SCI 발표논문

전체 4,588편

31482020

제1저자 이상협 · 교신저자 박도중

, , , , , , , , , , , , , , , , , , , ,
Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial.
JAMA Surg. 2020;155(8):703-711.

Abstract
IMPORTANCE The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy.
OBJECTIVE To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer.
DESIGN, SETTING, AND PARTICIPANTS The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results.
INTERVENTIONS Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks.
MAIN OUTCOMES AND MEASURES Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy.
RESULTS A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P < .001) in the 600-mg group. No significant adverse drug reactions were detected among the enrolled patients.
CONCLUSIONS AND RELEVANCE Administration of UDCA for 12 months significantly reduced the incidence of gallstones after gastrectomy for gastric cancer. These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02490111.
PubMed IF 15.6 소화기내과
31472020

제1저자 이영아, 임선화 · 교신저자 박영주, 김종일

, , , , , ,
Predominant DICER1 Pathogenic Variants in Pediatric Follicular Thyroid Carcinomas.
Thyroid. 2020;30(8):1120-1131.

Abstract
Background: Pediatric thyroid cancer has characteristics that are distinct from adulthood thyroid cancer. Due to its very low prevalence, little is known about the genetic characteristics of pediatric follicular thyroid cancer (FTC). Methods: We investigated genetic alterations in tumor tissues from 15 patients aged <20 years (median: 14.3 years; range: 2.4 - 19.0 years) using multifaceted approaches. Whole-exome sequencing, targeted next-generation sequencing using a cancer gene panel, and Sanger sequencing of the major exons of the H/K/N-RAS and DICER1 genes and the promoter region of the TERT gene were performed. Normal tissues or blood of patients with DICER1- or PTEN-positive tumors was also evaluated to determine whether the variant is germ line. Results: The median tumor size was 3.1 cm (range: 0.6 - 6.4 cm). Four patients exhibited angioinvasion and one extensive capsular invasion; none showed evidence of disease over a median of 8.1 years. Eight patients (53.3%) had DICER1 variants, including four with DICER1 syndrome (three patients were <10 years of age). One patient had a germ line PTEN frameshift variant with the diagnosis of PTEN hamartoma tumor syndrome. One patient had a PAX8/PPARγ rearrangement, and two patients had no genetic driver alteration other than multiple loss of heterozygosity with or without copy number alterations in their tumors. No RAS or TERT variants were found. Nodular hyperplasia and follicular adenoma (FA) coexisted in DICER1 variant-positive FTCs more frequently than variant-negative FTCs (p = 0.026). All DICER1 variant-positive FTCs had a somatic missense variant at metal binding sites (six at codon p.E1813 and two at codon p.D1709) within the RNase IIIb domain; seven had other missense, nonsense, or frameshift variants in the DICER1 gene. Six coexisting FAs of two patients with DICER1 syndrome (three of each) had additional somatic variants at metal binding sites within the RNase IIIb domain (codon p.E1705, p.D1709, p.D1810, or p.E1813), different from each other and from the indexed FTC tumor. Conclusions: Pediatric FTCs have distinct genomic alterations and pathogenesis compared with adults, particularly those characterized by DICER1 variants. The DICER1 variant should be considered in pediatric FTCs, especially in cases <10 years of age. In all DICER1 variant-positive FTCs and FAs, recurrent hotspot variants were found at metal binding sites within the RNase IIIb domain, suggesting they impact tumorigenesis.
PubMed IF 6.6 내분비대사내과
31462020

제1저자 김민관, 김학령 · 교신저자 조주희

, , , , , , , , ,
Echocardiographic parameters determining cardiovascular outcomes in patients after acute ischemic stroke.
Int J Cardiovasc Imaging. 2020;36(8):1445-1454.

