SCI 발표논문

2022년 265편

2052022

제1저자 송민경 · 교신저자 조선욱

, ,
Conditioned medium of amniotic fluid-derived stromal cells exerts a bone anabolic effect by enhancing progenitor population and angiogenesis.
J Tissue Eng Regen Med. 2022;16(10):923-933.

Abstract
A cell-free approach utilizing the paracrine effects of mesenchymal stromal cells is receiving attention in regenerative medicine. In the present study, we evaluated the effects of a conditioned medium of amniotic fluid-derived stromal cells (AFSC-CM) on bone metabolism. In mice, intraperitoneal injections of AFSC-CM increased bone mass and enhanced bone turnover. The precursor populations of myeloid and mesenchymal lineages, as well as endothelial cells in bone marrow, were also augmented by AFSC-CM administration. In an in vitro culture experiment, AFSC-CM increased osteoclast differentiation of bone marrow-derived macrophages, but had no significant effect on the osteogenic differentiation of preosteoblasts. However, AFSC-CM administration dramatically accelerated the migration and tube formation of endothelial cells, and a cytokine array showed that AFSC-CM contained many angiogenic factors. These results indicate that AFSC-CM exerts a bone anabolic effect by changing the bone marrow microenvironment, including angiogenesis and precursor expansion. Therefore, ameliorating marrow angiogenesis is a potential therapeutic strategy for bone regeneration, for which AFSCs can be a good cellular source.
PubMed IF 2 내분비대사내과
2042022

제1저자 이한명 · 교신저자 조수정

, , , ,
Extragastric Metastasis of Early Gastric Cancer After Endoscopic Submucosal Dissection With Lymphovascular Invasion and Negative Resected Margins.
J Gastric Cancer. 2022;22(4):339-347.

Abstract
PURPOSE Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology.
MATERIALS AND METHODS A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47).
RESULTS The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349).
CONCLUSIONS Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.
PubMed IF 5.1 소화기내과
2032022

제1저자 모요셉, 김유진 · 교신저자 강혜련

, , , , , ,
Mesenchymal Stem Cells Attenuate Asthmatic Inflammation and Airway Remodeling by Modulating Macrophages/Monocytes in the IL-13-Overexpressing Mouse Model.
Immune Netw. 2022;22(5):e40.

Abstract
Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.
PubMed IF 5.9 알레르기내과
2022022

제1저자 최훈지, 이은정, 원종철 · 교신저자 조영민

, , , , ,
Effects of Patient-Driven Lifestyle Modification Using Intermittently Scanned Continuous Glucose Monitoring in Patients With Type 2 Diabetes: Results From the Randomized Open-label PDF Study.
Diabetes Care. 2022;45(10):2224-2230.

Abstract
OBJECTIVE To investigate the effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes (T2D).
RESEARCH DESIGN AND METHODS We conducted a 12-week, open-label, randomized controlled trial. A total of 126 participants were 1:1 randomized to either the intervention group (structured education + isCGM) or the control group (standard care with blood glucose monitoring). The Self-Evaluation Of Unhealthy foods by Looking at postprandial glucose (SEOUL) algorithm was developed and applied to aid structured education in guiding patients to follow healthy eating behavior depending on the postprandial glycemic response. The primary end point was the change in HbA1c level from baseline.
RESULTS Implementation of the SEOUL algorithm with isCGM was associated with greater improvement in HbA1c than with standard care (risk-adjusted difference -0.50%, 95% CI -0.74 to -0.26, P < 0.001). Participants in the intervention group had a greater reduction in fasting blood glucose and body weight (-16.5 mg/dL, 95% CI -30.0 to -3.0, P = 0.017; -1.5 kg, 95% CI -2.7 to -0.3, P = 0.013, respectively). The score sum for the Korean version of the revised Summary of Diabetes Self-Care Activities Questionnaire increased in both groups but to a greater extent in the intervention group (mean difference 4.8, 95% CI 1.7-8.0, P = 0.003). No severe hyperglycemia or hypoglycemia was reported in either group of patients.
CONCLUSIONS Patient-driven lifestyle modification primarily focused on eating behavior using isCGM effectively lowered HbA1c levels in patients with T2D.
PubMed IF 22.6 내분비대사내과
2012022

제1저자 최진호, 남건희 · 교신저자 이상협

, , , , , , ,
Cytokine-Induced Killer Cell Immunotherapy Combined With Gemcitabine Reduces Systemic Metastasis in Pancreatic Cancer: An Analysis Using Preclinical Adjuvant Therapy-Mimicking Pancreatic Cancer Xenograft Model.
Pancreas. 2022;51(9):1251-1257.

