1.Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer
Il-Hyun PARK ; Dae-Soon SON ; Yoon-La CHOI ; Ji-Hyeon CHOI ; Ji-Eun PARK ; Yeong Jeong JEON ; Minseob CHO ; Hong Kwan KIM ; Yong Soo CHOI ; Young Mog SHIM ; Jung Hee KANG ; Suzy PARK ; Jinseon LEE ; Sung-Hyun KIM ; Byung-Chul LEE ; Jhingook KIM
Cancer Research and Treatment 2024;56(1):81-91
Purpose:
Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens.
Materials and Methods:
In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee.
Results:
The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients.
Conclusion
The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.
2.JAK2 Loss Arising From Tumor-SpreadThrough-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma:A Machine Learning Approach
Soohwan CHOI ; Hyung Suk KIM ; Kyueng-Whan MIN ; Yung-Kyun NOH ; Jeong-Yeon LEE ; Ji-Yong MOON ; Un Suk JUNG ; Mi Jung KWON ; Dong-Hoon KIM ; Byoung Kwan SON ; Jung Soo PYO ; Sun Kyun RO
Journal of Korean Medical Science 2024;39(2):e16-
Background:
Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates.
Methods:
This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis.
Results:
The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression.
Conclusion
In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.
3.Erratum: Correction of Figure in the Article “Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)”
Sang Hyun RA ; Euijin CHANG ; Ji-Soo KWON ; Ji Yeun KIM ; JuYeon SON ; Woori KIM ; Choi Young JANG ; Hyeon Mu JANG ; Seongman BAE ; Jiwon JUNG ; Min Jae KIM ; Yong Pil CHONG ; Sang-Oh LEE ; Sang-Ho CHOI ; Yang Soo KIM ; Keun Hwa LEE ; Sung-Han KIM
Journal of Korean Medical Science 2024;39(38):e304-
4.Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
Sang Hyun RA ; Euijin CHANG ; Ji-Soo KWON ; Ji Yeun KIM ; JuYeon SON ; Woori KIM ; Choi Young JANG ; Hyeon Mu JANG ; Seongman BAE ; Jiwon JUNG ; Min Jae KIM ; Yong Pil CHONG ; Sang-Oh LEE ; Sang-Ho CHOI ; Yang Soo KIM ; Keun Hwa LEE ; Sung-Han KIM
Journal of Korean Medical Science 2024;39(35):e237-
Background:
The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood.Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC.
Methods:
We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis.
Results:
Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range.
Conclusion
Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.
5.National Surgical Site Infection Surveillance System Results Report: July 2021 through June 2022
Jung Wan PARK ; Young Keun KIM ; Yoon-soo PARK ; Hong Bin KIM ; Jun Yong CHOI ; Hee Jung CHOI ; Chung Jong KIM ; Jeong Su PARK ; Shinwon LEE ; Yong Chan KIM ; Seong Jin CHOI ; Jongtak JUNG ; Sunggyun PARK ; Su Ha HAN ; Su Young KIM ; Su Hyun KIM ; Hee Jung SON ; Min Hee CHO ; Bock-Hui YOUN ; Jeong Hwa YEON ; Kyoung-Ho SONG
Korean Journal of healthcare-associated Infection Control and Prevention 2024;29(1):48-58
Background:
This report presents annual data from the surgical site infection (SSI) module of the Korean National Healthcare-associated Infections Surveillance System (KONIS) from July 2021 to June 2022.
Methods:
Surveillance of 20 surgeries (e.g., stomach, colon, rectal, gallbladder surgery, knee replacement, hip replacement, craniotomy, ventricular shunts, spinal fusion, laminectomy, cardiac artery bypass grafting - incision in the chest site only and incisions both the chest and donor site, cardiac, prostatectomy, abdominal hysterectomy, vaginal hysterectomy, appendectomy, thoracic, cesarean section, and head and neck surgeries) associated with SSI was performed between July 1, 2021, and June 30, 2022, according to the KONIS Manual 2020.
