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Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study

  • Eun Chong Yoon;Hyewon Lee;Hee-Young Yoon
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.4
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    • pp.473-482
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    • 2024
  • Background: Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroid (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases. Methods: We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability of treatment weighting (IPTW) to ensure a balanced analysis of covariates. Results: Of the 57,553 patients (mean age 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including nine among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI], 1.48 to 15.58). Higher risks were significant for patients ≥65 years (adjusted HR, 6.40; 95% CI, 1.28 to 31.94), females (adjusted HR, 10.91; 95% CI, 2.24 to 53.20), never-smokers (adjusted HR, 6.31; 95% CI, 1.49 to 26.64), systemic steroid users (adjusted HR, 50.19; 95% CI, 8.07 to 312.19), and those with higher comorbidity scores (adjusted HR, 6.64; 95% CI, 1.19 to 37.03). Conclusion: ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

Predictive Factors and Prognostic Relevance of Sunitinib-induced Subclinical and Overt Hypothyroidism in Korean Patients with Metastatic Renal Cell Carcinoma

  • Minoh Ko;Hyun Jee Kim;In-Wha Kim;Tae Min Kim;Jung Mi Oh
    • Korean Journal of Clinical Pharmacy
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    • v.34 no.3
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    • pp.184-193
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    • 2024
  • Background: Sunitinib, commonly used for metastatic renal cell carcinoma (mRCC), often induces hypothyroidism, affecting 27 to 85% of patients. There are clues suggesting an association between sunitinib-induced hypothyroidism and improved survival outcomes. This study aims to identify the predictive factors of sunitinib-induced hypothyroidism and evaluate whether the occurrence of overt or subclinical hypothyroidism predicts tumor outcome in patients with mRCC. Methods: Patients administered to sunitinib for mRCC was included in this retrospective study. Log-rank test and Cox proportional hazards model were conducted to identify predictive factors of hypothyroidism and prognostic factors of progression-free survival (PFS) and overall survival (OS). Results: A total of 156 patients with mRCC treated with sunitinib were included. Predictive factors of sunitinib-induced hypothyroidism were female (odds ratio (OR), 2.77), sunitinib-induced hypertension (OR, 2.99) and dose reduction of sunitinib due to intolerance (OR, 3.57). Sunitinib-induced overt hypothyroidism was a significant prognostic factor in predicting PFS and OS (hazard ratio, 0.38 and 0.23, respectively). Thyroid hormone replacement did not have an influence on PFS and OS. Conclusions: Female patients, patients who experienced sunitinib-induced hypertension and sunitinib dose reduction are at higher risk of hypothyroidism and need close monitoring. Overt hypothyroidism is a strong prognostic factor of sunitinib treatment outcome in mRCC patients and thyroid hormone replacement does not have a negative effect on tumor outcome.

Analysis of Restraint Stress-induced Behavioral Alteration and Liver Injury in Mice (구속 스트레스로 인한 동물모델의 행동학적 변화와 간 손상)

  • Ye Jin Yang;Young Zoo You;Min Jung Kim;Jae Dong Son;Tae Woo Oh;Kwang Il Park
    • Herbal Formula Science
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    • v.32 no.3
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    • pp.263-275
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    • 2024
  • Background : Recent studies have shown that stress fundamentally influences the functional modulation of organ and stress-related disease causes high morbidity and mortality rates. Objective : The present research investigated the effect of restraint stress on psychological and physiological responses. Results : Body weight and food intake were changed in stress group. Body weight has continuously decreased, and food intake has been slightly altered. As a result of measuring each tissue's weight, the liver and kidney's weight loss was greater than that of other organs. The lipid profile of stressed animals showed significant increases in cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels compared to control. As hepatic marker enzymes, serum glutamic pyruvic transaminase (GPT; alanine aminotransferase), glutamic oxalacetic transaminase (GOT; aspartate aminotransferase), and lactic dehydrogenase (LDH) were increased in the stress group. However, levels of serum cortisol and corticosterone did not affect. Results of the behavioral tests show that the stress group has increased activity, sluggish movements, and anxiety in the central part compared with the control group through the open field test. In the forced swim test, the stress group models had a longer duration of slowing movement, and its rate also increased. Also, in immunoblotting, stress increased the inflammatory factors Inducible Nitric Oxide Synthase (iNOS), cyclooxygenase-2 (COX-2) and activated the mitogen-activated protein kinase (MAPK) pathway. Conclusions : We observed that mouse model were affected behavioral response and liver injury when exposed to restraint stress, indicating the importance of the restraint stress in the development of psychological and physiological processes.

