Publications by authors named "Mi-Sook Kim"

162 Publications

mHealth Interventions for Lifestyle and Risk Factor Modification in Coronary Heart Disease: Randomized Controlled Trial.

JMIR Mhealth Uhealth 2021 Sep 24;9(9):e29928. Epub 2021 Sep 24.

Department of Prevention and Management, School of Medicine, Inha University Hospital, Inha University, Incheon, Republic of Korea.

Background: Self-management of lifestyle and cardiovascular disease risk factors is challenging in older patients with coronary heart disease (CHD). SMS text messaging could be a potential support tool for self-management and the most affordable and accessible method through a mobile phone. High-quality evidence had been lacking, and previous studies evaluated the effects of SMS text messaging on the subjective measures of short-term outcomes. Recently, a large-sized randomized controlled trial in Australia reported promising findings on the objective measures upon 6-month follow-up. However, an examination of the effectiveness of such interventions in an Asian population with unique demographic characteristics would be worthwhile.

Objective: This study examined the effectiveness of a 1-way SMS text messaging program to modify the lifestyle and cardiovascular disease risk factors of patients who underwent the first percutaneous coronary intervention (PCI).

Methods: A parallel, single-blinded, 1:1 random allocation clinical trial was conducted with 879 patients treated through PCI. They were recruited during hospital admission from April 2017 to May 2020 at 2 university hospitals in the Republic of Korea. In addition to standard care, the intervention group received access to a supporting website and 4 SMS text messages per week for 6 months regarding a healthy diet, physical activity, smoking cessation, and cardiovascular health. Random allocation upon study enrollment and SMS text messaging after hospital discharge were performed automatically using a computer program. The coprimary outcomes were low-density-lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and BMI. The secondary outcomes were change in lifestyle and adherence to the recommended health behaviors.

Results: Of the eligible population, 440 and 439 patients who underwent PCI were assigned to the intervention and control groups, respectively. The 1-way SMS text messaging program significantly enhanced physical activity (P=.02), healthy diet (P<.01), and medication adherence (P<.04) among patients with CHD. Hence, more people were likely to control their cardiovascular disease risk factors per the recommendations. The intervention group was more likely to control all 5 risk factors by 62% (relative risk 1.62, 95% CI 1.05-2.50) per the recommendations. On the other hand, physiological measures of the primary outcomes, including LDL-C levels, SBP, and BMI, were not significant. Most participants found the SMS text messaging program useful and helpful in motivating lifestyle changes.

Conclusions: Lifestyle-focused SMS text messages were effective in the self-management of a healthy diet, exercise, and medication adherence, but their influence on the physiological measures was not significant. One-way SMS text messages can be used as an affordable adjuvant method for lifestyle modification to help prevent the recurrence of cardiovascular disease.

Trial Registration: Clinical Research Information Service (CRiS) KCT0005087; https://cris.nih.go.kr/cris/search/detailSearch.do/19282.
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http://dx.doi.org/10.2196/29928DOI Listing
September 2021

A Patient-Derived Organoid-Based Radiosensitivity Model for the Prediction of Radiation Responses in Patients with Rectal Cancer.

Cancers (Basel) 2021 Jul 27;13(15). Epub 2021 Jul 27.

Department of Radiological & Clinical Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.

Patient-derived tumor organoids closely resemble original patient tumors. We conducted this co-clinical trial with treatment-naive rectal cancer patients and matched patient-derived tumor organoids to determine whether a correlation exists between experimental results obtained after irradiation in patients and organoids. Between November 2017 and March 2020, we prospectively enrolled 33 patients who were diagnosed with mid-to-lower rectal adenocarcinoma based on endoscopic biopsy findings. We constructed a prediction model through a machine learning algorithm using clinical and experimental radioresponse data. Our data confirmed that patient-derived tumor organoids closely recapitulated original tumors, both pathophysiologically and genetically. Radiation responses in patients were positively correlated with those in patient-derived tumor organoids. Our machine learning-based prediction model showed excellent performance. In the prediction model for good responders trained using the random forest algorithm, the area under the curve, accuracy, and kappa value were 0.918, 81.5%, and 0.51, respectively. In the prediction model for poor responders, the area under the curve, accuracy, and kappa value were 0.971, 92.1%, and 0.75, respectively. Our patient-derived tumor organoid-based radiosensitivity model could lead to more advanced precision medicine for treating patients with rectal cancer.
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http://dx.doi.org/10.3390/cancers13153760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345202PMC
July 2021

Did inter-hospital transfer reduce mortality in patients with acute myocardial infarction in the real world? A nationwide patient cohort study.

PLoS One 2021 5;16(8):e0255839. Epub 2021 Aug 5.

Department of Prevention and Management, Inha University Hospital, School of Medicine, Inha University, Incheon, Korea.

Introduction: Inter-hospital transfer (IHT) and primary percutaneous coronary intervention (PCI) are preferred over onsite thrombolysis when provided expeditiously. On the other hand, its benefit has not been evaluated in a real-world situation. This study examined the effects of IHT on the short- and long-term mortality in patients with acute myocardial infarction (AMI) and compared the reperfusion treatments and resources between the referring and receiving hospitals.