Abstract
OBJECTIVES To evaluate the efficacy and safety of cytokine-induced killer (CIK) cell therapy in pancreatic cancer.
METHODS An orthotopic murine model of pancreatic cancer and adjuvant therapy-mimicking xenograft murine model that underwent splenectomy was created. Eighty mice were randomized into four groups: the control, gemcitabine alone, CIK alone, and CIK with gemcitabine groups. The tumor growth was monitored using bioluminescence imaging once weekly.
RESULTS In the orthotopic murine model, the treatment groups showed a significantly longer survival than the control group (median: not reached vs 125.0 days; 95% confidence interval, 119.87-130.13; P = 0.04); however, the overall survival did not differ significantly among the treatment groups (P = 0.779). The metastatic recurrence rate and overall survival were also not significantly different among the groups in the adjuvant therapy-mimicking xenograft murine model (P = 0.497). However, the CIK and gemcitabine combination suppressed the metastatic recurrence effectively, with recurrence-free survival being significantly longer in the CIK with gemcitabine group than in the control group (median, 54 days; 95% confidence interval, 25.00-102.00; P = 0.013).
CONCLUSIONS The combination of CIK and gemcitabine suppressed systemic metastatic recurrence, with promising efficacy and good tolerability in an adjuvant setting of pancreatic cancer.
PubMed IF 2.2 소화기내과
2002022

제1저자 박진주 · 교신저자 조구영

, , , , ,
Myocardial strain for heart failure with preserved ejection fraction but without diastolic dysfunction.
ESC Heart Fail. 2022;9(5):3308-3316.

Abstract
AIMS Some patients with apparent heart failure (HF) have an ejection fraction (EF) ≥ 50% and elevated levels of natriuretic peptides (NPs), but no significant diastolic dysfunction. Among these, some may have HF, others may not. Myocardial strain is an excellent prognostic factor.
METHODS AND RESULTS Among 4312 consecutive patients with acute HF from three tertiary hospitals, we included 355 patients with EF of ≥50% and elevated levels of NPs, without significant diastolic dysfunction. Patients were classified as having impaired global longitudinal strain (GLS < 16%) or normal GLS (GLS ≥ 16%). The primary endpoint was 5 year all-cause mortality. The mean age was 70.3 years and 49% were female. Overall, 107 patients (30.1%) died at 5 years. As per the definition, 176 (49.6%) patients had impaired GLS and 179 (50.4%) had normal GLS. Patients with normal GLS had lower 5 year all-cause mortality than those with impaired GLS (P < 0.001). When comparing with the 11 365 age-matched and sex-matched controls, patients with normal GLS had the same long-term survival as the controls (P = 0.834), whereas those with impaired GLS had 48% increased risk of all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.17-1.89).
CONCLUSIONS Among patients with apparent HF and preserved EF but without diastolic dysfunction, those with impaired GLS may be considered to have HF.
PubMed IF 3.8 순환기내과
1992022

제1저자 이찬섭, 이선영 · 교신저자 윤성수, 윤홍석, 고영일

, , , , , , , ,
Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment.
Genome Med. 2022;14(1):111.

Abstract
BACKGROUND Although anti-apoptotic proteins of the B-cell lymphoma-2 (BCL2) family have been utilized as therapeutic targets in acute myeloid leukaemia (AML), their complicated regulatory networks make individualized therapy difficult. This study aimed to discover the transcriptional signatures of BCL2 family genes that reflect regulatory dynamics, which can guide individualized therapeutic strategies.
METHODS From three AML RNA-seq cohorts (BeatAML, LeuceGene, and TCGA; n = 451, 437, and 179, respectively), we constructed the BCL2 family signatures (BFSigs) by applying an innovative gene-set selection method reflecting biological knowledge followed by non-negative matrix factorization (NMF). To demonstrate the significance of the BFSigs, we conducted modelling to predict response to BCL2 family inhibitors, clustering, and functional enrichment analysis. Cross-platform validity of BFSigs was also confirmed using NanoString technology in a separate cohort of 47 patients.
RESULTS We established BFSigs labeled as the BCL2, MCL1/BCL2, and BFL1/MCL1 signatures that identify key anti-apoptotic proteins. Unsupervised clustering based on BFSig information consistently classified AML patients into three robust subtypes across different AML cohorts, implying the existence of biological entities revealed by the BFSig approach. Interestingly, each subtype has distinct enrichment patterns of major cancer pathways, including MAPK and mTORC1, which propose subtype-specific combination treatment with apoptosis modulating drugs. The BFSig-based classifier also predicted response to venetoclax with remarkable performance (area under the ROC curve, AUROC = 0.874), which was well-validated in an independent cohort (AUROC = 0.950). Lastly, we successfully confirmed the validity of BFSigs using NanoString technology.
CONCLUSIONS This study proposes BFSigs as a biomarker for the effective selection of apoptosis targeting treatments and cancer pathways to co-target in AML.
PubMed IF 10.8 혈액종양내과
1982022

제1저자 최평균, 홍지수 · 교신저자 박완범

, , , , , , , ,
Persistent Antibody Responses Up to 18 Months After Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
J Infect Dis. 2022;226(7):1224-1230.

