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Background@#Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. @*Methods@#In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. @*Results@#From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. @*Conclusion@#These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.
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Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.
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Background@#The goal of this study is to investigate the relationship between depression and glycated hemoglobin in the general Korean population. @*Methods@#Adults aged 19 to 80 years were surveyed as part of the 2019 Korea National Health and Nutrition Examination Survey. A total of 4,831 people were chosen to complete the health questionnaire, provide their body mass index, and get a HbA1c blood test. The general characteristics of groups with high and low glycated hemoglobin were identified. To find out the correlation between depression diagnosis and the general population with high glycated hemoglobin, a chi-square test was carried out. A t-test was also used to compare the means of glycated hemoglobin between the groups diagnosed with and not diagnosed with depression. In analyzing the relationship between depression and glycated hemoglobin, analysis of covariance was performed by adjusting the effects for demographic factors. @*Results@#Sex, age, income level, education level, drinking, smoking, exercise, and body mass index are all factors that influence glycated hemoglobin. The mean glycated hemoglobin was high in the group diagnosed with depression. The relationship between depression and glycated hemoglobin could not be confirmed using logistic regression after controlling for confounding variables. @*Conclusion@#There was no significant correlation between depression and glycated hemoglobin in the general population of Korea based on the results of this study.
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Objectives@#The aim of this study was to examine the clinical presentation, treatment delivery, and cisplatin eligibility of Korean patients with urothelial carcinoma (UC) in a real-world setting. @*Methods@#We performed a retrospective cohort study of patients initially diagnosed with UC from March 2013 to June 2018. Creatinine clearance >60 mL/min and Eastern Cooperative Oncology Group performance status (0–1) were adopted as cisplatin eligibility criteria. @*Results@#This study included 557 eligible patients. Median age was 71.0 years (range, 33–94 years), and males were dominant (80%). Primary tumor sites were: upper genitourinary tract, 18%; bladder, 81%; and urethra, 0.4%. Initial disease status was non-muscle invasive bladder cancer (313, 56%), diffuse infiltrating non-muscle invasive bladder cancer (19, 3%), cTanyN0 upper tract UC (75, 13%), cT2-4N0 bladder UC (82, 15%), TanyN1-3 UC (36, 7%), or initially metastatic UC (32, 6%). At the time of analysis (June 2019), following treatments were delivered to 134 patients with localized UC: radical operation with or without perioperative treatment (89, 67%), definitive chemoradiation (7, 5%), and palliative surgery or supportive care only (36, 28%). In total, 89 patients had metastatic UC, including those with recurrent disease (n=57), and 34 (38%) of the 89 were eligible for cisplatin. @*Conclusion@#Clinical presentations in East Asian UC patients were consistent with those of previous studies in other countries, except for a relatively high incidence of upper genitourinary tract. Our results can serve as a benchmark for further advances and future research for treatments of UC in East Asian patients.
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Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.
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Objectives@#The aim of this study was to examine the clinical presentation, treatment delivery, and cisplatin eligibility of Korean patients with urothelial carcinoma (UC) in a real-world setting. @*Methods@#We performed a retrospective cohort study of patients initially diagnosed with UC from March 2013 to June 2018. Creatinine clearance >60 mL/min and Eastern Cooperative Oncology Group performance status (0–1) were adopted as cisplatin eligibility criteria. @*Results@#This study included 557 eligible patients. Median age was 71.0 years (range, 33–94 years), and males were dominant (80%). Primary tumor sites were: upper genitourinary tract, 18%; bladder, 81%; and urethra, 0.4%. Initial disease status was non-muscle invasive bladder cancer (313, 56%), diffuse infiltrating non-muscle invasive bladder cancer (19, 3%), cTanyN0 upper tract UC (75, 13%), cT2-4N0 bladder UC (82, 15%), TanyN1-3 UC (36, 7%), or initially metastatic UC (32, 6%). At the time of analysis (June 2019), following treatments were delivered to 134 patients with localized UC: radical operation with or without perioperative treatment (89, 67%), definitive chemoradiation (7, 5%), and palliative surgery or supportive care only (36, 28%). In total, 89 patients had metastatic UC, including those with recurrent disease (n=57), and 34 (38%) of the 89 were eligible for cisplatin. @*Conclusion@#Clinical presentations in East Asian UC patients were consistent with those of previous studies in other countries, except for a relatively high incidence of upper genitourinary tract. Our results can serve as a benchmark for further advances and future research for treatments of UC in East Asian patients.