Abstract
Previous studies have focused on only 1 or 2 echocardiographic parameters as prognostic markers in patients with acute ischemic stroke (AIS). A total of 900 patients with AIS who underwent transthoracic echocardiography (72.6 ± 12.0 years and 60% males) were retrospectively reviewed. Composite clinical events, including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and coronary revascularization, were assessed during clinical follow-ups. During a median follow-up of 3.3 years (interquartile range 0.6-5.1 years), there were 151 (16.8%) composite events. In the multivariable analyses after controlling for potential confounders, left ventricular ejection fraction (LVEF) < 62% (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.14-2.30; p = 0.007) and AV sclerosis (AVs) (HR 1.56; 95% CI 1.10-2.21; p = 0.013) were independent prognostic factors associated with composite events. Multivariable analyses showed that HR for composite events gradually increased according to LVEF and AVs: HR was 2.6-fold higher in the highest-risk group than in the lowest group (p < 0.001). Compared with a clinical model (global chi-square = 69.6), LVEF, AVs, and both of them were significantly improved outcome prediction in sequential Cox model analysis (global chi-square = 75.6, 75.7, and 78.8, respectively; p < 0.05 for each) for each. In patients with AIS, LVEF < 62%, and the presence of AV sclerosis can predict future vascular events. Patients with AIS exhibiting reduced LVEF and AV sclerosis may benefit from aggressive secondary prevention.
PubMed IF 1.5 순환기내과
31452020

제1저자 조혜기, 장영 · 교신저자 이정훈

, , , , , , , , , , ,
Radiologic Nonalcoholic Fatty Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Suppressed Chronic Hepatitis B.
J Clin Gastroenterol. 2020;54(7):633-641.

Abstract
BACKGROUND AND GOALS Although nonalcoholic fatty liver disease (NAFLD) is a risk factor of hepatocellular carcinoma (HCC), it is unclear whether NAFLD additionally increases the risk of HCC among chronic hepatitis B (CHB) patients. This study evaluated the association between NAFLD and the risk of HCC in patients whose hepatitis B virus (HBV) was well controlled.
STUDY This study included consecutive CHB patients whose serum HBV DNA levels were continuously suppressed <2000 IU/mL with antiviral treatment. Fatty liver was radiologically diagnosed. Patients with concomitant hepatitis C infection, autoimmune hepatitis, or excessive alcohol use were excluded.
RESULTS Among 826 patients, 86 patients (10.4%) developed HCC during the study period (median, 43.1 mo). The patients with NAFLD (N=260) had a significantly higher risk for HCC compared with patients without NAFLD (N=566) (adjusted hazard ratio, 1.67; 95% confidence interval, 1.05-2.63; P=0.03) after adjustment for age, the presence of cirrhosis, hepatitis B envelop antigen positivity, low-level viremia and hypertension. There was significant association between incomplete biochemical response (IBR) (alanine aminotransferase levels ≥40 IU/L) and the presence of NAFLD (P<0.001 by χ test). IBR at the time of virological response was associated with a significantly higher risk of HCC development (adjusted hazard ratio, 1.63; 95% confidence interval, 1.06-2.54; P=0.03).
CONCLUSIONS NAFLD increases the risk of HCC in patients with CHB in whom HBV is effectively suppressed by antivirals. Patients with IBR should be suspected of concurrent NAFLD. Further study is warranted to evaluate whether improvement of NAFLD might decrease the risk of HCC development.
PubMed IF 2.7 소화기내과
31442020

제1저자 최평균 · 교신저자 오명돈

, , , , , ,
Prolonged (6-Month) Shedding of Middle East Respiratory Syndrome Coronavirus RNA in the Sputum of a Lymphoma Patient.
Open Forum Infect Dis. 2020;7(8):ofaa292.

Abstract
During the 2015 Korea Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, a lymphoma patient developed MERS pneumonia. His pneumonia improved by 45 days after illness onset, but the polymerase chain reaction tests remained (+) for 6 months. However, replication-competent virus was detected by 60 days after illness onset.
PubMed IF 3.8 감염내과
31432020

제1저자 박지은 · 교신저자 김범석

, , , , , , , , ,
Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines.
J Immunother Cancer. 2020;8(2):jitc-2020-000873.

Abstract
BACKGROUND Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines.
METHODS Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by ⁵¹Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. FcγRIIIa (CD16a)-V158F genotyping was performed for healthy donors.
RESULTS We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype.
CONCLUSION These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs.
PubMed IF 11.7 혈액종양내과
31422020

제1저자 박지숙, 한정규 · 교신저자 김효수

, , , , , , , , , ,
Impact of Intensive Glucose Control in Patients with Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: 3-Year Clinical Outcomes.
J Clin Med. 2020;9(8):jcm9082464.