Abstract
BACKGROUND Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity.
METHODS Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (immunoglobulin [Ig]A, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay.
RESULTS Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8- to 11-fold lower than against wild-type viruses (P<.001).
CONCLUSIONS Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. However, humoral immune activity against more recently circulating variants was reduced in this population.
PubMed IF 4.1 감염내과
1972022

제1저자 최영훈, 한경도 · 교신저자 정광현, 이상협

, , , , , , ,
Underweight Is Associated with a Higher Risk of Acute Pancreatitis in Type 2 Diabetes: A Nationwide Cohort Study.
J Clin Med. 2022;11(19):jcm11195641.

Abstract
Type 2 diabetes is known as a risk factor for acute pancreatitis, but the risk of acute pancreatitis according to glycemic status and body mass index (BMI) has remained unknown. Therefore, we aim to investigate the risk of acute pancreatitis according to BMI and glycemic status. We included 3,912,496 subjects from the Korean National Health Insurance System cohort who underwent the National Health Screening program in 2009. Each subject’s clinical course was examined through follow-ups until December 2018. BMI and glycemic status were each categorized into five groups. Hazard ratios (HRs) of acute pancreatitis according to BMI and glycemic status were calculated. The adjusted HRs of acute pancreatitis were the highest in the underweight group (BMI < 18.5) in all five glycemic status categories. The HR of acute pancreatitis in the underweight group increased as the glycemic status worsened, excluding the category of diabetes for more than five years (HR 1.381 for normal fasting glucose; 1.805 for impaired fasting glucose; 2.332 for new-onset diabetes; 4.51 for diabetes duration <5 years; 4.135 for diabetes duration ≥5 years). We found that the risk of acute pancreatitis was further increased in the underweight group, depending on the status and duration of type 2 diabetes.
PubMed IF 3.3 소화기내과
1962022

제1저자 남엘리엘, 고재훈, 송경호, 최주연 · 교신저자 정혜원, 김신우, 권기태, 김성순, 백경란

, , , , , , , , , , , , , , , , , , , , , , , , ,
Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea.
Front Immunol. 2022;13:968105.

Abstract
INTRODUCTION Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.
METHODS We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND₅₀) against wild type (WT) SARS-CoV-2 and that of the Delta variant.
RESULTS We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND₅₀ of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).
CONCLUSION Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.
PubMed IF 7 감염내과
1952022

제1저자 박찬순 · 교신저자 최의근

, , , , , , , , ,
Catheter ablation and thoracoscopic ablation in long persistent atrial fibrillation with large left atrium.
Front Cardiovasc Med. 2022;9:881831.

Abstract
BACKGROUND Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation, but the clinical outcomes of PVAI are unsatisfactory in patients with persistent AF and a large left atrium (LA).
OBJECTIVES We investigated the clinical outcomes following radiofrequency ablation (RFCA), cryoballoon ablation (CBA), and thoracoscopic maze in patients with persistent AF and a large LA.
METHODS We included patients with consecutive persistent AF who had a large LA (LA diameter >50 mm) and underwent RFCA, CBA, or thoracoscopic maze surgery. In the RFCA group, additional linear ablation was performed at the physician's discretion. The endpoint was 12 months without recurrence of an atrial arrhythmia, including AF, atrial flutter, and atrial tachycardia, following a 90-day blanking period.
RESULTS We recruited 89 persistent AF patients with a large LA who underwent RFCA (n = 32), CBA (n = 38), or the thoracoscopic maze procedure (n = 19). During the 12-month follow-up, 48 (53.9%) cases of AF recurrence were observed. There was no prognostic difference between groups (50.0% in RFCA vs. 52.6% in CBA vs. 63.2% in thoracoscopic maze, all P > 0.05). Early recurrence during the blanking period was a significant predictor of late recurrence for RFCA and CBA, but not for the thoracoscopic maze.
CONCLUSION In persistent AF patients with a large LA, we did not find a prognostic difference RFCA, CBA, or a thoracoscopic maze procedure in recurrence of atrial arrhythmia. Early recurrence predicted late recurrence in catheter ablation, but not in thoracoscopic maze.
PubMed IF 3 순환기내과
1942022

제1저자 최유정 · 교신저자 김형관

, , , , , , , , ,
Augmented risk of ischemic stroke in hypertrophic cardiomyopathy patients without documented atrial fibrillation.
Sci Rep. 2022;12(1):15785.

Abstract
Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424-1.895; P < 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156-3.486; P < 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101-2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure.
PubMed IF 4.9 순환기내과
1932022

제1저자 최진호, 김민규, 이상협 · 교신저자 백우현

, , , , , , , , , , ,
Proper adjuvant therapy in patients with borderline resectable and locally advanced pancreatic cancer who had received neoadjuvant FOLFIRINOX.
Front Oncol. 2022;12:945829.