ABSTRACT
Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.
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Background@#This study explores the correlation among obesity, suicide plans, and suicide attempts in adults over 19 years of age in South Korea. @*Methods@#The study used data from adults who had participated in the 2018 Korea National Health and Nutrition Examination Survey. Obesity was defined as having a body mass index of ≥25 kg/m 2 . To identify differences between the characteristics of those who had reported suicide plans and attempts, a complex sample chi-square test was conducted. To analyze the effect of obesity on suicide plans and attempts, a logistic regression analysis was performed. @*Results@#There was no significant difference in the rate of suicide plans in one year between obese and non-obese groups; however, the rate of actual suicide attempts was significantly high in the obese group (p<0.050). After correcting for variables that were significantly different between the groups, obesity was found to have no significant effect on suicide plans but was linked to a significant increase in suicide attempts (odds ratio=3.355, p=0.008). @*Conclusion@#Obesity was found to have no effect on the suicide planning rate; however, the probability of a suicide attempt was high in obese adults.
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Purpose@#The Advanced Prostate Cancer Consensus Conference (APCCC) 2015 was based on topics withcontroversy in the field of advanced prostate cancer. To understand the Korean urologists perspective regardingthe issues, we have conducted a questionnaire named Prostate Cancer Summit (PCAS) 2016, with 9 importantsubtopics. @*Materials and Methods@#Total 9 subtopics have been decided and questions were developed regarding eachsubtopic. The questions were based on that of APCCC 2015 and translated into Korean for better understanding.Total 51 panelists have voted online on 85 different questions. @*Results@#The survey concluded that testosterone should be measured as a diagnostic criterion for castrationresistance prostate cancer (CRPC) and that consensus was reached on issues such as the use of androgenreceptor pathway inhibitors in the treatment of predocetaxel and postdocetaxel in CRPC patients. In addition,76% of the participants agreed that imaging tests were needed before new treatment in CRPC patients, anda majority of participants agreed that periodic imaging tests are necessary regardless of symptoms during treatmentfor CRPC. However, some issues, such as the use of prostate-specific antigen-based triggers for remediationin CRPC patients, the endocrine manipulation in nonmetastatic CRPC patients, and the onset of treatment inasymptomatic metastatic CRPC patients, were not agreed. @*Conclusions@#The results from PCAS 2016 has addressed some of the issues with controversy. Although thevoting results are subjective, it will help guide treatment decisions in topics with less evidence.
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Background@#Calprotectin is the major cytosolic protein in neutrophil granulocytes.Although asthma is known to cause eosinophilic inflammation, some patients with asthma have non-eosinophilic inflammation, which is characterized by local neutrophilic inflammation. The aim of this study was to assess calprotectin expression levels in a mouse model of asthma, and to observe the relationship of serum calprotectin level and clinical variables in patients with asthma. @*Methods@#Mice were sensitized and challenged with 10 μg and 20 μg of Aspergillus fumigatus, respectively; mice treated with saline were used as a control. The levels of calprotectin were determined using enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemical analysis. The serum levels of calprotectin were also assessed in patients with asthma. The relationship between calprotectin and clinicopathological characteristics was determined. @*Results@#Calprotectin, S100A8, and S100A9 expression was elevated in the mouse lungs, Calprotectin levels were higher in the serum of patients with asthma (n = 33) compared with those of healthy individuals (n = 28). Calprotectin levels correlated with forced expiratory volume in one second/forced vital capacity (r = −0.215, P = 0.043), smoke amount (r = 0.413, P = 0.017), body mass index (r = −0.445,P= 0.000), and blood neutrophil percentage (r = 0.300, P = 0.004) in patients with asthma. @*Conclusion@#Our data suggest that calprotectin could potentially be used as a biomarker for asthma.