Abstract
We investigated whether intensive glucose control after percutaneous coronary intervention (PCI) improves clinical outcomes in diabetic patients. From the Grand-DES registry, we analyzed 2576 diabetic patients (median age 66 years, male 65.6%) who underwent PCI and had at least 2 records of HbA1c during the follow-up. Patients were categorized according to the mean HbA1c (≥7% or <7%). Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiac death, non-fatal myocardial infarction, and any revascularization. During a median follow-up of 33.6 months, MACE occurred in 335 (13.0%) patients. Intensive glucose control with follow-up mean HbA1c < 7.0% (42.2%; n = 1087) was not associated with lower risk of MACE, compared to control with mean HbA1c ≥ 7.0% (adjusted hazard ratio [aHR] [95% confidence interval] 1.06 [0.82-1.37], p = 0.672). In subgroup analysis, patients with sustained HbA1c of <7.0% throughout the follow-up were not associated with a lower risk of MACE compared to those with sustained HbA1c of ≥7.0% (aHR 1.15 [0.71-1.89], p = 0.566). More intensive glucose control with mean HbA1c ≤ 6.5% was not associated with lower risk of MACE, compared to loose control with a mean HbA1c ≥ 8.0% (aHR 1.15 [0.71-1.86], p = 0.583). Intensive glucose control after PCI was not associated with better clinical outcomes in diabetic patients undergoing PCI than lenient control.
PubMed IF 3.3 순환기내과
31412020

제1저자 강창경, 한기찬, 김민지 · 교신저자 김항래, 오명돈

, , , , , , , , , , , ,
Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.
Int J Infect Dis. 2020;97:313-321.

Abstract
OBJECTIVES We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.
METHODS We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry.
RESULTS The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4⁺ and CD8⁺ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4⁺ or CD8⁺ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group.
CONCLUSIONS Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.
PubMed IF 4.6 감염내과
31402020

제1저자 김영선 · 교신저자 김나영

,
Functional Dyspepsia: A Narrative Review With a Focus on Sex-Gender Differences.
J Neurogastroenterol Motil. 2020;26(3):322-334.

Abstract
Functional dyspepsia (FD) is among the most common gastrointestinal disorders affecting quality of life (QoL). As it frequently occurs in women than in men the comparison of various aspects including prevalence, clinical manifestations, and QoL in FD between women and men is very important for understanding the disease distribution and burden, evaluating treatment options, developing new drugs, and allocating medical resources. However, little is known about sex or gender differences among patients with FD. In spite of limited studies, consistent points are that FD occurs more often in women than in men and there are several symptom differences between men and women with FD. In addition, women with FD tend to have lower QoL than men with FD. Similarly, the pathophysiology of FD likely to vary depending on gender. Furthermore, a sex-gender-oriented approach in healthcare system could enhance understanding heterogeneous patients suffering from FD. Due to the sex-gender differences in physiological and psychological factors, treatment strategies should differ between women and men with FD. In conclusion, an individualized and multicomponent approach that considers sex and gender issues might improve FD treatment and improve patient Qol, especially for women.
PubMed IF 3.7 소화기내과
31392020

제1저자 김재형 · 교신저자 황진혁

, , , ,
Involvement of the NF-κB signaling pathway in proliferation and invasion inhibited by Zwint-1 deficiency in Pancreatic Cancer Cells.
J Cancer. 2020;11(19):5601-5611.

Abstract
Pancreatic cancer (PC) is an intractable cancer that is difficult to diagnose early and has a 5-year survival rate of less than 8%. ZW10-interacting kinetochore protein (ZWINT) is a crucial gene that contributes to chromosome instability and is essential for spindle assembly and kinetochore-microtubule attachment during meiosis and mitosis. However, the mechanism through which Zwint-1 promotes PC progression is yet to be elucidated. Here, we report that Zwint-1 is highly expressed in clinical PC specimens (based on analysis of the Gene Expression Profiling Interactive Analysis database) and various PC cell lines. Importantly, Zwint-1-deficient PC cells showed reduced nuclear factor-kappa B (NF-κB) (Ser536) phosphorylation along with inhibited proliferation and colony formation due to downregulation of NF-κB-regulated genes such as CCND1, cIAP1/2, and XIAP. In addition, Zwint-1-deficient PC cells showed reduced invasion and migration abilities, and decreased expression levels of the metalloproteinases MMP2 and MMP9. Furthermore, Zwint-1 deficiency arrested the PC cell cycle at the G₂/M phase because the chromosomes failed to segregate properly, and the apoptosis rate in these cells gradually increased, accompanied by increased caspase-3 activation and anti-poly (ADP ribose) polymerase cleavage. Apoptosis caused by Zwint-1 deficiency was demonstrated to occur through caspase-dependent pathways based on experiments involving treatment with a pan-caspase inhibitor (Z-VAD-Fmk). Thus, Zwint-1 contributes to cell growth, invasion, and survival through NF-κB signaling pathways, suggesting that it could serve as a PC biomarker and new therapeutic target.
PubMed IF 3.4 소화기내과
31382020