Effects of Administration of Pyritum on Activation of Osteoblast Cells in Human Body & on Tibia Bone Fracture in Mice (자연동(自然銅)의 투여가 인체의 뼈모세포 활성과 생쥐 정강이뼈 골절에 미치는 영향)

  • Hwang, Ji-Hye;Ahn, Ji-Hyun;Kim, Jin-Teck;Ahn, Sang-Hyun;Kim, Kyung-Ho;Cho, Hyun-Seok;Lee, Seung-Deok;Kim, Eun-Jung;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.26 no.2
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    • pp.159-170
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    • 2009
  • Backgrounds and Objectives: A fracture means a loss of continuity in the substance of bone. Bone differs from other musculoskeletal tissue due to its ability to repair and heal itself without leaving a scar. The cutter head has multinucleated osteoclast cells to resorb the dead bone. The tail, with its conical surface, is lined with osteoblast cells laying down new bone. The conjugation of fracture is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Pyritum, one of the important prescriptions in the oriental medicine, has been used for conjugation fracture. The purpose of this study is to evaluate the effects of administration of Pyritum on activation of osteoblast cells in human body & on tibia bone fracture in mice. Materials and Methods : Four weeks aged 30 female DBA mice were used for this study. They were divided three groups, normal group, control group(fracture elicitate mice: FE group) and experimental group(Pyritum administered mice group after fracture elicitation : PA group). Left tibia bones of mice in FE and PA groups were fractured by bone cutters. MG-63 cells in human body th Pyritum in the ratio of 1 mg/m${\ell}$, and the cells were further incubated for 24 hours. Activation of osteoblast was identified using osteopontin, FGF in vitro test. In vivo test, regeneration of fractured tibia through the morphological changes was observed, and also activation of inflammation through NF-${\kappa}$B p65, iNOS, COX-2, osteoblast through osteopontin, FGF and osteoblast's proliferation in each group was measured. Results and Conclusions : 1. In vitro test for activation of osteoblast cells in human body by Pyritum, osteopontin and FGF production were remarkably increased in Pyritum treated MG-63 cells. 2. In regeneration of fractured tibia by Pyritum, fractured area in external tibia morphology was decreased more in the PA group than that of the FE group. Osteogenesis in fractured area was increased more in the PA group than that of the FE group. Also, endochodrial ossification in central area of fracture and osteoid in lateral area of fracture were increased more in the PA group than those of the FE group. 3. In activation of inflammation by Pyritum administered, activation of NF-${\kappa}$B p65, increase of iNOS and COX-2 production were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher activation and increase than those of the FE group. 4. In activation of osteoblast by Pyritum, increase of osteopontin, FGF and osteoblast's proliferation were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher increase and proliferation than those of the FE group.

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Anti-Inflammatory Effect of Wheat Germ Oil on Lipopolysaccharide-stimulated RAW 264.7 Cells and Mouse Ear Edema (LPS로 유도한 RAW 264.7 세포 및 귀부종 동물 모델에 대한 밀배아유의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Min-Ji;Jeong, Da-Hyun;Kim, Koth-Bong-Woo-Ri;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.44 no.3
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    • pp.236-245
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    • 2016
  • This study investigated the anti-inflammatory effects of wheat germ oil (WGO) on RAW 264.7 cells. It was shown that WGO had no cytotoxicity against the treated cells or negative effect on their proliferation. WGO suppressed nitric oxide (NO) secretion considerably and had inhibitory effects on the production of LPS-induced NO and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). In particular, the IL-6 and TNF-α inhibition activities were over 90% at 100 μg/ml concentration of the oil. WGO also inhibited the LPS-induced expression of cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-kappa B (NF-κB), and reduced the expression of phosphorylated ERK and JNK. Moreover, the croton-oil-induced edema in mouse ears was reduced by WGO, and no mortalities occurred in mice administered 5,000 mg/kg body weight of WGO over a 2-week observation period. In conclusion, these results provide evidence for the anti-inflammatory effect of WGO that likely occurs via modulation of NF-κB and the JNK/ERK MAPK signaling pathway.

