Publications by authors named "Ho Kim"

1,856 Publications

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Retinal Optical Coherence Tomography in Neuromyelitis Optica.

Neurol Neuroimmunol Neuroinflamm 2021 Nov 15;8(6). Epub 2021 Sep 15.

From the Experimental and Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany: NeuroCure Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Department of Neurology (F.C.O., A.J.G.), University of California San Francisco, CA; Department of Pediatrics (L.C.), University of Utah, Salt Lake City; CIEM MS Research Center (M.A.L.P., M.A.F.), University of Minas Gerais, Medical School, Belo Horizonte, Brazil; Department of Neurology (H.J.K., J.-W.H.), National Cancer Center, Goyang, Republic of Korea; Department of Neurology (J.P., A.R.-F., M.I.L.), and Department of Ophthalmology (Srilakshmi Sharma), and Department of Ophthalmology (Srilakshmi Sharma), Oxford University Hospitals, National Health Service Trust, UK; Kashani MS Center (F.A.), School of Advanced Technologies in Medicine and Medical Image and Signal Processing Research Center (R.K.), Department of Ophthalmology, Isfahan Eye Research Center (A.D., Mohsen Pourazizi), Isfahan University of Medical Sciences, Iran; Department of Neurology (L.P., A.D'C.), KS Hegde Medical Academy, Nitte University, Mangalore, India; Department of Neurology (O.A., Marius Ringelstein, P.A.), Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Swedish Neuroscience Institute Neuro-Ophthalmology (E.M., C.T.), Seattle, WA; Experimental Neurophysiology Unit (L.L., Marco Pisa, Marta Radaelli), Institute of Experimental Neurology (INSPE) Scientific Institute Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy; Hospital Clinic of Barcelona-Institut d'Investigacions (E.H.M.-L.), Biomèdiques August Pi Sunyer, (IDIBAPS), Spain; Sackler School of Medicine (H.S.-K.), Tel Aviv University, Israel; Neuro-Ophthalmology Division (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel; Division of Neurology (Sasitorn Siritho), Department of Medicine, Siriraj Hospital and Bumrungrad International Hospital, Bangkok, Thailand; Neurology Service (J.d.S., Thomas Senger), University Hospital of Strasbourg, France; Institute of Clinical Neuroimmunology (J.H.), Biomedical Center and University Hospital, Ludwig-Maximilians Universitaet Muenchen, Munich, Germany; Neurology (R.M., A.C.C.), Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, France; Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (A.C.C.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Department of Neurology and Neurosurgery (D.B., I.M.T.), Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil; Departments of Neurology (N.A.), Slagelse Hospitals, Institute of Regional Health Research, University of Southern Denmark, Odense; Institute of Regional Health Research (N.A., K.S.), University of Southern Denmark, Odense; Department of Neurology (A.A., U.T.), and Department of Ophthalmology (R.Y.), Cerrahpasa Medical Faculty, Istanbul University, Turkey; The Walton Centre for Neurology and Neurosurgery (A.J., S.H.), Liverpool, UK; The Cleveland Clinic Abu Dhabi (A.J.), United Arab Emirates; NYU Multiple Sclerosis Comprehensive Care Center (Z.R., A.R.), Department of Neurology, NYU School of Medicine, New York; Department of Neurology (Y.M.-D.), University of Michigan Medical School, Ann Arbor; Department of Neurology (I.S.C.), Hospital Clínico de Maracaibo, Venezuela; Moorfield's Eye Hospital (A.P.), University College London, UK; Department of Medicine (M.R.Y.), Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA, United States of America; Department of Medicine (M.R.Y.), David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America; Departments of Ophthalmology and Visual Sciences (Terry Smith), Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, United States of America; Division of Metabolism (Terry Smith), Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor; Department of Neurology (A.U.B.), University of California, Irvine; and Department of Neurology (F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany.

Background And Objectives: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts.

Methods: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA).

Results: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, < 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC.

Discussion: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.
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http://dx.doi.org/10.1212/NXI.0000000000001068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448522PMC
November 2021

High-yield synthesis and purification of recombinant human GABA transaminase for high-throughput screening assays.

J Enzyme Inhib Med Chem 2021 Dec;36(1):2016-2024

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, South Korea.

Many studies have focussed on modulating the activity of γ-aminobutyric acid transaminase (GABA-T), a GABA-catabolizing enzyme, for treating neurological diseases, such as epilepsy and drug addiction. Nevertheless, human GABA-T synthesis and purification have not been established. Thus, biochemical and drug design studies on GABA-T have been performed by using porcine GABA-T mostly and even bacterial GABA-T. Here we report an optimised protocol for overexpression of 6xHis-tagged human GABA-T in human cells followed by a two-step protein purification. Then, we established an optimised human GABA-T (0.5 U/mg) activity assay. Finally, we compared the difference between human and bacterial GABA-T in sensitivity to two irreversible GABA-T inhibitors, gabaculine and vigabatrin. Human GABA-T in homodimeric form showed 70-fold higher sensitivity to vigabatrin than bacterial GABA-T in multimeric form, indicating the importance of using human GABA-T. In summary, our newly developed protocol can be an important first step in developing more effective human GABA-T modulators.
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http://dx.doi.org/10.1080/14756366.2021.1975697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439235PMC
December 2021

Mortality risk attributable to wildfire-related PM pollution: a global time series study in 749 locations.

Lancet Planet Health 2021 Sep;5(9):e579-e587

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Background: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM and mortality across various regions of the world.

Methods: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM exposure was calculated.

Findings: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM exposure during the study period.

Interpretation: Short-term exposure to wildfire-related PM was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.

Funding: Australian Research Council, Australian National Health & Medical Research Council.
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http://dx.doi.org/10.1016/S2542-5196(21)00200-XDOI Listing
September 2021

The Prevalence of Concomitant Abdominal Aortic Aneurysm and Cancer.

J Clin Med 2021 Aug 27;10(17). Epub 2021 Aug 27.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea.