제1저자 박진균 · 교신저자 송영욱

, , , , , , , , , , ,
Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis.
Arthritis Res Ther. 2020;22(1):176.

Abstract
OBJECTIVES Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA).
METHODS HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA).
RESULTS Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect.
CONCLUSION The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.
PubMed IF 5.4 류마티스내과
31372020

제1저자 김귀진, 김지원 · 교신저자 이근욱

, , , , , , , , , , , , ,
PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer.
Sci Rep. 2020;10(1):12308.

Abstract
PIK3CA mutations are frequently observed in various human cancers including gastric cancer (GC). This study was conducted to investigate the anti-tumor effects of alpelisib, a PI3K p110α-specific inhibitor, using preclinical models of GC. In addition, the combined effects of alpelisib and paclitaxel on GC were evaluated. Among the SNU1, SNU16, SNU484, SNU601, SNU638, SNU668, AGS, and MKN1 GC cells, three PIK3CA-mutant cells were predominantly sensitive to alpelisib. Alpelisib monotherapy decreased AKT and S6K1 phosphorylation and induced G₀/G₁ phase arrest regardless of PIK3CA mutational status. The alpelisib and paclitaxel combination demonstrated synergistic anti-proliferative effects, preferentially on PIK3CA-mutant cells, resulting in increased DNA damage response and apoptosis. In addition, alpelisib and paclitaxel combination potentiated anti-migratory activity in PIK3CA-mutant cells. Alpelisib partially reversed epithelial-mesenchymal transition markers in PIK3CA-mutant cells. In a xenograft model of MKN1 cells, the alpelisib and paclitaxel combination significantly enhanced anti-tumor activity by decreasing Ki-67 expression and increasing apoptosis. Moreover, this combination tended to prolong the survival of tumor-bearing mice. Our data suggest promising anti-tumor efficacy of alpelisib alone or in combination with paclitaxel in PIK3CA-mutant GC cells.
PubMed IF 4.9 혈액종양내과
31362020

제1저자 송진희 · 교신저자 김나영

, , , , ,
17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice.
Sci Rep. 2020;10(1):12283.

Abstract
The composition of the gut microbiota is influenced by sex hormones and colorectal cancer (CRC). Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice. Here, we investigated whether the composition of the gut microbiota is different between male and female, and is regulated by estrogen as a secondary outcome of previous studies. We established four groups of mice based on the sex and estrogen status [ovariectomized (OVX) female and E2-treated male]. Additionally, three groups of males were established by treating them with AOM/DSS, and E2, after subjecting them to AOM/DSS treatment. The mice were sacrificed at 21 weeks old. The composition of the gut microbiota was analyzed using 16S rRNA metagenomics sequencing. We observed a significant increase in the microbial diversity (Chao1 index) in females, males supplemented with E2, and males treated with AOM/DSS/E2 compared with normal males. In normal physiological condition, sex difference and E2 treatment did not affect the ratio of Firmicutes/Bacteroidetes (F/B). However, in AOM/DSS-treated male mice, E2 supplementation showed significantly lower level of the F/B ratio. The ratio of commensal bacteria to opportunistic pathogens was higher in females and E2-treated males compared to normal males and females subjected to OVX. Unexpectedly, this ratio was higher in the AOM/DSS group than that determined in other males and the AOM/DSS/E2 group. Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.
PubMed IF 4.9 소화기내과
31352020

제1저자 안수민, 이종찬 · 교신저자 황진혁

, , , ,
High PD-L1 expression is associated with therapeutic response to pembrolizumab in patients with advanced biliary tract cancer.
Sci Rep. 2020;10(1):12348.

