SCI 발표논문
전체 4,588편
- 39282023
제1저자 최광용 · 교신저자 이현우
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Rapid FEV1/FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population.J Korean Med Sci. 2023;38(1):e4.
PubMed IF 3.2 호흡기내과Abstract
BACKGROUND Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV1/FVC decline rate in the Korean general population and to identify whether rapid FEV1/FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality.
METHODS We evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV1/FVC decline rate, the most negative FEV1/FVC change (1st quartile of annual FEV1/FVC decline rate) was classified as rapid FEV1/FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV1/FVC decline.
RESULTS The annual FEV1/FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV1/FVC decline than in those with non-rapid FEV1/FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV1/FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105-1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089-1.680).
CONCLUSION The annual FEV1/FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV1/FVC decliners.
- 39272023
제1저자 강창경, 최백규 · 교신저자 이지연, 문준호, 송경호, 정인경
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Clinical impact of clonal hematopoiesis on severe COVID- 19 patients without canonical risk factors.Haematologica. 2023;108(1):257-260.
- 39262023
제1저자 안효정, 이소령 · 교신저자 최의근
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Evaluation of the Paradoxical Association Between Lipid Levels and Incident Atrial Fibrillation According to Statin Usage: A Nationwide Cohort Study.J Lipid Atheroscler. 2023;12(1):73-86.
PubMed IF 2.34 순환기내과Abstract
OBJECTIVE Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are associated with a lower risk of atrial fibrillation (AF). Statin use might exert confounding effects on the paradoxical associations; however, the relationships that distinguish statin users from non-users have not been thoroughly evaluated.
METHODS From the Korean National Health Insurance Database, we included 9,778,014 adults who underwent a health examination in 2009. The levels of TC and LDL-C at the health examination were categorized into quartile values of the total study population. We grouped the study population into statin users and non-users and investigated the associations between TC, LDL-C, and the risk of incident AF.
RESULTS Of the total population, 867,336 (8.9%) were taking statins. During a mean follow-up of 8.2 years, inverse associations of TC - AF and LDL-C - AF were observed; higher levels of TC and LDL-C were associated with the lower risk of AF in the total population. Overall, statin users showed higher AF incidence rate than non-users, but the inverse associations of TC - AF and LDL-C - AF were consistently observed irrespective of statin usage; adjusted hazard ratio with 95% confidence interval was 0.81 (0.79-0.84) for statin users and 0.81 (0.80-0.83) for non-users in the highest TC quartile, and 0.84 (0.82-0.87) for statin users and 0.85 (0.84-0.86) for non-users in the highest LDL-C quartile (all p<0.001).
CONCLUSION The paradoxical relationship between lipid levels (TC and LDL-C) and the risk of AF remains consistent in both statin users and non-users.
- 39252023
제1저자 양한모, 김준오 · 교신저자 김효수
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Resistin impairs mitochondrial homeostasis via cyclase-associated protein 1-mediated fission, leading to obesity-induced metabolic diseases.Metabolism. 2023;138:155343.
PubMed IF 16.7 순환기내과Abstract
OBJECTIVE One of the suggested mechanisms of obesity-induced insulin resistance is mitochondrial dysfunction in target tissues such as skeletal muscle. In our study, we examined whether resistin, an adipokine associated with obesity-mediated insulin resistance, induced metabolic disorders by impairing mitochondrial homeostasis.
METHODS The morphology and function of mitochondria of skeletal muscle were examined in resistin-knockout and humanized resistin mice that were subjected to high-fat diet for 3 months. Morphology was examined by transmission electron microscopy. Mitochondria bioenergetics of skeletal muscle were evaluated using a Seahorse XF96 analyzer. Human skeletal myoblasts were used for in vitro studies on signaling mechanisms in responses to resistin.
