, 7 days of an emergency room admission using a spirometer and a Ferraris PEFR meter. The degree of discrepancy between FEV1 and PEFR expressed as % predicted values was determined. RESULTS: When predictive equations that recommended by the instrument manufacturers were used, PEFR measured with the PEFR meter (f-PEFR) was significantly higher than FEV1 at all time points, with 16.1% mean difference and unacceptable wide limits of agreement (-20.0~52.3%). The classification in severity was significantly different between FEV1 and f-PEFR (p < 0.001). The discrepancy was inter-instrumental in large part because f-PEFR was 10.1% higher than spirometric PEFR. Different predictive equations altered the degree of the differences but could not completely correct it. CONCLUSION: These results indicate that f-PEFR values underestimate the severity of airflow obstruction in acute asthma despite using recommended predictive equations. Therefore, these confounding factors should be considered when the severity of airflow obstruction is assessed with PEFR.
Acute Disease ; Adult ; Aged ; Airway Obstruction/diagnosis/*physiopathology ; Asthma/*physiopathology ; Comparative Study ; Female ; Forced Expiratory Volume/physiology ; Human ; Male ; Middle Age ; Peak Expiratory Flow Rate/*physiology ; Predictive Value of Tests

BACKGROUND: A number of alternative donor options exist for patients who fail to find domestic HLA-matched donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed physicians' perspectives on allo-HSCT donor selection when a matched domestic donor is not available. METHODS: We administered a questionnaire survey to 55 hematologists (response rate: 28%) who attended the annual spring conference of the Korean Society of Haematology in 2015. The questionnaire contained four clinical allo-HSCT scenarios and the respondents were asked to choose the most preferred donor among the given options. RESULTS: In all four scenarios, the hematologists preferred a matched international donor over partially mismatched unrelated domestic or haplo-matched family donors. The numbers of hematologists who chose a matched international donor (HLA 8/8) in cases of acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, and aplastic anemia were 37 (67.3%), 41 (74.6%), 33 (60.0%), and 36 (65.5%), respectively. The important factors that affected donor selection included “expecting better clinical outcomes (40.5%)” and “lower risk of side effects (23.4%).” The majority of participants (80%) responded that allo-HSCT guidelines for donor selection customized for the Korean setting are necessary. CONCLUSION: Although hematologists still prefer perfectly matched foreign donors when a fully matched domestic allo-HSCT donor is not available, we confirmed that there was variation in their responses. For evidence-based clinical practice, it is necessary to provide further comparative clinical evidence on allo-HSCT from haplo-matched family donors and fully matched unrelated international donors.
Anemia, Aplastic ; Donor Selection* ; Hematopoietic Stem Cell Transplantation ; Humans ; Korea* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Stem Cell Transplantation* ; Stem Cells* ; Surveys and Questionnaires ; Tissue Donors* ; Unrelated Donors

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN). Methods: This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN. Results: CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level. Conclusion On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

Catastrophic antiphospholipid syndrome (APS) is defined as a rare, life-threatening autoimmune disorder leading to multiorgan failure. Probable APS, with clinical manifestations similar to APS without antiphospholipid antibodies, was suggested to be seronegative catastrophic APS. The triggering factors of catastrophic APS are various, including infection, trauma, malignancy, and surgery. In approximately 40% of patients, catastrophic APS develops from an unknown cause. We report a case of seronegative catastrophic APS due to an unknown origin. A 20-year-old man presented with cough, abdominal pain, skin lesions, tunnel vision, and watery diarrhea without fever. His symptoms and laboratory test suggested disseminated intravascular coagulation. Considering seronegative catastrophic APS, we treated with intravenous steroid and intravenous immunoglobulin, but the effects were limited. After weekly treatment with rituximab, an immune-modulating agent, his laboratory findings including thrombocytopenia and coagulation tests, returned to normal. We conclude that rituximab can be an effective treatment for seronegative catastrophic APS.
Abdominal Pain ; Antibodies, Antiphospholipid* ; Antiphospholipid Syndrome ; Autoimmune Diseases ; Cough ; Diarrhea ; Disseminated Intravascular Coagulation* ; Fever ; Humans ; Immunoglobulins ; Skin ; Thrombocytopenia ; Young Adult ; Rituximab

Bacillus Calmette-Guerin (BCG) is reported to suppress Th2 response and asthmatic reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections with BCG are known to result in inducing various cytokines. Thus, DCs are likely to play a role in the effects of BCG on asthma. This study aims at investigating that cytokine milieu secreted by BCG-treated DCs directly enhances allergen-specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics. DCs were cultured with and without BCG and subjected to flow cytometric analysis. IL-12 and IL-10 were determined from the culture supernatants. Some DCs were cocultured with T cells in the presence of D. farinae extracts after adding the culture supernatants from BCG-treated DCs, and IL-5 and IFN-gamma were determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86, and CD40, and the productions of IL-12 and IL-10. Addition of culture supernatants from BCG-treated DCs up-regulated production of IFN-gamma by T cells stimulated by DCs and D. farinae extracts (p<0.05), but did not down-regulate production of IL-5 (p>0.05). The cytokine milieu secreted by BCG-treated DCs directly enhanced allergen-specific Th1 response, although did not suppress Th2 response.
Antigens, Dermatophagoides/*immunology ; Asthma/*immunology ; Cells, Cultured ; Coculture Techniques ; Culture Media ; Cytokines/*immunology/secretion ; Dendritic Cells/cytology/*immunology/secretion ; Humans ; Hypersensitivity/immunology ; Interferon Type II/immunology/secretion ; Interleukin-10/immunology/secretion ; Interleukin-12/immunology/secretion ; Interleukin-5/immunology/secretion ; Lymphocyte Activation/immunology ; Mycobacterium bovis/*immunology ; Research Support, Non-U.S. Gov't ; Th2 Cells/cytology/immunology/secretion ; Up-Regulation/immunology

The role of lung mast cells in exercise-induced asthma (EIA) is controversial. To investigate whether the skin mast cell releasability is increased after exercise in EIA, 49 young atopic men with or without asthma took part in a free-running test for 6 min and were given skin prick tests using morphine, a mast cell secretagogue, before and after the exercise. The mean diameters of the wheal induced by morphine in patients with EIA were not significantly different from those in patients without EIA before exercise, although the baseline lung function was significantly lower and the airway hyperresponsiveness, the peripheral blood eosinophil count, and the size of the wheal in response to Dermatophagoides pteronyssinus were significantly higher in patients with EIA. However, the differences of the morphine-induced wheal diameter between patients with EIA and those without EIA became significant at 120 min after exercise (p<0.05), while the responses to histamine were not significantly different. These results suggest that exercise increases the releasability of skin mast cells in EIA patients whose asthma/allergy are relatively severe.
Adolescent ; Adult ; Analgesics, Opioid/diagnostic use ; Asthma/*immunology/physiopathology ; *Exercise ; Histamine/diagnostic use ; Humans ; Male ; Mast Cells/drug effects/*immunology ; Morphine/diagnostic use ; Skin/cytology/*immunology ; Skin Tests