1.Circulating microRNAs as markers for scrub typhus-associated acute kidney injury
Haeun LEE ; Jung Min KIM ; A Young CHO ; Ju Hwan OH ; Kwang Young LEE ; Chang-Seop LEE ; In O SUN
Kidney Research and Clinical Practice 2024;43(6):797-806
Circulating microRNAs (miRNAs) are potential biomarkers for various kidney diseases. In this study, we aimed to identify a circulating miRNA signature for detecting acute kidney injury (AKI) in scrub typhus. Methods: We prospectively enrolled 40 patients with scrub typhus (20 with AKI, AKI group; 20 without AKI, non-AKI group) and 20 healthy volunteers (the HV group). Thereafter, we performed microarray analysis to assess the serum miRNA profiles of all the participants. Then, to identify miRNAs predictive of scrub typhus-associated AKI, we compared miRNA profiles among these three groups. Results: The proportions of miRNAs, small nucleolar RNAs, and small Cajal body-specific ribonucleoproteins were higher in patients with scrub typhus than in the HVs. Further, relative to the HVs, we identified 120 upregulated and 449 downregulated miRNAs in the non-AKI group and 101 upregulated and 468 downregulated miRNAs in the AKI group. We also identified 11 and 110 upregulated and downregulated miRNAs, respectively, in the AKI group relative to the non-AKI group, and among these miRNAs, we noted 14 miRNAs whose levels were significantly upregulated or downregulated in the AKI group relative to their levels in the HV and non-AKI groups. Biological pathway analysis of these 14 miRNAs indicated their potential involvement in various pathways associated with tumor necrosis factor alpha. Conclusion: We identified miRNAs associated with AKI in patients with scrub typhus that have predictive potential for AKI. Thus, they can be used as surrogate markers for the detection of scrub typhus-associated AKI.
3.Circulating microRNAs as markers for scrub typhus-associated acute kidney injury
Haeun LEE ; Jung Min KIM ; A Young CHO ; Ju Hwan OH ; Kwang Young LEE ; Chang-Seop LEE ; In O SUN
Kidney Research and Clinical Practice 2024;43(6):797-806
Circulating microRNAs (miRNAs) are potential biomarkers for various kidney diseases. In this study, we aimed to identify a circulating miRNA signature for detecting acute kidney injury (AKI) in scrub typhus. Methods: We prospectively enrolled 40 patients with scrub typhus (20 with AKI, AKI group; 20 without AKI, non-AKI group) and 20 healthy volunteers (the HV group). Thereafter, we performed microarray analysis to assess the serum miRNA profiles of all the participants. Then, to identify miRNAs predictive of scrub typhus-associated AKI, we compared miRNA profiles among these three groups. Results: The proportions of miRNAs, small nucleolar RNAs, and small Cajal body-specific ribonucleoproteins were higher in patients with scrub typhus than in the HVs. Further, relative to the HVs, we identified 120 upregulated and 449 downregulated miRNAs in the non-AKI group and 101 upregulated and 468 downregulated miRNAs in the AKI group. We also identified 11 and 110 upregulated and downregulated miRNAs, respectively, in the AKI group relative to the non-AKI group, and among these miRNAs, we noted 14 miRNAs whose levels were significantly upregulated or downregulated in the AKI group relative to their levels in the HV and non-AKI groups. Biological pathway analysis of these 14 miRNAs indicated their potential involvement in various pathways associated with tumor necrosis factor alpha. Conclusion: We identified miRNAs associated with AKI in patients with scrub typhus that have predictive potential for AKI. Thus, they can be used as surrogate markers for the detection of scrub typhus-associated AKI.