RESULTS A high-fat diet in humanized resistin mice increased fragmented and shorter mitochondria in the skeletal muscle, whereas resistin-knockout mice had healthy normal mitochondria. In vitro studies showed that human resistin treatment impaired mitochondrial homeostasis by inducing mitochondrial fission, leading to a decrease in ATP production and mitochondrial dysfunction. Induction of mitochondrial fission by resistin was accompanied by increased formation of mitochondria-associated ER membranes (MAM). At the same time, resistin induced up-regulation of the protein kinase A (PKA) pathway. This activation of PKA induced phosphorylation of Drp1 at serine 616, leading to Drp1 activation and subsequent induction of mitochondrial fission. The key molecule that mediated human resistin-induced mitochondrial fission was adenylyl cyclase-associated protein 1 (CAP1), which was reported as a bona fide receptor for human resistin. Moreover, our newly developed biomimetic selective blocking peptide could repress human resistin-mediated mitochondrial dysfunction. High-fat diet-fed mice showed lower exercise capacity and higher insulin resistance, which was prevented by a novel peptide to block the binding of resistin to CAP1 or in the CAP1-knockdown mice.
CONCLUSIONS Our study demonstrated that human resistin induces mitochondrial dysfunction by inducing abnormal mitochondrial fission. This result suggests that the resistin-CAP1 complex could be a potential therapeutic target for the treatment of obesity-related metabolic diseases such as diabetes and cardiometabolic diseases.
- 39242023
제1저자 권주성, 윤창환 · 교신저자 채인호
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BioMatrix Versus Orsiro Stents for Coronary Artery Disease: A Multicenter, Randomized, Open-Label Study.Circ Cardiovasc Interv. 2023;16(1):e012307.
PubMed IF 7.2 순환기내과Abstract
BACKGROUND Comparative studies of ultrathin-strut biodegradable polymer sirolimus-eluting stent (BP-SES) have reported promising results and validated its excellent outcomes in terms of safety and efficacy. However, there are limited studies comparing BP drug-eluting stents with struts of different thicknesses. We compared the long-term clinical outcomes of patients treated with an ultrathin-strut BP-SES or a thick-strut biodegradable polymer biolimus-eluting stent (BP-BES).
METHODS The BIODEGRADE trial (Biomatrix and Orsiro Drug-Eluting Stents in Angiographic Result in Patients With Coronary Artery Disease) is a multicenter prospective randomized study comparing coronary revascularization in patients with ultrathin-strut BP-SES and thick-strut BP-BES with the primary end point of target lesion failure at 18 months posttreatment. We performed the prespecified analysis of 3-year clinical outcomes.
RESULTS In total, 2341 patients were randomized to receive treatment with ultrathin-strut BP-SES (N=1175) or thick-strut BP-BES (N=1166). The 3-year incidence rate of target lesion failure was 3.2% for BP-SES and 5.1% for BP-BES (P=0.023). The difference was primarily due to differences in ischemia-driven target lesion revascularization (BP-SES, 1.5%; BP-BES, 2.8%; P=0.035) between groups. A landmark analysis of the late follow-up period showed significant differences in target lesion failure, with outcomes being better in BP-SES. Cardiac death and target lesion revascularization were significantly lower in the BP-SES group.
CONCLUSIONS In a large, randomized trial, the long-term clinical outcome of target lesion failure at 3 years was significantly better among patients treated with the ultrathin-strut BP-SES. The results indicate the superiority of the ultrathin-strut BP-SES compared with the thick-strut BP-BES.
REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02299011.
- 39232023
제1저자 조수민 · 교신저자 조재영
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Impact of the COVID-19 pandemic on adherence to positive airway pressure treatment in patients with obstructive sleep apnea: systematic review and meta-analysis.Ther Adv Respir Dis. 2023;17:17534666231214040.
PubMed IF 3.2 호흡기내과Abstract
BACKGROUND The adverse effects of the COVID-19 pandemic on sleep have been well studied. However, whether the COVID-19 pandemic impacted positive airway pressure (PAP) adherence in patients with obstructive sleep apnea (OSA) remains unclear.
OBJECTIVES To evaluate the impact of the COVID-19 pandemic on adherence to PAP therapy in patients with OSA.
DESIGN A retrospective cohort study, systematic review, and meta-analysis.
DATA SOURCES AND METHODS The retrospective study included adults with OSA who received PAP prescriptions within the year before and the year after the start date of COVID-19 social distancing (22 March 2020) in South Korea. The threshold of clinical significance for PAP adherence was defined as 0.5 h/day. We also searched for relevant studies published up to 15 January 2023 using the MEDLINE and Embase databases. We performed a random-effects meta-analysis of our findings with the identified studies regarding the standardized mean change (SMC) with a 95% CI of PAP adherence.