Methods: Patients newly diagnosed with AMI and admitted to hospital were selected from the national health insurance database from 2004 to 2018. The 30-day and one-year mortality in the transferred and non-transferred patients were estimated and compared using stabilized inverse probability of treatment weighting to account for confounding bias.

Results: Of the 258,291 participants, 10,158 were transferred to one or more hospitals. IHT was more likely to occur to older or more comorbid people, patients in rural areas, and those whose insurance was medical aid. The 30-day and one-year mortality of the non-IHT group was 9.7% and 15.8%, respectively, whereas the figure was 11.4% and 20.5% in the IHT group. After balancing the baseline characteristics, the transferred patients were 1.12 (95% CI: 1.06-1.20) and 1.25 (95% CI: 1.20-1.31) times more likely to die during the subsequent 30 days and one year, respectively, than those treated solely at the presenting hospital. In ST-segment elevation myocardial infarction (STEMI), the hazard ratios of the 30-day and 1-year mortality were 1.14 (95% CI: 0.97-1.35) and 1.31 (95% CI: 1.15-1.49) in the transferred patients after balancing cardiogenic shock and cardiac arrest. On-site thrombolysis was rarely performed in the referring hospitals.

Conclusion: Patients transferred for the treatment of AMI experienced higher short- and long-term mortality. Therefore, onsite thrombolysis and the estimated time delay to PCI should be considered in regional hospitals to reduce mortality with the organization of STEMI treatment networks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255839PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341481PMC
August 2021

Identification of Video Game Addiction Using Heart-Rate Variability Parameters.

Sensors (Basel) 2021 Jul 8;21(14). Epub 2021 Jul 8.

Department of Clothing and Textiles, Kyung Hee University, Seoul 02447, Korea.

The purpose of this study is to determine heart rate variability (HRV) parameters that can quantitatively characterize game addiction by using electrocardiograms (ECGs). 23 subjects were classified into two groups prior to the experiment, 11 game-addicted subjects, and 12 non-addicted subjects, using questionnaires (CIUS and IAT). Various HRV parameters were tested to identify the addicted subject. The subjects played the game for 30-40 min. The experimenter measured ECG during the game at various window sizes and specific events. Moreover, correlation and factor analyses were used to find the most effective parameters. A logistic regression equation was formed to calculate the accuracy in diagnosing addicted and non-addicted subjects. The most accurate set of parameters was found to be pNNI20, RMSSD, and LF in the 30 s after the "being killed" event. The logistic regression analysis provided an accuracy of 69.3% to 70.3%. AUC values in this study ranged from 0.654 to 0.677. This study can be noted as an exploratory step in the quantification of game addiction based on the stress response that could be used as an objective diagnostic method in the future.
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http://dx.doi.org/10.3390/s21144683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309595PMC
July 2021

Exploring Nursing Students' Perspectives on Telenursing Using Q-methodology.

Comput Inform Nurs 2021 May 27. Epub 2021 May 27.

Author Affiliations: Department of Nursing, Youngsan University (Dr I.-J. Kim); and Department of Nursing, Kaya University (Drs M.S. Kim and M.K. Jeon), Gyeongsangnam-do, Republic of Korea.

With the rapid development of information and communications technologies, the medical care paradigm has been transformed, making telenursing a reality. Along with the introduction of telenursing, new changes are anticipated in the following central nursing domains: "human," "environment," "nursing," and "health." Current nursing students living in a hyperconnected world are expected to expand telenursing and foster changes in nursing. Therefore, it is important to understand nursing students' perceptions about telenursing to prepare innovatively for this changing field. This study explored nursing students' subjective perceptions about telenursing in South Korea using Q-methodology. Forty Q-statements, which reflected the nursing metaparadigm, were extracted from 175 generated statements; then, 40 nursing students-recruited purposively through snowball sampling-ranked the set of Q-statements. The data were analyzed using the PQMethod program. Five perceptions concerning telenursing were identified: "concerns and suggestions for telenursing," "complete support for telenursing," "inevitable acceptance of telenursing," "distrust and criticism regarding telenursing," and "optional acceptance of telenursing." This study provides strategies for introducing and implementing telenursing services in countries with commercial 5G coverage and informs policies related to nursing education.
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http://dx.doi.org/10.1097/CIN.0000000000000767DOI Listing
May 2021

Surveillance of the infection prevention and control practices of healthcare workers by an infection control surveillance-working group and a team of infection control coordinators during the COVID-19 pandemic.

J Infect Public Health 2021 Apr 30;14(4):454-460. Epub 2021 Jan 30.

Infection Control Department, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul, 03312, Republic of Korea; Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul, 03312, Republic of Korea. Electronic address:

Background: During the ongoing coronavirus disease (COVID-19) pandemic, hospitals have strengthened their guidelines on infection prevention and control (IPC), and a rigorous adherence to these guidelines is crucial. An infection control surveillance-working group (ICS-WG) and infection control coordinators (ICCs) team were created to monitor the IPC practices of the healthcare workers (HCWs) in a regional hospital in Korea. This study analyzed the surveillance results and aimed to identify what IPC practices needed improvement.