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Background@#This study aims to investigate the relationship between metabolic syndrome and depression in Korean adults using data from the 2016 and 2018 Korean National Health and Nutrition Examination Surveys (KNHANES). @*Methods@#The total number of participants in the 7th period 1st year (2016) and 3rd year (2018) surveys of KNHANES was 16142. This study was conducted with 10,722 subjects who met the diagnostic criteria for metabolic syndrome and responded to the Patient Health Questionnaire-9 (PHQ-9). Analysis of covariance was used to adjust the differences due to demographic factors, laboratory findings, and underlying diseases to understand the relationship between metabolic syndrome and PHQ-9 scores, if any. @*Results@#The prevalence of metabolic syndrome was determined to be 25.6% in this study. The PHQ-9 scores with and without metabolic syndrome were 2.56 and 2.48, respectively, and there was no significant difference when the confounding variable was corrected (p=0.406). According to the analysis of each PHQ-9 item and metabolic syndrome, the results were not significant. @*Conclusion@#In this cross-sectional study conducted in Korean adults, no significant correlation was found between metabolic syndrome and depression.
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PURPOSE: To evaluate changes in the expression of androgen receptor (AR) and its variants (ARVs) in human prostate cancer (PCa) tissues according to disease status, and its prognostic significance following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 282 PCa cases were evaluated, which included 252 localized PCa, 8 metastatic castration resistant prostate cancer (CRPC), and 22 benign prostatic hyperplasia (BPH) cases. Samples were collected from patients who underwent RP or transurethral resection and were stored in ethically approved tissue banks. Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed for AR and ARVs. Each tissue was confirmed as cancerous (greater than 80%) using hematoxylin and eosin staining. AR and ARVs expression was compared according to disease status. The biochemical recurrence free survival (BCRFS) rates in men with localized PCa was analyzed according to AR and ARV7 expression using the Kaplan-Meier curve. RESULTS: Only 58 of the 252 localized PCa were included in the analysis because of insufficient cancer tissue. AR and ARV7 mRNA expression was higher in the CRPC tissue than in the localized PCa tissue (p=0.025, p=0.002, respectively). In localized PCa tissue, high AR mRNA and protein level was associated with a low BCRFS rate (log-ranked, p=0.019, p < 0.001, respectively). CONCLUSIONS: Overall AR and ARV7 mRNA expression levels were increased in CRPC tissues compared to localized PCa and BPH tissues. High AR protein and mRNA expression in the tumor tissue may be considered a predictive factor of BCRFS following RP.
Subject(s)
Humans , Male , Blotting, Western , Castration , Eosine Yellowish-(YS) , Hematoxylin , Immunohistochemistry , Passive Cutaneous Anaphylaxis , Prostate , Prostatectomy , Prostatic Hyperplasia , Prostatic Neoplasms , Real-Time Polymerase Chain Reaction , Receptors, Androgen , Recurrence , RNA, Messenger , Tissue BanksABSTRACT
Idiopathic interstitial pneumonia (IIP) is a histologically identifiable pulmonary disease without a known cause that usually infiltrates the lung interstitium. IIP is largely classified into idiopathic pulmonary fibrosis, idiopathic non-specific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease (ILD), cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Each of these diseases has a different prognosis and requires specific treatment, and a multidisciplinary approach that combines chest high-resolution computed tomography (HRCT), histological findings, and clinical findings is necessary for their diagnosis. Diagnosis of IIP is made based on clinical presentation, chest HRCT findings, results of pulmonary function tests, and histological findings. For histological diagnosis, video-assisted thoracoscopic biopsy and transbronchial lung biopsy are used. In order to identify ILD associated with connective tissue disease, autoimmune antibody tests may also be necessary. Many biomarkers associated with disease prognosis have been recently discovered, and future research on their clinical significance is necessary. The diagnosis of ILD is difficult because patterns of ILD are both complicated and variable. Therefore, as with other diseases, accurate history taking and meticulous physical examination are crucial.
