Publications by authors named "Young-Seok Cho"

325 Publications

Usefulness of Tc-SESTAMIBI Scintigraphy in Persistent Hyperparathyroidism after Kidney Transplant.

Nucl Med Mol Imaging 2021 Dec 30;55(6):285-292. Epub 2021 Oct 30.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Purpose: Tc-labeled sestamibi scintigraphy combined with single-photon emission computed tomography (SPECT) has a high positive predictive value for localizing hyperfunctioning parathyroid lesions in primary hyperparathyroidism (pHPT) but relatively low sensitivity and specificity in secondary hyperparathyroidism (sHPT) and tertiary hyperparathyroidism (tHPT). The purpose of this study is to investigate the usefulness of Tc-sestamibi scintigraphy in persistent hyperparathyroidism after kidney transplant (KT).

Methods: Retrospectively evaluated 50 patients who received parathyroidectomy after KT at a single medical center. The parathyroid lesion with the highest sestamibi uptake intensity of a patient was graded from 0 to 3. Uptake intensity was analyzed in correlation with parathyroid hormone (PTH), calcium, ionized calcium, phosphorus, and vitamin D.

Results: Per-patient analysis, 43 patients had hyperplasia, 6 patients had adenomas, and 1 patient had a carcinoma. Only 3 patients with hyperplasia did not demonstrate any sestamibi uptake in the parathyroid scans. Out of the 148 pathologically confirmed parathyroid lesions, SPECT/CT images were able to identify 89 lesions (60%) and planar images of 71 lesions (48%). The average of sestamibi uptake intensity was mild at grade 1.6. Uptake intensity showed a positive correlation with parathyroid hormone (PTH) level but not with phosphorus, calcium, ionized calcium, or vitamin D levels. The largest lesion showed a high positive predictive value, especially in lesions with a diameter over 1.0 cm.

Conclusions: Regardless of relatively low and less discrete uptake in KT patients, it well depicts the largest and the most hyperfunctioning lesion.
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http://dx.doi.org/10.1007/s13139-021-00722-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602544PMC
December 2021

Management of cardiovascular disease using an mHealth tool: a randomized clinical trial.

NPJ Digit Med 2021 Dec 3;4(1):165. Epub 2021 Dec 3.

Division of Cardiology, Department of Internal Medicine, Seoul National University and Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death and morbidity worldwide. This randomized controlled, single-center, open-label trial tested the impact of a mobile health (mHealth) service tool optimized for ASCVD patient care. Patients with clinical ASCVD were enrolled and randomly assigned to the intervention or control group. Participants in the intervention group were provided with a smartphone application named HEART4U, while a dedicated interface integrated into the electronic healthcare record system was provided to the treating physicians. A total of 666 patients with ASCVD were enrolled, with 333 patients in each group. The estimated baseline 10-year risk of cardiovascular disease was 9.5% and 10.8% in the intervention and control groups, respectively, as assessed by the pooled cohort risk equations. The primary study endpoint was the change in the estimated risk at six months. The estimated risk increased by 1.3% and 1.1%, respectively, which did not differ significantly (P = 0.821). None of the secondary study endpoints showed significant differences between the groups. A post-hoc subgroup analysis showed the benefit was greater if a participant in the intervention group accessed the application more frequently. The present study demonstrated no significant benefits associated with the use of the mHealth tool in terms of the predefined study endpoints in stable patients with ASCVD. However, it also suggested that motivating patients to use the mHealth tool more frequently may lead to greater clinical benefit. Better design with a positive user experience needs to be considered for developing future mHealth tools for ASCVD patient care.Trial Registration: ClinicalTrials.gov NCT03392259.
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http://dx.doi.org/10.1038/s41746-021-00535-zDOI Listing
December 2021

Comparison of precutting endoscopic mucosal resection and endoscopic submucosal dissection for large (20-30 mm) flat colorectal lesions.

J Gastroenterol Hepatol 2021 Nov 29. Epub 2021 Nov 29.

Division of Gastroenterology, Department of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea.

Background And Aims: The complete and safe removal of large (≥20 mm) colorectal lesions is an area of concern. Endoscopic submucosal dissection (ESD) effectively removes these lesions compared to endoscopic mucosal resection (EMR). However, ESD requires advanced techniques, longer procedure time, and high cost. Precutting EMR (EMR-P) is a modified EMR method that overcomes the limitations of EMR. This study aimed to compare the efficacy and safety of EMR-P and ESD in large (20-30 mm) flat colorectal lesions.

Methods: This was a retrospective analysis of cases in which 20-30 mm flat colorectal lesions were resected at Seoul St. Mary's Hospital from January 2014 to December 2019. Propensity score matching was performed to control for possible confounders.

Results: Two-hundred ninety-nine patients were included in this study. After matching, 90 patients were assigned to each group. There were no significant difference in complete resection rates (92.2% vs 92.2%, P=1.000), en bloc resection rates (95.6% vs 97.8%, P=0.682), and mean size of lesions (22.9±3.1mm vs 23.0±3.1mm, P=0.867) between EMR-P and ESD. Procedure time was significantly shorter with EMR-P (11.0±6.5 min vs 37.0±19.3 min, P<0.001). The adverse events rate was not significantly different between both groups. No local recurrence occurred in both groups.

Conclusions: EMR-P was not significantly different to ESD in terms of complete resection rate and en bloc resection rate for 20-30 mm flat colorectal lesions without fibrosis. Furthermore, EMR-P has shorter procedure time than ESD. EMR-P could be considered one of standard treatments for large flat colorectal lesions.
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http://dx.doi.org/10.1111/jgh.15744DOI Listing
November 2021

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels.

Sci Rep 2021 Nov 16;11(1):22322. Epub 2021 Nov 16.

Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Serum thyrotropin (TSH) level after thyroid surgery affects the prognosis of differentiated thyroid cancer (DTC). However, the effects of preoperative serum TSH levels on the prognosis of DTC remain contradictory. In this study, to better understand the relationship between preoperative TSH levels and the prognosis of DTC, we performed pattern analysis of prognostic factors of DTC according to preoperative serum TSH levels. We retrospectively reviewed the clinical records of patients who were diagnosed and treated for DTC at the Samsung Medical Center, between 1994 and 2016. We reviewed preoperative serum TSH levels and performed a pattern analysis with prognostic risk factors for DTC. For pattern analysis, TSH was divided into 10 groups of equal fractions (TSH decile). We found a linear association between preoperative TSH levels and extra-thyroidal extension and lymph node metastasis. However, primary tumor size and initial distant metastasis showed a bimodal peak, which was similar to the pattern of overall and disease-specific death. We found that preoperative TSH range which showed the lowest mortality rate was about 0.8 to 1.59 mIU/L, which are slightly lower normal TSH levels. Although there was no linear trend, the primary tumor size, initial distant metastasis, and mortality of DTC were closely related with preoperative TSH decile and they showed a bimodal pattern. The results obtained in this study provide additional information for understanding the association between preoperative TSH levels and DTC prognosis.
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http://dx.doi.org/10.1038/s41598-021-01898-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595371PMC
November 2021

One-shot dual gene editing for drug-resistant pancreatic cancer therapy.

Biomaterials 2021 Dec 12;279:121252. Epub 2021 Nov 12.

Laboratory of Nanopharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, South Korea; Moogene Medi Institute, Korea-Bio Park, Seongnam, South Korea. Electronic address:

It is challenging to diagnose patients with pancreatic ductal adenocarcinoma (PDAC) early on, and their treatment is often complex. Gemcitabine (GEM) is the first-line treatment for PDAC, but its efficacy is limited in most patients due to the GEM resistance from KRAS and P53 gene mutations. We describe the correction of a double gene mutation and therapeutic effect for the GEM resistant PDAC. Bio-available nanoliposomes (NL) possessing Cas9-ribonucleoproteins and adenine-base editors were developed to conduct KRAS and P53 mutation gene editing directly. NLs were conjugated with EGFR antibodies to tumor-specific delivery, and the anti-cancer effect was verified in vitro and in vivo Model. Our GEM-combinatorial therapeutic strategies using double gene editing systems with one-shot may be a potent therapy for PDAC, overcoming chemoresistance.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121252DOI Listing
December 2021

Comparison of cold snare polypectomy and endoscopic mucosal resection for 3-10-mm colorectal polyps in end-stage renal disease patients.

Saudi J Gastroenterol 2021 Nov 9. Epub 2021 Nov 9.

Division of Gastroenterology, Department of Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: : Patients with end-stage renal disease (ESRD) have a higher incidence of clinically relevant complications, such as bleeding and perforation after polyp resection, compared to patients without underlying diseases. Cold snare polypectomy (CSP) is increasingly used for the removal of small polyps and diminutive polyps due to its shorter procedure time and low risk of bleeding and perforation. However, there have been few studies on the effectiveness and safety of CSP in patients with ESRD. The aim of this study was to compare the efficacy and safety of CSP and endoscopic mucosal resection (EMR) in ESRD patients.

Methods: : This study was a retrospective study. We performed propensity score-matched analysis in patients with ESRD who underwent endoscopic resection for 3-10-mm-sized colorectal polyps at Seoul St. Mary's Hospital, from January 2014 to December 2019.

Results: : After 1:1 ratio matching, 406 polyps were included: 203 polyps were resected with CSP and 203 polyps with EMR. There was no difference between the CSP group and EMR group in incomplete resection rate (4.43% vs. 1.97%, P = 0.16). There were no differences between the CSP and EMR group for immediate bleeding (5.42% vs. 7.88%, P = 0.32) and delayed bleeding (0% vs. 0.49%, P = 1.00). No perforation occurred in either group.

Conclusions: : There were no differences between the CSP and EMR group in terms of efficacy and safety. CSP can be one of the standard methods for the removal of 3-10-mm-sized colorectal polyps in patients with ESRD.
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http://dx.doi.org/10.4103/sjg.sjg_371_21DOI Listing
November 2021

KSNM60 in Clinical Nuclear Oncology.

Nucl Med Mol Imaging 2021 Oct 31;55(5):210-224. Epub 2021 Aug 31.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, Republic of Korea.

Since the foundation of the Korean Society of Nuclear Medicine in 1961, clinical nuclear oncology has been a major part of clinical nuclear medicine in Korea. There are several important events for the development of clinical nuclear oncology in Korea. First, a scintillating type gamma camera was adopted in 1969, which enabled to perform modern oncological gamma imaging. Second, Tc-99 m generator was imported to Korea since 1979, which promoted the wide clinical use of gamma camera imaging by using various kinds of Tc-99 m labeled radiopharmaceuticals. Third, a gamma camera with single photon emission tomography (SPECT) capability was first installed in 1980, which has been used for various kinds of tumor SPECT imaging. Fourth, in 1994, clinical positron emission tomography (PET) scanner and cyclotron with a production of F-18 fluorodeoxyglucose were first installed in Korea. Fifth, Korean Board of Nuclear Medicine was established in 1995, which contributed in the education and manpower training of dedicated nuclear medicine physicians in Korea. Finally, an integrated PET/CT scanner was first installed in 2002. Since that, PET/CT imaging has been a major imaging tool in clinical nuclear oncology in Korea. In this review, a brief history of clinical nuclear oncology in Korea is described.
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http://dx.doi.org/10.1007/s13139-021-00711-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517057PMC
October 2021

Efficacy and safety of split-dose bowel preparation with 1 L polyethylene glycol and ascorbate compared with 2 L polyethylene glycol and ascorbate in a Korean population: a phase IV, multicenter, randomized, endoscopist-blinded study.

Gastrointest Endosc 2021 Oct 12. Epub 2021 Oct 12.

Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

Background And Aims: The 1-L polyethylene glycol (PEG)-based bowel preparation agent NER1006 (Plenvu; Norgine, Harefield, UK) has shown high cleansing efficacy and tolerability in clinical trials in Europe and North America. However, no clinical trials have yet been reported in Asia. Therefore, the aim of this study was to evaluate the efficacy and safety of 1L PEG-based bowel preparation with Plenvu compared with 2L PEG plus ascorbate bowel preparation in a Korean population.