Cancers and abdominal aortic aneurysms (AAA) cause substantial morbidity and mortality and commonly develop in old age. It has been previously reported that AAA patients have a high prevalence of cancers, which has raised the question of whether this is a simple collision, association or causation. Clinical trials or observational studies with sufficient power to prove this association between them were limited because of the relatively low frequency and slow disease process of both diseases. We aimed to determine whether there is a significant association between AAA and cancers using nationwide data. The patients aged > 50 years and diagnosed with AAA between 2002 and 2015, patients with heart failure (HF) and controls without an AAA or HF matched by age, sex and cardiovascular risk factors were enrolled from the national sample cohort from the National Health Insurance claims database of South Korea. The primary outcome was the prevalence rate of cancers in the participants with and without an AAA. The secondary outcome was cancer-related survival and cancer risk. Overall, 823 AAA patients (mean (standard deviation) age, 71.8 (9.4) years; 552 (67.1%) men) and matching 823 HF patients and 823 controls were identified. The prevalence of cancers was 45.2% (372/823), 41.7% (343/823) and 35.7% (294/823) in the AAA, HF and control groups, respectively; it was significantly higher in the AAA group than in the control group ( < 0.001). The risk of developing cancer was higher in the AAA patients than in the controls (adjusted odds ratio (OR), 1.52 (95% confidence interval [CI], 1.24-1.86), < 0.001) and in the HF patients (adjusted OR, 1.37 (1.24-1.86), = 0.006). The cancer-related death rate was 2.64 times higher (95% CI, 2.22-3.13; < 0.001) for the AAA patients and 1.63 times higher (95% CI, 1.37-1.92; < 0.001) for the HF patients than for the controls. The most common causes of death in the AAA patients were cancer and cardiovascular disease. There was a significantly increased risk of cancer in the AAA than in the HF and control groups. Therefore, appropriate screening algorithms might be necessary for earlier detection of both diseases to improve long-term survival.
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http://dx.doi.org/10.3390/jcm10173847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432173PMC
August 2021

Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension.

Mult Scler 2021 Sep 9:13524585211038291. Epub 2021 Sep 9.

Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.

During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks-5.2 years). At 192 weeks (~4 years), 96% of these patients were free from adjudicated relapses (Kaplan-Meier analysis; 95% confidence interval, 75.7-99.4). During PREVENT, 95% (20/21) of patients receiving eculizumab monotherapy had no disability worsening. Eculizumab monotherapy provides effective long-term relapse prevention, relieving the chronic immunosuppression burden in patients with AQP4-IgG + NMOSD. ClinicalTrials.gov; PREVENT: NCT01892345; open-label extension: NCT02003144.
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http://dx.doi.org/10.1177/13524585211038291DOI Listing
September 2021

Changes in the Prosthesis Types Used for Aortic Valve Replacement after the Introduction of Sutureless and Rapid Deployment Valves in Korea: A Nationwide Population-Based Cohort Study.

J Chest Surg 2021 Sep 8. Epub 2021 Sep 8.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Korea.

Background: Sutureless and rapid deployment valves for aortic valve replacement (AVR) were introduced in Korea in December 2016. This study evaluated changing trends in the prosthetic valves used for AVR in Korea after the introduction of sutureless and rapid deployment valves.

Methods: From December 2016 to December 2018, 4,899 patients underwent AVR in Korea. After applying the exclusion criteria, 4,872 patients were analyzed to determine changes in the type of prosthetic valve used for AVR. The study period was divided into 5 groups corresponding to 5-month intervals.

Results: The total number of AVR cases was 194.88±28.78 per month during the study period. Mechanical valves were used in approximately 27% to 33% of cases, and the proportion of mechanical valve use showed a tendency to decrease, with marginal significance overall (p=0.078) and significant decreases in patients less than 60 years of age and in men (p=0.013 and p=0.023, respectively). The use of sutureless valves increased from 13.4% to 25.8% of cases (p<0.001), especially in elderly patients (>70 years) and those requiring concomitant surgery. In a comparison between sutureless and rapid deployment valves, the use of Perceval S valves (a type of sutureless valve), gradually increased (p<0.001).

Conclusion: After the introduction of sutureless and rapid deployment valves in Korea, the rate of use of these new valves remarkably increased, especially in elderly patients and those requiring concomitant surgery. Further studies should investigate the clinical outcomes of these new prostheses.
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http://dx.doi.org/10.5090/jcs.21.033DOI Listing
September 2021

Association of aortic valvular complex calcification burden with procedural and long-term clinical outcomes after transcatheter aortic valve replacement.

Eur Heart J Cardiovasc Imaging 2021 Sep 7. Epub 2021 Sep 7.

Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Aims: This study aimed to assess the impact of valvular/subvalvular calcium burden on procedural and long-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS).

Methods And Results: In this prospective observational cohort study, we included patients with AS undergoing TAVR between March 2010 and December 2019. Calcium burden at baseline was quantified using multidetector computed tomography and the patients were classified into tertile groups according to the amount of calcium. Procedural outcomes [paravalvular leakage (PVL) or permanent pacemaker insertion (PPI)] and 12-month clinical outcomes (composite of death, stroke, or rehospitalization, and all-cause mortality) were assessed. A total of 676 patients (age, 79.8 ± 5.4 years) were analysed. The 30-day rates of moderate or severe PVL (P-for-trend = 0.03) and PPI (P-for-trend = 0.002) proportionally increased with the tertile levels of calcium volume. The 12-month rate of primary composite outcomes was 34.2% in low-tertile, 23.9% in middle-tertile, and 25.8% in high-tertile groups (log-rank P = 0.02). After multivariable adjustment, the risk for primary composite outcomes at 12 months was not significantly different between the tertile groups of calcium volume [reference = low-tertile; middle-tertile, hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.54-1.22; P = 0.31; high-tertile, HR 0.93; 95% CI 0.56-1.57; P = 0.80]. A similar pattern was observed for all-cause mortality.

Conclusion: The rates of PVL and PPI proportionally increased according to the levels of valvular/subvalvular calcium volume, while the adjusted risks for composite outcomes and mortality at 12 months were not significantly different.
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http://dx.doi.org/10.1093/ehjci/jeab180DOI Listing
September 2021

New biodegradable drug delivery system for patients with dry eye.

Korean J Ophthalmol 2021 Sep 6. Epub 2021 Sep 6.

Department of Ophthalmology, Chosun University College of Medicine, Gwangju, Korea.

Purpose: This study aimed to develop a new type of drug delivery system (DDS) for treatment of dry eye.