Abstract
BACKGROUND The complete resection rate of pancreatic cancer has increased because of the advent of efficacious first-line treatments for unresectable pancreatic cancer. Still, strategies regarding adjuvant therapy after neoadjuvant FOLFIRINOX treatment remain to be established.
METHODS Data on 144 patients with borderline resectable and locally advanced pancreatic cancer who underwent resection after neoadjuvant FOLFIRINOX between January 2013 and April 2021 were retrospectively reviewed.
RESULTS Among the study patients, 113 patients (78.5%) were diagnosed with borderline resectable pancreatic cancer and 31 patients (21.5%) were diagnosed with locally advanced pancreatic cancer. Seventy-five patients (52.1%) received radiotherapy before surgery. After radical resection, 84 patients (58.3%) received 5-fluorouracil-based adjuvant therapy and 60 patients (41.7%) received non-5-fluorouracil-based adjuvant therapy. Adjuvant therapy with 5-fluorouracil-based regimen [hazard ratio (HR), 0.43 (95% CI, 0.21-0.87); p = 0.019], preoperative assessment as locally advanced pancreatic cancer [HR, 2.87 (95% CI, 1.08-7.64); p = 0.035], positive resection margin [HR, 3.91 (95% CI, 1.71-8.94); p = 0.001], and presence of pathologic lymph node involvement [HR, 2.31 (95% CI, 1.00-5.33), p = 0.050] were associated with decreased recurrence-free survival. Adjuvant therapy with 5-fluorouracil-based regimen [HR, 0.35 (95% CI, 0.15-0.84); p = 0.018], positive resection margin [HR, 4.14 (95% CI, 1.75-9.78); p = 0.001], presence of pathologic lymph node involvement [HR, 3.36 (95% CI, 1.23-9.15); p = 0.018], poor differentiation [HR, 5.69 (95% CI, 1.76-18.36); p = 0.004], and dose reduction during adjuvant therapy [HR, 1.78 (95% CI, 1.24-24.37); p = 0.025] were associated with decreased overall survival.
CONCLUSIONS The 5-fluorouracil-based adjuvant therapy seems to be the proper adjuvant therapy for patients who received neoadjuvant FOLFIRINOX for borderline resectable and locally advanced pancreatic cancer.
PubMed IF 3.4 소화기내과
1922022

제1저자 이현우 · 교신저자 이창훈

, , ,
Different inhaled corticosteroid doses in triple therapy for chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.
Sci Rep. 2022;12(1):15698.

Abstract
A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52-0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51-0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37-0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36-0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.
PubMed IF 4.9 호흡기내과
1912022

제1저자 김현진 · 교신저자 김광일

,
Blood Pressure Target in Type 2 Diabetes Mellitus.
Diabetes Metab J. 2022;46(5):667-674.

Abstract
The prevalence of diabetes mellitus continues to increase worldwide, and it is a well-established cardiovascular risk factor. Hypertension is also an important cardiovascular risk factor to be controlled and is common among patients with diabetes mellitus. Optimal blood pressure (BP) goals have been the subject of great debate in the management of hypertension among patients with diabetes mellitus. This review provides detailed results from randomized controlled trials and meta-analyses of clinical outcomes according to the target BP in patients with type 2 diabetes mellitus. In addition, the target BP in patients with diabetes mellitus recommended by different guidelines was summarized and presented. A target BP of <140/90 mm Hg is recommended for patients with hypertension and diabetes mellitus, and BP should be controlled to <130/80 mm Hg in patients with diabetes mellitus who have high-risk clinical features. We hope that this review will be helpful to clinicians and patients by promoting the understanding and appropriate application of BP control in the comprehensive management of patients with diabetes mellitus.
PubMed IF 8.2 소화기내과
1902022

제1저자 김미영 · 교신저자 강혜련

, , , , , , , , , , , , , , , , , ,
HLA-A*24:02 increase the risk of allopurinol-induced drug reaction with eosinophilia and systemic symptoms in HLA-B*58:01 carriers in a Korean population; a multicenter cross-sectional case-control study.
Clin Transl Allergy. 2022;12(9):e12193.

Abstract
BACKGROUND HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01.
METHODS Subjects with B*58:01 were enrolled (21 allopurinol-induced DRESS and 52 allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson's chi-square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development.
RESULTS Frequencies of A*24:02 (71.4 vs. 17.3%, p < 0.001, odds ratio [OR] = 12.0; 95% confidence interval [CI], 3.6-39.2) were significantly higher in B*58:01 (+) DRESS than B*58:01 (+) tolerant controls. In addition, DRB1*13:02 further increased the risk of DRESS. The phenotype frequency of A*24:02/DRB1*13:02 was significantly higher in the B*58:01 (+) DRESS group than in the B*58:01 (+) tolerant controls (52.4% vs. 5.8%, p < 0.001, OR, 66.0; 95% CI, 6.1-716.2). In 2782 allopurinol user cohort, the overall prevalence of DRESS was 0.22%, which increased to 1.62% and 2.86% in the presence of B*58:01 and B*58:01/A*24:02, respectively.
CONCLUSION The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.
PubMed IF 4.2 알레르기내과
1892022

제1저자 정광록 · 교신저자 황진혁

, , , , ,
Real-World Outcomes of Gemcitabine, Cisplatin, and Nab-Paclitaxel Chemotherapy Regimen for Advanced Biliary Tract Cancer: A Propensity Score-Matched Analysis.
Gut Liver. 2022;16(5):798-805.