Methods: In this multicenter, endoscopist-blinded, randomized study, patients at 9 hospitals in South Korea undergoing colonoscopy received either Plenvu or 2L PEG + ascorbate (2L PEG) with a split dose. The primary endpoint was overall bowel cleansing success (Boston Bowel Preparation Scale [BBPS] score ≥2 for all segments of the colon). Secondary endpoints were high-quality bowel cleansing success (overall, BBPS score = 9; segmental colon, BPPS score = 3), polyp detection rate (PDR), and adenoma detection rate (ADR).

Results: Of 360 included patients, cleansing efficacy was analyzed in 346 (Plenvu, 174; 2L PEG, 172). The Plenvu group showed noninferior bowel cleansing success rates compared with 2L PEG (93.10% vs 91.86%; difference, 1.24%; 1-sided 97.5% lower confidence limit, -4.31%; P < .0001; P = .661). The Plenvu group had higher high-quality bowel cleansing success rates for overall and right-sided colon segments than the 2L PEG group (49.43% vs 37.79% [P = .029] and 60.92% vs 48.84% [P = .024], respectively). The PDR was greater with Plenvu than with 2L PEG (48.85% vs 37.79%, P = .038). However, ADR did not differ between the 2 groups (24.71% vs 20.35%, P = .331). Although treatment-emergent adverse events (TEAEs) were slightly higher in the Plenvu group than in the 2L PEG group (65.71% vs 52.91%, P = .015), most TEAEs were mild (85.55%) and most patients recovered without any management (99.23%).

Conclusions: Plenvu showed noninferior overall bowel cleansing success rates comparable with 2L PEG but greater high-quality bowel cleansing in overall and right-sided colon, which might help improve the PDR in the Asian population. (Clinical trial registration number: KCT0005894.).
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http://dx.doi.org/10.1016/j.gie.2021.09.041DOI Listing
October 2021

Association Among Local Hemodynamic Parameters Derived From CT Angiography and Their Comparable Implications in Development of Acute Coronary Syndrome.

Front Cardiovasc Med 2021 13;8:713835. Epub 2021 Sep 13.

Department of Internal Medicine and Cardiovascular Center, Seoul National University, Seoul, South Korea.

Association among local hemodynamic parameters and their implications in development of acute coronary syndrome (ACS) have not been fully investigated. A total of 216 lesions in ACS patients undergoing coronary CT angiography (CCTA) before 1-24 months from ACS event were analyzed. High-risk plaque on CCTA was defined as a plaque with ≥2 of low-attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign. With the use of computational fluid dynamics analysis, fractional flow reserve (FFR) derived from CCTA (FFR) and local hemodynamic parameters including wall shear stress (WSS), axial plaque stress (APS), pressure gradient (PG) across the lesion, and delta FFR across the lesion (ΔFFR) were obtained. The association among local hemodynamics and their discrimination ability for culprit lesions from non-culprit lesions were compared. A total of 66 culprit lesions for later ACS and 150 non-culprit lesions were identified. WSS, APS, PG, and ΔFFR were strongly correlated with each other (all < 0.001). This association was persistent in all lesion subtypes according to a vessel, lesion location, anatomical severity, high-risk plaque, or FFR ≤ 0.80. In discrimination of culprit lesions causing ACS from non-culprit lesions, WSS, PG, APS, and ΔFFR were independent predictors after adjustment for lesion characteristics, high-risk plaque, and FFR ≤ 0.80; and all local hemodynamic parameters significantly improved the predictive value for culprit lesions of high-risk plaque and FFR ≤ 0.80 (all < 0.05). The risk prediction model for culprit lesions with FFR ≤ 0.80, high-risk plaque, and ΔFFR had a similar or superior discrimination ability to that with FFR ≤ 0.80, high-risk plaque, and WSS, APS, or PG; and the addition of WSS, APS, or PG into ΔFFR did not improve the model performance. Local hemodynamic indices were significantly intercorrelated, and all indices similarly provided additive and independent predictive values for ACS risk over high-risk plaque and impaired FFR.
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http://dx.doi.org/10.3389/fcvm.2021.713835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475759PMC
September 2021

Impact of statin intensity on adverse cardiac and cerebrovascular events in older adult patients with myocardial infarction.

J Geriatr Cardiol 2021 Aug;18(8):609-622

Department of Cardiology, Incheon Sejong Hospital, Incheon, South Korea.

Background: There is insufficient evidence regarding the effect of high-intensity statin therapy in older adults. This study aimed to investigate the effects of high-intensity statin treatment on the clinical outcomes in older adults with myocardial infarction (MI).

Methods: Consecutive patients with MI aged at least 75 years were analyzed retrospectively. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of all-cause death, MI, rehospitalization due to unstable angina, repeat revascularization, and ischemic stroke. The high-intensity group was compared to the low-to-moderate intensity group in the propensity score-matched cohort.

Results: Average age of total 546 patients was 81 years. Among them, 84% of patients underwent percutaneous coronary intervention. The unadjusted seven-year MACCE rate differed by statin intensity (high-intensity statin group: 38%, moderate-intensity statin group: 42%, low-intensity statin group: 56%, and no-statin group: 61%, = 0.004). However, among these groups, many baseline characteristics were significantly different. Among the 74 propensity score-matched pairs, which lacked any significant differences in all baseline characteristics, the high-intensity group had a significantly lower rate of MACCE than the low-to-moderate intensity group (37% 53%, = 0.047). Follow-up low-density lipoprotein cholesterol levels were significantly lower in the high-intensity group than that in the low-to-moderate intensity group (69.4 ± 16.0 mg/dL 77.9 ± 25.9 mg/dL, = 0.026).

Conclusions: In older adult patients with MI, the use of high-intensity statin caused significantly less occurrence of MACCE in comparison to that in low-to-moderate intensity for up to seven years of follow-up.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390935PMC
August 2021

Caspase-cleavable peptide-doxorubicin conjugate in combination with CD47-antagonizing nanocage therapeutics for immune-mediated elimination of colorectal cancer.

