Publications by authors named "Jin Soo Lee"

400 Publications

Interpreting complex geochemistry of groundwater in a coastal paddy field near a mine using isotopic signatures of sulfate and water.

Environ Geochem Health 2021 Mar 28. Epub 2021 Mar 28.

Institute of Mine Reclamation Technology, Korea Mine Reclamation Corporation (MIRECO), Wonju, Gangwon-do, 26464, South Korea.

In the area around the abandoned Seoseong mine, South Korea, coastal paddy fields undergo seawater intrusion and possible sulfate reduction. Here, channel water is used for irrigation, fertilizers are applied, and some paddy fields are contaminated by mining activities, which subsequently contaminate a groundwater well with arsenic. In this complex environment, the isotopic signatures of sulfate and water in water samples were assessed to reveal sources of sulfate, water and processes in the groundwater system. Sulfur and oxygen isotopes of sulfate indicated three major sources of sulfate-namely the mine including tailings, intruded seawater, and fertilizer-and an additional process of sulfate reduction. The sulfate sources and sulfate reduction could be distinguished more clearly after the variable of sulfate contribution from seawater was introduced. According to the analysis results of hydrogen and oxygen isotopes of water, areas affected by irrigation from a reservoir and its downstream channel were distinguished, possibly because the reservoir underwent evaporation effect. A schematic diagram was proposed to explain complex sources and processes in the studied area. Especially, a suggested plot of δS against the sulfate contribution from seawater [f(SO)] could efficiently differentiate various contamination sources (e.g., mining activity and fertilizer) and processes (e.g., seawater intrusion and sulfate reduction) in coastal aquifer.
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http://dx.doi.org/10.1007/s10653-021-00869-3DOI Listing
March 2021

Determination of soil contamination sources in mining area using Zn/Cd ratios with mobile Cd.

Environ Geochem Health 2021 Mar 27. Epub 2021 Mar 27.

Institute of Mine Reclamation Technology, Korea Mine Reclamation Corporation (MIRECO), Wonju, Gangwon-do, 26464, South Korea.

Paddy fields near metalliferous mining area are sometimes contaminated by tailings or mine water. In the contaminated paddy fields around the abandoned Seoseong mine, South Korea, groundwater, surface water, and soil samples were assessed to infer sources (tailings and/or mine water) of soil contamination. Major contaminants in the soil included As and Pb which were not detected in the adit water. Moreover, δS values of groundwater at contaminated downstream paddy fields were higher than those of ground and surface water in the mining area, which indicated water-derived contamination is not evident. The Zn/Cd ratios of soil were assessed to verify the source (tailings) of soil contamination. Plots of the Zn/Cd ratio against Zn and As contents showed that soil samples contaminated from tailings had Zn/Cd ratios (108-247) which were similar with the Zn/Cd range of the tailings. In contrast, the ratios of the soil samples were different from the Zn/Cd range of contaminated water samples. The Zn/Cd ratios were determined using 0.1 M HCl-extractable Cd, and the fraction of 0.1 M HCl-extractable Cd in aqua regia-digestible Cd increased with increasing aqua regia-digestible Cd content. These observations suggest that Zn/Cd ratios in contaminated soil are primarily controlled by 0.1 M HCl-extractable Cd, possibly due to the greater exchangeability of 0.1 M HCl-extractable Cd than that of total Cd. This suggests that Zn/Cd ratios determined using 0.1 M HCl-extractable Cd can be especially sensitive and useful for determining sources of soil contamination in mining areas such as tailings or contaminated water.
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http://dx.doi.org/10.1007/s10653-021-00820-6DOI Listing
March 2021

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

Stroke Vasc Neurol 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiology, Beaumont Hospital, Dublin, Ireland.

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.

Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.

Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile.

Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
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http://dx.doi.org/10.1136/svn-2020-000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006491PMC
March 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.

Neurology 2021 Mar 25. Epub 2021 Mar 25.

Department of Neurology, University of North Carolina at Chapel Hill, North Carolina, USA.

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
March 2021

Factors Contributing to an Efficacious Endovascular Treatment for Acute Ischemic Stroke in Asian Population.

Neurointervention 2021 Mar 26. Epub 2021 Mar 26.

Department of Neurology, Keimyung University Dongsan Hospital, Kyemyung University School of Medicine, Daegu, Korea.

Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.
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http://dx.doi.org/10.5469/neuroint.2020.00339DOI Listing
March 2021

Dp44mT regulates the levels of inflammatory mediators through blocking NF-κB nuclear translocation in LPS-stimulated RAW 264.7 macrophages.