Abstract
BACKGROUND/AIMS Advanced biliary tract cancer (BTC) is associated with poor survival. A recent phase II study of triplet combination chemotherapy, including gemcitabine, cisplatin, and nanoparticle albumin-bound (nab)-paclitaxel, has shown promising results. This study aimed to compare the efficacy of triplet and standard doublet chemotherapy in a real-world setting.
METHODS Patients with advanced BTC treated with triplet and doublet chemotherapy regimens were recruited. The propensity-score nearest neighbor matching method with a ratio of one-to-one was used to create a matched cohort for comparison. Progression-free survival (PFS), overall survival (OS), and safety profiles were examined in both groups.
RESULTS A total of 68 patients (n=34 per group) were included in the matched cohort, and their baseline characteristics were well balanced. Survival outcomes in the triplet chemotherapy group were not better than those in the doublet chemotherapy group, with a median PFS of 7.5 months (95% confidence interval [CI], 4.1 to 10.9) versus 7.2 months (95% CI, 5.6 to 8.9) (hazard ratio [HR], 0.93; 95% CI, 0.53 to 1.62; p=0.793) and a median OS of 13.7 months (95% CI, 8.8 to 18.7) versus 12.2 months (95% CI, 8.4 to 16.0) (HR 0.73; 95% CI, 0.38 to 1.41; p=0.354), respectively. In addition, the treatment-related severe adverse events, such as neutropenia, were more common in the triplet chemotherapy group.
CONCLUSIONS Gemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC. The benefits of triplet chemotherapy in advanced BTC require examination in large randomized controlled trials.
PubMed IF 4.1 소화기내과
1882022

제1저자 정윤주, 김희진 · 교신저자 김나영, 박선자

, , , ,
Effects of Reproductive Factors on Lauren Intestinal-Type Gastric Cancers in Females: A Multicenter Retrospective Study in South Korea.
Gut Liver. 2022;16(5):706-715.

Abstract
BACKGROUND/AIMS Gastric cancers (GCs), particularly the Lauren intestinal type, show a male predominance. The aim of this study was to investigate the effects of reproductive factors on GCs in females, according to Lauren classification.
METHODS Medical records of 1,849 males and 424 females who underwent radical gastrectomy or endoscopic resection for GCs between 2010 and 2018 were reviewed. The incidences of intestinal-type GCs were compared between males and groups of females stratified according to postmenopausal period. Associations between reproductive factors in females and intestinaltype GCs were analyzed using multivariate models.
RESULTS The proportions of intestinal-type GCs were significantly lower in premenopausal (19%), less than 10 years postmenopausal (30.4%), and 10 to 19 years postmenopausal females (44.1%) than in males (61.0%) (p<0.05 for all). Females ≥20 years postmenopause had a proportion of intestinal-type GCs similar to that in males (60.6% vs 61.0%; p=0.948). Multivariate analysis revealed that age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.039 to 1.113; p<0.001) and parity ≥3 (OR, 1.775; 95% CI, 1.012 to 3.114; p=0.045) were positively associated with an increased risk of intestinal-type GCs in postmenopausal females, while long fertility duration (OR, 1.147; 95% CI, 1.043 to 1.261; p=0.005) was positively associated with an increased risk of intestinal-type GCs in premenopausal females.
CONCLUSIONS There were no significant differences in the proportions of intestinal-type GCs between males and females ≥20 years postmenopause, suggesting that female reproductive factors play a role in the prevention of intestinal-type GC.
PubMed IF 4.1 소화기내과
1872022

제1저자 강민정, Raisa Kharbash, 변자민,전재민 · 교신저자 홍준식, 김윤식

, , , , , , , , , , , , , ,
Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents.
Mol Ther Nucleic Acids. 2022;29:370-383.