Methods: A new lens-type biodegradable DDS was manufactured using GelMA, antibiotics, and conjunctival epithelial cells as bio-inks in a Bio X 3D BIOPRINTER (Cell link corporation, Phoenix, USA). GelMA was used as a base, and the conditions were analyzed to maintain the overall shape by using a mixture of 0.1%, 0.15%, and 0.3% hyaluronic acid. In addition, an experiment was conducted to measure the appropriate concentration by evaluating its cytotoxicity according to the concentration of antibiotics mixed therein to prevent infection. The degree of degradation according to the storage temperature and post-processing of the new lens-type biodegradable DDS was measured.

Results: Optimal conditions were maintained when using a nozzle pressure of 80 kPa and speed of 4 mm/s, nozzle pressure of 50 kPa and speed of 3 mm/s, nozzle pressure of 60 kPa and speed of 8 mm/s for 0.1%, 0.15%, and 0.3% hyaluronic acid concentrations, respectively. Degradation did not occur at 4℃ and all the lenses were degraded at 37℃ within 24 hours. In addition, the degradation rate was delayed according to the UV crosslink treatment time. Tobramycin 1% was used as an antibiotic during manufacture.

Conclusions: A new lens-type biodegradable DDS that can control the degree of degradation was designed using a 3D bioprinter. This DDS will contribute to ease of treatment, protection of the cornea, and regeneration of the epithelium in patients with dry eye.
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http://dx.doi.org/10.3341/kjo.2021.0126DOI Listing
September 2021

Validity evaluation of indirect adjustment method for multiple unmeasured confounders: A simulation and empirical study.

Environ Res 2021 Sep 3;204(Pt A):111992. Epub 2021 Sep 3.

Interdisciplinary Program in Precision Public Health, Korea University, Seoul, Republic of Korea; School of Health Policy and Management, College of Health Science, Korea University, Seoul, Republic of Korea. Electronic address:

Background: An indirect adjustment method was developed to control for unmeasured confounders in a large administrative cohort study. A previous study that proposed the indirect adjustment method assessed the validity of the method by simulations but did not consider the direction of bias and scenarios with multiple missing confounders. In this study, we evaluated the direction and the magnitude of bias of the indirect adjustment method with multiple correlated unmeasured confounders using simulation and empirical datasets.

Methods: A simulation study was conducted to compare the bias of the indirect adjustment by varying the number of confounders, magnitude of correlation between confounders, and the number of adjustment variables. An empirical study was conducted by applying the indirect adjustment method to the association between PM and mortality using the Korea National Health and Nutrition Examination Survey linked Cause of Death data for 2007-2016.

Results: The simulations of the present study demonstrated that 1) when a confounder is positively associated with both exposure and outcome, indirect adjustment might bias the effect size downward; 2) the magnitude of bias might depend on the correlation between unmeasured confounders; and 3) indirect adjustment for multiple missing confounders at once could result in a higher bias than that for some of the missing confounders. Empirical analyses also showed consistent results, but the bias of indirectly adjusted effect estimates was sometimes larger than that of unadjusted effect estimates.

Conclusions: The indirect adjustment method is a promising technique to reduce the bias from unmeasured confounding; however, it should be implemented carefully, particularly when there are multiple correlated unmeasured confounders of the same direction.
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http://dx.doi.org/10.1016/j.envres.2021.111992DOI Listing
September 2021

A Novel Method for Estimating Patient-Specific Primary dose in Cone-Beam Computed Tomography.

Radiat Prot Dosimetry 2021 Sep 6. Epub 2021 Sep 6.

Center for Advanced Medical Engineering Research, Pusan National University, Busan 46241, Republic of Korea.

For the purpose of real-time scan-protocol optimisation and patient-specific dose management in cone-beam computed tomography, we introduce a numerical algorithm that estimates the primary dose distributions in reconstructed images. The proposed algorithm is based on the ray-tracing technique and utilises reconstructed voxel data and scanning protocol. The algorithm is validated with the Monte Carlo (MC) and conventional model-based dose reconstruction methods for the simple cylindrical water and anthropomorphic head phantoms. The algorithm shows good agreement with both methods in terms of the zeroth-order x-ray interactions, which exclude the higher-order x-ray interactions at sites distant from the first interactions, and it consumes a significantly lower computational cost compared with the MC method. The differences between the proposed algorithm and the model-based dose reconstruction method as well as the improvement strategies of the algorithm are discussed in detail.
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http://dx.doi.org/10.1093/rpd/ncab128DOI Listing
September 2021

The Effect of Particulate Matter Reduction by Indoor Air Filter Use on Respiratory Symptoms and Lung Function: A Systematic Review and Meta-analysis.

Allergy Asthma Immunol Res 2021 Sep;13(5):719-732

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Exposure to particulate matter (PM) is a key public health issue, but effective intervention has not yet been established. A systematic literature review and meta-analysis has been conducted to assess the relationship between the use of air filters, one of the most commonly studied interventions, and respiratory outcomes in patients with chronic respiratory diseases.

Methods: We systematically reviewed intervention studies on PM using PubMed, EMBASE, and Cochrane databases up to September 2019. Studies that included data on PM concentration changes and respiratory symptoms or lung function in patients with respiratory diseases were eligible for inclusion. Effect estimates were quantified separately using the random-effects model.

Results: Six studies were included in the quantitative analysis. Air filter use reduced indoor PM2.5 by 11.45 µg/m (95% confidence interval [CI], 6.88, 16.01 µg/m). Air filter use was not associated with improvements in respiratory symptoms in 5 of the 6 studies or significant changes in the predicted forced expiratory volume in one second (FEV1) (mean change, -1.77%; 95% CI, -8.25%, 4.71%). Air filter use was associated with improved peak expiratory flow rate by 5.86 (95% CI, 3.5, 8.19 of standardized difference).

Conclusions: The findings of this systematic review suggest that air filters may reduce indoor PM and increase peak expiratory rate in asthmatic patients. However, most studies showed no significant effects of air filters on respiratory symptoms or FEV1. Further studies in regions with high-density PM may provide additional information on this issue.

Trial Registration: PROSPERO Identifier: CRD42020156258.
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http://dx.doi.org/10.4168/aair.2021.13.5.719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419638PMC
September 2021

Deletion of BCATm increases insulin-stimulated glucose oxidation in the heart.

Metabolism 2021 Sep 1;124:154871. Epub 2021 Sep 1.