RESULTS Our study included a total of 306 patients (mean age, 59.7 years; men, 73.5%). The average daily PAP usage was 5.10 ± 1.63 h before the COVID-19 pandemic and 4.79 ± 1.96 h during the pandemic (mean difference, -0.31 h/day; 95% CI, -0.46 to -0.15 h/day; p < 0.001 using paired t-test). After identifying 10 observational before-and-after studies through a systematic review, we conducted a meta-analysis that included our original data and showed that adherence to PAP treatment was not different before and during the COVID-19 pandemic (SMC, 0.01; 95% CI, -0.18 to 0.19; p = 0.952).
CONCLUSION Although the COVID-19 pandemic had a statistically negative impact on adherence to PAP treatment in South Korea, the effect was not clinically relevant in patients with OSA. According to our meta-analysis, adherence to PAP treatment was not different before and during the COVID-19 pandemic in patients with OSA.
TRIAL REGISTRATION PROSPERO database; No.: CRD42023414268; URL: https://www.crd.york.ac.uk/PROSPERO.
- 39222023
제1저자 배세연, 김기병 · 교신저자 이은영, 박성호, 박민경현
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RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts.Cell Mol Immunol. 2023;20(1):94-109.
PubMed IF 23.9 류마티스내과Abstract
Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions.
- 39212023
제1저자 윤지선 · 교신저자 오도연
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Recent Progress in Immunotherapy for Gastric Cancer.J Gastric Cancer. 2023;23(1):207-223.
PubMed IF 5.1 혈액종양내과Abstract
Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.
- 39202023
제1저자 임수 · 교신저자 임수
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How to cope with emerging viral diseases: lessons from South Korea's strategy for COVID-19, and collateral damage to cardiometabolic health.Lancet Reg Health West Pac. 2023;30:100581.
PubMed IF 8.559 내분비대사내과Abstract
South Korea is a unique country in many aspects in terms of its strategy against the COVID-19 pandemic. From February 2020, the South Korean government adopted active epidemiological investigations, strict isolation of affected patients, and extensive public lockdowns, which were helpful in controlling spread until the end of 2021. This stable situation in South Korea has changed dramatically since the Omicron variant-reportedly less severe but more infective than the original strain-became dominant from January 2022. From mid-February to mid-April 2022, daily cases of COVID-19 in South Korea increased steeply, reaching > 600,000 cases/day: the highest incidence rate in the world at that time. Despite this rapid increase, the South Korean government has eased its preventive strategies progressively, based on the belief in the efficacy of >80% of vaccine coverage in the population. Now, in June 2022, the COVID-19 situation in South Korea is improving. The mortality rate is 0·13%: the lowest among the 30 countries with the highest case counts. High vaccine coverage rate (87·7%), the efficient healthcare system, and active co-operation between private sectors and the central government seem to have contributed to this. However, it should also be noted that the COVID-19 pandemic and its preventive measures have had a negative influence on cardiometabolic profiles in the country. Considering the likelihood of another novel variant of SARS-CoV-2 or new infectious disease emerging in the future, understanding the situation in South Korea and the strategies flexibly adopted by its government could be beneficial for many countries.
- 39192023
제1저자 손준혁 · 교신저자 이상협
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Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway.In Vivo. 2023;37(3):1077-1084.
PubMed IF 1.8 소화기내과Abstract
BACKGROUND/AIM Cholangiocarcinoma is a devastating malignancy with limited treatment options and poor prognosis. Natural products have gained considerable attention for showing antitumor effects with less toxicities. Flavokawain B (FKB), a natural product, has been studied for its antitumor effects on various cancer cells. However, the anti-tumor effect of FKB on cholangiocarcinoma cells remains unknown. This study aimed at investigating the antitumor effect of FKB on cholangiocarcinoma cells in vitro and in vivo.
MATERIALS AND METHODS SNU-478, a human cholangiocarcinoma cell line, was used in this study. Effects of FKB on cell growth inhibition and apoptosis were investigated. The synergistic anti-tumor effect of FKB and cisplatin in combination was also evaluated. Western blotting was performed to examine the underlying molecular mechanisms of the effect of FKB. A xenograft mouse model study was performed to investigate the effect of FKB in vivo.