Abstract
Hypomethylating agents (HMAs), such as azacitidine and decitabine, induce cancer cell death by demethylating DNAs to promote the expression of tumor-suppressor genes. HMAs also reactivate the transcription of endogenous double-stranded RNAs (dsRNAs) that trigger the innate immune response and subsequent apoptosis via viral mimicry. However, the expression patterns of endogenous dsRNAs and their relevance in the efficacy of HMAs remain largely uninvestigated. Here, we employ amidine-conjugated spiropyran (Am-SP) to examine the dynamic expression pattern of total dsRNAs regulated by HMAs. By analyzing the bone-marrow aspirates of myelodysplastic syndrome or acute myeloid leukemia patients who received the HMAs, we find a dramatic increase in total dsRNA levels upon treatment only in patients who later benefited from the therapy. We further apply our approach in solid tumor cell lines and show that the degree of dsRNA induction correlates with the effectiveness of decitabine in most cases. Notably, when dsRNA induction is accompanied by increased expression of nc886 RNA, decitabine becomes ineffective. Collectively, our study establishes the potential application of monitoring the total dsRNA levels by a small molecule as an analytical method and a dynamic marker to predict the clinical outcome of the HMA therapy.
PubMed IF 6.5 혈액종양내과
1862022

제1저자 이현우, 백민경 · 교신저자 이하나, 강혜련

, , , , , , , , , , ,
Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.
Respir Res. 2022;23(1):237.

Abstract
BACKGROUND Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics.
METHODS Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed.
RESULTS In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified.
CONCLUSIONS Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.
PubMed IF 5.7 알레르기내과
1852022

제1저자 김민주, 최소현 · 교신저자 박영주

, , , , , , , , , , ,
Sex, menopause, and age differences in the associations of persistent organic pollutants with thyroid hormones, thyroxine-binding globulin, and peripheral deiodinase activity: A cross-sectional study of the general Korean adult population.
Environ Res. 2022;212(Pt A):113143.

Abstract
Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p'-DDE, and p,p'-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p'-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (β = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (β = 0.032, p = 0.040) and males aged ≥50 (β = -0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (G_D). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p'-DDE, p,p'-DDT, and Factor 1 were positively associated with G_D, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with G_D and total T3 in males aged ≥50. BDE-47 and β-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and G_D.
PubMed IF 8.2 내분비대사내과
1842022

제1저자 이지원 · 교신저자 강혜련, 권오상

, , , , , , , ,
Skin manifestations and clinical features of drug reaction with eosinophilia and systemic symptoms: a retrospective multicentre study of 125 patients.
J Eur Acad Dermatol Venereol. 2022;36(9):1584-1592.

Abstract
BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated.
OBJECTIVES This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features.
METHODS We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews.
RESULTS Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P < 0.01).
CONCLUSIONS Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.
PubMed IF 9.2 알레르기내과
1832022

제1저자 구본권, Xinyang Hu, 강지훈 · 교신저자 탁승재, Jian\'an Wang

, , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI.
N Engl J Med. 2022;387(9):779-789.

Abstract
BACKGROUND In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear.
METHODS We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm² or less or measuring 3 to 4 mm² with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points).
RESULTS The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups.
CONCLUSIONS In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).
PubMed IF 84.5 순환기내과
1822022

제1저자 황도연 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Prognostic Implications of Fractional Flow Reserve After Coronary Stenting: A Systematic Review and Meta-analysis.
JAMA Netw Open. 2022;5(9):e2232842.

Abstract
IMPORTANCE Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is generally considered to reflect residual disease. Yet the clinical relevance of post-PCI FFR after drug-eluting stent (DES) implantation remains unclear.
OBJECTIVE To evaluate the clinical relevance of post-PCI FFR measurement after DES implantation.
DATA SOURCES MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant published articles from inception to June 18, 2022.
STUDY SELECTION Published articles that reported post-PCI FFR after DES implantation and its association with clinical outcomes were included.
DATA EXTRACTION AND SYNTHESIS Patient-level data were collected from the corresponding authors of 17 cohorts using a standardized spreadsheet. Meta-estimates for primary and secondary outcomes were analyzed per patient and using mixed-effects Cox proportional hazard regression with registry identifiers included as a random effect. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data.
MAIN OUTCOMES AND MEASURES The primary outcome was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR). The secondary outcome was a composite of cardiac death or TVMI at 2 years.
RESULTS Of 2268 articles identified, 29 studies met selection criteria. Of these, 28 articles from 17 cohorts provided data, including a total of 5277 patients with 5869 vessels who underwent FFR measurement after DES implantation. Mean (SD) age was 64.4 (10.1) years and 4141 patients (78.5%) were men. Median (IQR) post-PCI FFR was 0.89 (0.84-0.94) and 690 vessels (11.8%) had a post-PCI FFR of 0.80 or below. The cumulative incidence of TVF was 340 patients (7.2%), with cardiac death or TVMI occurring in 111 patients (2.4%) at 2 years. Lower post-PCI FFR significantly increased the risk of TVF (adjusted hazard ratio [HR] per 0.01 FFR decrease, 1.04; 95% CI, 1.02-1.05; P < .001). The risk of cardiac death or MI also increased inversely with post-PCI FFR (adjusted HR, 1.03; 95% CI, 1.00-1.07, P = .049). These associations were consistent regardless of age, sex, the presence of hypertension or diabetes, and clinical diagnosis.
CONCLUSIONS AND RELEVANCE Reduced FFR after DES implantation was common and associated with the risks of TVF and of cardiac death or TVMI. These results indicate the prognostic value of post-PCI physiologic assessment after DES implantation.
PubMed IF 11.7 순환기내과
1812022

제1저자 한민주, 이소령 · 교신저자 최의근

, , , , , , , , , , , ,
Habitual Alcohol Intake and Risk of Atrial Fibrillation in Young Adults in Korea.
JAMA Netw Open. 2022;5(9):e2229799.