Methods: During phase 1 (March to April 2020), the ICS-WG performed random audits, recorded incidences of improper IPC practices, and provided advice to the violators. During phase 2 (April to July), the ICCs inspected the hospital units and proposed practical ideas about IPC. The surveillance and proposals targeted the following practices: patient screening, usage of personal protective equipment (PPE), hand and respiratory hygiene, equipment reprocessing, environmental cleaning, management of medical waste, and social distancing.

Results: In phase 1, of the 127 violations observed, most (32.3%) corresponded to hand and respiratory hygiene. In phase 2, the highest proportion of violation per category was observed in the management of medical waste (37.8%); among these, a higher proportion of violation (71.4%) was observed in the collection of medical waste. Of the 106 proposals made by the ICCs, the most addressed practice was patient screening (28.3%). No case of nosocomial infection was reported during the study period.

Conclusion: Adherence to proper hand and respiratory hygiene was inadequate at the early stage of the COVID-19 pandemic. The results indicate that more attention and further training are needed for the management of medical waste, particularly medical waste collection, and that continuous upgrading of the strategies for patient screening is essential. These results will be useful in helping other healthcare facilities to establish their IPC strategies.
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http://dx.doi.org/10.1016/j.jiph.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847193PMC
April 2021

Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer.

J Med Chem 2021 03 25;64(5):2501-2520. Epub 2021 Feb 25.

Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceuticals Company Ltd., Cambridge, Massachusetts 02139, United States.

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01491DOI Listing
March 2021

Molecular mechanisms underlying the enhancement of carbon ion beam radiosensitivity of osteosarcoma cells by miR-29b.

Am J Cancer Res 2020 1;10(12):4357-4371. Epub 2020 Dec 1.

Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology Chiba, Japan.

Carbon ion radiotherapy (CIRT) is more effective than conventional photon beam radiotherapy in treating osteosarcoma (OSA); however, the outcomes of CIRT alone are still unsatisfactory. In this study, we aimed to investigate whether acts as a radiosensitizer for CIRT. The OSA cell lines U2OS and KHOS were treated with carbon ion beam alone, γ-ray irradiation alone, or in combination with an mimic. OSA cell death as well as invasive and migratory abilities were analyzed through viability, colony formation, Transwell, and apoptosis assays. expression was downregulated in OSA tissues compared to that in normal tissues and was associated with metastasis and relapse in patients with OSA. Further, was found to directly target the transcription factor Sp1 and suppress the activation of the phosphatase and tensin homolog (PTEN)-AKT pathway. Conversely, Sp1 was found to attenuate the inhibitory effects of in OSA cells. When used in combination with mimic, carbon ion beam markedly inhibited invasion, migration, and proliferation of OSA cells and promoted apoptosis by inhibiting AKT phosphorylation in a Sp1/PTEN-mediated manner. Taken together, mimic improved the radiosensitivity of OSA cells via the PTEN-AKT-Sp1 signaling pathway, presenting a novel strategy for the development of carbon ion beam combination therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783744PMC
December 2020

Clinical outcomes of prolonged dual antiplatelet therapy after coronary drug-eluting stent implantation in dialysis patients.

Clin Kidney J 2020 Oct 3;13(5):803-812. Epub 2020 May 3.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: End-stage renal disease yields susceptibility to both ischemia and bleeding. The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is not established in dialysis patients, who are usually excluded from randomized studies. Since recent studies implied the benefits of prolonged DAPT >12 months in chronic kidney disease, we investigated the effectiveness and safety of prolonged DAPT in dialysis patients with higher cardiovascular risks.

Methods: In this nationwide population-based study, we analyzed dialysis patients who underwent DES implantation from 2008 to 2015. Continued DAPT was compared with discontinued DAPT using landmark analyses, including free-of-event participants at 12 ( = 2246), 15 ( = 1925) and 18 months ( = 1692) after DES implantation. The primary outcome was major adverse cardiovascular events (MACEs): a composite of mortality, nonfatal myocardial infarction, coronary revascularization and stroke. Major bleeding was a safety outcome. Inverse probability of treatment weighting Cox regression was performed.

Results: Mean follow-up periods were 278.3-292.4 days, depending on landmarks. Overall, incidences of major bleeding were far lower than those of MACE. Continued DAPT groups showed lower incidences of MACE and higher incidences of major bleeding, compared with discontinued DAPT groups. In Cox analyses, continued DAPT reduced the hazards of MACE at the 12- [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.61-0.90; P=0.003], 15- (HR = 0.78, 95% CI 0.64-0.96; P=0.019) and 18-month landmarks (HR = 0.79, 95% CI 0.63-0.99; P=0.041), but without a significant increase in major bleeding at 12 (HR = 1.39, 95% CI 0.90-2.16; P=0.14), 15 (HR = 1.13, 95% CI 0.75-1.70; P=0.55) or 18 months (HR = 1.27, 95% CI 0.83-1.95; P=0.27).