RESULTS FKB inhibited cell proliferation of cholangiocarcinoma cells in a concentration- and time-dependent manner. FKB also induced cellular apoptosis additively in combination with cisplatin. Akt pathway was suppressed by FKB either alone or in combination with cisplatin. In the xenograft model, FKB treatment in combination with cisplatin/gemcitabine significantly inhibited tumor growth of SNU-478 cells.
CONCLUSION FKB showed an antitumor effect through the induction of apoptosis, which was mediated by suppressing the Akt pathway in cholangiocarcinoma cells. However, the synergistic effect of FKB and cisplatin was not definite.
- 39182023
제1저자 이진용 · 교신저자 이해영
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Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort.Korean J Intern Med. 2023;38(1):56-67.
PubMed IF 2.2 순환기내과Abstract
BACKGROUND/AIMS This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension.
METHODS The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension.
RESULTS The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events.
CONCLUSION This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.
- 39172023
제1저자 윤혁, 김남은 · 교신저자 박영수
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Analysis of the gut microbiome using extracellular vesicles in the urine of patients with colorectal cancer.Korean J Intern Med. 2023;38(1):27-38.
PubMed IF 2.2 소화기내과Abstract
BACKGROUND/AIMS We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC.
METHODS EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA.
RESULTS A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal).
CONCLUSION A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.
- 39162023
제1저자 손민지 · 교신저자 임수
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Effect of Lactobacillus plantarum LMT1-48 on Body Fat in Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial.Diabetes Metab J. 2023;47(1):92-103.
PubMed IF 8.2 내분비대사내과Abstract
BACKGROUND We investigated whether Lactobacillus plantarum strain LMT1-48, isolated from Korean fermented foods and newborn feces, is a suitable probiotic supplement to treat overweight subjects.
METHODS In this randomized, double-blind, placebo-controlled clinical trial, 100 volunteers with a body mass index of 25 to 30 kg/m2 were assigned randomly (1:1) to receive 2×1010 colony forming units of LMT1-48 or to a placebo treatment group. Body composition was measured by dual-energy X-ray absorptiometry, and abdominal visceral fat area (VFA) and subcutaneous fat area were measured by computed tomography scanning. Changes in body fat, VFA, anthropometric parameters, and biomarkers were compared between the two treatment groups (ClinicalTrials.gov number: NCT03759743).
RESULTS After 12 weeks of treatment, the body weight decreased significantly from 76.6±9.4 to 75.7±9.2 kg in the LMT1-48 group but did not change in the placebo group (P=0.022 between groups). A similar pattern was found in abdominal VFA between the two groups (P=0.041). Serum insulin levels, the corresponding homeostasis model assessment of insulin resistance, and leptin levels decreased in the LMT1-48 group but increased in the placebo group (all P<0.05). Decrease in body weight and body mass index by treatment with LMT1-48 was correlated with increase in Lactobacillus levels significantly. LMT1-48 also increased Oscillibacter levels significantly, which were negatively correlated with triglyceride and alanine transaminase levels.
CONCLUSION Administration of LMT1-48 decreased body weight, abdominal VFA, insulin resistance, and leptin levels in these subjects with overweight, suggesting its anti-obesogenic therapeutic potential.
- 39152023
제1저자 김인호 · 교신저자 석승혁, 이해영
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Development of a Zebrafish Larvae Model for Diabetic Heart Failure With Reduced Ejection Fraction.Korean Circ J. 2023;53(1):34-46.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND AND OBJECTIVES Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF.
METHODS DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated.
RESULTS The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed.
CONCLUSIONS We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.
- 39142023
제1저자 김춘영, 이철민 · 교신저자 최수연, 한경도
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The Association of Smoking Status and Clustering of Obesity and Depression on the Risk of Early-Onset Cardiovascular Disease in Young Adults: A Nationwide Cohort Study.Korean Circ J. 2023;53(1):17-30.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND AND OBJECTIVES To evaluate the impact of smoking in young adults on the risk of cardiovascular disease (CVD) and the clustering effect of behavioral risk factors such as smoking, obesity, and depression.
METHODS A Korean nationwide population-based cohort of a total of 3,280,826 participants aged 20-39 years old who underwent 2 consecutive health examinations were included. They were followed up until the date of CVD (myocardial infarction [MI] or stroke), or December 2018 (median, 6 years).