Abstract
IMPORTANCE Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers.
OBJECTIVE To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults.
DESIGN, SETTING, AND PARTICIPANTS Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (<105 g per week), moderate (105-210 g per week), and heavy (≥210 g per week) drinking, respectively. Data were analyzed from May to June 2021.
EXPOSURE Amount of alcohol intake in 4 years.
MAIN OUTCOMES AND MEASURES The primary outcome was incident atrial fibrillation during the follow-up period.
RESULTS A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-to-mild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47, CI 1.18-1.83).
CONCLUSIONS AND RELEVANCE Persistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years.
PubMed IF 11.7 순환기내과
1802022

제1저자 우현성 · 교신저자 송경호, 범재원

, , , , , , , , , , , , ,
Comprehensive Rehabilitation in Severely Ill Inpatients With COVID-19: A Cohort Study in a Tertiary Hospital.
J Korean Med Sci. 2022;37(34):e262.

Abstract
BACKGROUND This study aimed to investigate the effects of comprehensive rehabilitation management on functional recovery and examine the correlation between clinical parameters and improvements in functional outcomes in severe-to-critical inpatients with coronavirus disease 2019 (COVID-19) in a tertiary hospital.
METHODS Post-acute COVID-19 patients who had a World Health Organization (WHO) ordinal scale of 5-7, underwent intensive care, and received comprehensive rehabilitation management, including exercise programs, nutritional support, dysphagia evaluation, and psychological care were included. The appendicular skeletal muscle mass index (SMI), Medical Research Council sum score, handgrip strength, number of repetitions in the 1-minute sit-to-stand test, gait speed, Berg Balance Scale (BBS), and Functional Ambulation Classification (FAC) were evaluated at hospital stay, discharge, and 1-month follow-up. The correlation between the rehabilitation dose and improvement in each outcome measure was analyzed.
RESULTS Overall, 37 patients were enrolled, of whom 59.5% and 32.4% had a score of 6 and 7 on the WHO ordinal scale, respectively. Lengths of stay in the intensive care unit and hospital were 33.6 ± 23.9 and 63.8 ± 36.5 days. Outcome measures revealed significant improvements at discharge and 1-month follow-up. The SMI was significantly increased at the 1-month follow-up (6.13 [5.24-7.76]) compared with that during the hospital stay (5.80 [5.39-7.05]). We identified dose-response associations between the rehabilitation dose and FAC (ρ = 0.46) and BBS (ρ = 0.50) scores. Patients with older age, longer hospitalization, longer stay at the intensive care unit, longer duration of mechanical ventilation, tracheostomy, a more depressive mood, and poorer nutritional status revealed poorer improvement in gait speed at the 1-month follow-up.
CONCLUSION Comprehensive rehabilitation management effectively improved muscle mass, muscle strength, and physical performance in severe-to-critical COVID-19 patients. Dose-response relationship of rehabilitation and functional improvement emphasizes the importance of intensive post-acute inpatient rehabilitation in COVID-19 survivors.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05104411.
PubMed IF 3.2 감염내과
1792022

제1저자 전중원 · 교신저자 이상협

, , , , , , , , , ,
A real-world analysis of nanoliposomal-irinotecan with 5-fluorouracil and folinic acid as third- or later-line therapy in patients with metastatic pancreatic adenocarcinoma.
Ther Adv Med Oncol. 2022;14:17588359221119539.