Conclusions: Prolonged DAPT reduced MACE without significantly increasing major bleeding in patients who were event-free at 12 months after DES implantation. In deciding on DAPT duration, prolonged DAPT should be considered in dialysis patients.
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http://dx.doi.org/10.1093/ckj/sfaa037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577762PMC
October 2020

Indirect cell death and the LQ model in SBRT and SRS.

J Radiosurg SBRT 2020 ;7(1):1-4

Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, MN, USA.

High-dose hypofractionated SBRT and SRS indirectly kills substantial fractions of tumor cells via causing vascular damage. The LQ formula may work well for certain clinical cases of SBRT and SRS when the indirect/additional tumor cell death secondary to vascular damage is small. However, when the indirect cell death is extensive, the LQ model will underestimate the clinical outcome of SBRT and SRS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406346PMC
January 2020

Patterns of percutaneous transthoracic needle biopsy (PTNB) of the lung and risk of PTNB-related severe pneumothorax: A nationwide population-based study.

PLoS One 2020 10;15(7):e0235599. Epub 2020 Jul 10.

School of Medicine, Inha University, Incheon, Republic of Korea.

Background: As percutaneous transthoracic needle biopsy (PTNB) of the lung is a well-established diagnostic method for the evaluating pulmonary lesions, evidence of safety based on representative data is limited. This study investigated the practice patterns of PTNB of the lung and assessed the incidence and risk factors of PTNB-related severe pneumothorax in Korea.

Methods: We used a national-level health insurance database between January 1, 2007 and December 31, 2015. Patients who underwent PTNB of the lung were identified using procedure codes for organ biopsy, fluoroscopy, computed tomography, chest radiography, and lung-related diagnosis codes. The annual age-/sex-standardized rate of PTNB and the incidence of PTNB-related severe pneumothorax were calculated. We defined severe pneumothorax as the pneumothorax requiring intervention. The odds ratios of risk factors were assessed by a generalized estimating equation model with exchangeable working correlation matrix to address clustering effect within institution.

Results: A total of 66,754 patients were identified between 2007 and 2015. The annual age-/sex-standardized rate of PTNB per 100,000 population was 19.6 in 2007 and 22.4 in 2015, and it showed an increasing trend. The incidence of severe pneumothorax was 2.4% overall: 2.5% in men and 1.2% in women, and 2.6%, 2.7%, 2.1%, 2.1%, 1.9%, 2.4%, and 2.4% from 2009 to 2015. Older age (≥60), male sex, presence of chronic obstructive pulmonary disease, receiving treatment in an urban or rural area versus a metropolitan area, and receiving treatment at a general hospital were significantly associated with the risk of severe pneumothorax.

Conclusions: Considering the increasing trend of PTNB, more attention needs to be paid to patients with risk factors for severe pneumothorax.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235599PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351186PMC
September 2020

Infection, antibiotic exposure and development of atopic dermatitis: A nationwide case-control study.

J Dermatol 2020 Jul 22;47(7):707-713. Epub 2020 May 22.

Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

Previous studies suggest an association between atopic dermatitis (AD) and exposure to microorganisms and antibiotics. However, these studies have limitations, and the sole influence on the development of AD was elusive. We performed a nationwide population-based case-control study in a Korean population to investigate the association between AD and early-life infection or antibiotic exposure. A total of 244 805 children with AD from the 2 283 601 children born between January 2010 and December 2014 and an equal number of sex- and age-matched healthy children were enrolled. A conditional logistic regression analysis showed that the episode of infection and antibiotic exposure were associated with an increased risk of AD (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.58-1.63 for infection; and OR, 1.11; 95% CI, 1.09-1.13 for antibiotic exposure). A dose-dependent relationship was observed between risk for AD, the number of infection episodes and antibiotic cycles and the duration of antibiotic exposure. On further analysis using a conditional logistic model, the risk of AD was less when the antibiotics were used during the infection episode than that without the use of antibiotics, especially if the duration of the infection was short. Although our study could not consider the effect of cause or severity of infection, class of antibiotics and genetic or environmental factors of enrolled subjects, our results suggested that infection and antibiotic exposure were associated with an increased risk of AD. In addition, the results also implied that the use of antibiotics during an infection episode can decrease the risk of AD induced by the infection and that appropriate management of infections can minimize the risk of AD induced by infection or antibiotics.
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http://dx.doi.org/10.1111/1346-8138.15387DOI Listing
July 2020

Cost analysis of depression using the national insurance system in South Korea: a comparison of depression and treatment-resistant depression.

BMC Health Serv Res 2020 Apr 6;20(1):286. Epub 2020 Apr 6.

Department of Neuropsychiatry, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care.

Methods: This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA.

Results: Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists.

Conclusions: TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients.
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http://dx.doi.org/10.1186/s12913-020-05153-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137426PMC
April 2020

Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells.

Cancers (Basel) 2020 Mar 16;12(3). Epub 2020 Mar 16.

Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.