Anti-inflammatory Effect of Sargassum coreanum Ethanolic Extract through Suppression of NF-κB Pathway in LPS Induced RAW264.7 Cells in Mice (LPS로 유도된 RAW 264.7 cell로부터 NF-κB 조절 억제와 마우스 모델을 통한 큰잎모자반 에탄올 추출물의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bark, Si-Woo;Pak, Won-Min;Ahn, Na-Kyung;Choi, Yeon-Uk;Bae, Nan-Young;Park, Ji-Hye;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.43 no.2
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    • pp.112-119
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    • 2015
  • The anti-inflammatory effect of Sargassum coreanum ethanolic extract (SCEE) was investigated using lipopolysaccharide (LPS)-induced inflammatory responses in this study. It was shown that there was no cytotoxicity in the viability of macrophages treated with SCEE when compared to the control. The production of NO was considerably suppressed by SCEE, approximately up to 50% at 100 μg/ml. This significantly decreased levels of IL-6, TNF-α, and IL-1β. In addition, the expression of iNOS, COX-2, NF-κB was suppressed by SCEE treatment. In in vivo testing, the croton oil-induced mouse ear edema was attenuated by SCEE and there were no mortalities in mice administered with 5000 mg/kg body weight of SCEE over a 2 week observation period. From these results, SCEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SCEE could be a potential agent for anti-inflammatory therapies.

The Prognostic Significance of the Number of Resected Lymph Nodes in Gastric Cancer Patients (근치 절제술을 시행한 위암에서 절제림프절 수의 임상적 의의)

  • Kim, Se-Jin;Jang, You-Jin;Kim, Jong-Han;Park, Sung-Soo;Park, Seong-Heum;Kim, Seung-Ju;Mok, Young-Jae;Kim, Chong-Suk;Ahn, Hyong-Gin
    • Journal of Gastric Cancer
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    • v.9 no.4
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    • pp.246-255
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    • 2009
  • Purpose: The objectives of this study were to investigate the impact of the number of resected lymph nodes on the survival of gastric cancer patients who underwent curative resection, and to evaluate the cut-off values that can have an influence on survival on the tumor stage-stratified analysis. Materials and Methods: The subjects were 949 gastric cancer patients who underwent curative resection at Korea University Medical Center from 1992 to 2002. They were classified according to the depth of tumor invasion, and the influence of the number of resected lymph nodes on survival was investigated. The cut-off value for the number of resected lymph nodes was determined as the smallest value that showed a significant survival difference. Results: The tumor size, location, lymph node stage, the number of metastatic lymph nodes and the number of resected lymph nodes were significantly different according to the tumor stage. The average number of resected lymph nodes was about 39, and it showed linear correlation with the number of metastatic lymph nodes. On the Cox proportional hazard model, the cut-off values of the number of resected lymph nodes, as corrected by the number of metastatic lymph nodes, was 14 for all the patients, 15 for the pT1 patients, 28 for the pT2 patients and 37 for the pT3 patients, respectively. Conclusion: Retrieving a number of lymph nodes that is more than the cut-off value could improve the survival of gastric cancer patients. Surgeons should also make efforts to perform an exact and thorough D2 lymph node dissection. Therefore, we urge surgeons to perform D2 dissection and pathologists should examine an certain exact number of lymph nodes.

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Effect of Steviol β-Glucopyranosyl Ester on The Production of Nitric Oxide and Inflammatory Cytokines in RAW 264.7 Cells (Steviol β-Glucopyranosyl Ester가 RAW 264.7 세포의 산화질소 및 염증성 사이토카인 생성에 미치는 영향)

  • Jung, Heehoon;Cho, Uk Min;Hwang, Hyung Seo;Cho, Kun;Lee, Sang Rin;Kim, Moo Sung
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.44 no.3
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    • pp.239-247
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    • 2018
  • Chronic inflammation is known to have effects on various diseases such as gout, cancer, dementia, atopic disease, and obesity. In addition, since some signal cascades involved in the development of inflammation are known to affect the damage and aging of the skin tissue, studies are being conducted actively to control the inflammation mechanism. In order to mitigate or prevent inflammatory response, a number of researches have been made to develop anti-inflammatory materials from some plants. In particular, Stevia rebaudiana produces steviol glycosides (SG), a natural sweetener with a distinctive flavor. Studies on some of SG have been shown to have anti-inflammatory activity. Researchers of this study expected that more SG also possess anti-inflammatory activity, besides stevioside, rebaudioside A, and steviol. In order to confirm this possibility, the researchers screened inhibition activity of various steviol glucosides for NO production in RAW 264.7 cell lines. As a result, steviol ${\beta}-glucopyranosyl$ ester (SGE) showed the highest inhibitory activity among steviol derivatives treated at the same molar concentration. In addition, we found that mRNA expression level of $interleukin-1{\alpha}$ ($IL-1{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), cyclooxygenase-2 (COX-2), nuclear factor kappa-light chain-enhancer of activated B cells ($NF-{\kappa}B$) and inducible nitric oxide synthase (iNOS) was also decreased in a dose-dependent manner. These results show that SGE inhibits anti-inflammatory activity and NO production in mouse macrophage RAW 264.7 cells. It was confirmed that SGE has potential to be applied as an anti-inflammatory material.