Abstract
BACKGROUND Nanoliposomal encapsulation of irinotecan (nal-IRI) with 5-fluorouracil and leucovorin (5-FU/LV) has shown a survival benefit for gemcitabine-pretreated patients with metastatic pancreatic adenocarcinoma (mPAC). The aim of this study was to evaluate the effectiveness and safety of nal-IRI with 5-FU/LV for use beyond second-line treatment after standard frontline therapy for mPAC.
METHOD This multicenter, retrospective, non-comparative observational study included mPAC patients who received nal-IRI plus 5-FU/LV as third- or later-line therapy after disease progression on first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel.
RESULTS In all, 128 patients who received nal-IRI plus 5-FU/LV beyond second-line treatment between October 2017 and July 2021 were analyzed. Most patients (82%) received nal-IRI plus 5-FU/LV as a third-line treatment. The median overall survival (OS) was 4.9 months and the median progression-free survival (PFS) was 2.4 months. Patients with better Eastern Cooperative Oncology Group (ECOG) performance status experienced significantly longer OS (ECOG 0, 8.7 months; ECOG 1, 4.8 months; ECOG 2, 2.9 months; p < 0.001) and PFS (3.9 months; 2.1 months; 1.5 months; p = 0.019). Patients who had not been previously treated with FFX or had a time to progression of 7 months or more on FFX experienced longer OS and PFS than those who did not (6.1 months and 5.6 versus 4.1 months, p = 0.053; 3.6 months and 2.4 versus 2.1 months, p = 0.002). The most common adverse events were neutropenia (56%) and anemia (51%).
CONCLUSION Our real-world data indicated that nal-IRI plus 5-FU/LV can be effective not only as second-line therapy, but also as third-line or later-line treatment in selected patients. Nal-IRI plus 5-FU/LV may be particularly beneficial for the survival of patients that maintain good general condition or those with favorable prior experience to irinotecan.
PubMed IF 4.1 소화기내과
1782022

제1저자 정우진 · 교신저자 김진욱

, , , , , , , , , ,
Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients.
Sci Rep. 2022;12(1):14482.

Abstract
Transarterial chemoembolization (TACE) is often used as a locoregional therapy for early hepatocellular carcinoma (HCC) when local ablation or resection are not feasible, but incomplete response and recurrence are commonly observed. In this study, we sought to determine the association between metformin administration and TACE outcomes for single nodular HCC in patients with type 2 diabetes mellitus (T2DM). The retrospective cohort analysis included 164 T2DM patients with single nodular HCC who underwent TACE as an initial treatment, and 91 were exposed to metformin before and after TACE. Propensity score (PS) matching was used to balance covariates. Logistic regression analysis was used to determine the predictors of tumor response after TACE, and Cox regression analysis assessed independent predictors of local tumor recurrence (LTR) in patients with complete response after TACE. Metformin use was associated with significantly higher objective response rate (ORR) in the overall and PS-matched cohort (79.1% vs. 60.3 and 78.7% vs. 57.5%; p = 0.008 and p = 0.029, respectively). Logistic regression analysis showed that metformin use was an independent predictor of ORR in all and PS-matched patients (odds ratio = 2.65 and 3.06; p = 0.016 and 0.034, respectively). Cox regression analysis showed metformin administration was an independent predictor for lower LTR in all and PS-matched patients (hazard ratio = 0.28 and 0.27; p = 0.001 and 0.007, respectively). Metformin administration is associated with better initial response and lower local recurrence after TACE for single nodular HCC in T2DM.
PubMed IF 4.9 알레르기내과
1772022

제1저자 이소령, 정진형 · 교신저자 최의근

, , , , , , , , , ,
Net clinical benefit of antithrombotic therapy for atrial fibrillation patients with stable coronary artery disease.
Front Cardiovasc Med. 2022;9:991293.

Abstract
OBJECTIVES To compare the net clinical benefit of oral anticoagulant (OAC) monotherapy to OAC plus single antiplatelet therapy (SAPT) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) at 1- and 3-year after percutaneous coronary intervention (PCI).
BACKGROUND It has not been studied whether the net clinical benefit of the antithrombotic treatment options differs depending on the elapsed time from the index PCI.
METHODS Using the Korean nationwide claims database, we included AF patients who underwent PCI from 2009 to 2019 and constructed two cohorts: 1- and 3-year after PCI. In each cohort, the baseline characteristics of two groups were balanced using propensity score weighting. Ischemic stroke, myocardial infarction, major bleeding, and composite clinical outcomes were analyzed.
RESULTS Among patients with 1-year after PCI, OAC monotherapy (n = 678), and OAC plus SAPT (n = 3,159) showed comparable results for all clinical outcomes. In patients with 3-year after PCI, OAC monotherapy (n = 1,038) and OAC plus SAPT (n = 2,128) showed comparable results for ischemic stroke and myocardial infarction, but OAC monotherapy was associated with a lower risk of composite clinical outcomes (HR 0.762, 95% CI 0.607-0.950), mainly driven by the reduction of major bleeding risk (HR 0.498, 95% CI 0.345-0.701).
CONCLUSION Oral anticoagulant monotherapy may be a comparable choice for patients with AF and stable CAD compared to OAC plus SAPT. In patients with stable CAD more than 3-year after index PCI, OAC monotherapy would be a better choice, being associated with less major bleeding and a positive net clinical benefit.
PubMed IF 3 순환기내과
1762022

제1저자 김충종, 송경호 · 교신저자 안정훈, 김홍빈

, , , , , , , , , , , , , , , , , , , ,
Socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Korea.
Sci Rep. 2022;12(1):13934.

Abstract
We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.
PubMed IF 4.9 감염내과

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.