RESULTS Current smoking, early age of smoking initiation, and smoking intensity were associated with an increased risk of CVD incidence. Even after quitting smoking, the risk of MI was still high in quitters compared with non-smokers. Cigarette smoking, obesity, and depression were independently associated with a 1.3-1.7 times increased risk of CVD, and clustering of 2 or more of these behavioral risk factors was associated with a 2-3 times increased risk of CVD in young adults.
CONCLUSIONS In young adults, cigarette smoking was associated with the risk of CVD, and the clustering of 2 or more behavioral risk factors showed an additive risk of CVD.
- 39132023
제1저자 송진희 · 교신저자 김나영
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Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model.Cancer Res Treat. 2023;55(1):196-218.
PubMed IF 4.2 소화기내과Abstract
PURPOSE Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model.
MATERIALS AND METHODS Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch.
RESULTS The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls.
CONCLUSION In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.
- 39122023
제1저자 이민우, 백우현 · 교신저자 이상협
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Usefulness of Liquid-Based Cytology in Diagnosing Biliary Tract Cancer Compared to Conventional Smear and Forceps Biopsy.Dig Dis Sci. 2023;68(1):274-283.
PubMed IF 2.8 소화기내과Abstract
BACKGROUND/AIMS Liquid-based cytology (LBC) has been shown to improve the diagnostic efficacy of brush cytology for thyroid, cervical and pancreatic cancer. To evaluate the diagnostic performance of LBC for biliary tract cancer, we compared it with conventional smears and forceps biopsies.
METHODS A retrospective study was conducted of all consecutive patients who underwent brush cytology under ERCP from January 2010 to April 2020. The primary outcome was the diagnostic efficacy of conventional smears and LBC. The difference between the two groups was corrected using inverse probability weighting (IPW). The secondary outcome was the sensitivity and specificity of brush cytology and forceps biopsy. The secondary outcome was evaluated in patients who underwent both methods.
RESULTS Among 162 patients, conventional smears were performed in 70 patients and LBC was performed in 92 patients. In the primary analysis using IPW, the sensitivity of conventional smears and LBC was 56.00% and 78.26% respectively (P = 0.009). The specificity was 100% for both methods. The accuracy was 66.15% for conventional smears and 83.33% for LBC (P = 0.012). In the secondary analysis, the sensitivity of conventional smears versus forceps biopsies was 62.16% versus 78.38% (P = 0.034) and 81.16% for both LBC and forceps biopsies. The specificity of both cytological examination and forceps biopsies was 100%.
CONCLUSIONS Liquid-based cytology demonstrated better sensitivity and accuracy than conventional smears. Moreover, its diagnostic performance was close to that of forceps biopsies.
- 39112023
제1저자 전유경 · 교신저자 임종필, 한경도
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Positive Results from the Fecal Immunochemical Test Can Be Related to Dementia: A Nationwide Population-Based Study in South Korea.J Alzheimers Dis. 2023;91(4):1515-1525.
PubMed IF 3.4 소화기내과Abstract
BACKGROUND The fecal immunochemical test (FIT) is widely used in screening for colorectal cancer (CRC), but FIT results can be positive for diseases other than CRC.
OBJECTIVE We investigated the association between positive results of FIT and the incidence of dementia using a nationwide database.
METHODS FIT-positive participants were collected from a database provided by the Korean National Health Insurance Service.
RESULTS The incidence of all kinds of dementia was higher in FIT-positive than FIT-negative subjects (p < 0.0001). FIT-positive participants had a higher risk of Alzheimer's disease (AD) (p < 0.0001) and vascular dementia (p = 0.0002), compared to participants with FIT negativity. The risk of all kinds of dementia or AD in FIT-positive participants was higher in younger (age < 65 years) than older participants (p < 0.0001 for all kinds of dementia; p = 0.0002 for AD).
CONCLUSION FIT positivity was correlated with an increased risk of dementia, especially in participants under 65 years of age. The study suggests that clinicians can consider dementia when FIT-positive participants fail to show any malignancies.