In Vitro Cell Dev Biol Anim 2021 Mar 16;57(3):332-341. Epub 2021 Feb 16.

Department of Bio-Convergence System, Graduate School, Hoseo University, 20 Hoseo-ro,79 Beon-gil, Baebang-eup, Asan, 31499, Republic of Korea.

Inflammation is increased by infection with pathogens such as viruses, bacteria, and parasites. High levels of inflammatory mediators and infiltration of macrophages into inflammatory lesions were reported in severe inflammatory diseases. Here, the aim of this study was to evaluate an anti-inflammatory activity of di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Dp44mT (1-100 ng/mL) had no effect on viability of RAW 264.7 macrophages. Dp44mT (100 ng/mL) significantly reduced LPS-induced release of nitric oxide and expression of inducible nitric oxide synthase and cyclooxygenase-2. A significant upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by LPS stimulation was downregulated by treatment with Dp44mT. Dp44mT blocked activation of nuclear factor-κB by the interruption of IκBα phosphorylation. Dp44mT suppressed the phagocytosis. Furthermore, administration of Dp44mT significantly reduced the serum levels of TNF-α and IL-6 in LPS-treated mice without side effects. In conclusion, these results indicate that Dp44mT has an anti-inflammatory activity and may be of therapeutic significant for the prevention and treatment of inflammatory diseases.
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http://dx.doi.org/10.1007/s11626-021-00552-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886191PMC
March 2021

Etiological Approach to Understanding Recanalization Failure in Intracranial Large Vessel Occlusion and Thrombectomy: Close to Embolism but Distant From Atherosclerosis.

Front Neurol 2020 18;11:598216. Epub 2021 Jan 18.

Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, South Korea.

In patients with intracranial large vessel occlusion (LVO) who undergo endovascular treatment (EVT), recanalization failure may be related to intracranial atherosclerotic stenosis (ICAS). We evaluated whether the risk factors of recanalization failure could possibly be a marker of ICAS among various types of LVO. From a multicenter registry, patients with middle cerebral artery M1 segment occlusions who underwent thrombectomy within 24 h were included. Based on the on-procedure and post-procedure angiographic findings, patients were classified into embolic, ICAS-related, tandem occlusion, and recanalization failure groups. Recanalization failure was defined if the occluded vessel could not be recanalized by stent retrieval, contact aspiration, or local lytics treatment. Risk factors, imaging markers, and EVT methods were compared between groups. Among 326 patients, 214 were classified as embolism, 76 as ICAS, 16 as tandem, and 20 as recanalization failure. The group with recanalization failure showed higher scores on the National Institutes of Health Stroke Scale (NIHSS) (median, 16.0 vs. 14.5 vs. 14.0 vs. 17.0, = 0.097), frequent atrial fibrillation (59.3 vs. 18.4 vs. 0 vs. 40.0% < 0.001), and elevation in erythrocyte sedimentation rate (ESR) (14.5 ± 15.7 vs. 15.0 ± 14.1 vs. 21.2 ± 19.5 vs. 36.0 ± 32.9, < 0.001) among the groups. The rate of computed tomography angiography-based truncal-type occlusion in recanalization failure group was not as high as that in the ICAS group (8.1 vs. 37.5 vs. 0 vs. 16.7%, < 0.001). Balloon guide catheters (BGC) were less frequently utilized in the recanalization failure group as compared to their use in the other groups (72.0 vs. 72.4 vs. 62.5 vs. 30.0%, = 0.001). In the multivariable analysis, initial higher NIHSS [odds ratio (OR), 1.11 95% confidence interval (CI), 1.01-1.22 = 0.027], higher ESR (OR, 1.03 CI, 1.01-1.05 = 0.006), and non-use of BGCs (OR, 3.41 CI, 1.14-10.17 = 0.028) were associated with recanalization failure. In M1 occlusions, the predominant mechanism of recanalization failure was presumed to be embolic in 80% and due to ICAS in 20%. The analysis of recanalization failures does not suggest an underlying predominant ICAS mechanism. Sufficient utilization of thrombectomy devices and procedures may improve the rates of recanalization.
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http://dx.doi.org/10.3389/fneur.2020.598216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848124PMC
January 2021

The immune-enhancing effect of anthocyanin-fucoidan nanocomplex in RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice.

J Food Biochem 2021 Apr 2;45(4):e13631. Epub 2021 Feb 2.

Biochip Research Center, Hoseo University, Asan, 31499, Republic of Korea.

