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.

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: 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

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: 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.

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.
Animal ; Asthma/immunology* ; BCG Vaccine/immunology* ; Disease Models, Animal ; Disease Models, Animal ; Eosinophils/immunology ; Leukocyte Count ; Lung/immunology* ; Male ; Muscle, Smooth, Vascular/immunology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vaccination

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.
Animal ; Asthma/immunology* ; BCG Vaccine/immunology* ; Disease Models, Animal ; Disease Models, Animal ; Eosinophils/immunology ; Leukocyte Count ; Lung/immunology* ; Male ; Muscle, Smooth, Vascular/immunology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vaccination

It has been suggested that dendritic cells (DCs) are critical antigen presenting cells for eosinophilic airway inflammation in a mouse model of asthma, and cysteinyl leukotrienes may play a role in DC trafficking in asthmatics. We investigated whether the number of DCs is increased in the induced sputum of both atopic and nonatopic asthmatics and is related to activated eosinophil count in the sputum. Sputum was induced by inhalation of hypertonic saline in 9 atopic and 12 nonatopic asthmatics and 10 nonatopic normal controls, and differential cell counts were performed. DCs and activated eosinophils were identified by immunocytochemistry with monoclonal antibodies (anti-CD1a and EG2, respectively). There were significantly higher percentages of eosinophils, EG2+ cells, and CD1a+ DC in the sputum of atopic and nonatopic asthmatics compared with normal controls, respectively. In asthmatics, the percentage of CD1a+ DC was significantly correlated with that of EG2+ cells (Rs=0.62, p=0.004). We demonstrated that the increased number of DCs was evident in the induced sputum of both atopic and nonatopic asthmatics, and the DC number was related to the activated eosinophil count, which suggests that DCs may contribute to the ongoing eosinophilic inflammation in asthmatic airways, and vice versa.
Adult ; Aged ; Antigens, CD1/analysis ; Asthma/*immunology/pathology ; Comparative Study ; Dendritic Cells/*immunology ; Eosinophil Granule Proteins/analysis ; Eosinophils/cytology/*immunology ; Female ; Humans ; Immunohistochemistry ; Leukocyte Count ; Male ; Middle Aged ; Research Support, Non-U.S. Gov't ; Sputum/cytology/*immunology