- 39102022
제1저자 문민경 · 교신저자 박영주, 최경호
Moon MK, Kim MJ, Lee I, Kim S, Choi S, Park J, Cho YH, Hong S, Yoo J, Park H, Cheon GJ, Park YJ, Choi K
Exposure to Bisphenol A, S, and F and its Association with Obesity and Diabetes Mellitus in General Adults of Korea: Korean National Environmental Health Survey (KoNEHS) 2015–2017.Exposure and Health. 2022;11 March.
IF 8.835 내분비대사내과 - 39092022
제1저자 Del Orbe DV, 박형주 · 교신저자 임 수, 이대식
Del Orbe DV, Park HJ, Kwack MJ, Lee HK, Kim DY, Lim JG, Park I, Sohn M, Lim S, Lee DS.
Breath analyzer for personalized monitoring of exercise-induced metabolic fat burning.Sensors & Actuators: B. Chemical. 2022;369p:132192..
IF 9.221 내분비대사내과 - 39082022
제1저자 추아정, 성파멜라 · 교신저자 정지봉
, , , , , , ,
Association of body composition fat parameters and breast density in mammography by menopausal status.Sci Rep. 2022;12(1):22224.
PubMed IF 4.9 소화기내과Abstract
We investigated the relationship between body fat-driven obesity and breast fat density in mammography according to menopausal status. We retrospectively analyzed 8537 women (premenopausal, n = 4351; postmenopausal, n = 4186). Body fat parameters included BMI (body mass index), waist circumference (WC), waist-hip ratio (WHR), fat mass index (FMI), Percentage of body fat (PBF), and visceral fat area (VFA). Body fat-driven obesity was defined as follows: overall obesity, BMI ≥ 25 kg/m2; central obesity, WC > 85 cm; abdominal obesity, WHR > 0.85; excessive FMI, the highest quartile (Q4) of FMI; excessive PBF, the highest quartile (Q4) of VFA; visceral obesity, and the highest quartile (Q4) of VFA). Breast density was classified according to BI-RADS (grade a, b, c, and d), which defined as an ordinal scale (grade a = 1, grade b = 2, grade c = 3, and grade d = 4). All body fat-driven obesity parameters were negatively associated with the grade of breast density in both groups of women (p < 0.001): The more fatty parameters are, the less dense breast is. In multivariable binary logistic regression, all body fat-driven obesity parameters also showed a negative association with grade d density (vs. grade a, b, or c). In premenopausal women, BMI was a more associated parameter with grade d density than those of the other fat-driven parameters (OR 0.265, CI 0.204-0.344). In postmenopausal women, WC was more associated with grade d density than the others (OR 0.315, CI 0.239-0.416). We found that BMI, WC, WHR, FMI, PBF and VFA were negatively correlated with dense breast, and the association degree pattern between body fat-driven obesity and dense breast differs according to menopausal status.
- 39072022
제1저자 이경희 · 교신저자 유철규
, , , ,
YPL-001 Shows Various Beneficial Effects against Cigarette Smoke Extract-Induced Emphysema Formation: Anti-Inflammatory, Anti-Oxidative, and Anti-Apoptotic Effects.Antioxidants (Basel). 2022;12(1):antiox12010015.
PubMed IF 8.2 호흡기내과Abstract
Inflammation, oxidative stress, and apoptosis are thought to be important causes of chronic obstructive pulmonary disease (COPD). We investigated the effect of YPL-001 (under phase 2a study, ClinicalTrials.gov identifier NCT02272634), a drug derived from Pseudolysimachion rotundum var. subintegrum, on cigarette smoke extract (CSE)-induced inflammation, the anti-oxidative pathway, and apoptosis in human lung epithelial cells and on CSE-induced emphysema in mice. YPL-001 suppressed CSE-induced expression of IL8 mRNA and protein. This was due to the reduction in NF-κB transcriptional activity by YPL-001, which resulted from the blockade of acetylation of the NF-κB subunit p65 (Lys310). Histone deacetylases (HDACs) prevent gene transcription by condensing the DNA structure and affecting NF-κB nuclear binding. YPL-001 alone increased HDAC2 activity and enhanced CSE-induced activation of HDAC2. YPL-001-induced suppression of NF-κB transcriptional activity might be caused by increased HDAC2 activity. YPL-001 increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression via both degradation of its inhibitory protein, Kelch-like ECH-associated protein 1, and an increase in de novo protein synthesis. YPL-001 increased the DNA binding activity of Nrf2. Consequently, YPL-001 upregulated the expression of Nrf2-targeted anti-oxidant genes such as NAD(P)H quinone dehydrogenase 1 and heme oxygenase 1. Moreover, YPL-001 significantly suppressed CSE-induced apoptotic cell death. In vivo study showed that CSE-induced emphysematous changes, neutrophilic inflammation, protein leakage into bronchoalveolar space, and lung cell apoptosis in mice were suppressed by YPL-001 treatment. Taken together, these results suggest that YPL-001 is a good therapeutic candidate for the treatment of COPD by blocking inflammation and apoptosis and activating the anti-oxidative pathway.