Aronia, a healthy fruit well known as black chokeberry, has health-promoting effects on hypertension, oxidative stress, and diabetes. Despite many reports of bioactivities of aronia, there is little scientific research on the potential for immune-enhancement. So, anthocyanin-fucoidan nanocomplex (AFNC, a nanocomplex of aronia extract and fucoidan) has been developed to improve immune-enhancement. This study aimed to identify immunomodulatory effects and underlying mechanisms of AFNC using RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice. As a result, AFNC-treated RAW264.7 macrophages elevated the production of IL-2, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO). AFNC-enhanced inducible NO synthase expression via nuclear factor-κB signaling pathways. AFNC dose-dependently increased levels of IL-2, IL-6, TNF-α, IL-10, IL-12, interferon-γ, or IL-4 in the serum and spleen of immunosuppressed mice. Taken together, AFNC encourages the immune-enhancing activity through immunostimulatory cytokine production by activation of macrophage. Therefore, these results suggest that AFNC is useful for immunodeficiency-related disorders. PRACTICAL APPLICATIONS: In these days of prevalence of infectious diseases, individual immunity is very important. AFNC has the immune-enhancing effects through immunostimulatory cytokine production by activation of macrophage. Therefore, AFNC could be widely applied to ameliorate a variety of diseases caused by immunosuppression such as infectious diseases.
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http://dx.doi.org/10.1111/jfbc.13631DOI Listing
April 2021

Altered Influenza Vaccination Coverage and Related Factors in Pregnant Women in Korea from 2007 to 2019.

J Korean Med Sci 2021 Feb 1;36(5):e42. Epub 2021 Feb 1.

Division of Infectious Diseases, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.

Background: Pregnant women are at a high-risk of influenza infection. We have previously reported a low influenza vaccination coverage rate (4.0%) in Korea during the 2006-2007 influenza season. We conducted follow-up studies in 2011-2012 and 2018-2019 to observe changes in influenza vaccination coverage.

Methods: Women who delivered at Inha University Hospital (Incheon, Korea) in 2011-2012 and 2018-2019 were enrolled in the study. We surveyed the rate of influenza vaccination, perception scores, and related factors through telephonic interviews and compared the results from 2011-2012 and 2018-2019 with those from 2006-2007.

Results: The number of survey respondents was 227 in 2006-2007, 152 in 2011-2012, and 171 in 2018-2019. The rate of vaccination coverage increased from 4.0% in 2006-2007 to 42.0% in 2011-2012 and 59.3% in 2018-2019. Perception scores also increased progressively from 3.8 in 2006-2007 to 4.2 in 2011-2012 and 5.1 in 2018-2019. Physician recommendations for influenza vaccination also increased from 4.8% in 2006-2007 to 36.8% in 2011-2012 and 49.7% in 2018-2019. The most common reason for not getting vaccinated was the lack of awareness of influenza vaccination during pregnancy (36.9%). The perception scores and physician recommendation rates were significantly lower for unvaccinated women (3.87 and 8.4%, respectively) than for vaccinated women (5.14 and 69.1%, respectively).

Conclusion: The influenza vaccination coverage rate in pregnant women has increased significantly since our study in 2006-2007. However, further improvement in the coverage rate is needed. There is a need for active and comprehensive publicity and education regarding this issue among physicians and pregnant women.
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http://dx.doi.org/10.3346/jkms.2021.36.e42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850865PMC
February 2021

Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke.

Neurology 2021 02 20;96(7):e1012-e1023. Epub 2021 Jan 20.

From the Department of Neurology (J.-W.C., O.Y.B., S.J.K.), Samsung Medical Center, Sungkyunkwan University; Translational and Stem Cell Research Laboratory on Stroke (J.-W.C., O.Y.B., G.J.M.) and Stem Cell and Regenerative Medicine Institute (G.J.M.), Samsung Medical Center; Department of Physical and Rehabilitation Medicine (W.H.C., Y.-H.K.), Center for Prevention and Rehabilitation, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; School of Life Sciences (G.J.M.), BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu; Department of Neurology (S.-K.K.), Gyeongsang National University School of Medicine, Jinju; Department of Neurology (J.S.L.), Ajou University Hospital, School of Medicine, Suwon; and Department of Neurology (S.-I.S.), Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea. Dr. Moon is currently affiliated with the Stem Cell Center, Asan Institute for Life Science and the Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Objective: To test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.

Methods: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.

Results: A total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range 28-83) years, and mean interval between stroke onset to randomization was 20.2 (range 5-89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months ( = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, = 0.023), which was notable among patients with low predicted recovery potential. There were no serious treatment-related adverse events.