Cardiovascular Research Centre, University of Alberta, Edmonton, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, Canada. Electronic address:

Backgrounds: Branched chain amino acid (BCAA) oxidation is impaired in cardiac insulin resistance, leading to the accumulation of BCAAs and the first products of BCAA oxidation, the branched chain ketoacids. However, it is not clear whether it is the BCAAs, BCKAs or both that are mediating cardiac insulin resistance. To determine this, we produced mice with a cardiac-specific deletion of BCAA aminotransferase (BCATm), the first enzyme in the BCAA oxidation pathway that is responsible for converting BCAAs to BCKAs.

Methods: Eight-week-old BCATm cardiac specific knockout (BCATm) male mice and their α-MHC (myosin heavy chain) - Cre expressing wild type littermates (WT-Cre) received tamoxifen (50 mg/kg i.p. 6 times over 8 days). At 16-weeks of age, cardiac energy metabolism was assessed in isolated working hearts.

Results: BCATm mice have decreased cardiac BCAA oxidation rates, increased cardiac BCAAs and a reduction in cardiac BCKAs. Hearts from BCATm mice showed an increase in insulin stimulation of glucose oxidation and an increase in p-AKT. To determine the impact of reversing these events, we perfused isolated working mice hearts with high levels of BCKAs, which completely abolished insulin-stimulated glucose oxidation rates, an effect associated with decreased p-AKT and inactivation of pyruvate dehydrogenase (PDH), the rate-limiting enzyme in glucose oxidation.

Conclusion: This implicates the BCKAs, and not BCAAs, as the actual mediators of cardiac insulin resistance and suggests that lowering cardiac BCKAs can be used as a therapeutic strategy to improve insulin sensitivity in the heart.
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http://dx.doi.org/10.1016/j.metabol.2021.154871DOI Listing
September 2021

Overexpression of IbLfp in sweetpotato enhances the low-temperature storage ability of tuberous roots.

Plant Physiol Biochem 2021 Aug 27;167:577-585. Epub 2021 Aug 27.

Plant Systems Engineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Daejeon, 34141, Republic of Korea; Department of Environmental Biotechnology, KRIBB School of Biotechnology, University of Science and Technology (UST), 217 Gajeong-ro, Daejeon, 34113, Republic of Korea. Electronic address:

Sweetpotato (Ipomoea batatas [L.] Lam) is a prospective food crop that ensures food and nutrition security under the dynamic changes in global climate. Peroxidase (POD) is a multifunctional enzyme involved in diverse plant physiological processes, including stress tolerance and cell wall lignification. Although various POD genes were cloned and functionally characterized in sweetpotato, the role of POD in lignification and low-temperature storage ability of sweetpotato tuberous roots is yet to be investigated. In this study, we isolated the cold-induced lignin forming peroxidase (IbLfp) gene of sweetpotato, and analyzed its physiological functions. IbLfp showed more predominant expression in fibrous roots than in other tissues. Moreover, IbLfp expression was up-regulated in leaves and roots under cold stress, and was altered by other abiotic stresses. Tuberous roots of transgenic sweetpotato lines overexpressing IbLfp (LP lines) showed improved tolerance to low temperature, with lower malondialdehyde and hydrogen peroxide contents than non-transgenic sweetpotato plants under cold stress. The enhanced cold tolerance of LP lines could be attributed to the increased basal activity of POD, which is involved in reactive oxygen species (ROS) scavenging. Moreover, greater accumulation of lignin could also contribute to the enhanced cold tolerance of LP lines, as lignin acts as a protective barrier against invading pathogens, which is a secondary symptom of chilling injury in sweetpotato. Overall, the results of this study enhance our understanding of the function of POD in low-temperature storage of sweetpotato tuberous roots.
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http://dx.doi.org/10.1016/j.plaphy.2021.08.041DOI Listing
August 2021

[Clinical and Technical Guideline for Endoscopic Ultrasound-guided Tissue Acquisition of Pancreatic Solid Tumor: Korean Society of Gastrointestinal Endoscopy].

Korean J Gastroenterol 2021 08;78(2):73-93

Department of Internal Medicine, Cha University Bundang Medical Center, Cha University, Seongnam, Korea.

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy appointed a Task Force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence- based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice.
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http://dx.doi.org/10.4166/kjg.2021.057DOI Listing
August 2021

Long-term efficacy of ultrasound-guided laser ablation for papillary thyroid microcarcinoma: Results of a 10-year retrospective study.

Thyroid 2021 Aug 27. Epub 2021 Aug 27.

Raphael hospital, Internal Medicine, 303, Jungang-daero, Jung-gu, Daegu, Republic of Korea, Daegu, Korea (the Republic of), 700-803;

Background: The aim of this study was to evaluate the 10-year efficacy and safety of laser ablation (LA) for the treatment of solitary papillary thyroid microcarcinoma (PTMC).

Methods: LA was performed on patients with low-risk PTMC (diagnosed using fine-needle aspiration cytology) who refused or were ineligible for surgery between 2008 and 2011. Ultrasonography was performed to evaluate the ablated volumes and potential recurrences on the day after the procedure, as well as at 1 week, 1, 3, and 6 months, and every 6 months thereafter for 10 years. Computed tomography (CT) with contrast enhancement and positron emission tomography/CT was performed to evaluate local recurrences and distant metastases.

Results: A total of 90 PTMCs in 90 patients were treated in a single session of LA, and the procedure was well tolerated by the patients. The mean follow-up duration was 112 months. By 3-10 months after the LA, all the ablation areas had disappeared or presented as scars. The disappearance rate was 100% after 12 months. Thyroid hormone and autoantibody levels did not change significantly after the treatment. Three patients experienced transient voice changes, but each recovered within 1 month. Additional PTMC foci were subsequently detected in previously untreated areas in five patients (5.5%) 17-56 months after the treatment. A metastatic lymph node was detected in one patient (1.1%) within 2 months of the treatment; however, it was determined to be an undetected cancer metastasis, rather than a recurrence. All the patients with recurrence underwent surgery, and there were no instances of recurrence after > 5 years.

Conclusions: LA is effective and safe for the treatment of low-risk PTMCs. A thorough examination of multifocality and lymph node metastasis status is required before considering LA treatment.
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http://dx.doi.org/10.1089/thy.2021.0151DOI Listing
August 2021

Myelin-oligodendrocyte glycoprotein antibody-associated disease.