Subject(s)
Biomarkers , Biopsy , Classification , Connective Tissue Diseases , Cryptogenic Organizing Pneumonia , Diagnosis , Idiopathic Interstitial Pneumonias , Idiopathic Pulmonary Fibrosis , Lung , Lung Diseases , Lung Diseases, Interstitial , Physical Examination , Prognosis , Respiratory Function Tests , ThoraxABSTRACT
BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Subject(s)
Humans , Blood Glucose , Diabetes Mellitus, Type 2 , Fasting , Glucose , Glycated Hemoglobin , Hypoglycemia , Metformin , Weight LossABSTRACT
BACKGROUND: The purpose of this study was to investigate the relationship between metabolic syndrome and depressive symptoms by administering the nine-item depression module from the Patient Health Questionnaire-9 (PHQ-9) to participants from the general population of Korea.METHODS: In total, 8,150 adults participated in the 1st year of the 7th Korea National Health and Nutrition Examination Survey, which was conducted in 2016. Of them, 5,556 participants underwent tests pertaining to the criteria for metabolic syndrome and responded to PHQ-9; 2,594 respondents were excluded. Analysis of covariance was performed to analyze the relationship between the presence of metabolic syndrome and the PHQ-9 score after adjusting for the effects of demographic and hematologic characteristics and underlying diseases.RESULTS: The total PHQ-9 score (mean=2.98) was significantly higher in participants with metabolic syndrome than in those without it (mean=2.59) (p=0.002). Among the individual PHQ-9 items, changes in sleep, thoughts of suicide or self-harm, and depressive mood showed the greatest differences.CONCLUSION: The PHQ-9 scores in Korea were higher in adults with metabolic syndrome, suggesting an association between metabolic syndrome and depressive symptoms.
Subject(s)
Adult , Humans , Depression , Korea , Nutrition Surveys , Suicide , Surveys and QuestionnairesABSTRACT
Idiopathic interstitial pneumonia (IIP) is a histologically identifiable pulmonary disease without a known cause that usually infiltrates the lung interstitium. IIP is largely classified into idiopathic pulmonary fibrosis, idiopathic non-specific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease (ILD), cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Each of these diseases has a different prognosis and requires specific treatment, and a multidisciplinary approach that combines chest high-resolution computed tomography (HRCT), histological findings, and clinical findings is necessary for their diagnosis. Diagnosis of IIP is made based on clinical presentation, chest HRCT findings, results of pulmonary function tests, and histological findings. For histological diagnosis, video-assisted thoracoscopic biopsy and transbronchial lung biopsy are used. In order to identify ILD associated with connective tissue disease, autoimmune antibody tests may also be necessary. Many biomarkers associated with disease prognosis have been recently discovered, and future research on their clinical significance is necessary. The diagnosis of ILD is difficult because patterns of ILD are both complicated and variable. Therefore, as with other diseases, accurate history taking and meticulous physical examination are crucial.
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PURPOSE: The tight junction protein claudin-5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability. The role of CLDN5 in chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the association between CLDN5 levels and clinical variables in patients with COPD. METHODS: In total, 30 patients with COPD and 30 healthy controls were enrolled in the study. The plasma CLDN5 level was checked in patients with stable or exacerbated COPD and in healthy controls. RESULTS: The mean plasma CLDN5 level of patients with COPD was 0.63 ± 0.05 ng/mL and that of healthy controls was 6.9 ± 0.78 ng/mL (P = 0.001). The mean plasma CLDN5 level was 0.71 ± 0.05 ng/mL in exacerbated COPD patients and 0.63 ± 0.04 ng/mL in patients with stable COPD (P < 0.05). The plasma CLDN5 level among COPD subjects was correlated with the smoking amount (r = −0.530, P = 0.001). The plasma CLDN5 level in stable COPD patients was correlated with forced expiratory volume in one second (FEV1, %pred.) (r = −0.481, P = 0.037). CONCLUSIONS: The plasma CLDN5 level was not correlated with age. CLDN5 may be involved in the pathogenesis of COPD. Further studies having a larger sample size will be needed to clarify CLDN5 in COPD.
Subject(s)
Humans , Claudin-5 , Forced Expiratory Volume , Permeability , Plasma , Pulmonary Disease, Chronic Obstructive , Sample Size , Smoke , Smoking , Tight JunctionsABSTRACT
BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.
Subject(s)
Humans , Asthma , Blood Cell Count , Body Mass Index , Bronchial Provocation Tests , Diagnosis , Eosinophils , Forced Expiratory Volume , Immunoglobulin E , Immunoglobulins , Methacholine Chloride , Respiratory Hypersensitivity , Smoke , SmokingABSTRACT
BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.
Subject(s)
Humans , Cell Transplantation , Cytogenetics , Leukemia, Myeloid, Acute , Multivariate Analysis , Myelodysplastic Syndromes , Retrospective Studies , TransplantsABSTRACT
BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB). METHODS: We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels. RESULTS: Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends. CONCLUSION: Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.