Conclusions: IV application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.

Classification Of Evidence: This study provides Class III evidence that autologous MSCs do not improve 90-day outcomes in patients with chronic stroke.

Clinicaltrialsgov Identifier: NCT01716481.
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http://dx.doi.org/10.1212/WNL.0000000000011440DOI Listing
February 2021

Global impact of COVID-19 on stroke care.

Int J Stroke 2021 Mar 29:1747493021991652. Epub 2021 Mar 29.

Neurology, Grady Memorial Hospital, Emory University, Atlanta, Georgia, USA.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.

Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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http://dx.doi.org/10.1177/1747493021991652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010375PMC
March 2021

-coumaric acid, an active ingredient of , ameliolates atopic dermatitis-like skin lesions through inhibition of thymic stromal lymphopoietin in mice.

J Ginseng Res 2021 Jan 5;45(1):176-182. Epub 2020 Jul 5.

Division of Food and Pharmaceutical Engineering, BioChip Research Center, Hoseo University, Asan, Chungnam, Republic of Korea.

Background: Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. -coumaric acid (CA) is an active ingredient of Meyer (Araliaceae).

Methods: Here, we estimated an anti-AD effect of CA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions.

Results: The treatment with CA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-ɑ, IL-6, and IL-1β in HMC-1 cells. CA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBɑ/NF-κB in HMC-1 cells. CA also decreased the productions of TSLP, TNF-ɑ, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, CA-treated group alleviated pathological changes of AD-like lesions. CA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by CA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-ɑ, IL-6, and IL-4 were suppressed following treatment with CA.

Conclusion: This study suggests that CA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.
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http://dx.doi.org/10.1016/j.jgr.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790890PMC
January 2021

Effect of a serum lactate monitoring recommendation policy on patients treated with linezolid.

Medicine (Baltimore) 2021 Jan;100(1):e23790

Division of Infectious Diseases, Department of Internal Medicine, Inha University college of Medicine, Incheon.

Abstract: Lactic acidosis is one of the most fatal adverse effects of linezolid, an antibiotic used to treat serious infections caused by antibiotic-resistant bacteria. However, the measures to prevent lactic acidosis have not been well established.We performed a retrospective study to analyze the impact of applying a serum lactate monitoring recommendation policy in patients treated with linezolid.Since September 2011, we have recommended inpatient monitoring of serum lactate levels in patients treated with linezolid at our hospital. Patients were divided into two groups according to whether they were seen during the non-recommendation or recommendation periods. The frequency of serum lactate monitoring, linezolid-induced lactatemia, lactic acidosis, critical illness, and death were compared between the two periods.After September 2011, adherence to the recommendation to monitor serum lactate increased from 6.1% to 60.1%. No difference was observed in the incidence of linezolid-induced lactatemia and lactic acidosis between the two periods. However, there was a significant difference in the incidence of linezolid-induced critical illness between the non-recommendation and recommendation periods (3 vs 0 cases, P = .044).In patients treated with linezolid, serum lactate monitoring led to early detection of lactatemia, thus enabling rapid rescue. We recommend regular monitoring of serum lactate in all patients treated with linezolid.
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http://dx.doi.org/10.1097/MD.0000000000023790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793345PMC
January 2021

Effects of Resveratrol on Thymic Stromal Lymphopoietin Expression in Mast Cells.

Medicina (Kaunas) 2020 Dec 28;57(1). Epub 2020 Dec 28.

Department of Food Science & Technology and Research Institute for Basic Science, Hoseo University, Chungnam 31499, Korea.

Cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathogenesis of atopic diseases such as atopic dermatitis, allergic rhinitis, and asthma. Resveratrol (RSV) exerts various pharmacological effects such as antioxidant, anti-inflammatory, neuroprotective, and anticancer. Although, it has been verified the beneficial effects of RSV on various subjects, the effect of RSV on thymic stromal lymphopoietin (TSLP) regulation has not been elucidated. Here, we examined how RSV regulates TSLP in HMC-1 cells. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, Western blotting, and calcium assay were performed to evaluate the effect of RSV. TSLP production and mRNA expression were reduced by RSV. RSV down-regulated nuclear factor-κB activation, IκBα phosphorylation as well as activation of receptor-interacting protein2 and caspase-1 in HMC-1 cells. In addition, RSV treatment decreased the up-regulation of intracellular calcium in HMC-1 cells. These results suggest that RSV might be useful for the treatment of atopic diseases through blocking of TSLP.
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http://dx.doi.org/10.3390/medicina57010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824250PMC
December 2020

Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer.

