SCI 발표논문

전체 4,588편

38382022

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
38372022

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
38362022

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
38352022

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
38342022

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
38332022

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
38322022

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
38312022

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
38302022

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
38292022

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
38282022

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
38272022

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
38262022

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
38252022

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
38242022

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
38232022

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
38222022

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
38212022

제1저자 이찬미 · 교신저자 박상원

, , , , , ,
Breakthrough COVID-19 Infection During the Delta Variant Dominant Period: Individualized Care Based on Vaccination Status Is Needed.
J Korean Med Sci. 2022;37(32):e252.

Abstract
BACKGROUND The clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon.
METHODS We retrospectively analyzed hospitalized COVID-19 patients during a delta variant-dominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status.
RESULTS A total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients.
CONCLUSION In the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.
PubMed IF 3.2 감염내과
38202022

제1저자 최광현 · 교신저자 정숙향

, , , , , , , , , , ,
Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.
World J Gastroenterol. 2022;28(30):4182-4200.

Abstract
BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries.
AIM To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR.
METHODS This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results.
RESULTS During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis.
CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.
PubMed IF 7.7 소화기내과
38192022

제1저자 손민지 · 교신저자 임수

, ,
Cilostazol treatment for preventing adverse cardiovascular events in patients with type 2 diabetes and coronary atherosclerosis: Long-term follow-up of the ESCAPE study.
J Diabetes. 2022;14(8):524-531.

Abstract
BACKGROUND Previously, in the ESCAPE study, a randomized controlled trial, we found that 12 months of cilostazol administration significantly decreased coronary artery stenosis and the noncalcified plaque component compared with aspirin. The goal of the current study was to evaluate the effect of cilostazol treatment on cardiovascular events up to 7 years after the end of the original study.
METHODS After the end of the ESCAPE study with patients with type 2 diabetes mellitus (T2DM) and mild to moderate coronary artery stenosis, we decided to extend the ESCAPE study to investigate the long-term effect of cilostazol and aspirin, named the ESCAPE-extension study. The study participants had been investigated for cardiovascular events for up to 7 years, bringing the total follow-up time to a median of 5.2 years (interquartile range 3.6-6.7 years). Adverse events were also investigated.
RESULTS Among 100 participants from the original study, 88 were included in this extension study. Cilostazol treatment reduced the incidence of cardiovascular events in the patients with T2DM when compared with aspirin for a 5.2-year median follow-up (hazard ratio 0.24; 95% CI, 0.07-0.83). The cardiovascular benefit of cilostazol therapy was maintained along with age, sex, systolic blood pressure, low-density lipoprotein cholesterol, and coronary artery calcium score. No serious adverse events in the cilostazol group were noted in the follow-up period.
CONCLUSIONS In this ESCAPE-extension study, cilostazol treatment proved its efficacy in reducing cardiovascular events compared with aspirin in diabetic patients with subclinical coronary artery disease, suggesting the beneficial role of cilostazol in the primary prevention of cardiovascular disease.
PubMed IF 5.9 내분비대사내과
38182022

제1저자 김효수 · 교신저자 김효수

,
The unsolved issue with limited evidence: antiplatelet therapy during the chronic maintenance period after percutaneous coronary intervention.
EuroIntervention. 2022;18(5):e355-e356.

PubMed IF 9.2 순환기내과
38172022

제1저자 이현정 · 교신저자 김형관, 한경도

, , , , , , ,
Age-dependent associations of body mass index with myocardial infarction, heart failure, and mortality in over 9 million Koreans.
Eur J Prev Cardiol. 2022;29(10):1479-1488.

Abstract
AIMS While obesity is a well-known cardiovascular risk factor, little is known whether age has a modifying effect. The aim of this study is to determine the age-dependent associations of body mass index (BMI) with cardiovascular outcomes.
METHODS AND RESULTS A population-based cohort of 9 278 433 Koreans without prior cardiovascular disease were followed up for the incidence of myocardial infarction (MI), heart failure (HF), and all-cause death. The effect of BMI with optimal normal weight (18.5-22.9 kg/m2) as reference was analysed according to age groups [young (20-39 years), middle-aged (40-64 years), and elderly (≥65 years)] and age decades. During 8.2 years, MI, HF, and all-cause death occurred in 65 607 (0.71%), 131 903 (1.42%), and 306 065 (3.30%), respectively. Associations between BMI and all outcomes were significantly modified by age (P-for-interaction < 0.001). There was a proportional increase in incident MI according to BMI in young subjects; this relationship became U-shaped in middle-aged subjects and inversely proportional/plateauing in elderly subjects. A U-shaped relationship between BMI and incident HF was observed, but the impact of obesity was stronger in young subjects while the impact of underweight was stronger in middle-aged and elderly subjects. Meanwhile, lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity was associated with the greatest survival benefit. These associations were independent of sex, smoking, physical activity, and comorbidities.
CONCLUSION The impact of BMI on cardiovascular risk differs according to age. Weight loss may be recommended for younger overweight subjects, while being mildly overweight may be beneficial at old age.
PubMed IF 10 순환기내과
38162022

제1저자 공성혜, 이재원 · 교신저자 김정희

, , , , , ,
Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm.
Endocrinol Metab (Seoul). 2022;37(4):674-683.