Abstract
Pembrolizumab appears promising for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. However, data on immunotherapy for biliary tract cancers (BTC) are limited. We aimed to investigate the predictive value of PD-L1 expression as an immunotherapeutic biomarker in BTC. Patients with advanced BTC (n = 175) were screened for PD-L1 expression using PharmDx assay and microsatellite instability (MSI) status. Of the total of 175 patients, 125 (71%) showed tumoral PD-L1 positivity (≥ 1%) while only two (2/142, 1.4%) showed MSI-High. Among 175 patients, 26 patients were treated with pembrolizumab as a second-line therapy, and tumor response was evaluated. Separating these patients into two groups by PD-L1 expression (high [≥ 50%] vs. low [< 50%]), overall response rate was 23% (56% [5/9] in high PD-L1 group vs. 6% [1/17] in low PD-L1 group, P = 0.004). Disease control rate was also higher in high PD-L1 group (78% vs. 35%, P = 0.019). The six responders showed median progression-free survival of 5.8 months after starting pembrolizumab, and none of them was MSI-High. High PD-L1 expression was associated with a better response to pembrolizumab. PD-L1 expression can potentially serve as an alternative predictive biomarker for pembrolizumab therapy in advanced BTC.
PubMed IF 4.9 소화기내과
31342020

제1저자 박현경 · 교신저자 변자민, 윤성수

, , , , , ,
Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant? (Running Title: The Role of Salvage alloSCT in MM).
J Clin Med. 2020;9(8):jcm9082354.

Abstract
BACKGROUND Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear.
METHODS Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017.
RESULTS The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%).
CONCLUSION AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.
PubMed IF 3.3 혈액종양내과
31332020

제1저자 변자민 · 교신저자 윤성수, 이정림

, , , , , , , , , , , , , , , , ,
Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia.
J Clin Med. 2020;9(7):jcm9072310.

Abstract
Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.
PubMed IF 3.3 혈액종양내과
31322020

제1저자 강은정, 한승석 · 교신저자 오국환

, , , , , , , , ,
Discrepant glomerular filtration rate trends from creatinine and cystatin C in patients with chronic kidney disease: results from the KNOW-CKD cohort.
BMC Nephrol. 2020;21(1):280.

Abstract
BACKGROUND Serum creatinine (Cr) and cystatin C (CysC) can both be used to estimate glomerular filtration rate (eGFR_Cr and eGFR_CysC). However, certain conditions may cause discrepancies between eGFR trends from Cr and CysC, and these remain undetermined in patients with chronic kidney disease (CKD).
METHODS A total of 1069 patients from the Korean CKD cohort (KNOW-CKD), which enrolls pre-dialytic CKD patients, whose Cr and CysC had been followed for more than 4 years were included in the sample. We performed trajectory analysis using latent class mixed modeling and identified members of the discrepancy group when patient trends between eGFR_Cr and eGFR_CysC differed. Multivariate logistic analyses with Firth's penalized likelihood regression models were performed to identify conditions related to the discrepancy.
RESULTS Trajectory patterns of eGFR_Cr were classified into three groups: two groups with stable eGFR_Cr (stable with high eGFR_Cr and stable with low eGFR_Cr) and one group with decreasing eGFR_Cr. Trajectory analysis of eGFR_CysC also showed similar patterns, comprising two groups with stable eGFR_CysC and one group with decreasing eGFR_CysC. Patients in the discrepancy group (decreasing eGFR_Cr but stable & low eGFR_CysC; n = 55) were younger and had greater proteinuria values than the agreement group (stable & low eGFR_Cr and eGFR_CysC; n = 706), differences that remained consistent irrespective of the measurement period (4 or 5 years).
CONCLUSIONS In the present study, we identify conditions related to discrepant trends of eGFR_Cr and eGFR_CysC. Clinicians should remain aware of such potential discrepancies when tracing both Cr and CysC.
PubMed IF 2.9 신장내과
31312020

제1저자 조인국, 김혜령 · 교신저자 황진혁

, , , , , , ,
Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator.
Gut Liver. 2020;14(4):521-528.