Biomaterials 2021 10 28;277:121105. Epub 2021 Aug 28.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Here we report a novel combination of a caspase-cleavable peptide-doxorubicin conjugate (MPD-1) with CD47-antagonizing nanocage therapeutics for the treatment of microsatellite-stable (MSS) colorectal cancer (CRC). MPD-1 (i) upregulated markers of immunogenic cell death (ICD) in tumor, and increased co-stimulatory markers on dendritic cells (DCs), (ii) enhanced CD8 T cell infiltration and antigen presenting cell (APC) activation, and (iii) showed negligible off-target immune-related toxicity compared to free dox. Then, the CD47 antagonist FS nanocage, a SIRPα-expressing ferritin nanocage, was co-administered with MPD-1 that resulted in 95.2% (p < 0.001) tumor growth inhibition in an established CRC model. T cell-mediated elimination of tumors was also confirmed by the tumor-specific activation of T cells detected by IFNγ and tumor-free mice were observed (95%) that bared a memory response when re-challenged. The strategically developed MPD-1 is an ideal adjuvant to immunotherapy and the combination with FS nanocage triggers potent immunity against MSS CRC. In summary, we present an approach to initiate and stimulate immune-mediated eradication of cancer cells using synergistic immunogenic agents targeting the MSS CRC.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121105DOI Listing
October 2021

Convolutional neural network-based object detection model to identify gastrointestinal stromal tumors in endoscopic ultrasound images.

J Gastroenterol Hepatol 2021 Aug 8. Epub 2021 Aug 8.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.

Background And Aim: We aimed to develop a convolutional neural network (CNN)-based object detection model for the discrimination of gastric subepithelial tumors, such as gastrointestinal stromal tumors (GISTs), and leiomyomas, in endoscopic ultrasound (EUS) images.

Methods: We used 376 images from 114 patients with histologically confirmed gastric GIST or leiomyoma to train the EUS-CNN. We constructed the EUS-CNN using an EfficientNet CNN model for feature extraction and a weighted bi-directional feature pyramid network for object detection. We assessed the performance of our EUS-CNN by calculating its accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC) using a validation set of 170 images from 54 patients. Four EUS experts and 15 EUS trainees were asked to judge the same validation dataset, and the diagnostic yields were compared between the EUS-CNN and human assessments.

Results: In the per-image analysis, the sensitivity, specificity, accuracy, and AUC of our EUS-CNN were 95.6%, 82.1%, 91.2%, and 0.9234, respectively. In the per-patient analysis, the sensitivity, specificity, accuracy, and AUC for our object detection model were 100.0%, 85.7%, 96.3%, and 0.9929, respectively. The EUS-CNN outperformed human assessment in terms of accuracy, sensitivity, and negative predictive value.

Conclusions: We developed the EUS-CNN system, which demonstrated high diagnostic ability for gastric GIST prediction. This EUS-CNN system can be helpful not only for less-experienced endoscopists but also for experienced ones. Additional EUS image accumulation and prospective studies are required alongside validation in a large multicenter trial.
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http://dx.doi.org/10.1111/jgh.15653DOI Listing
August 2021

Prognosis of Atrial Fibrillation Patients Undergoing PCI According to Anticoagulants and Antiplatelet Agents.

J Clin Med 2021 Jul 29;10(15). Epub 2021 Jul 29.

Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam-si 13620, Korea.

There are limited data evaluating conformation of antithrombotic therapy usage to the guideline recommendations. We investigated clinical trends and prognoses of patients with atrial fibrillation (AF) according to anticoagulants and antiplatelet agents beyond 1 year after percutaneous coronary intervention (PCI). We analyzed the records of patients with AF who underwent PCI using the Korean National Health Insurance Service database. The primary endpoint was a composite of major adverse cardiac events (MACE). The safety outcome was bleeding complications. Of 4193 participants, 81.6% received antiplatelet therapy, whereas 27.3% had oral anticoagulant (OAC)-based therapy at 18 months after PCI. The dominant therapy was dual antiplatelet therapy (37.2%), and only 3.3% of participants had OAC monotherapy. At the 1-year follow-up, the incidence of MACE was significantly lower among those receiving a combination of OAC and single antiplatelet therapy (SAPT) than among those receiving OAC monotherapy (4.78% vs. 9.42%, = 0.017). Bleeding complication events (5.01% vs. 5.80%, = 0.587) did not differ between the groups. In clinical practice, most patients with AF who underwent PCI continued to receive antiplatelet agents beyond 1-year post-PCI. OAC with SAPT seemed to be more effective than OAC monotherapy, without a difference in safety.
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http://dx.doi.org/10.3390/jcm10153370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348599PMC
July 2021

Long-Term Antithyroid Drug Treatment of Graves' Disease in Children and Adolescents: A 20-Year Single-Center Experience.

Front Endocrinol (Lausanne) 2021 14;12:687834. Epub 2021 Jun 14.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background/purpose: Graves' disease (GD) is the most common cause of thyrotoxicosis in children and adolescents. There is some debate regarding the optimal treatment and predicting factors of remission or relapse in children and adolescents with GD. In this study, we report a retrospective study of 195 children and adolescents with GD treated at a single tertiary institution in Korea.

Methods: This study included children and adolescents with GD diagnosed before 19 years of age from January of 2000 to October of 2020. The diagnosis of GD was based on clinical features, high thyroxine (FT4), suppressed thyroid-stimulating hormone, and a positive titer of thyrotropin receptor antibodies. Remission was defined as maintenance of euthyroid status for more than six months after discontinuing antithyroid drug (ATD).

Results: A total of 195 patients with GD were included in this study. The mean age at diagnosis was 12.9 ± 3.2 years, and 162 patients (83.1%) were female. Among all 195 patients, five underwent thyroidectomy and three underwent radioactive iodine therapy. The mean duration of follow-up and ATD treatment were 5.9 ± 3.8 years and 4.7 ± 3.4 years, respectively. The cumulative remission rates were 3.3%, 19.6%, 34.1%, 43.5%, and 50.6% within 1, 3, 5, 7, and 10 years of starting ATD, respectively. FT4 level at diagnosis (P = 0.001) was predicting factors for remission [HR, 0.717 (95% CI, 0.591 - 0.870), P = 0.001]. Methimazole (MMI)-related adverse events (AEs) occurred in 11.3% of patients, the most common of which were rash and hematologic abnormalities. Of a total of 26 AEs, 19 (73.1%) occurred within the first month of taking MMI.