Osteosarcoma (OSA) is the most common malignant bone tumor in children and adolescents. The overall five-year survival rate for all bone cancers is below 70%; however, when the cancer has spread beyond the bone, it is about 15-30%. Herein, we evaluated the effects of carbon-ion beam irradiation alone or in combination with zoledronic acid (ZOL) on OSA cells. Carbon-ion beam irradiation in combination with ZOL significantly inhibited OSA cell proliferation by arresting cell cycle progression and initiating KHOS and U2OS cell apoptosis, compared to treatments with carbon-ion beam irradiation, X-ray irradiation, and ZOL alone. Moreover, we observed that this combination greatly inhibited OSA cell motility and invasion, accompanied by the suppression of the Pi3K/Akt and MAPK signaling pathways, which are related to cell proliferation and survival, compared to individual treatments with carbon-ion beam or X-ray irradiation, or ZOL. Furthermore, ZOL treatment upregulated microRNA (miR)-29b expression; the combination with a miR-29b mimic further decreased OSA cell viability via activation of the caspase 3 pathway. Thus, ZOL-mediated enhancement of carbon-ion beam radiosensitivity may occur via miR-29b upregulation; co-treatment with the miR-29b mimic further decreased OSA cell survival. These findings suggest that the carbon-ion beam irradiation in combination with ZOL has high potential to increase OSA cell death.
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http://dx.doi.org/10.3390/cancers12030698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140041PMC
March 2020

Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study.

Nephrol Dial Transplant 2021 04;36(5):909-917

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Given the cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs), it is essential to identify the relationship between NSAIDs and cardiovascular outcomes in dialysis patients who have elevated cardiovascular risk.

Methods: A case-crossover study was conducted to assess the association of NSAIDs with major adverse cardiac and cerebrovascular events (MACCEs) and mortality using the Korean Health Insurance dataset. The case period was defined as 1-30 days prior to the event date and the control periods were defined as 61-90 days and 91-120 days prior to the event date.

Results: There were 3433 and 8524 incident dialysis patients who experienced MACCEs and mortality, respectively, after exposure to NSAIDs within 120 days before each event. NSAIDs significantly increased the risk of MACCEs {adjusted odds ratio [aOR] 1.37 [95% confidence interval (CI) 1.26-1.50]} and mortality [aOR 1.29 (95% CI 1.22-1.36)]. Nonselective NSAIDs, but not selective cyclooxygenase-2 inhibitors, significantly increased the risk of MACCEs and mortality. However, the MACCE and mortality risk did not increase in a dose-dependent manner in the analysis according to the cumulative defined daily dosage of NSAIDs. The incidence of MACCEs in the case period tended to be more common in patients who had recent exposure to NSAIDs than in patients who did not have recent exposure to NSAIDs.

Conclusions: Clinicians should be particularly cautious when prescribing NSAIDs to dialysis patients considering the associations of NSAIDs with cardiovascular outcomes and mortality, which might occur independent of the dose and duration of exposure.
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http://dx.doi.org/10.1093/ndt/gfz276DOI Listing
April 2021

Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study.

Lipids Health Dis 2020 Jan 11;19(1). Epub 2020 Jan 11.

Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

Background: Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS).

Methods: This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD).

Results: Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015).

Conclusions: LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.
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http://dx.doi.org/10.1186/s12944-019-1158-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954559PMC
January 2020

Clinical utilization of radiation therapy in Korea, 2016.

J Radiat Res 2020 Mar;61(2):249-256

Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

Radiotherapy (RT) is one of the primary cancer treatment modalities. To estimate the actual utilization of RT and infrastructure in Korea, the current study was performed. Data from 2012 to 2016 were extracted from the Health Insurance Review and Assessment Service. In addition, a nationwide survey was conducted to collect the statistics of RT facilities, equipment and human resources in Korea. The total number of patients treated with RT was 72 563 in 2016. The five cancers that were most commonly treated with RT in 2016 were breast, lung, colorectal, liver and prostate cancer. According to analyses of specific treatment modalities, the number of patients treated with intensity-modulated radiotherapy (IMRT), stereotactic radiation therapy (SRT) and proton therapy increased from 6670, 6306 and 50 in 2012 to 21584, 9048 and 703 in 2016, respectively. Ninety radiation oncology centers were working in 2015 and there were a total of 213 megavoltage teletherapy machines. In 2015, 310 patients were treated per megavoltage RT machine, 246 patients per radiation oncologist, 501 patients per medical physicist and 111 patients per radiotherapy technologist. In conclusion, the number of patients who underwent RT in Korea has increased steadily from 2012 to 2016. The IMRT utilization rate remarkably increased in 2016, and the number of patients treated with advanced treatment modalities such as IMRT, SRT and proton therapy is expected to increase.
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http://dx.doi.org/10.1093/jrr/rrz095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246057PMC
March 2020

Post-operative radiation therapy with or without chemotherapy for anal squamous cell carcinoma incidentally discovered after local excision: a propensity score matched analysis of retrospective multicenter study.

Br J Radiol 2020 Feb 17;93(1106):20190667. Epub 2019 Dec 17.

Department of Radiation Oncology, Konkuk University School of Medicine, Seoul, Republic of Korea.