Lancet Neurol 2021 09;20(9):762-772

Brain Institute of Rio Grande do Sul and School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.
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http://dx.doi.org/10.1016/S1474-4422(21)00218-0DOI Listing
September 2021

Overexpression of 4-hydroxyphenylpyruvate dioxygenase (IbHPPD) increases abiotic stress tolerance in transgenic sweetpotato plants.

Plant Physiol Biochem 2021 Aug 14;167:420-429. Epub 2021 Aug 14.

Plant Systems Engineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Daejeon, 34141, Republic of Korea. Electronic address:

Tocopherols are lipid-soluble compounds regarded as vitamin E compounds and they function as antioxidants in scavenging lipid peroxyl radicals and quenching reactive oxygen species (ROS). In our previous studies, we isolated five tocopherol biosynthesis genes from sweetpotato (Ipomoea batatas [L.] Lam) plants including 4-hydroxyphenylpyruvate dioxygenase (IbHPPD). HPPD is the first regulatory enzyme in vitamin E biosynthesis and serves to catalyze in the first steps α-tocopherol and plastoquinone biosynthesis by converting 4-hydroxyphenylpyruvate (HPP) to homogentisic acid (HGA). In this study, we generated transgenic sweetpotato plants overexpressing IbHPPD under the control of cauliflower mosaic virus (CaMV) 35S promoter (referred to as HP plants) via Agrobacterium-mediated transformation to understand the function of IbHPPD in sweetpotato. Three transgenic lines (HP3, HP14 and HP15) with high transcript levels of IbHPPD were selected for further characterization. Compared with non-transgenic (NT) plants, HP plants exhibited enhanced tolerance to multiple environmental stresses, including salt, drought, and oxidative stresses. In addition, HP plants showed increased tolerance to the herbicide sulcotrione, which is involved in the inhibition of the HPPD. Interestingly, after stress treatments, HP plants also showed higher abscisic acid (ABA) contents than NT plants. Under dehydrated condition, HP plants displayed an elevated α-tocopherol content to 19-27% in leaves compared with NT plants. These results indicate that increased abiotic stress tolerance in HP plants is related to inducing enhancement of α-tocopherol and ABA contents.
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http://dx.doi.org/10.1016/j.plaphy.2021.08.025DOI Listing
August 2021

The relationship between smoking cigarettes and metabolic syndrome: A cross-sectional study with non-single residents of Seoul under 40 years old.

PLoS One 2021 19;16(8):e0256257. Epub 2021 Aug 19.

Department of Family Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.

Introduction: Young adults receive health screenings at lower rates than other age groups, and it may be difficult to detect diseases in the early stages for this group. We examined differences in health status relative to smoking in a young age group using the results of health screenings conducted in engaged and newly married couples in a cross-sectional database.

Methods: The participants in this study were 808 young adults who visited a municipal hospital health screening center from July 2017 to March 2019. They completed a self-administered questionnaire, and physical measurements and a blood test were taken. They were classified into non-cigarette smokers, past cigarette smokers, and current cigarette smokers according to smoking behavior. In this study, we compared metabolic syndrome, the main components of which include obesity, high blood pressure, high blood triglycerides, low levels of HDL cholesterol and insulin resistance, with smoking behavior.

Results: The mean age of the participants was 30.9±3.3 years (males 32.0±3.2, females 29.8±3.1), and 13.9% were current cigarette smokers (males 22.8%, females 5.1%). The proportion of men in their 30s was 76.6% for male group and 50.0% for female group, indicating that the male group had a relatively higher proportion of older and current smokers. Significant differences were found in age, sex, blood pressure, metabolic abnormalities, and drinking status according to smoking status. Cigarette smokers had a 2.4-fold greater risk of metabolic syndrome (95% confidence interval [CI], 1.43-3.96) than non-cigarette smokers; in particular, they had a 2.6-fold (95% CI, 1.44-4.55) greater risk of hypertriglyceridemia and a three-fold (95% CI, 1.45-6.35) greater risk of low HDL cholesterol.

Conclusions: In comparison with non-single, young and generally healthy city dwellers, the risk of metabolic syndrome was significantly higher in smokers than in non-smokers, and in particular, it was confirmed that the risk of hypertriglyceridemia and low HDL cholesterolemia was higher. Smoking cessation is necessary, even for the young, because smoking may cause changes in blood lipids even if the smoking duration is short.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256257PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376018PMC
August 2021

Inhibition of STAT3 enhances sensitivity to tamoxifen in tamoxifen-resistant breast cancer cells.

BMC Cancer 2021 Aug 18;21(1):931. Epub 2021 Aug 18.

Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: The mechanisms of endocrine resistance are complex, and deregulation of several oncogenic signalling pathways has been proposed. We aimed to investigate the role of the EGFR and Src-mediated STAT3 signalling pathway in tamoxifen-resistant breast cancer cells.

Methods: The ER-positive luminal breast cancer cell lines, MCF-7 and T47D, were used. We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. Cell viability was determined using an MTT assay, and protein expression levels were determined using western blot. Cell cycle and annexin V staining were analysed using flow cytometry.

Results: TamR cells showed decreased expression of estrogen receptor and increased expression of EGFR. TamR cells showed an acceleration of the G1 to S phase transition. The protein expression levels of phosphorylated Src, EGFR (Y845), and STAT3 was increased in TamR cells, while phosphorylated Akt was decreased. The expression of p-STAT3 was enhanced according to exposure time of tamoxifen in T47D cells, suggesting that activation of STAT3 can cause tamoxifen resistance in ER-positive breast cancer cells. Both dasatinib (Src inhibitor) and stattic (STAT3 inhibitor) inhibited cell proliferation and induced apoptosis in TamR cells. However, stattic showed a much stronger effect than dasatinib. Knockdown of STAT3 expression by siRNA had no effect on sensitivity to tamoxifen in MCF-7 cells, while that enhanced sensitivity to tamoxifen in TamR cells. There was not a significant synergistic effect of dasatinib and stattic on cell survival. TamR cells have low nuclear p21(Cip1) expression compared to MCF-7 cells and inhibition of STAT3 increased the expression of nuclear p21(Cip1) in TamR cells.

Conclusions: The EGFR and Src-mediated STAT3 signalling pathway is activated in TamR cells, and inhibition of STAT3 may be a potential target in tamoxifen-resistant breast cancer. An increase in nuclear p21(Cip1) may be a key step in STAT3 inhibitor-induced cell death in TamR cells.
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http://dx.doi.org/10.1186/s12885-021-08641-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371881PMC
August 2021

Effects of urbanization on vulnerability to heat-related mortality in urban and rural areas in South Korea: a nationwide district-level time-series study.