Abstract
BACKGROUND/AIMS Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes.
METHODS We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes.
RESULTS The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107).
CONCLUSIONS Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.
PubMed IF 4.1 소화기내과
31302020

제1저자 백성민 · 교신저자 김나영

, , , , , , , , ,
Role of Serum Pepsinogen II and Helicobacter pylori Status in the Detection of Diffuse-Type Early Gastric Cancer in Young Individuals in South Korea.
Gut Liver. 2020;14(4):439-449.

Abstract
BACKGROUND/AIMS The utility of serum pepsinogen (sPG) I and the sPGI/II ratio as biomarkers for screening individuals with gastric cancer (GC) has not been established in Korea. The aim of this study was to define the role of sPG, especially sPGII, in GC screening.
METHODS This study enrolled 2,940 subjects, including patients with GC (n=1,124) or gastric dysplasia (n=353) and controls (n=1,463). Tests to determine sPG levels and Helicobacter pylori (HP) infection status were performed. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for sPG. The usefulness of sPG levels for the detection of GC and gastric dysplasia was validated by multivariate logistic regression.
RESULTS The sPGI/II ratio was associated with the risk of gastric dysplasia and advanced-stage intestinal-type GC (IGC). In contrast, sPGII was associated with the risk of early-stage diffuse-type GC (DGC). Significantly higher risk was indicated by an sPGI/II ratio <3 for gastric dysplasia and advanced-stage IGC and by sPGII levels ≥20 µg/L for early-stage DGC. Positive HP status showed a stronger association with DGC than with IGC. When sPGII level and HP status were combined, the prevalence of DGC was higher in the ≥20 µg/L sPGII and HP-positive group. Age younger than 40 years was strongly related to early-stage DGC, especially in females (odds ratio, 21.00; p=0.006).
CONCLUSIONS sPGII ≥20 ng/mL and positive HP status suggest a risk of early-stage DGC, particularly in young adult females in South Korea.
PubMed IF 4.1 소화기내과
31292020

제1저자 기유정, 정지현 · 교신저자 한정규

, , , , , , , , , , , , , ,
Clinical Implications of Bifurcation Angles in Left Main Bifurcation Intervention Using a Two-Stent Technique.
J Interv Cardiol. 2020;2020:2475930.

Abstract
OBJECTIVES The aim of this study was to assess the clinical impact of 3 bifurcation angles in left main (LM) bifurcation treated with the 2-stent technique.
BACKGROUND Data are limited regarding the impact of bifurcation angles after LM percutaneous coronary intervention (PCI).
METHODS Using patient-level 4 multicenter registries in Korea, 462 patients undergoing LM bifurcation PCI with the 2-stent technique were identified (181 crush, 167 T-stenting; 63% 1^st generation drug-eluting stent (DES), 37% 2^nd generation DES). Three bifurcation angles, between the LM and left anterior descending (LAD), the LM and left circumflex (LCX), and the LAD and LCX, were measured. The primary outcome was target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR).
RESULTS In patients treated with the crush technique, the best cutoff value (BCV) to predict TLF was 152° of the LM-LAD angle. In the crush group, a significantly higher TLF rate, mostly driven by TLR, was observed in the LM-LAD angle ≥152° group compared with the <152° group (35.7% vs. 14.6%; adjusted hazard ratio 3.476; 95% confidence interval 1.612-7.492). An LM-LAD angle ≥152° was an independent predictor of TLF. In the T-stenting, no bifurcation angle affected the clinical outcomes.
CONCLUSIONS In LM bifurcation PCI using the 2-stent technique, wide LM-LAD angle (≥152°) was associated with a greater risk of TLF in the crush, whereas none of the bifurcation angles affected T-stenting outcomes.
PubMed IF 1.4 순환기내과
31282020

제1저자 김범석, 강창경 · 교신저자 박완범, 김유정

, , , , , , , , , , , , , , , , , , , , , , ,
Immunogenicity of Influenza Vaccination in Patients with Cancer Receiving Immune Checkpoint Inhibitors.
Clin Infect Dis. 2020;71(2):422-425.

Abstract
Among prospectively enrolled adult patients with cancer receiving immune checkpoint inhibitors (ICIs; n = 46) or cytotoxic agents (n = 90), seroprotection and seroconversion rates after seasonal quadrivalent influenza vaccinations were higher with ICI than with cytotoxic chemotherapy. These results support annual influenza vaccinations for cancer patients receiving ICIs. Clinical Trials Registration clinicaltrials.gov (NCT03590808).
PubMed IF 8.3 감염내과
31272020

제1저자 박혜주 · 교신저자 윤성수, 고영일

, , , , ,
Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial-mesenchymal transition utilizing RAF/MAPK pathway.
Carcinogenesis. 2020;41(6):817-827.