Abstract
BACKGRUOUND Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.
METHODS This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.
RESULTS Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.
CONCLUSION DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.
PubMed IF 5.1 내분비대사내과
38152022

제1저자 이소령, 권순일 · 교신저자 최의근

, , , , , ,
Proton Pump Inhibitor Co-Therapy in Patients with Atrial Fibrillation Treated with Oral Anticoagulants and a Prior History of Upper Gastrointestinal Tract Bleeding.
Cardiovasc Drugs Ther. 2022;36(4):679-689.

Abstract
PURPOSE The risk of gastrointestinal bleeding (GIB) can be mitigated by proton pump inhibitor (PPI) co-therapy in patients with atrial fibrillation (AF) treated with anticoagulants. We aimed to evaluate the effect of PPIs on the risk of GIB in Asian patients with AF, treated with oral anticoagulants (OACs), and with a prior history of upper GIB.
METHODS Using a nationwide claims database, OAC-naïve patients with AF and a history of upper GIB before initiating OAC treatment between January 2010 and April 2018 were included. Patients were categorized into 10 groups according to the index OAC (warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban) and whether or not they received PPI co-therapy, and were followed up for incidence of major GIB.
RESULTS Among a total of 42,048 patients, 40% were prescribed PPIs as co-therapy with OACs. Over a median 0.6 years (interquartile ranges 0.2-1.7 years) of follow-up, rivaroxaban use without PPIs showed the highest crude incidence of major GIB (2.62 per 100 person-years), followed by the use of warfarin without a PPI (2.20 per 100 person-years). Compared to the patients without PPI use, PPI co-therapy was associated with a significantly lower risk of major GIB, by 40% and 36%, in the rivaroxaban and warfarin groups, respectively. In dabigatran, apixaban, and edoxaban users, PPI co-therapy did not show a significant reduction in the risk of major GIB.
CONCLUSION Among patients with AF receiving anticoagulant treatment and with a prior history of upper GIB, PPI co-therapy was associated with a significant reduction in the risk of major GIB in patients treated with rivaroxaban and warfarin.
PubMed IF 3.5 순환기내과
38142022

제1저자 문도담 · 교신저자 이은주, 김효수

, , , , , , , ,
Smart gene therapeutics for selective targeting of myofibroblasts derived from hepatic stellate cells and limited expression under inflamed conditions.
Clin Transl Med. 2022;12(8):e991.

PubMed IF 7.9 순환기내과
38132022

제1저자 이찬미 · 교신저자 박경화, 김남중

, , , , , , , , , , , ,
Positivity rates of mycobacterial culture in patients with tuberculous spondylitis according to methods and sites of biopsies: An analysis of 206 cases.
Int J Infect Dis. 2022;121:161-165.

Abstract
OBJECTIVES We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS.
METHODS We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues.
RESULTS During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13-11.99, P = 0.030).
CONCLUSIONS We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0-85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS.
PubMed IF 4.6 감염내과
38122022

제1저자 정고은, 정수민 · 교신저자 한경도, 유수종

, , , , , , , , , ,
Association of fatty liver index with all-cause and disease-specific mortality: A nationwide cohort study.
Metabolism. 2022;133:155222.

Abstract
BACKGROUND Population-based data regarding the prognostic implications of hepatic steatosis have been inconsistent. We examined the association between the fatty liver index (FLI) with all-cause and disease-specific mortality in the general population.
METHODS We included subjects who underwent a health examination in 2009 using the Korean nationwide health screening database. Death and cause of death data were provided by Statistics Korea. The causes of death were classified using 10th Revision of the International Classification of Diseases codes.
RESULTS Among the included 10,585,844 participants, there were 418,296 deaths during a median follow-up period of 8.3 years. When adjusting for possible confounding factors, the risk of all-cause mortality linearly increased with a higher FLI score (hazard ratio [HR], 95% confidence interval [CI]: FLI 30-59, 1.19, 1.18-1.20; FLI ≥ 60, 1.67, 1.65-1.69, P for trend <0.001). The risk of disease-specific mortality including cardiovascular disease (CVD), cancer, respiratory disease and liver disease, linearly increased as the FLI score became higher (HR, 95% CI: FLI 30-59, 1.18, 1.16-1.20, FLI ≥ 60: 1.61, 1.56-1.65 for CVD; FLI 30-59, 1.13, 1.11-1.14, FLI ≥ 60, 1.41, 1.38-1.44 for cancer; FLI 30-59, 1.26, 1.22-1.29, FLI ≥ 60, 1.96, 1.88-2.05 for respiratory disease, FLI 30-59, 2.29, 2.21-2.38, FLI ≥ 60, 5.57, 5.31-5.85 for liver disease). The risk of all-cause mortality increased as the FLI score became higher across all the body mass index groups, and the greatest risk was observed in those who were underweight (HR, 95% CI = 2.43, 2.09-2.82 in FLI ≥ 60).
CONCLUSION FLI may serve as a prognostic indicator of death and a high FLI is associated with a poor prognosis particularly in the underweight group.
PubMed IF 16.7 소화기내과
38112022

제1저자 이현우 · 교신저자 이현우

, , , , ,
Rapid FEV1 Decline and Lung Cancer Incidence in South Korea.
Chest. 2022;162(2):466-474.