Results:
A total of 133,281 surgical cases were collected and 1,100 SSIs were identified, resulting in a SSI rate of 0.83%. The SSI rates for 30-day surveillance surgeries were 1.9% for stomach, 2.82% for colon, 1.88% for rectal, 0.29% for gallbladder, 0.25% for lumbar laminectomy, 0.33% for cesarean section, 0.67% for abdominal hysterectomy, 0.74% for vaginal hysterectomy, 0.23% for prostatectomy, 1.39% for appendectomy, and 0.06% for thoracic surgeries. Neck surgery could not be analyzed due to no reported cases. The SSI rates for the 90-day surveillance surgeries were 0.16% for knee replacement, 0.54% for hip replacement, 0.89% for spinal fusion, 0.70% for craniotomy, 0.92% for ventricular shunt, 1.13% for cardiac, 1.80% for cardiac artery bypass grafting (chest only incision), and 1.64% for cardiac artery bypass grafting (chest and leg incision) surgeries. In total, 608 strains were isolated and cultured from 1,286 infections.
Conclusion
Compared with the incidence of SSI (1.06%) in 2018, the overall incidence decreased, and most site-specific infection rates decreased or remained the same.
6.Performance Comparison Between Fourier-Transform Infrared Spectroscopy–based IR Biotyper and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for Strain Diversity
Son Young JUN ; Young Ah KIM ; Suk-Jun LEE ; Woon-Won JUNG ; Hyun-Sook KIM ; Sung-Soo KIM ; Hyunsoo KIM ; Dongeun YONG ; Kyungwon LEE
Annals of Laboratory Medicine 2023;43(2):174-179
Background:
Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy–based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method.
Methods:
Eighty-three extended-spectrum β-lactamase–producing Escherichia coli isolates were tested using WGS, MALDI-TOF MS, and IR Biotyper. Simpson’s diversity index (SDI), a statistical analysis for testing the homogeneity of a dendrogram, and the adjusted Rand index (aRI) were used to compare the discriminatory ability between typing tests.
Results:
The SDI (95% confidence interval) was 0.969 (0.952–0.985) for WGS, 0.865 (0.807–0.924) for MALDI-TOF MS, and 0.974 (0.965–0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS.
Conclusions
IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.
7.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
8.Vaccine Effect on Household Transmission of Omicron and Delta SARS-CoV-2 Variants
Yong Chan KIM ; Bongyoung KIM ; Nak-Hoon SON ; Namwoo HEO ; Yooju NAM ; Areum SHIN ; Andrew Jihoon YANG ; Min Hyung KIM ; Taeyoung KYONG ; Eawha KANG ; Yoon Soo PARK ; Heejung KIM
Journal of Korean Medical Science 2023;38(1):e9-
Background:
We evaluated the household secondary attack rate (SAR) of the omicron and delta severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, according to the vaccination status of the index case and household contacts; further, in vaccinated index cases, we evaluated the effect of the antibody levels on household transmission.
Methods:
A prospective cross-sectional study of 92 index cases and 197 quarantined household contacts was performed. Tests for SARS-CoV-2 variant type and antibody level were conducted in index cases, and results of polymerase chain reaction tests (during the quarantine period) were collected from contacts. Association of antibody levels in vaccinated index cases and SAR was evaluated by multivariate regression analysis.
Results:
The SAR was higher in households exposed to omicron variant (42%) than in those exposed to delta variant (27%) (P = 0.040). SAR was 35% and 23% for unvaccinated and vaccinated delta variant exposed contacts, respectively. SAR was 44% and 41% for unvaccinated and vaccinated omicron exposed contacts, respectively. Booster dose immunisation of contacts or vaccination of index cases reduced SAR of vaccinated omicron variant exposed contacts. In a model with adjustment, anti-receptor-binding domain antibody levels in vaccinated index cases were inversely correlated with household transmission of both delta and omicron variants.Neutralising antibody levels had a similar relationship.
Conclusion
Immunisation of household members may help to mitigate the current pandemic.
9.Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidencebased, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG
Journal of Gastric Cancer 2023;23(2):365-373
10.Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center:A Preliminary Result of Randomized Controlled Trial
Hyeonji SEO ; Haein KIM ; Seongman BAE ; Seonghee PARK ; Hyemin CHUNG ; Heung-sup SUNG ; Jiwon JUNG ; Min Jae KIM ; Sung-Han KIM ; Sang-Oh LEE ; Sang-Ho CHOI ; Yang Soo KIM ; Ki Young SON ; Yong Pil CHONG
Infection and Chemotherapy 2022;54(1):102-113
Background:
This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC).
Materials and Methods:
A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater.
Results:
Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration.
Conclusion
In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

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