Conclusions: In this study, the cumulative remission rate increased according to the ATD treatment duration. Long-term MMI treatment is a useful treatment option before definite treatment in children and adolescents with GD.
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http://dx.doi.org/10.3389/fendo.2021.687834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236938PMC
June 2021

Safety of Endoscopy in Peritoneal Dialysis Patients.

Clin Transl Gastroenterol 2021 07 1;12(7):e00379. Epub 2021 Jul 1.

Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Introduction: Endoscopic procedures can provoke peritonitis in patients receiving peritoneal dialysis (PD). The aim of this study was to assess the development of peritonitis after endoscopic procedures in PD patients.

Methods: We retrospectively reviewed the data from PD patients who underwent endoscopies in 3 tertiary hospitals between 2008 and 2018. The patients were grouped into nonprophylactic, prophylactic, and prior antibiotic therapy groups. The incidence of peritonitis within 7 days of endoscopy was assessed. We also examined the factors associated with peritonitis.

Results: There were 1,316 endoscopies performed in 570 PD patients. The peritonitis rate after endoscopy was 3.0%. Specifically, the peritonitis rate was 1.8% for esophagogastroduodenoscopies, 4.2% for the colonoscopy group, and 5.3% for the sigmoidoscopy group. The prior antibiotic therapy group showed a significantly higher risk of peritonitis (odds ratio = 4.6; 95% confidence interval: 2.2-9.6; P < 0.01). Prophylactic antibiotics were not associated with reducing peritonitis. Therapeutic colonoscopies such as polypectomy were associated with an increased risk of developing peritonitis (odds ratio = 6.5; 95% confidence interval: 1.6-25.9). However, biopsies were not associated with an increased risk of peritonitis.

Discussion: Prophylactic antibiotics did not reduce the risk of peritonitis after endoscopy in PD patients. Therapeutic colonoscopies such as polypectomy and prior antibiotic therapy before endoscopy were associated with an increased risk of peritonitis.
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http://dx.doi.org/10.14309/ctg.0000000000000379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345910PMC
July 2021

Dual mechanistic TRAIL nanocarrier based on PEGylated heparin taurocholate and protamine which exerts both pro-apoptotic and anti-angiogenic effects.

J Control Release 2021 08 16;336:181-191. Epub 2021 Jun 16.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea. Electronic address:

The selective cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) to cancer cells but not to normal cells makes it an attractive candidate for cancer therapeutics. However, the disadvantages of TRAIL such as physicochemical instability and short half-life limit its further clinical applications. In this study, TRAIL was encapsulated into a novel anti-angiogenic nanocomplex for both improved drug distribution at the tumor site and enhanced anti-tumor efficacy. A nanocomplex was prepared firstly by entrapping TRAIL into PEG-low molecular weight heparin-taurocholate conjugate (LHT7), which is previously known as a potent angiogenesis inhibitor. Then, protamine was added to make a stable form of nanocomplex (PEG-LHT7/TRAIL/Protamine) by exerting electrostatic interactions. We found that entrapping TRAIL into the nanocomplex significantly improved both pharmacokinetic properties and tumor accumulation rate without affecting the tumor selective cytotoxicity of TRAIL. Furthermore, the anti-tumor efficacy of nanocomplex was highly augmented (73.77±4.86%) compared to treating with only TRAIL (18.49 ± 19.75%), PEG-LHT7/Protamine (47.84 ± 14.20%) and co-injection of TRAIL and PEG-LHT7/Protamine (56.26 ± 9.98%). Histological analysis revealed that treatment with the nanocomplex showed both anti-angiogenic efficacy and homogenously induced cancer cell apoptosis, which suggests that accumulated TRAIL and LHT7 in tumor tissue exerted their anti-tumor effects synergistically. Based on this study, we suggest that PEG-LHT7/Protamine complex is an effective nanocarrier of TRAIL for enhancing drug distribution as well as improving anti-tumor efficacy by exploiting the synergistic mechanism of anti-angiogenesis.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.019DOI Listing
August 2021

COVID-19 Vaccination-Associated Lymphadenopathy on FDG PET/CT: Distinctive Features in Adenovirus-Vectored Vaccine.

Clin Nucl Med 2021 Oct;46(10):814-819

From the Department of Nuclear Medicine.

Purpose: This study investigated 18F-FDG PET/CT features of adenovirus-vectored vaccination against COVID-19 in healthy subjects.

Patients And Methods: Thirty-one health care workers had been vaccinated Vaxzevria and underwent FDG PET/CT as an optional test for a cancer screening program. Size and FDG uptake of the hypermetabolic lymph nodes were measured. Uptake value of spleen was also measured with liver for comparison.

Results: All examinees who underwent FDG PET/CT within 14 days' interval showed hypermetabolic lymphadenopathies ipsilateral to vaccine injection. All examinees with hypermetabolic lymphadenopathy had simultaneous muscular uptakes until 23 days' interval. Among 12 examinees who underwent FDG PET/CT more than 15 days after vaccination, only 3 male examinees did not show hypermetabolism in the axillary lymph nodes. There was no female examinee with negative hypermetabolic lymphadenopathy until 29 days after vaccination.

Conclusions: Hypermetabolic reactive lymphadenopathy in the ipsilateral axillary area with or without supraclavicular area is most likely to occur in a healthy person with recent adenovirus-vectored COVID-19 vaccination on FDG PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000003800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411598PMC
October 2021

Changes in Thyrotropin Receptor Antibody Levels Following Total Thyroidectomy or Radioiodine Therapy in Patients with Refractory Graves' Disease.

Thyroid 2021 08 21;31(8):1264-1271. Epub 2021 Jul 21.

Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The actions of thyrotropin-binding inhibitory immunoglobulins (TBIIs) against thyrotropin receptors in thyroid follicular cells have been studied as important etiological factors in Graves' disease (GD). The purpose of this study was to investigate changes in the TBII levels of patients undergoing total thyroidectomy (TTx) or radioactive iodine (RAI) therapy for GD refractory to antithyroid drugs (ATDs). We enrolled patients who underwent TTx or RAI for GD with previous ATD use between January 2011 and December 2017 at the Samsung Medical Center in Seoul, Korea. Thorough retrospective reviews of medical records were performed in 130 patients. Patients with goiter, ophthalmopathy, high levels of TBIIs, and high doses of ATDs received TTx. Elderly patients with arrhythmia received RAI. We observed that TBII levels continued to decrease after TTx. On the contrary, TBIIs initially increased for 138 days (estimated median time) and then decreased slowly after RAI. A faster decline in TBII levels was observed in the TTx group than in the RAI group ( < 0.001). The estimated median time for TBIIs to decrease below 4.5 IU (3 × upper normal limit, which is known to be a risk factor for fetal hyperthyroidism) was 318 days in the TTx group and 659 days in the RAI group, respectively. In the RAI group, high levels of TBII (>4.5 IU/L) were present in 70 (82%) at 6 months, 57 (67%) at 1 year, and 3 (3%) at 2 years. In the TTx group, rapid decreases in TBII levels were observed in younger patients and those with lower baseline TBII levels. In the RAI group, smaller thyroid volume was correlated with more rapid decrease in TBII levels. The changes in TBII levels following TTx or RAI were different in patients with refractory GD. When deciding on TTx or RAI, this difference should be considered with patient age, severity of hyperthyroidism, goiter, ophthalmopathy, and future pregnancy plans (for young female patients).
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http://dx.doi.org/10.1089/thy.2020.0756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377510PMC
August 2021

Treatment strategies for osteochondral lesions of the talus: A review of the recent evidence.

Foot (Edinb) 2021 Jun 20;47:101805. Epub 2021 Apr 20.

East Kent Hospitals NHS University Foundation Trust, Ashford, United Kingdom.

Background: There has been no consensus regarding the treatment of osteochondral lesions of the talus, there has been many attempts to formulate a treatment pathway, with multiple proposed modalities and adjuncts used.

Objectives: The aim of this paper was to investigate the evidence published in the recent history, identify the relevant papers, review and summarize the findings, to help clarify the available operative treatment options and their respective efficacies based on the level of evidence provided.

Study Design & Methods: A literature search through electronic databases MEDLINE and EMBASE was done, these databases were screened for publications and papers form June 2004 to June 2019. Key words were utilised in the search 'talus, talar, tibia, cartilage, osteochondral, ankle, osteochondritis dissecans, articular cartilage'. Studies on adults aged 18-60 years were included. Exclusion criteria were studies with less than 10 patients, or no clear outcome was recorded. Papers were reviewed by the authors and data extracted as per a pre-defined proforma.

Results: Following screening, 28 published articles were included and reviewed. Of these publications 5 were level I, 7 level II, 4 level III and 12 level IV. The total number of patients was 1061 patients. Treatment modalities included arthroscopic microfracture, drilling, hyaluronic acid injection, platelet rich plasma, osteochondral autologous transplantation (OAT), vascularised free bone graft among others. The most common functional measures used to assess efficacy were the Visual analogue scale (VAS) and the American Orthopaedic Foot and Ankle (AOFAS) score. Follow up ranged from 26 weeks upto 4 years.

Conclusions: Despite the abundance of treatment options, high level evidence (level I) remains limited and does not conclude a definitive treatment modality as superior to others. Further research, in the form highly organised randomised clinical trials, is needed to help improve the efficacy and develop new treatment modalities in the future.
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http://dx.doi.org/10.1016/j.foot.2021.101805DOI Listing
June 2021

Circumferential submucosal incision prior to endoscopic mucosal resection versus conventional endoscopic mucosal resection for colorectal lesions with endoscopic features of sessile serrated lesions.

Surg Endosc 2021 Apr 28. Epub 2021 Apr 28.

Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea.

Background And Aims: Sessile serrated lesions (SSLs) are more prone to incomplete resection than conventional adenomas. This study evaluated whether circumferential submucosal incision prior to endoscopic mucosal resection (CSI-EMR) can increase the rate of complete and en bloc resections of colorectal lesions with endoscopic features of SSL.

Methods: Retrospective analyses and propensity score matching were performed for the resection of colorectal lesions ≥ 10 mm with endoscopic features of SSL.

Results: After 1:1 ratio matching, 127 lesions in the CSI-EMR group and 127 in the EMR group were selected for analysis. The median size of the lesions was 15 mm (IQR 12-16) in both groups. There was no significant difference in either the complete resection rate or en bloc resection rate between CSI-EMR and EMR groups (96.9% vs. 92.9%, P = 0.155; 92.1% vs. 89.0%, P = 0.391). By contrast, the R0 resection rate was significantly higher in the CSI-EMR group than in the EMR group (89.8% vs. 59.8%, P < 0.001). The median procedure time was significantly longer in the CSI-EMR group than in the EMR group (6.28 min vs. 2.55 min, P < 0.001), whereas there was no significant difference between the two groups in the incidence of adverse events or recurrence rate. Multivariate analysis showed that CSI-EMR was the only factor significantly associated with R0 resection (P < 0.001).

Conclusions: For colorectal lesions with endoscopic features of SSL, CSI-EMR does not increase the complete or en bloc resection rate, but does increase the R0 resection rate. The procedure time is longer for CSI-EMR than EMR. The association of CSI-EMR with R0 resection and non-recurrence should be further evaluated.
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http://dx.doi.org/10.1007/s00464-021-08495-xDOI Listing
April 2021

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force.

Endocrinol Metab (Seoul) 2021 Apr 6;36(2):322-338. Epub 2021 Apr 6.

Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
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http://dx.doi.org/10.3803/EnM.2020.908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090459PMC
April 2021

Adherence to Surveillance Guidelines after the Removal of Colorectal Polyps: A Multinational, Multicenter, Prospective Survey.

Gut Liver 2021 11;15(6):878-886

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: As the number of colonoscopies and polypectomies performed continues to increase in many Asian countries, there is a great demand for surveillance colonoscopy. The aim of this study was to investigate the adherence to postpolypectomy surveillance guidelines among physicians in Asia.

Methods: A survey study was performed in seven Asian countries. An email invitation with a link to the survey was sent to participants who were asked to complete the questionnaire consisting of eight clinical scenarios.