- 39062022
제1저자 Shivani Handa, 이정옥 · 교신저자 Jae H Park
, , , , , , , , , , , , , ,
Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy.Blood. 2022;140(25):2663-2671.
PubMed IF 23.9 혈액종양내과Abstract
Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.
- 39052022
제1저자 최정민, 이소령 · 교신저자 최의근
, , , , ,
Impact of Socioeconomic Status on Emergency Department Visits in Patients With Atrial Fibrillation: A Nationwide Population-Based Cohort Study.J Am Heart Assoc. 2022;11(24):e027192.
PubMed IF 6 순환기내과Abstract
Background Socioeconomic status (SES) differences could influence management and clinical outcomes in patients with atrial fibrillation (AF), reflecting health inequalities. The authors aimed to investigate emergency department (ED) visits in patients with AF according to SES level. Methods and Results The authors performed a cross-sectional analysis of ED visits in patients with nonvalvular AF using the Korean National Health Insurance Service database in 2016. The patients were divided into health premium quartiles and medical aid groups, with quartile 4 the highest SES and medical aid the lowest SES. Among patients with AF, patients who had ≥1 ED visits in 2016 were identified. The prevalence and cause of ED visits, 30- and 90-day mortality, and rehospitalization risk after ED visits were evaluated. Among the total 371 017 AF patients, 99 306 patients visited the ED in 2016. The medical aid group showed the highest ED visit rate (n=11 833, 38.0%), and patients with the highest quartile of SES (quartile 4 group) showed the lowest ED visit rate (n=38 037, 30.0%). The most common cause of ED visits was cerebral infarction in all groups. The 30- and 90-day mortality rates and rehospitalization risk after ED visits was higher in groups with lower SES. Conclusions Patients with AF and with lower SES had a higher risk of ED visit rate, higher 30- and 90-day mortality rates, and rehospitalization risk after ED visit. Tailored AF management according to different SES levels in patients with AF is needed to improve clinical outcomes.
- 39042022
제1저자 박도현 · 교신저자 박완범
, , , , ,
How We Have Treated Severe to Critically Ill Patients With Coronavirus Disease 2019 in Korea.J Korean Med Sci. 2022;37(49):e353.
PubMed IF 3.2 감염내과Abstract
Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and the coronavirus disease 2019 (COVID-19) pandemic currently continues. In response to this unprecedented pandemic, several researchers and medical staff have struggled to find appropriate treatments for COVID-19. Patients with mild symptoms can recuperate with symptomatic care, however establishing treatment for severe to critically ill patients who can have a high mortality has been essential. Accordingly, the guidelines for COVID-19 treatment have evolved through numerous trials and errors and have been relatively well established to date. In the Republic of Korea, several evidence-based guidelines for COVID-19 treatment were released and revised, reflecting various research and regional medical conditions. To date, approximately 3 years after the beginning of the COVID-19 pandemic, we are reflecting on the changes in the guidelines thus far and have summarized the treatment experience of severe to critically ill patients with COVID-19. The Korean guidelines for COVID-19 treatment have been updated continuously as the National Institutes of Health (NIH) guidelines have changed. Dexamethasone is currently used as the backbone for the treatment of severe to critically ill patients with COVID-19, and remdesivir, baricitinib, and tocilizumab can be added depending on a patient's situation. In addition, venous thromboembolism prophylaxis is one of the important adjunctive therapies for patients with severe COVID-19. In the clinical field, treatment of severely ill patients with COVID-19 based on guidelines is widely practiced by medical staff and established currently.