Objective: To evaluate the results of post-operative radiation therapy (RT) for anal squamous cell carcinoma (ASCC) incidentally detected after excision, and compare these outcomes with those of definitive RT without excision for exploring the possibility of treatment de-intensification.

Methods And Materials: A total of 25 patients with T1-2N0-1 ASCC who underwent RT following incidental tumor resection were selected from multicenter retrospective database. And, we selected one-to-one matched 25 patients receiving definitive RT from the same database using propensity score matching method, and the outcomes were compared.

Results: Median age was 60 years (range, 30-76), and 18 patients (72%) were female. 19 patients (76%) had T0/1 tumors and four patients (16%) had regional lymph node metastases. Hemorrhoidectomy was performed in eight patients (32%) and the others underwent local excision. 12 patients (48%) had microscopic or gross residual diseases. Median RT dose to the primary lesion was 50.4 Gy (range, 40-60). Concurrent chemotherapy was delivered to 23 patients (92%). Median follow-up period was 71 months (range, 4.5-203.1 months). None of the patients showed recurrence during follow-up. However, one patient died after 6 months due to the chemotherapy-related hematologic toxicity. When compared with those patients receiving definitive RT, clinicopathological variables were well-balanced between the two groups. While matched paired patients treated with definitive RT received a higher median RT dose of 54 Gy (range, 45-61.2) and concurrent chemotherapy was given to 22 patients (88%), overall survival was not significantly different ( = 0.262).

Conclusion: Patients treated with RT for early stage ASCC after local excision showed favorable treatment outcomes. Further study is warranted to justify the de-intensification of the treatment for these patients.

Advances In Knowledge: Post-operative RT can achieve favorable treatment outcomes in incidental ASCC with residual diseases after local excision.
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http://dx.doi.org/10.1259/bjr.20190667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055428PMC
February 2020

Synergistic Autophagy Effect of miR-212-3p in Zoledronic Acid-Treated In Vitro and Orthotopic In Vivo Models and in Patient-Derived Osteosarcoma Cells.

Cancers (Basel) 2019 Nov 18;11(11). Epub 2019 Nov 18.

Department of Orthopaedic Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.

Osteosarcoma (OS) originates from osteoid bone tissues and is prone to metastasis, resulting in a high mortality rate. Although several treatments are available for OS, an effective cure does not exist for most patients with advanced OS. Zoledronic acid (ZOL) is a third-generation bisphosphonate that inhibits osteoclast-mediated bone resorption and has shown efficacy in treating bone metastases in patients with various types of solid tumors. Here, we sought to clarify the mechanisms through which ZOL inhibits OS cell proliferation. ZOL treatment inhibited OS cell proliferation, viability, and colony formation. Autophagy inhibition by RNA interference against Beclin-1 or ATG5 inhibited ZOL-induced OS cell death. ZOL induced autophagy by repressing the protein kinase B/mammalian target of rapamycin/p70S6 kinase pathway and extracellular signal-regulated kinase signaling-dependent autophagy in OS cell lines and patient-derived OS cells. Microarrays of miRNA showed that ZOL increased the levels of miR-212-3p, which is known to play an important role in autophagy, in OS in vitro and in vivo systems. Collectively, our data provided mechanistic insight into how increased miR-212-3p through ZOL treatment induces autophagy synergistically in OS cells, providing a preclinical rationale for conducting a broad-scale clinical evaluation of ZOL + miR-212-3p in treating OS.
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http://dx.doi.org/10.3390/cancers11111812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895802PMC
November 2019

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

Cancer 2020 01 20;126(2):363-372. Epub 2019 Nov 20.

Department of Radiation Oncology, Hanyang University Hospital, Seoul, Korea.

Background: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area.

Methods: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates.

Results: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively.

Conclusions: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.
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http://dx.doi.org/10.1002/cncr.32502DOI Listing
January 2020

Comparison of bleeding risks among non-vitamin K antagonist oral anticoagulants using the Korea adverse event reporting system database.

Ther Adv Drug Saf 2019 24;10:2042098619876737. Epub 2019 Sep 24.

Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Background: In order to ensure safer use of non-vitamin K antagonist oral anticoagulants (NOACs), continuously detecting unexpected adverse drug reactions (ADRs) after market approval is necessary.

Methods: We performed disproportionality analysis to evaluate association between ADRs and NOACs including apixaban, dabigatran, and rivaroxaban using data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database (KIDS-KD) between 2012 and 2016. There was no significant signal other than bleeding when considering quantity, signal strength, seriousness, and causality. In order to evaluate the NOAC reports about bleeding, we selected 62 WHO-ART diagnostic codes associated with bleeding. Among the 26 codes that referred to major bleeding, 18 codes referred to gastrointestinal bleeding and 8 were referred to intracranial bleeding. We evaluated the significance of the signals using reporting odds ratios (RORs) adjusted for age and sex.