Abstract
BACKGROUND Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer.
RESEARCH QUESTION Is accelerated lung function decline associated with the development of lung cancer?
STUDY DESIGN AND METHODS A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV₁ > 60 mL per year were defined as rapid FEV₁ decliners. The relationship between lung cancer and rapid FEV₁ decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV₁/FVC, and WBC count.
RESULTS Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV₁ decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged ≥ 45 years and those with ≥ 30 pack-years of smoking, low baseline FEV₁/FVC, low forced expiratory flow between 25% and 75% of vital capacity, rapid FEV₁ decline, and increased WBC count. Rapid FEV₁ decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95% CI, 1.28-4.28; P = .006). Time-dependent net reclassification improvement showed a benefit of FEV₁ decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95% CI, 0.00-0.64]; continuous, 0.83 [95% CI, 0.14-1.25]).
INTERPRETATION The FEV₁ decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV₁ decline warrant lung cancer assessment or screening.
PubMed IF 9.8 호흡기내과
38102022

제1저자 강소현 · 교신저자 민사홍, 김진원

, , , , , , , , , , , , , ,
Safety and Efficacy of Intraperitoneal Paclitaxel Plus Intravenous Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) for Gastric Cancer with Peritoneal Metastasis.
Ann Surg Oncol. 2022;29(8):5084-5091.

Abstract
BACKGROUND Peritoneal metastasis (PM) remains a major obstacle in the treatment of stage IV gastric cancer. This is a dose-escalation study of intraperitoneal (IP) paclitaxel combined with intravenous (IV) fluorouracil, leucovorin, and oxaliplatin (FOLFOX) to determine the recommended phase II dose in gastric cancer patients.
METHODS Patients with gastric adenocarcinoma and PM were enrolled. The recommended phase II dose of IP paclitaxel was determined using the standard "3 + 3" dose escalation with planned doses ranging from 40 to 100 mg/m². IV FOLFOX was administered on the same day (oxaliplatin 100 mg/m² (day 1), leucovorin 100 mg/m² (day 1), fluorouracil 2,400 mg/m² over 46 hours (day 1)). Both IP and IV regimens were repeated every 2 weeks.
RESULTS Among the 13 patients, there was no DLT at 40 and 60 mg/m². Two patients had grade 3 febrile neutropenia at 80 mg/m², and the recommended phase II dose was 60 mg/m². Other patients underwent IP paclitaxel and FOLFOX without serious adverse events. Seven patients underwent second-look diagnostic laparoscopy, and the average change in PCI score was -7.0 ± 9.7. Conversion surgery rate was 23.1% (n = 3). The median overall survival was 16.6 months (95% confidence interval, 16.6-N/A), and progression-free survival was 9.6 months (95% confidence interval, 4.7-N/A). All adverse events were tolerable and manageable.
CONCLUSIONS The biweekly regimen of IP paclitaxel and FOLFOX is safe and the recommended dose of IP paclitaxel for a phase II trial is 60 mg/m².
PubMed IF 3.8 혈액종양내과
38092022

제1저자 오경석 · 교신저자 오도연

, , , , , , ,
A synthetic lethal strategy using PARP and ATM inhibition for overcoming trastuzumab resistance in HER2-positive cancers.
Oncogene. 2022;41(32):3939-3952.

Abstract
Despite its clinical efficacy in HER2-positive cancers, resistance to trastuzumab inevitably occurs. The DNA damage response (DDR) pathway is essential for maintaining genomic stability and cell survival. However, the role of the DDR pathway in HER2-positive tumors and trastuzumab resistance remains elusive. In this study, we verified that increased PARP1 expression in trastuzumab-resistant (TR) cells, owing to its augmented stability by escape from proteasomal degradation, confers tolerability to trastuzumab-induced DNA damage. Interruption of PARP1 in TR cells restrains its cellular growth, while simultaneously activating ATM to retain its genome stability. Dual inhibition of PARP and ATM induces synthetic lethality in TR cells by favoring the toxic NHEJ pathway instead of the HRR pathway. Our results highlight the potential of clinical development of DDR-targeting strategies for trastuzumab-resistant HER2-positive cancer patients.
PubMed IF 9.1 혈액종양내과

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