- 39032022
제1저자 이정환 · 교신저자 조수정
, , , , , , , ,
Endoscopic submucosal dissection for papillary early gastric carcinoma: Insights from a large-scale analysis of post-gastrectomy pathology specimens.Medicine (Baltimore). 2022;101(50):e32085.
PubMed IF 2 소화기내과Abstract
Gastric papillary adenocarcinoma is considered a differentiated adenocarcinoma in the current endoscopic submucosal dissection indication guidelines. However, the safety of endoscopic submucosal dissection remains controversial. Currently, data regarding which papillary early gastric cancer should be considered for endoscopic submucosal dissection are unavailable. Thus, the aim of this study was to investigate lymph node metastasis and the safety of endoscopic submucosal dissection in patients with papillary early gastric cancer. This observational study recruited 4264 consecutive patients with early gastric cancer who underwent curative gastrectomy between October 2000 and December 2017 at the National Cancer Center, Korea. Of these, 45 had pathologically confirmed papillary early gastric cancer, 2106 had differentiated non-papillary early gastric cancer, and 2113 had undifferentiated early gastric cancer. Logistic regression analysis was performed to identify risk factors for lymph node metastasis. Mucosal tumors were less common in papillary early gastric cancer (37.9%) than in differentiated non-papillary early gastric cancer (48.8%) and undifferentiated early gastric cancer (60.4%) (both P < .001). Lymph node metastasis was more common in papillary early gastric cancer (20.0%) than in differentiated non-papillary early gastric cancer (9.2%) and undifferentiated early gastric cancer (11.7%; both P < .001). In multivariate analysis, non-mixed-type papillary early gastric cancer showed marginally increased odds of lymph node metastasis than differentiated early gastric cancer (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.0-6.3). Rates of lymph node metastasis (1/10, 10%) and angiolymphatic invasion (2/10, 20%) for papillary early gastric cancer meeting expanded criteria were higher than those for other histology types meeting endoscopic submucosal dissection absolute or expanded criteria (P = .03 and P < .001, respectively). Endoscopic submucosal dissection should be considered carefully for papillary early gastric cancer, especially if it meets expanded endoscopic submucosal dissection indications since it is associated with high rates of submucosal invasion and lymph node metastasis.
- 39022022
제1저자 이한준 · 교신저자 황진혁, 조석기, 조지열
, , , , , ,
Serum protein profiling of lung, pancreatic, and colorectal cancers reveals alcohol consumption-mediated disruptions in early-stage cancer detection.Heliyon. 2022;8(12):e12359.
PubMed IF 3.6 소화기내과Abstract
While the link between serum proteins and cancer has been studied in an effort to enable early-stage cancer detection, factors that might perturb this link has been poorly understood. To ask this question, we performed serum protein profiling on a prospective cohort of 601 individuals with or without lung, pancreatic, or colorectal cancers and identified ten distinct serum protein signatures with distinct link to the patient metadata. Importantly, we discovered that a positive history of alcohol consumption is a major factor that diminishes the sensitivity of serum protein-mediated liquid biopsy in early-stage malignancies, resulting in a 44% decline in the sensitivity of detecting American Joint Committee on Cancer (AJCC) stage I malignancies. Our data provide evidence that patient lifestyle can affect the sensitivity of liquid biopsy and suggest the potential need for abstinence from alcohol before measurement during serum protein-based cancer screening.
- 39012022
제1저자 정재협 · 교신저자 황진혁
, , , , , , , ,
Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer.Front Oncol. 2022;12:1050070.
PubMed IF 3.4 소화기내과Abstract
INTRODUCTION FOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.
METHODS To this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.
RESULTS Fifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3-28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4-30.3) and 16.7 months (95% CI: 13.0-20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042-3.930, p = 0.037).
CONCLUSION Our findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.
- 39002022
제1저자 강준원 · 교신저자 박완범, Veas F, 권성훈
, , , , , , , , , , , , , , , , , ,
Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.Anal Chem. 2022;94(49):17186-17194.
PubMed IF 7.3 감염내과Abstract
A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.
- 38992022
제1저자 김진영, 장의진 · 교신저자 박완범, 이경훈
, , , , , , , , , ,
Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.Oncologist. 2022;27(12):e931-e937.
PubMed IF 4.7 감염내과Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies.
MATERIALS AND METHODS In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments.
RESULTS Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy.
CONCLUSION Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.
서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.