Lung Cancer 2021 01 19;151:8-15. Epub 2020 Nov 19.

Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea. Electronic address:

Objectives: Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients.

Materials And Methods: This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes.

Results: Metformin group showed no significant difference in the risk of progression and death compared to control group (progression: hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 - 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67-1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose (FDG) uptake on baseline PET image than non-SqCC NSCLC (P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12-0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18-0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatment in metformin group compared to control group (P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment.

Conclusions: Addition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.011DOI Listing
January 2021

Splenic infarction and infectious diseases in Korea.

BMC Infect Dis 2020 Dec 2;20(1):915. Epub 2020 Dec 2.

Division of Infectious Diseases, Department of Internal Medicine, Inha University School of Medicine, Incheon, 22212, Republic of Korea.

Background: The spleen contains immune cells and exhibits a pattern of infarction different from other organs; as such, splenic infarction (SI) may provide important clues to infection. However, the nature of the relationship between SI and infectious disease(s) is not well understood. Accordingly, this retrospective study investigated the relationship between SI and infection.

Methods: Hospital records of patients with SI, who visited Inha University Hospital (Incheon, Republic of Korea) between January 2008 and December 2018, were reviewed. Patient data regarding clinical presentation, causative pathogens, risk factors, and radiological findings were collected and analyzed.

Results: Of 353 patients with SI, 101 with infectious conditions were enrolled in this study, and their data were analyzed to identify associations between SI and infection. Ten patients were diagnosed with infective endocarditis (IE), and 26 exhibited bacteremia without IE. Twenty-seven patients experienced systemic infection due to miscellaneous causes (negative result on conventional automated blood culture), including the following intracellular organisms: parasites (malaria [n = 12], babesiosis [n = 1]); bacteria (scrub typhus [n = 5]); viruses (Epstein-Barr [n = 1], cytomegalovirus [n = 1]); and unidentified pathogen[s] (n = 7). Splenomegaly was more common among patients with miscellaneous systemic infection; infarction involving other organs was rare. Thirty-eight patients had localized infections (e.g., respiratory, intra-abdominal, or skin and soft tissue infection), and most (35 of 38) had other risk factors for SI.

Conclusions: In this study, various infectious conditions were found to be associated with SI, and intracellular organisms were the most common causative pathogens. Further studies are needed to examine other possible etiologies and the underlying pathophysiological mechanisms.
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http://dx.doi.org/10.1186/s12879-020-05645-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708890PMC
December 2020

Prediction of Infarct Growth and Neurological Deterioration in Patients with Vertebrobasilar Artery Occlusions.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Korea.

We aimed to identify predictors of infarct growth and neurological deterioration (ND) in vertebrobasilar occlusions (VBOs) with a focus on clinical-core mismatch. From 2010 to 2018, VBO patients were selected from a university hospital registry. In total, 138 VBO patients were included. In these patients, a posterior circulation Alberta Stroke Program Early CT score (PC-ASPECTS) less than 6 was associated with futile outcome. Within patients with feasible cores, a decrease in PC-ASPECTS score of 2 or more on follow-up imaging was classified as infarct growth and could be predicted by a National Institutes of Health Stroke Scale (NIHSS) mental status subset of 1 or higher (odds ratio (OR): 3.34, 95% confidence interval (CI) (1.19-9.38), = 0.022). Among the 73 patients who did not undergo reperfusion therapy, 13 patients experienced ND (increase in discharge NIHSS score of 4 or more compared to the initial presentation). Incomplete occlusion (vs. complete occlusion, OR 6.17, 95% CI (1.11-34.25), = 0.037), poorer collateral status (BATMAN score, OR: 1.91, 95% CI (1.17-3.48), = 0.009), and larger infarct cores (PC-ASPECTS, OR: 1.96, 95% CI (1.11-3.48), = 0.021) were predictive of ND. In patients with VBO, an initial PC-ASPECTS of 6 or more, but with a decrease in the mental status subset of 1 or more can predict infarct growth, and may be used as a criterion for clinical-core mismatch. ND in VBO patients presenting with milder symptoms can be predicted by incomplete occlusion, poor collaterals, and larger infarct cores.
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http://dx.doi.org/10.3390/jcm9113759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700123PMC
November 2020

Predictors and prognoses of Willisian collateral failure during mechanical thrombectomy.

Sci Rep 2020 11 30;10(1):20874. Epub 2020 Nov 30.

Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, 164, World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, South Korea.