Int J Epidemiol 2021 Aug 12. Epub 2021 Aug 12.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, South Korea.

Background: Although urbanization is often an important topic in climate change studies, the complex effect of urbanization on heat vulnerability in urban and rural areas has rarely been studied. We investigated the disparate effects of urbanization on heat vulnerability in urban and rural areas, using nationwide data.

Methods: We collected daily weather data for all 229 administrative districts in South Korea (2011-17). Population density was applied as an urbanization indicator. We calculated the heat-mortality risk using a distributed lag nonlinear model and analysed the relationship with population density. We also examined district characteristics that can be related to the spatial heterogeneity in heat-mortality risk.

Results: We found a U-shaped association between population density and heat-mortality risk, with the highest risk for rural populations; in urban areas, risk increases with increasing population density. Higher heat-mortality risk was associated with a lower number of hospital beds per person and higher percentage of people requiring recuperation. The association between hospital beds and heat-mortality risk was prominent in high-density urban areas, whereas the association between the percentage of people requiring recuperation and heat-mortality risk was pronounced in rural areas.

Conclusions: Our findings indicate that the association between population density and heat-mortality risk is different in urban and rural areas, and that district characteristics related to heat-mortality risk also differ by urbanicity. These results can contribute to understanding the complex role of urbanization on heat vulnerability and can provide evidence to policy makers for prioritizing resources.
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http://dx.doi.org/10.1093/ije/dyab148DOI Listing
August 2021

Factors Influencing Patient Satisfaction with Upper Blepharoplasty in Elderly Patients.

Plast Reconstr Surg Glob Open 2021 Aug 6;9(8):e3727. Epub 2021 Aug 6.

Department of Plastic and Reconstructive Surgery, College of Medicine, Kosin University, Seo-gu, Busan, South Korea.

Upper blepharoplasty in elderly patients has characteristics that differ from those of younger patients. Blepharoptosis in elderly patients causes not only aesthetic problems but also functional problems such as entropion, visual disturbance, and sore eyes. We hypothesized that factors influencing patient satisfaction with upper blepharoplasty in elderly patients include aesthetic outcomes, functional outcomes, and personal factors.

Methods: This study included 57 patients aged >65 years who underwent upper blepharoplasty between April 2018 and March 2019. All surgeries were performed through the "Upper Blepharoplasty Service Project" of the public health center in Geoje City. To evaluate the individual characteristics of the patients, a preoperative questionnaire (including sociodemographic characteristics, main symptoms of discomfort in the upper eyelid, and degree of expectation of surgical results) was administered to the patients. After 6 months, a satisfaction survey was conducted accordingly.

Results: The main symptoms of discomfort were sagging of the skin of the upper eyelid. The mean score for patient satisfaction was 3.84 ± 0.40, and satisfaction with the results of surgery relative to the cost was 4.53 ± 0.63, which was the highest score. Significant verification of the regression coefficients showed that functional improvement and cognitive degree of postsurgery precautions had a significant effect on patient satisfaction, whereas aesthetic outcomes and expectations of surgical results were not correlated with patient satisfaction.

Conclusion: The findings indicated that elderly patients tended to be satisfied with functional improvement that resolved their symptoms of discomfort and personal factors such as cost and cognitive degree of precautions after upper blepharoplasty.
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http://dx.doi.org/10.1097/GOX.0000000000003727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345909PMC
August 2021

Reproducible imaging-based prediction of molecular subtype and risk stratification of gliomas across different experience levels using a structured reporting system.

Eur Radiol 2021 Oct 10;31(10):7374-7385. Epub 2021 Aug 10.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 43 Olympic-ro 88, Songpa-Gu, Seoul, 05505, Korea.

Objectives: To determine reproducible MRI parameters predictive of molecular subtype and risk stratification in glioma and develop a structured reporting system.

Methods: All study patients were initially diagnosed with glioma, 141 from the Cancer Genome Atlas and 131 from our tertiary institution, as training and validation sets, respectively. Images were analyzed by three neuroradiologists with 1-7 years of experience. MRI features including contrast enhancement pattern, necrosis, margin, edema, T2/FLAIR mismatch, internal cyst, and cerebral blood volume higher than normal cortex were reported using a structured reporting system. The pathology was stratified into five risk types: (1) oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, 1p19q co-deleted; (2) diffuse astrocytoma, IDH-mutant, grade II-III; (3) glioblastoma, IDH-mutant, grade IV; (4) diffuse astrocytoma, IDH-wild, grade II-III; and (5) glioblastoma, IDH-wild, grade IV. Significant predictors were selected using multivariate logistic regression, and diagnostic performance was tested using a validation set.

Results: Reproducible imaging parameters exhibiting > 50% agreement across readers included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. In the validation set, prediction of risk type 5 exhibited the highest diagnostic performance with AUCs of 0.92 (reader 1) and 0.93 (reader 2) with predominant enhancement, followed by risk type 2 with AUCs of 0.95 and 0.95 with T2/FLAIR mismatch sign and no necrosis, and risk type 1 with AUCs of 0.84 and 0.83 with internal cyst or necrosis. Risk types 3 and 4 were difficult to visually predict.

Conclusions: Imaging parameters with high reproducibility enabling prediction of IDH-wild-type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant diffuse astrocytoma were identified.

Key Points: • Reproducible MRI parameters for determining molecular subtypes of glioma included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. • IDH-wild type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant low-grade astrocytoma were identified using MRI parameters with high inter-reader reproducibility. • Identification of IDH-wild type low-grade glioma and IDH-mutant glioblastoma was difficult by visual analysis.
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http://dx.doi.org/10.1007/s00330-021-08015-4DOI Listing
October 2021

Tumor habitat analysis by magnetic resonance imaging distinguishes tumor progression from radiation necrosis in brain metastases after stereotactic radiosurgery.

Eur Radiol 2021 Aug 6. Epub 2021 Aug 6.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.

Objectives: The identification of viable tumor after stereotactic radiosurgery (SRS) is important for future targeted therapy. This study aimed to determine whether tumor habitat on structural and physiologic MRI can distinguish viable tumor from radiation necrosis of brain metastases after SRS.