Results: Treatments with apixaban, dabigatran, and rivaroxaban were associated with 1989, 1668, and 2960 adverse events, respectively. Any type of bleeding with apixaban, dabigatran, rivaroxaban, and warfarin was reported in 174 (8.8%), 209 (12.5%), 523 (17.8%), and 620 (9.5%) events, respectively. For any bleeding, adjusted RORs of apixaban, dabigatran, and rivaroxaban were 0.99 [95% confidence interval (CI): 0.83-1.17], 1.47 (95% CI: 1.25-1.75), and 2.48 (95% CI: 2.16-2.84), respectively. With respect to major bleeding, the adjusted RORs of apixaban, dabigatran, and rivaroxaban were 1.08 (95% CI: 0.82-1.41), 1.46 (95% CI: 1.10-1.90), and 1.82 (95% CI: 1.43-2.32), respectively.

Conclusion: Rivaroxaban might have stronger association with bleeding than apixaban and dabigatran.
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http://dx.doi.org/10.1177/2042098619876737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759695PMC
September 2019

Effects of Community-Based Primary Care Management on Patients With Hypertension and Diabetes.

Asia Pac J Public Health 2019 09 15;31(6):522-535. Epub 2019 Sep 15.

Sungkyunkwan University, Gyeonggi-do, Republic of Korea.

As the prevalence of chronic diseases is continuously increasing, the socioeconomic cost of those conditions in Korea is also rising. In order to effectively manage chronic diseases, the "Community-Based Primary Care Project" was implemented from 2014 to 2016 and focused on primary medical care and physician-led chronic disease management. The purpose of this study is evaluating the effects of the project through the DID (difference in difference) model. The project's database and the National Health Insurance claims database were both used to compare the project and control groups (n = 6092 vs 24 368). Results of the analysis show that medication adherence was increased more in the project group compared with the control group. Hospitalization days, outpatient days, and number of primary medical clinic visits increased more in the participant group than the control group. As the project showed an improvement in treatment persistence, it will be necessary to monitor for a longer period of time.
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http://dx.doi.org/10.1177/1010539519867797DOI Listing
September 2019

Effects of Community-Based Primary Care Management on Patients With Hypertension and Diabetes.

Asia Pac J Public Health 2019 09 15;31(6):522-535. Epub 2019 Sep 15.

Sungkyunkwan University, Gyeonggi-do, Republic of Korea.

As the prevalence of chronic diseases is continuously increasing, the socioeconomic cost of those conditions in Korea is also rising. In order to effectively manage chronic diseases, the "Community-Based Primary Care Project" was implemented from 2014 to 2016 and focused on primary medical care and physician-led chronic disease management. The purpose of this study is evaluating the effects of the project through the DID (difference in difference) model. The project's database and the National Health Insurance claims database were both used to compare the project and control groups (n = 6092 vs 24 368). Results of the analysis show that medication adherence was increased more in the project group compared with the control group. Hospitalization days, outpatient days, and number of primary medical clinic visits increased more in the participant group than the control group. As the project showed an improvement in treatment persistence, it will be necessary to monitor for a longer period of time.
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http://dx.doi.org/10.1177/1010539519867797DOI Listing
September 2019

Reoxygenation and Repopulation of Tumor Cells after Ablative Hypofractionated Radiotherapy (SBRT and SRS) in Murine Tumors.

Radiat Res 2019 08 12;192(2):159-168. Epub 2019 Jun 12.

a Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota.

In this work, we investigated the change in tumor microenvironment caused by semi-ablative high-dose irradiation and its implication on tumor cell survival, reoxygenation of hypoxic cells and repopulation in FSaII tumors grown subcutaneously in the hind legs of C3H mice. Tumors were exposed to 10-30 Gy of X-ray radiation in a single exposure, and the vascularity and blood perfusion were assessed based on the levels of CD31 expression and Hoechst 33342 perfusion, respectively. The tumor hypoxia was assessed by staining for pimonidazole adduct formation and the expression of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9). Tumor cell survival was determined using excision assay method. The proportion of hypoxic cells in the tumor was determined from the surviving cell fraction in tumors exposed to a test dose under aerobic and hypoxic conditions. Radiation expsoure markedly reduced the functional vascularity and blood perfusion, and profoundly increased the expression of HIF-1α and CA9 pointing to an increase in tumor hypoxia. The overall clonogenic cell survival progressively decreased during 2-5 days postirradiation, most likely due to the radiation-induced vascular dysfunction. In turn, the proportion of surviving hypoxic cells decreased over several days postirradiation, presumably due to reoxygenation of hypoxic cells. The oxygen supplied through small fractions of blood vessels that survived the high-dose exposure, together with a reduction of oxygen consumption due to massive cell death, appeared to be the cause of the reoxygenation of hypoxic cells. The surviving tumor cells then subsequently repopulated. The findings from this study using a murine tumor model suggest that the efficacy of stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) may be significantly improved by allowing an inter-fraction time for reoxygenation while avoiding repopulation.
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http://dx.doi.org/10.1667/RR15346.1DOI Listing
August 2019

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery.

Ann Coloproctol 2019 Apr 30;35(2):100-106. Epub 2019 Apr 30.

Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.

Purpose: In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT).

Methods: Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors.

Results: The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145-0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061-4.985).