Results: Of the 137 doctors invited, 123 (89.8%) provided valid responses. Approximately 50% of the participants adhered to the guidelines regardless of the risk of adenoma, except in the case of tubulovillous adenoma ≥10 mm combined with high-grade dysplasia, in which 35% of the participants adhered to the guidelines. The participants were stratified according to the number of colonoscopies performed: ≥20 colonoscopies per month (high volume group) and <20 colonoscopies per month (low volume group). Higher adherence to the postpolypectomy surveillance guidelines was evident in the high volume group (60%) than in the low volume group (25%). The reasons for nonadherence included concern of missed polyps (59%), the low cost of colonoscopy (26%), concern of incomplete resection (25%), and concern of medical liability (15%).

Conclusions: A discrepancy between clinical practice and surveillance guidelines among physicians in Asia was found. Physicians in the low volume group frequently did not adhere to the guidelines, suggesting a need for continuing education and appropriate control. Concerns regarding the quality of colonoscopy and complete polypectomy were the main reasons for nonadherence.
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http://dx.doi.org/10.5009/gnl20166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593505PMC
November 2021

Zr anti-CD44 immuno-PET monitors  CD44 expression on splenic myeloid cells and HT29 colon cancer cells.

Sci Rep 2021 02 16;11(1):3876. Epub 2021 Feb 16.

Department of Nuclear Medicine, Samsung Medical Center, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea.

CD44 is a cell-surface glycoprotein involved in cell-cell interaction, adhesion, and migration. CD44 is found on colon cancer cells and on immune cells. Previous studies of Zr PET imaging of CD44 have relied on an anti-human antibody (Ab), which can influence biodistribution in murine models. In this study, we used an Ab that cross-reacts with both human and mouse origin CD44 of all isoforms to unveil the type of leukocyte responsible for high splenic anti-CD44 uptake and investigate how its regulation can influence tumor immuno-PET. The Ab was site-specifically labeled with Zr-deferoxamine on cysteine residues. Zr-anti-CD44 demonstrated high-specific binding to HT29 human colon cancer cells and monocytic cells that showed CD44 expression. When Zr-anti-CD44 was administered to Balb/C nude mice, there was remarkably high splenic uptake but low SNU-C5 tumor uptake (1.2 ± 0.7%ID/g). Among cells isolated from Balb/C mouse spleen, there was greater CD44 expression on CD11b positive myeloid cells than lymphocytes. In cultured monocytic and macrophage cells, LPS stimulation upregulated CD44 expression and increased Zr-anti-CD44 binding. Similarly, normal Balb/C mice that underwent lipopolysaccharide (LPS) stimulation showed a significant upregulation of CD44 expression on splenic myeloid cells. Furthermore, LPS treatment stimulated a 2.44-fold increase of Zr-anti-CD44 accumulation in the spleen, which was attributable to splenic myeloid cells. Finally, in Balb/C nude mice bearing HT29 tumors, we injected Zr-anti-CD44 with greater Ab doses to reduce binding to splenic cells. The results showed lower spleen uptake and improved tumor uptake (2.9 ± 1.3%ID/g) with a total of 300 μg of Ab dose, and further reduction of spleen uptake and greater tumor uptake (5.7 ± 0.0%ID/g) with 700 μg Ab dose. Thus, using an Zr labeled Ab that cross-reacts with both human and mouse CD44, we demonstrate that CD44 immuno-PET has the capacity to monitor CD44 regulation on splenic myeloid cells and may also be useful for imaging colon tumors.
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http://dx.doi.org/10.1038/s41598-021-83496-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887231PMC
February 2021

Prognostic Significance of Metabolic Parameters by F-FDG PET/CT in Thymic Epithelial Tumors.

Cancers (Basel) 2021 Feb 9;13(4). Epub 2021 Feb 9.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors.

Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUV, SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model.

Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage ( < 0.001); histologic types ( = 0.009); treatment modality ( = 0.001); and SUV, SUV, MTV, and TLG (all < 0.001) were significant prognostic factors. SUV ( < 0.001) and Masaoka stage ( = 0.001) were independent prognostic factors on multivariate analysis.

Conclusion: SUV and Masaoka stage are independent prognostic factors in thymic epithelial tumors.
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http://dx.doi.org/10.3390/cancers13040712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916204PMC
February 2021

Fecal Microbiota Transplantation Is Effective for the Treatment of Partially Treated Infection.

Authors:
Young-Seok Cho

Gut Liver 2021 01;15(1):1-2

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.5009/gnl20368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817926PMC
January 2021

Comparison of thrombus, gut, and oral microbiomes in Korean patients with ST-elevation myocardial infarction: a case-control study.

Exp Mol Med 2020 12 18;52(12):2069-2079. Epub 2020 Dec 18.

Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Korea.

ST-segment elevation myocardial infarction (STEMI) is characterized by thrombotic coronary artery occlusions caused by atherosclerotic plaque rupture. The gut microbiome potentially contributes to the pathogenesis of coronary artery diseases. This study investigated the microbial diversity and composition of coronary thrombi in STEMI patients and the composition of the thrombus microbiome relative to that of the oral and gut microbiomes. A case-control study was performed with 22 STEMI patients and 20 age- and sex-matched healthy controls. Coronary thrombi were acquired from STEMI patients via manual thrombus aspiration during primary coronary intervention. Oral swab and stool samples were collected from both groups, and 16S rRNA sequencing and metagenomic microbiome analyses were performed. Microbial DNA was detected in 4 of 22 coronary thrombi. Proteobacteria (p) and Bacteroidetes (p) were the most abundant phyla. The oral and gut microbiomes significantly differed between patients and healthy controls. The patient group presented microbial dysbiosis, as follows: a higher relative abundance of Proteobacteria (p) and Enterobacteriaceae (f) in the gut microbiome and a lower abundance of Firmicutes (p) and Haemophilus (g) in the oral microbiome. Furthermore, 4 significantly abundant genera were observed in the coronary thrombus in the patients: Escherichia, 1.25%; Parabacteroides, 0.25%; Christensenella, 0.0%; and Bacteroides, 7.48%. The present results indicate that the relative abundance of the gut and oral microbiomes was correlated with that of the thrombus microbiome.
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http://dx.doi.org/10.1038/s12276-020-00543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080616PMC
December 2020

Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer.