Outcomes of the Modified Maze Procedure for Chronic Atrial Fibrillation Combined with Rheumatic Mitral Valve Disease (류마티스성 승모판막질환과 동반된 만성 심방세동 치료에 대한 변형 Maze 술식의 결과)

  • Baek Man-Jong;Kim Jae-Hyun;Seo Hong-Joo;Lee Chang-Ha;Oh Sam-Se;Na Chan-Young
    • Journal of Chest Surgery
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    • v.39 no.9 s.266
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    • pp.681-691
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    • 2006
  • Background: The aim of this study was to investigate the mid-term outcomes of our modifications to the maze procedure using cryoablation for treating atrial fibrillation associated with rheumatic mitral valve disease. Material and Method: Between March 2000 and February 2004, 177 consecutive patients underwent the modified maze procedure with the use of cryoablation concomitant with mitral valve surgery for atrial fibrillation associated with rheumatic mitral valve disease, and were divided into three groups: (1) modified Cox-maze III (CM group, n=88): (2) modified Kosakai-maze (KM group, n=63): and (3) left atrial maze procedure (LA group, n=26). The postoperative and follow-up results were analyzed and compared between the groups. Result: There were three hospital deaths (1.7%) and no significant differences in the incidence of postoperative complications between the three groups. The operative time, such as the cardiopulmonary bypass and aortic crossclamp time, were significantly longer in the CM group than in the KM and LA groups, respectively (p<0.0001). The mean follow-up was $22.4{\pm}15.1$ months ($1\sim52.6$ months) for all patients. One late death developed in the CM group (0.0%). At last follow-up, 139 patients exhibited sinus rhythm (79.9%), which was also regained in 67 patients (77.9%) in the CM group, 50 (80.7%) in the KM group and 22 (84.6%) in the LA group (p=0.743). The actuarial freedom from stroke at 4 years was $84.5{\pm}9.4%$ in the CM group, $95.0{\pm}4.9%$ in the KM group, and $92.9{\pm}6.9%$ in the LA group (p=0.916). Conclusion: The modified maze procedure using cryoablation is safe and effective in treating chronic atrial fibrillation associated with rheumatic mitral valve disease.

Analysis of Effect and Prognostic Factors Associated with Catheter Intervention on Ascites in Terminal Cancer Patient (복수가 있는 말기 암환자에서 복수 배액관 시술의 효과와 예후요인 분석)

  • Jang, Mungsun;Kim, Chul-Min;Yoon, Johi;Nah, Jung-Ran;Chang, Seung-Nam;Kim, Myung Ok;Lee, Ja Young
    • Journal of Hospice and Palliative Care
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    • v.19 no.4
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    • pp.303-309
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    • 2016
  • Purpose: Malignant ascites is a common complication in terminal cancer patients. Less-invasive pigtail catheter insertion is the most frequent procedure in patients who need repeated ascites drainage. This study investigated effects and adverse events associated with catheter insertion for ascites drainage and evaluated prognostic outcomes. Methods: We reviewed medical records between 2010 and 2013 of hospice and palliative care institutions in Seoul, South Korea. Among 2,608 inpatients, 67 patients received ascites pigtail catheter drainage. We reviewed demographic data, palliative performance scale, laboratory data, duration of catheter insertion, prevalence and type of complications, use and duration of antibiotics, and survival time. Univariate and multivariate Cox regression models were used to evaluate prognostic outcomes related with catheter insertion. Results: Ascites drainage was performed most commonly in hepatobiliary and gastric cancer patients. Ascites symptoms improved in 55 patients after the catheter drainage. Adverse events included pain (19.4%), leakage (14.9%), disconnection (7.5%), catheter occlusion (6%) and fever (4.5%). In Cox regression analysis, survival time from the catheter insertion was significantly associated with Palliative Performance Scale (PPS) (HR 0.73; P value 0.045) and serum sodium level (HR 2.77; P value 0.003) in a multivariate model. Conclusion: Patients' PPS and serum sodium level should be considered before making a decision of pigtail catheter insertion.