• Journal of Gastric Cancer
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• 제23권4호
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• pp.609-621
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• 2023

Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval [CI], 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions: T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.

• Korean Journal of Radiology
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• 제22권2호
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• pp.233-242
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• 2021

Objective: To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs). Materials and Methods: We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase (IDH)-mutation, IDH mutation and a chromosome arm 1p/19q-codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q-nondeleted (IDHmut1p/19qnondel), and IDH wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared. Results: IDHmut G3 gliomas showed a larger volume (p = 0.017), lower nCBF (p = 0.048), and higher nADC (p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV (p = 0.024) and lower nADC (p = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas (p < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs. Conclusion: We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to IDH mutation and 1p/19q codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.

• IMMUNE NETWORK
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• 제23권5호
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• pp.39.1-39.15
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• 2023

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log₁₀ IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A⁺ NK cells was observed in the CD56^dimCD16⁺ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A⁺ NK cells.

• IMMUNE NETWORK
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• 제23권6호
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• pp.43.1-43.10
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• 2023

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

• 정신신체의학
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• 제32권1호
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• pp.1-9
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• 2024

노쇠는 스트레스 요인에 대한 취약성이 증가하여 생리적인 예비능력이 감소되고 항상성을 유지하는 능력이 저하되는 증후군으로 입원, 장애 및 사망의 위험을 증가시킨다. 노쇠는 다양한 원인에 의해 발생하며 다차원적인 접근이 필요하고 조기에 발견해서 관리하는 것이 중요하다. 노쇠는 통증이나 우울증과 같은 신경정신과적 문제와도 깊은 관련이 있다. 노쇠를 평가하는데 있어서 질병, 영양, 움직임, 감각기능 등의 신체적 영역뿐만 아니라 심리사회적인 영역까지 포괄적으로 고려하는 것이 바람직하며, 대표적인 척도로 Fried의 신체적 노쇠 기준과 Rockwood의 노쇠 척도를 들 수 있다. 노쇠 관리를 위해서는 신체적 활동과 적절한 단백질 섭취가 중요하며, 부적절한 약물 사용을 줄이고 구강관리, 인지기능, 낙상에도 유의해야한다. 노쇠와 통증은 서로 영향을 미칠 수 있으며 통증이 노쇠를 촉진시킬 수 있다. 노쇠와 통증 연구 분야에서 호르몬과 단백질의 이상, 면역체계 활성과 염증반응, 그리고 후성 유전학의 기전이 공통적으로 작용하고 있다는 증거들이 발표되고 있다. 향후 좀 더 광범위하고 수준 높은 연구가 이루어져야 할 것이며, 그 결과를 노쇠와 통증의 억제와 치료에 적용한다면 삶의 질이 높아질 것이다.

• 대한영상의학회지
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• 제83권2호
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• pp.317-330
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• 2022

목적 본 연구는 신장종양 환자에서 시행한 고주파절제술 이후 신장 기능에 영향을 미치는 다양한 요소들에 대한 평가를 통해서 이들의 상관관계와 임상적 가치를 평가하기 위한 것이다. 대상과 방법 2010년 1월부터 2018년 12월까지 본원에서 ultrasonography, CT 유도하에 고주파절제술을 시행 받은 91명을 대상으로 선정하였다. 신기능을 평가하는 방법으로 시술 직전과 시술 이후 혈청 크레아티닌, 사구체 여과율을 측정하였다. 시술 전과 비교하여 혈청 크레아티닌 수치가 0.3 mg/dL 이상 증가하는 것을 유의미한 것으로 정하고, 이에 근거하여 두 그룹으로 분류하였다. 신장 기능 손상에 영향을 미치는 요소를 평가하기 위해서 다변수 로지스틱 회귀분석을 이용해서 그룹 간에 비교를 시행하였다. 결과 단일 신장, 3단계 이상의 만성 콩팥병, 요관 손상은 신장 기능 손상에서 통계적으로 유의한 의미가 있었다. 성별, 연령, 다른 암, 종양 크기, 위치, 성장 형태, 집합계와의 근접성 등은 통계적으로 유의하지 않았다. 신장 기능 수치의 시간에 따른 변화는 단일 신장, 3단계 이상의 만성 콩팥병, 요관 손상 유무에 따라서 통계적으로 유의하게 달랐다. 결론 고주파절제술 시행 전의 의학적 상태 중 단일 신장, 3단계 이상의 만성 콩팥병, 시술 이후 발생한 합병증 중 요관 손상은 시술 이후 발생하는 신장 기능 손상의 위험요소로 생각할 수 있다.

• IMMUNE NETWORK
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• 제21권4호
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• pp.25.1-25.16
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• 2021

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)⁺ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR⁺ILC3 frequencies and microbial diversity in the lung. Sputum NCR⁺ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR⁺ILC3s may contribute to a healthy commensal diversity and normal lung function.

• IMMUNE NETWORK
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• 제21권5호
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• pp.34.1-34.16
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• 2021

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

• IMMUNE NETWORK
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• 제21권6호
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• pp.41.1-41.13
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• 2021

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

• IMMUNE NETWORK
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• 제22권3호
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.