Cancer Res Treat 2021 Jul 9;53(3):803-812. Epub 2020 Dec 9.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer.

Materials And Methods: We identified 116 patients treated with definitive RT, including FDG-PET/CT-guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed.

Results: We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors.

Conclusion: Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.
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http://dx.doi.org/10.4143/crt.2020.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291185PMC
July 2021

Genipin enhances the antitumor effect of elesclomol in A549 lung cancer cells by blocking uncoupling protein-2 and stimulating reactive oxygen species production.

Oncol Lett 2020 Dec 21;20(6):374. Epub 2020 Oct 21.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

The uncoupling protein-2 (UCP2) serves a role in tumor aggressiveness and anticancer resistance, which is considered to be associated with its ability to attenuate reactive oxygen species (ROS) production. We hypothesized that UCP2 may protect cancer cells from elesclomol-induced cytotoxicity, and that this may be overcome by blocking UCP2 function with genipin. In A549 lung cancer cells that exhibited high UCP2 expression, treatment with elesclomol alone induced limited changes in glucose uptake, ROS production and cell survival. By contrast, both UCP2 knockdown and genipin treatment mildly reduced glucose uptake, increased ROS production and decreased cell survival. Combining genipin and elesclomol further reduced glucose uptake and increased cellular and mitochondrial ROS production. Moreover, co-treatment with genipin and elesclomol reduced the colony forming capacity to 50.6±7.4% and the cell survival to 42.0±3.4% of that in the control cells (both P<0.001). Suppression of cell survival by treatment with elesclomol and genipin was enhanced in the presence of an exogenous ROS inducer and attenuated by a ROS scavenger. The cytotoxic effects of combining genipin and elesclomol were accompanied by reduced mitochondrial membrane potential and occurred through apoptosis as demonstrated by Annexin V assay and increased protein cleavage of PARP and caspase-3. Finally, in an A549 ×enograft mouse model, tumor growth was only modestly retarded by treatment with elesclomol or genipin alone, but was markedly suppressed by combining the two drugs compared with that in the control group (P=0.008). Therefore, high UCP2 expression may limit the antitumor effect of elesclomol by attenuating ROS responses, and this may be overcome by co-treatment with genipin; combining elesclomol and genipin may be an effective strategy for treating cancers with high UCP2.
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http://dx.doi.org/10.3892/ol.2020.12237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608048PMC
December 2020

Personal exposure to fine particulate air pollutants impacts blood pressure and heart rate variability.

Sci Rep 2020 10 6;10(1):16538. Epub 2020 Oct 6.

Department of Internal Medicine, Cardiovascular Center, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, South Korea.

Air pollution has increasingly been recognized as a major healthcare concern. Air pollution, particularly fine particulate matter (≤ 2.5 μm in aerodynamic diameter [PM]) has demonstrated an increase in adverse cardiovascular events. This study aimed to assess the cardiovascular response to personal exposure to different levels of PM. This prospective cohort study enrolled healthy volunteers aged ≥ 18 years with no cardiovascular disease. Study subjects carried personal exposure monitor of PM, digital thermo-hygrometer for temperature and humidity, 24-h blood pressure monitor, and continuous electrocardiogram monitor. Measurements were repeated twice with an interval of 6-12 months. Statistical models consisted of generalized estimation equations to various repeated measures of each subject. A total of 22 subjects were enrolled in this study between July 2018 and January 2019. Measurement was performed twice in all participants, and a total of 36 data were collected except for insufficient data collection. The mean age of the study population was 41.6 years, and 95% of the subjects were females. No study subjects had hypertension or other cardiovascular diseases. The average systolic blood pressure increased with higher PM levels with marginal significance (0.22 mmHg [95% confidential intervals - 0.04 to 0.48 mmHg] per 10 μg/m of PM). All parameters for heart rate variability significantly decreased with a higher level of PM. In this study, we measured individual personal exposure to PM by using a portable device. We found that 24-h exposure to high levels of PM was associated with a significant decrease in heart rate variability, suggesting impaired autonomous nervous function.
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http://dx.doi.org/10.1038/s41598-020-73205-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538889PMC
October 2020

New-onset paroxysmal atrial fibrillation in acute myocardial infarction: increased risk of stroke.

BMJ Open 2020 09 23;10(9):e039600. Epub 2020 Sep 23.

Division of Cardiology and Cardiovascular Center, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, The Republic of Korea.

Objective: To investigate the long-term prognostic implications of transient new-onset atrial fibrillation (AF) in patients with acute myocardial infarction (AMI).

Design: Retrospective observational study.

Setting: Single tertiary centre.

Participants: This study included 2523 patients who presented with AMI from 3 June 2003 to 24 February 2015, after the exclusion of those with prior AF or in-hospital death.

Outcome Measures: Patients were divided into three groups according to the occurrence and type of new-onset AF: (1) sinus rhythm (SR) group; (2) paroxysmal AF (PaAF: AF converted to SR prior to discharge) group and (3) persistent AF (PeAF: AF persisted during the hospitalisation) group. Post-discharge all-cause mortality and stroke incidences were compared between the groups.

Results: New-onset AF was observed in 271 patients (10.7%; PaAF: 230, PeAF: 41). The median follow-up period was 7.2 years (IQR: 5.2-9.4). The incidence of all-cause death and stroke was highest in the PeAF group, followed by the PaAF and SR groups (all-cause mortality: 48.8% vs 26.5% vs 14.7%, p<0.001; stroke 22.0% vs 8.3% vs 4.4%, p<0.001). In the multivariable analysis, PaAF and PeAF were associated with an increased risk of stroke (PaAF, HR: 1.972, 95% CI: 1.162-3.346; PeAF, HR: 5.160, CI: 2.242-11.873) compared with SR. The PaAF group showed a higher incidence of post-discharge AF than the SR group (29.1% vs 4.2%, p<0.001).

Conclusions: New-onset AF following AMI is associated with poor long-term outcomes. Even when AF episodes are brief and are converted to SR, new-onset AF remains associated with an increased risk of recurrent AF and stroke.
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http://dx.doi.org/10.1136/bmjopen-2020-039600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513639PMC
September 2020
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