During mechanical thrombectomy in the anterior cerebral circulation, thrombus embolization resulting in Willisian collateral failure may lead to critical stroke outcomes due to a shutdown of leptomeningeal collaterals. We hypothesized that the outcomes of dynamic Willisian collateral failure (DWF), induced during mechanical thrombectomy, would be associated with grave outcomes. We evaluated this hypothesis in consecutive patients, between January 2011 and May 2016, who underwent mechanical thrombectomy for anterior circulation occlusions, with an onset-to-puncture of 24 h. Patients with initial Willisian collateral failure (IWF) were identified first, with remaining patients classified into the DWF and Willisian collateral sparing (WCS) groups. Comparative and multivariable analyses were performed to predict grave outcomes (3-month modified Rankin Scale score of 5-6). Among 567 patients, 37 were in the IWF group, 38 in the DWF group, and 492 in the WCS group. Compared to the WCS and DWF groups, the IWF group had a higher baseline National Institute of Health Stroke Scale score and lower Alberta Stroke Program Early CT Score. The prevalence of grave outcomes was similarly high in the IWF (48.6%) and DWF (47.4%) groups, but lower in the WCS group (22.0%; p < 0.001). IWF and DWF were independent risk factors for a grave outcome.
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http://dx.doi.org/10.1038/s41598-020-77946-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704636PMC
November 2020

A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis.

Br J Cancer 2021 01 18;124(1):290-298. Epub 2020 Nov 18.

College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.

Background: Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated.

Methods: Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed.

Results: In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments.

Conclusions: Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.
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http://dx.doi.org/10.1038/s41416-020-01146-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782829PMC
January 2021

Current Status and a Perspective of Mosquito-Borne Diseases in the Republic of Korea.

Vector Borne Zoonotic Dis 2021 Feb 2;21(2):69-77. Epub 2020 Nov 2.

Division of Infectious Diseases, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea.

Mosquito-borne diseases in the Republic of Korea have a unique epidemiology due to the rapid improvement in hygiene and economic status, occurrence of four distinct seasons, and separation from North Korea owing to the political situation. Therefore, we aimed to analyze and review the epidemiology of mosquito-borne diseases in Korea. The incidence and geographical distribution of malaria, Japanese encephalitis (JE), Zika virus infection, chikungunya fever, and dengue fever were investigated using data from the Korean Centers for Disease Control and Prevention. Lymphatic filariasis and West Nile fever, which have rarely been reported in Korea, have also been discussed in this literature review. Malaria disappeared from Korea in 1979, but since its re-emergence in 1993 there has been constant occurrence with local transmission. In Korea, vivax malaria is the only prevailing disease, and the clinically problematic chloroquine resistance has not been reported. The incidence of JE has greatly reduced since the introduction of the national vaccination program for children in 1985. However, the incidence of JE has been increasing recently, especially in adults >40 years of age. Filariasis, which was previously endemic to Jeju Island and the southern coastal area, has not been reported since 2002. Although there are numerous imported cases with increasing overseas travel, there are still no indigenous cases of Zika, chikungunya, and dengue fever reported in Korea. The West Nile virus was isolated from migratory birds, but there has been only one imported human case to date.
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http://dx.doi.org/10.1089/vbz.2019.2588DOI Listing
February 2021

Medical management of septic arthritis of sternoclavicular joint: A case report.

Medicine (Baltimore) 2020 Oct;99(44):e22938

Department of Internal Medicine, Inha University School of Medicine, Jung-gu, Incheon, Republic of Korea.

Rationale: Sternoclavicular joint septic arthritis is an unusual disease in healthy adults, and Staphylococcus aureus is the most common causative pathogen. The current treatment of choice is surgery with sternoclavicular joint resection and pectoralis flap closure, especially when the disease is complicated by osteomyelitis and abscess.

Patient Concerns: Here, we report a 76-year-old woman without risk factors who visited our hospital for pain and redness, swelling on the left anterior chest wall.

Diagnosis: Magnetic resonance imaging showed infectious arthritis in the left SCJ, with multiple abscess pockets at the subcutaneous layer of anterior chest wall communicating with the joint cavity. Streptococcus agalactiae was isolated from blood culture.

Intervention: She was treated with 6 weeks of antibiotic therapy.

Outcomes: After antibiotic treatment, she was successfully treated without recurrence.

Lessons: Besides surgery, medical treatment should also be considered for sternoclavicular joint septic arthritis, depending on patient status and the causative pathogen. Physicians should be aware of this rare disease to facilitate its prompt diagnosis and management.
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http://dx.doi.org/10.1097/MD.0000000000022938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598876PMC
October 2020

Optic nerve sheath diameter change in prediction of malignant cerebral edema in ischemic stroke: an observational study.