Conclusion: Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.
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http://dx.doi.org/10.3393/ac.2018.10.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529757PMC
April 2019

Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death.

Int J Radiat Oncol Biol Phys 2021 05 2;110(1):21-34. Epub 2019 Mar 2.

Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota.

Purpose: To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).

Methods And Materials: We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS.

Results: Irradiation with doses higher than approximately 10 Gy/fraction causes significant vascular injury in tumors, leading to secondary tumor cell death. Irradiation of tumors with high doses has also been reported to increase the antitumor immunity, and various approaches are being investigated to further elevate antitumor immunity. The mechanism of normal tissue damage by high-dose irradiation needs to be further investigated.

Conclusions: In addition to directly killing tumor cells, high-dose irradiation used in SBRT and SRS induces indirect tumor cell death via vascular damage and antitumor immunity. Further studies are warranted to better understand the biological mechanisms underlying the high efficacy of clinical SBRT and SRS and to further improve the efficacy of SBRT and SRS.
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http://dx.doi.org/10.1016/j.ijrobp.2019.02.047DOI Listing
May 2021

Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study.

Clin Pharmacol Ther 2019 07 25;106(1):182-194. Epub 2019 Feb 25.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007-2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4-metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45), unlike CYP3A4-metabolized statins (HR 1.03, 95% CI 0.98-1.07). PPIs with high CYP2C19-inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02-1.61). Joint effects of PPIs and CYP3A4-metabolized statins were nonsignificant (relative excess risk due to interaction -0.14, 95% CI -0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4-metabolized statins did not exacerbate PPI-associated risks.
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http://dx.doi.org/10.1002/cpt.1361DOI Listing
July 2019

Radiation Therapy for Anal Squamous Cell Carcinoma: A Retrospective Multicenter Study.

Anticancer Res 2018 Dec;38(12):6931-6938

Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

Aim: To analyze the treatment outcomes, patterns of failures and prognostic factors for patients with anal cancer treated with radiotherapy (RT).

Materials And Methods: Between January 2000 and December 2015, 83 patients with anal squamous cell carcinoma were treated with definitive RT. The median RT dose applied to the primary carcinoma site was 55 (range=45-64) Gy. Seventy-six patients (91.6%) received concurrent chemotherapy, and the most common regimen was 5-fluorouracil plus mitomycin C.

Results: The median age of patients was 64 (range=36-86) years, and there were 21 males and 62 females. The overall complete remission rate was 89.2%. The median duration of follow-up was 51 (range=3-173) months. The actuarial 5-year overall, progression-free survival (PFS), locoregional progression-free, and distant metastasis-free survival rates were 85.0%, 70.4%, 78.2%, and 82.6%, respectively. On multivariate analysis, eventual treatment response was the only prognostic factor for overall (p=0.023) and progression-free (p<0.001) survival. Age (p=0.013) and eventual treatment response (p<0.001) were significantly associated with locoregional progression-free survival. Initial treatment response, lymph node involvement and RT technique significantly affected distant metastasis-free survival (p=0.016, 0.048 and 0.002, respectively).

Conclusion: RT, mainly with concurrent chemotherapy, showed acceptable treatment outcomes and safe toxicity profiles.
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http://dx.doi.org/10.21873/anticanres.13071DOI Listing
December 2018

The association between antidepressant use and deaths from road traffic accidents: a case-crossover study.

Soc Psychiatry Psychiatr Epidemiol 2019 Apr 24;54(4):485-495. Epub 2018 Nov 24.

School of Medicine, Inha University, Incheon, Republic of Korea.

Purpose: Antidepressants are some of the most commonly used psychiatric medications, but little information is available about the effects of antidepressant treatment on the risk of traffic accidents across classes of antidepressants or associated with each substance individually. To investigate the relationship between exposure to antidepressants and risk of fatality in road traffic accidents.

Methods: We used a Korean national road traffic authority database linked with a national health insurance database between January 1, 2010 and December 31, 2014 and applied a case-crossover design. The study subjects were drivers in South Korea who died from traffic accidents and who had prescriptions for antidepressants within 1 year prior to the date of the accident. We compared the status of prescription for antidepressants with the hazard period and four matched control periods using conditional logistic regression, adjusting for other drug use. The trends of antidepressant utilization were described in terms of the number of prescriptions. A case-case-time-control design was applied to drugs with an increasing trend in use and a significant case-crossover odds ratio (OR).

Results: A total of 1250 antidepressant-using drivers were included, and an increased risk was observed during the 30-day hazard period (adjusted OR 1.30; 95% CI 1.03-1.63). Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) showed significant risks, but tricyclic antidepressants did not. However, the associations of all antidepressants, SSRIs, SNRIs, escitalopram, and duloxetine did not remain significant after adjusting for trends in utilization. Paroxetine and milnacipran were associated with increased risks, with no obvious increase in their utilization, but the possibility of confounding by indication could have affected the results for milnacipran.

Conclusion: Considering the trends of antidepressant prescription and utilization, the use of paroxetine increased the risk of fatal traffic accidents.
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http://dx.doi.org/10.1007/s00127-018-1637-4DOI Listing
April 2019
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