5.Circulating microRNAs as markers for scrub typhus-associated acute kidney injury
Haeun LEE ; Jung Min KIM ; A Young CHO ; Ju Hwan OH ; Kwang Young LEE ; Chang-Seop LEE ; In O SUN
Kidney Research and Clinical Practice 2024;43(6):797-806
Circulating microRNAs (miRNAs) are potential biomarkers for various kidney diseases. In this study, we aimed to identify a circulating miRNA signature for detecting acute kidney injury (AKI) in scrub typhus. Methods: We prospectively enrolled 40 patients with scrub typhus (20 with AKI, AKI group; 20 without AKI, non-AKI group) and 20 healthy volunteers (the HV group). Thereafter, we performed microarray analysis to assess the serum miRNA profiles of all the participants. Then, to identify miRNAs predictive of scrub typhus-associated AKI, we compared miRNA profiles among these three groups. Results: The proportions of miRNAs, small nucleolar RNAs, and small Cajal body-specific ribonucleoproteins were higher in patients with scrub typhus than in the HVs. Further, relative to the HVs, we identified 120 upregulated and 449 downregulated miRNAs in the non-AKI group and 101 upregulated and 468 downregulated miRNAs in the AKI group. We also identified 11 and 110 upregulated and downregulated miRNAs, respectively, in the AKI group relative to the non-AKI group, and among these miRNAs, we noted 14 miRNAs whose levels were significantly upregulated or downregulated in the AKI group relative to their levels in the HV and non-AKI groups. Biological pathway analysis of these 14 miRNAs indicated their potential involvement in various pathways associated with tumor necrosis factor alpha. Conclusion: We identified miRNAs associated with AKI in patients with scrub typhus that have predictive potential for AKI. Thus, they can be used as surrogate markers for the detection of scrub typhus-associated AKI.
7.Circulating microRNAs as markers for scrub typhus-associated acute kidney injury
Haeun LEE ; Jung Min KIM ; A Young CHO ; Ju Hwan OH ; Kwang Young LEE ; Chang-Seop LEE ; In O SUN
Kidney Research and Clinical Practice 2024;43(6):797-806
Circulating microRNAs (miRNAs) are potential biomarkers for various kidney diseases. In this study, we aimed to identify a circulating miRNA signature for detecting acute kidney injury (AKI) in scrub typhus. Methods: We prospectively enrolled 40 patients with scrub typhus (20 with AKI, AKI group; 20 without AKI, non-AKI group) and 20 healthy volunteers (the HV group). Thereafter, we performed microarray analysis to assess the serum miRNA profiles of all the participants. Then, to identify miRNAs predictive of scrub typhus-associated AKI, we compared miRNA profiles among these three groups. Results: The proportions of miRNAs, small nucleolar RNAs, and small Cajal body-specific ribonucleoproteins were higher in patients with scrub typhus than in the HVs. Further, relative to the HVs, we identified 120 upregulated and 449 downregulated miRNAs in the non-AKI group and 101 upregulated and 468 downregulated miRNAs in the AKI group. We also identified 11 and 110 upregulated and downregulated miRNAs, respectively, in the AKI group relative to the non-AKI group, and among these miRNAs, we noted 14 miRNAs whose levels were significantly upregulated or downregulated in the AKI group relative to their levels in the HV and non-AKI groups. Biological pathway analysis of these 14 miRNAs indicated their potential involvement in various pathways associated with tumor necrosis factor alpha. Conclusion: We identified miRNAs associated with AKI in patients with scrub typhus that have predictive potential for AKI. Thus, they can be used as surrogate markers for the detection of scrub typhus-associated AKI.
9.A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols
Min Chong KIM ; Eun Yoon CHO ; So Yeon PARK ; Hee Jin LEE ; Ji Shin LEE ; Jee Yeon KIM ; Ho-chang LEE ; Jin Ye YOO ; Hee Sung KIM ; Bomi KIM ; Wan Seop KIM ; Nari SHIN ; Young Hee MAENG ; Hun Soo KIM ; Sun Young KWON ; Chungyeul KIM ; Sun-Young JUN ; Gui Young KWON ; Hye Jeong CHOI ; So Mang LEE ; Ji Eun CHOI ; Ae Ri AN ; Hyun Joo CHOI ; EunKyung KIM ; Ahrong KIM ; Ji-Young KIM ; Jeong Yun SHIM ; Gyungyub GONG ; Young Kyung BAE
Cancer Research and Treatment 2024;56(4):1096-1104
Purpose:
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods:
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results:
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.
10.Magnitude and Duration of Serum Neutralizing Antibody Titers Induced by a Third mRNA COVID-19 Vaccination against Omicron BA.1 in Older Individuals
Jun-Sun PARK ; Jaehyun JEON ; Jihye UM ; Youn Young CHOI ; Min-Kyung KIM ; Kyung-Shin LEE ; Ho Kyung SUNG ; Hee-Chang JANG ; BumSik CHIN ; Choon Kwan KIM ; Myung-don OH ; Chang-Seop LEE
Infection and Chemotherapy 2024;56(1):25-36
Background:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals.
Materials and Methods:
Adults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively).Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND 50 ) >10 was considered indicative of protective NAb titers.
Results:
In total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 -193), and 182 (175 - 198) days after the second dose. Overall, ND 50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND 50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P= 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND 50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99).
Conclusion
A third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2.

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