BMC Neurol 2020 Sep 22;20(1):354. Epub 2020 Sep 22.

Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, Republic of Korea.

Background: In acute large anterior circulation infarct patients with large core volume, we evaluated the role of optic nerve sheath diameter (ONSD) change rates in prediction of malignant progression.

Methods: We performed a retrospective observational study including patients with anterior circulation acute ischemic stroke with large ischemic cores from January 2010 to October 2017. Primary outcome was defined as undergoing decompressive surgery or death due to severe cerebral edema, and termed malignant progression. Patients were divided into malignant progressors and nonprogressors. Malignant progression was divided into early progression that occurred before D1 CT, and late progression that occurred afterwards. Retrospective analysis of changes in mean ONSD/eyeball transverse diameter (ETD) ratio, and midline shifting (MLS) were evaluated on serial computed tomography (CT). Through analysis of CT at baseline, postprocedure, and at D1, the predictive ability of time based change in ONSD/ETD ratio in predicting malignant progression was evaluated.

Results: A total of 58 patients were included. Nineteen (32.8%) were classified as malignant; 12 early, and 7 late progressions. In analysis of CT, A 1 mm/hr. rate of change in MLS during the CT-CT time phase lead to a 6.7 fold increased odds of early malignant progression (p < 0.05). For ONSD/ETD, 1%/hr. change lead to a 1.6 fold increased odds, but this association was trending (p = 0.249). In the CT, 1%/day change of ONSD/ETD in the CT-CT time phase lead to a 1.4 fold increased odds of late malignant progression (p = 0.021) while 1 mm/day rate of change in MLS lead to a 1.5 fold increased odds (p = 0.014).

Conclusions: The rate of ONSD/ETD changes compared to baseline at D1 CT can be a predictor of late malignant progression along with MLS. ONSD/ETD change rates evaluated at postprocedure did not predict early malignant progression.
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http://dx.doi.org/10.1186/s12883-020-01931-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510108PMC
September 2020

Hif-1α Inhibitors Could Successfully Inhibit the Progression of Differentiated Thyroid Cancer in Vitro.

Pharmaceuticals (Basel) 2020 Aug 24;13(9). Epub 2020 Aug 24.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Hypoxia-inducible factor (HIF)-1α plays an important role in cancer progression. In various cancers, including thyroid cancer, overexpression of HIF-1α is related to poor prognosis or treatment response. However, few studies have investigated the role of HIF-1α inhibition in thyroid cancer progression. We evaluated the utility of the HIF-1α inhibitor IDF-11774 in vitro utilizing two thyroid cancer cell lines, K1 and BCPAP. Both cell lines were tested to elucidate the effects of IDF-11774 on cell proliferation and migration using soft agar and invasion assays. Here, we found that a reduction of HIF-1α expression in BCPAP cells was observed after treatment with IDF-11774 in a dose-dependent manner. Moreover, cell proliferation, migration, and anchorage-independent growth were effectively inhibited by IDF-11774 in BCPAP cells but not in K1 cells. Additionally, invasion of BCPAP but not K1 cells was controlled with IDF-11774 in a dose-dependent manner. Our findings suggest that promoting the degradation of HIF-1α could be a strategy to manage progression and that HIF-1α inhibitors are potent drugs for thyroid cancer treatment.
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http://dx.doi.org/10.3390/ph13090208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558478PMC
August 2020

Chryseobacterium arthrosphaerae ventriculitis: A case report.

Medicine (Baltimore) 2020 Aug;99(34):e21751

Division of Infectious diseases, Department of Internal Medicine.

Introduction: Chryseobacterium arthrosphaerae is a gram-negative bacteria, known for its intrinsic multidrug resistance, which can lead to treatment difficulties.

Patient Concerns: A 56-year-old male had an indwelling external ventricular drainage catheter for 6 months and had been frequently treated with antibiotics for nosocomial infections. He showed cerebrospinal fluid pleocytosis and an abrupt fever during hospitalization.

Diagnosis: He was diagnosed as a ventriculitis caused by Chryseobacterium arthrosphaerae (C arthrosphaerae).

Intervention: Initially, we used ciprofloxacin as the backbone in combination with minocycline (and rifampin). However, fever and pleocytosis persisted, and improvement was slow. We then switched the minocycline and rifampin regiment to trimethoprim/sulfamethoxazole. Following this switch of antibiotics, the patient's pleocytosis rapidly improved, allowing the replacement of his external ventricular drainage catheters. C arthrospharae was no longer growing in cerebrospinal fluid and he was recovered from ventriculitis.