Method: Multiparametric contrast-enhanced T1- and T2-weighted imaging, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) were obtained from 52 patients with 69 metastases, showing enlarging enhancing masses after SRS. Voxel-wise clustering identified three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable). Habitat-based predictors for viable tumor or radiation necrosis were identified by logistic regression. Performance was validated using the area under the curve (AUC) of the receiver operating characteristics curve in an independent dataset with 24 patients.

Results: None of the physiologic MRI habitats was indicative of viable tumor. Viable tumor was predicted by a high-volume fraction of solid low-enhancing habitat (low T2-weighted and low CE-T1-weighted values; odds ratio [OR] 1.74, p <.001) and a low-volume fraction of nonviable tissue habitat (high T2-weighted and low CE-T1-weighted values; OR 0.55, p <.001). Combined structural MRI habitats yielded good discriminatory ability in both development (AUC 0.85, 95% confidence interval [CI]: 0.77-0.94) and validation sets (AUC 0.86, 95% CI:0.70-0.99), outperforming single ADC (AUC 0.64) and CBV (AUC 0.58) values. The site of progression matched with the solid low-enhancing habitat (72%, 8/11).

Conclusion: Solid low-enhancing and nonviable tissue habitats on structural MRI can help to localize viable tumor in patients with brain metastases after SRS.

Key Points: • Structural MRI habitats helped to differentiate viable tumor from radiation necrosis. • Solid low-enhancing habitat was most helpful to find viable tumor. • Providing spatial information, the site of progression matched with solid low-enhancing habitat.
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http://dx.doi.org/10.1007/s00330-021-08204-1DOI Listing
August 2021

Amino-Substituted 3-Aryl- and 3-Heteroarylquinolines as Potential Antileishmanial Agents.

J Med Chem 2021 Aug 6;64(16):12152-12162. Epub 2021 Aug 6.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0509 United States.

Leishmaniasis, a disease caused by protozoa of the species, afflicts roughly 12 million individuals worldwide. Most existing drugs for leishmaniasis are toxic, expensive, difficult to administer, and subject to drug resistance. We report a new class of antileishmanial leads, the 3-arylquinolines, that potently block proliferation of the intramacrophage amastigote form of parasites with good selectivity relative to the host macrophages. Early lead was rapidly acting and possessed good potency against (EC = 120 nM), 30-fold selectivity for the parasite relative to the macrophage (EC = 3.7 μM), and also blocked proliferation of parasites resistant to antimonial drugs. Finally, another early lead, , which exhibited reasonable in vivo tolerability, impaired disease progression during the dosing period in a murine model of cutaneous leishmaniasis. These results suggest that the arylquinolines provide a fruitful departure point for the development of new antileishmanial drugs.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404201PMC
August 2021

Reduced-port laparoscopic distal gastrectomy in obese gastric cancer patients.

PLoS One 2021 5;16(8):e0255855. Epub 2021 Aug 5.

Division of Gastroenterologic Surgery, Department of General Surgery, Chonnam National University Hospital, Gwang-ju, South Korea.

Background: Reduced-port laparoscopic gastrectomy is currently widely performed for patients with gastric cancer. However, its safety in obese patients has not yet been verified. This is the first study on reduced-port laparoscopic distal gastrectomy (RpLDG) in obese patients with gastric cancer. This study aimed to evaluate the short-term surgical outcomes and investigate the feasibility and safety of RpLDG in obese patients with gastric carcinoma.

Material And Methods: A total of 271 gastric cancer patients who underwent RpLDG at our institution were divided into two groups: non-obese [body mass index (BMI) <30 kg/m2, n = 251; NOG] and obese (BMI ≥30 kg/m2, n = 20; OG). The mean age of the enrolled patients was 64.8 ± 11.4 years, with 72.0% being men and 28.0% women. Operative details and short-term surgical outcomes, including hospital course and postoperative complications, were compared by retrospectively reviewing the medical records.

Results: No significant difference in operation time was found between the NOG and OG (205.9 ± 40.0 vs. 211.3 ± 37.3 minutes, P = 0.563). Other operative outcomes in the OG, including estimated blood loss (54.1 ± 86.1 vs. 54.0 ± 39.0 mL, P = 0.995) and retrieved lymph nodes (36.2 ± 16.4 vs. 35.5 ± 18.2, P = 0.875), were not inferior to those in the NOG. There were also no statistical differences in short-term surgical outcomes, including the incidence of surgical complications (13.9% vs. 10.0%, P = 1).

Conclusion: RpLDG can be performed safely in obese gastric cancer patients by an experienced surgeon. It should be considered a feasible alternative to conventional port distal gastrectomy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255855PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341504PMC
August 2021

Treatment and Outcomes of Metastatic Pancreatic Cancer in Elderly Patients.

Chemotherapy 2021 Aug 4:1-6. Epub 2021 Aug 4.

Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Hwaseong-si, Republic of Korea.

Background And Aims: Although pancreatic cancers are common in older age-groups, the prognosis remains poor due to limited studies on treatment approaches and outcomes in a given population. We aimed to examine treatment patterns and their outcomes in older patients with metastatic pancreatic cancer in a real-world context.

Materials And Methods: We conducted a retrospective study including 167 patients with metastatic pancreatic cancer (aged ≥70 years and male/female: 78/89) between January 2010 and July 2015. Patients' retrieved data from medical records were analyzed according to treatment types, followed by a review of clinicopathologic variables and treatment outcomes.

Results: Of the 167 eligible patients for the study, only 21.6% (n = 36) received palliative chemotherapy. The median age of the chemotherapy group was 74.0 years and 78.6 years for the supportive care group. The median survival of the chemotherapy group was 9.2 months (range: 1.0-24.9 months), compared with that of the supportive care group, which was 2.3 months (range: 0.1-31.8 months). Among the patients in the chemotherapy group, 50% (n = 18) received gemcitabine-based double therapy, and 30% patients (n = 9) received second-line chemotherapy.

Conclusions: Our results showed that older patients with metastatic pancreatic cancer were less likely to receive chemotherapy. However, the survival benefit from chemotherapy was comparable to that of younger patients' counterpart. Thus, further study involving identification of older patients who would benefit from cytotoxic chemotherapy is needed.
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http://dx.doi.org/10.1159/000517245DOI Listing
August 2021

Right Ventricular Assist Device With Extracorporeal Membrane Oxygenation for Bridging Right Ventricular Heart Failure to Lung Transplantation: A Single-Center Case Series and Literature Review.

J Cardiothorac Vasc Anesth 2021 Jul 10. Epub 2021 Jul 10.

Department of Pulmonary and Critical Care, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Objective: Right ventricular heart failure (RVHF) is a critical complication in patients with respiratory failure, particularly among those who transitioned to lung transplantation using venovenous (VV) extracorporeal membrane oxygenation (ECMO). In these patients, both cardiac and respiratory functions are supported using venoarterial or venoarterial-venous ECMO. However, these modalities increase the risk of device-related complications, such as thromboembolism, bleeding, and limb ischemia, and they may disturb early rehabilitation. Due to these limitations, a right ventricular assist device with an oxygenator (Oxy-RVAD) using ECMO may be considered for patients with RVHF with VV ECMO.

Design: A retrospective case series and literature review.

Setting: A single tertiary care university hospital.

Participants: The study comprised lung transplantation candidates on ECMO bridging who developed right-sided heart failure.

Interventions: An RVAD with ECMO.

Measurements And Main Results: Of eight patients who underwent the study protocol, seven were bridged successfully to lung transplantation (BTT), and all patients with BTT were discharged, with a 30-day survival rate of 100% (7/7 patients). The 180-day survival rate was 85% (6/7 patients).

Conclusions: The study suggested that Oxy-RVAD using ECMO may be a viable option for bridging patients with RVHF to lung transplantation.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1053/j.jvca.2021.07.010DOI Listing
July 2021

Impact of coexistent preserved ratio impaired spirometry on the survival of patients with lung cancer: Analysis of data from the Korean Association for Lung Cancer Registry.

Thorac Cancer 2021 Sep 1;12(18):2478-2486. Epub 2021 Aug 1.

Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.

Background: Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor.

Methods: We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV ] < 80% predicted and FEV /forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis.

Results: Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel-Cox log-rank test, p < 0.05). In the risk-adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC.

Conclusions: PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre-existing PRISm should be considered a predictive factor of poor prognosis.
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http://dx.doi.org/10.1111/1759-7714.14095DOI Listing
September 2021

Benefit of Sarcopenia Screening in Older Patients Undergoing Surgical Aortic Valve Replacement.

Ann Thorac Surg 2021 Jul 29. Epub 2021 Jul 29.

Department of Cardiology, College of Medicine, University of Ulsan, Seoul, Republic of Korea. Electronic address:

Background: Sarcopenia, known as physical frailty, is highly prevalent in older patients and is related to adverse outcomes post-cardiac surgery. However, whether sarcopenia assessment can reclassify an individual patients' risk, which is estimated by Society of Thoracic Surgeons-predicted risk of mortality scores in patients who undergo surgical aortic valve replacement, is unclear.

Methods: This retrospective, single center, cohort study comprised 874 patients aged ≥65 years who underwent surgical aortic valve replacement between 2009 and 2016. Total skeletal muscle area was calculated using height-squared and was measured by preoperative computed tomography at the third lumbar vertebra inferior border using machine learning-based analysis. Sex-specific Z-scores were calculated and patients in the lowest Z-score tertile were considered to have sarcopenia. The primary endpoint was 30-day mortality, and secondary endpoints were in-hospital events, 1-year mortality, and long-term mortality.

Results: Thirty-day mortality, 30-day in-hospital events, and one-year mortality rates were 4.7%, 17.6%, and 8.0%, respectively. As the Z-score decreased, early adverse event odds showed a stepwise increase. Sarcopenia were independently associated with higher 30-day mortality, 30-day in-hospital events, and 1-year mortality. Reclassification analyses showed improvements in the ability to predict early adverse events after adding the Z-scores over and above the Society of Thoracic Surgeons-predicted risk of mortality scores (All, p <0.005).

Conclusions: Sarcopenic patients had significantly higher risks of early adverse events and long-term mortality after undergoing surgical aortic valve replacement than non-sarcopenic patients. Sarcopenia determined by preoperative computed tomography can enhance the prediction of postoperative outcome risk.
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http://dx.doi.org/10.1016/j.athoracsur.2021.06.067DOI Listing
July 2021

Association between Comorbidities and Preserved Ratio Impaired Spirometry: Using the Korean National Health and Nutrition Examination Survey IV-VI.

Respiration 2021 Jul 28:1-9. Epub 2021 Jul 28.

Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.

Background: Preserved ratio impaired spirometry (PRISm) patients have more frequent respiratory symptoms and an increased risk of mortality. However, studies on comorbidities in these patients are lacking.

Objectives: We investigated the association between PRISm and comorbidities using the Korea National Health and Nutrition Examination Survey (KNHANES).

Method: This cross-sectional study included participants aged ≥50 years from the KNHANES (2007-2015). Participants who did not undergo spirometry or performed inadequately were excluded. We classified participants into 3 groups according to spirometry: PRISm (forced expiratory volume in one second [FEV1] /forced vital capacity [FVC] ≥ 0.7 and FEV1 <80%), chronic obstructive pulmonary disease (COPD) (FEV1/ FVC <0.7), and normal. Multivariate logistic regression analyses were used to evaluate the risk of comorbidities in the PRISm group compared to that in the normal group.

Result: The study included 17,515 participants: 12,777 (73.0%), 1,563 (8.9%), and 3,175 (18.1%) in normal, PRISm, and COPD groups, respectively. After adjustment for known risk factors of each disease, hypertension (adjusted odds ratio [95% confidence interval]; 1.31 [1.14-1.50]), diabetes (1.51 [1.29-1.78]), hypercholesterolemia (1.20 [1.04-1.37]), obesity (1.31 [1.15-1.48]), ischemic heart disease (1.58 [1.13-2.22]), chronic renal disease (2.31 [1.09-4.88]), and thyroid disease (1.41 [1.09-1.83]) risks were significantly higher in the PRISm group than in the normal group. The average number of comorbidities was 2.45 in the PRISm group, which was higher than that in the normal (2.1) and COPD (2.03) groups (p < 0.05).

Conclusion: The number of comorbidities was significantly higher in the PRISm group than in others. Hypertension, diabetes, obesity, ischemic heart disease, chronic renal disease, and thyroid disease were associated with PRISm after adjustment for risk factors.
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http://dx.doi.org/10.1159/000517599DOI Listing
July 2021
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