Outcomes: The patient remains alive without any incidence of C arthrosphaerae recurrence.

Conclusion: We propose trimethoprim/sulfamethoxazole alone or in combination with ciprofloxacin to be good candidates for the treatment of ventriculitis by C arthrosphaerae.
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http://dx.doi.org/10.1097/MD.0000000000021751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447447PMC
August 2020

A comparison of epidemiology and clinical outcomes between influenza A H1N1pdm09 and H3N2 based on multicenter surveillance from 2014 to 2018 in South Korea.

Influenza Other Respir Viruses 2021 Jan 25;15(1):99-109. Epub 2020 Aug 25.

Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Background: After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist.

Objectives: We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes.

Methods: Data were retrospectively collected from the hospital-based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited.

Results: A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P < .001) and pneumococcal vaccination rates (41.0% vs 51.9%, P < .001), and fewer underlying diseases (67.5% vs 74.0%, P = .035) than the A(H3N2) group. Influenza A subtypes were not associated with pneumonia risk (adjusted odds ratios [AOR] of A(H1N1)pdm09: 0.7 [95% confidence interval [CI]: 0.4-1.2, P = .172]) and in-hospital mortality (hazard ratio (HR) of A(H1N1)pdm09: 1.0 (95% CI: 0.3-3.1, P = .983)). Influenza vaccination reduced in-hospital mortality in hospitalized patients (HR: 0.3 (95% CI: 0.1-0.7), P = .005).

Conclusions: A(H1N1)pdm09 infection was more common in younger patients without significant difference in pneumonia risk and in-hospital mortality between subtypes. Influenza vaccination was associated with reduced in-hospital mortality.
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http://dx.doi.org/10.1111/irv.12795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767957PMC
January 2021

The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy.

Neurocrit Care 2020 Aug 18. Epub 2020 Aug 18.

Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, South Korea.

Background/objective: Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry.

Methods: Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82 ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5 °C) was maintained for at least 48 h.

Results: We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3 months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants.

Conclusions: Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.
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http://dx.doi.org/10.1007/s12028-020-01069-0DOI Listing
August 2020

Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase-Low Squamous Cell Lung Cancer.

Cancer Res Treat 2021 Jan 13;53(1):87-92. Epub 2020 Aug 13.

Division of Hematology and Oncology, Department of Internal Medicine, National Cancer Center, Goyang, Korea.

Purpose: Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.

Materials And Methods: In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate.

Results: Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2.

Conclusion: Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
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http://dx.doi.org/10.4143/crt.2020.741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812006PMC
January 2021

Nutritional status of patients with COVID-19.

Int J Infect Dis 2020 Nov 11;100:390-393. Epub 2020 Aug 11.

Division of Infectious Diseases, Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea. Electronic address:

The relationship between immunity and nutrition is well known and its role in coronavirus disease 2019 (COVID-19) is also being paid great attention. However, the nutritional status of COVID-19 patients is unknown. Vitamin B1, B6, B12, vitamin D (25-hydroxyvitamin D), folate, selenium, and zinc levels were measured in 50 hospitalized patients with COVID-19. Overall, 76% of the patients were vitamin D deficient and 42% were selenium deficient. No significant increase in the incidence of deficiency was found for vitamins B1, B6, and B12, folate, and zinc in patients with COVID-19. The COVID-19 group showed significantly lower vitamin D values than the healthy control group (150 people, matched by age/sex). Severe vitamin D deficiency (based on a cut-off of ≤10 ng/dl) was found in 24.0% of the patients in the COVID-19 group and 7.3% in the control group. Among 12 patients with respiratory distress, 11 (91.7%) were deficient in at least one nutrient. However, patients without respiratory distress showed a deficiency in 30/38 cases (78.9%; p =  0.425). These results suggest that a deficiency of vitamin D or selenium may decrease the immune defenses against COVID-19 and cause progression to severe disease. However, more precise and large-scale studies are needed.
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http://dx.doi.org/10.1016/j.ijid.2020.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418699PMC
November 2020

Sequential Treatment with an Immune Checkpoint Inhibitor Followed by a Small-Molecule Targeted Agent Increases Drug-Induced Pneumonitis.

Cancer Res Treat 2021 Jan 6;53(1):77-86. Epub 2020 Aug 6.

Department of Internal Medicine, National Cancer Center, Goyang, Korea.

Purpose: Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis.

Materials And Methods: In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated.

Results: Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).

Conclusion: Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
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http://dx.doi.org/10.4143/crt.2020.543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812016PMC
January 2021