Abstract
MYH8 is an actin-based motor protin involved in integrin-mediated cell adhesion and migration. Heretofore, the association of MYH8 mutation and cancer is unclear. In this study, we investigated the biologic significance of novel MYH8 tail truncation mutation, R1292X, in acute myeloid leukemia (AML) which was discovered by whole-exome sequencing and targeted re-sequencing of 209 AML patients. The patients harboring the mutation all relapsed within 3.8-20.9 months. To explore the functional consequence of the mutation in AML progress, we established knock-in cell lines using CRISPR-Cas9 genome editing. Using the established mutant model, we assessed traits of cancer progress. The mutant cells had improved motility, which was confirmed by immunofluorescence staining, wound healing, transwell migration and adhesion assay. The cell morphology and cell cycle were altered to be accessible to migration and epithelial-to-mesenchymal transition (EMT) transcription factors were also increased. The Raf and p44/42 MAPK pathway was a major regulator of these characteristics proved by a screening of signal transduction and inhibitor assay. Further, a public cancer genome database (cBioPortal) shows that MYH8 tail truncation mutations occurring near the R1292 position of the genome may have a significant function in cancer. In conclusion, truncation of MYH8 could be a novel prognostic marker related to poor prognosis by inducing cell migration and EMT features, and inhibition of the Raf/MAPK pathway would be a therapeutic strategy for AML patients with MYH8 tail truncation.
PubMed IF 3.8 혈액종양내과
31262020

제1저자 허건, 최진호 · 교신저자 이상협

, , , , , , , , ,
Innovation of EUS-guided transmural gallbladder drainage using a novel self-expanding metal stent.
Sci Rep. 2020;10(1):11159.

Abstract
Endoscopic ultrasonography (EUS)-guided transmural drainage has been accepted as a modality of choice in peripancreatic fluid collection and acute cholecystitis. Each type of stent, including double-pigtail plastic stents, tubular self-expandable metal stents (SEMS), and lumen-apposing metal stents, for these procedure has its own advantages and disadvantages. To overcome their disadvantages, this animal study evaluated the feasibility of a newly designed twisted fully covered SEMS with spiral coiled ends. We performed the EUS-guided cholecystogastrostomy with a newly developed metal stent in eight mini pigs with surgically induced gallbladder distension. This novel stent is a twisted fully covered SEMS with spiral coiled ends, a diameter of 8 mm, and a length of 6 cm. The stent has been maintained for four to seven weeks after EUS-guided cholecystogastrostomy. The primary outcome was the technical success rate, and the secondary outcomes were adverse events, stent dysfunction, stent removability, and fistula formation. The stent was placed successfully between the gallbladder and the stomach in all cases without any adverse event. We observed neither stent migration nor dysfunction during the study period, and all the stents were removed easily as scheduled. We confirmed successful cholecysto-gastric fistula formation at endoscopic and histologic level in all cases. EUS-guided transmural drainage and fistula formation using a new twisted fully covered metal stent with spiral coiled ends was technically feasible without any adverse event in this animal study. Further clinical studies are needed to evaluate its efficacy and safety in real practice.
PubMed IF 4.9 소화기내과
31252020

제1저자 윤준식, 이동호 · 교신저자 조은주, 배은정

, , , , , , , , , , , ,
Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance.
Cancers (Basel). 2020;12(7):cancers12071805.

Abstract
Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.
PubMed IF 4.8 소화기내과
31242020

제1저자 손경희, 함종호 · 교신저자 강혜련, 김혜영

, , , ,
Analysis of Innate and Adaptive Immunological Characteristics in Patients with IgG4-Related Disease.
Int Arch Allergy Immunol. 2020;181(10):807-812.

Abstract
BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunological disorder characterized by fibro-inflammatory conditions; however, the pathobiology of IgG4-RD has not been fully identified.
OBJECTIVE This study aimed to analyze systemic differences of innate and adaptive immune cells from healthy controls and patients with IgG4-RD.
METHODS Healthy controls (n = 9) and IgG4-RD patients (n = 7) were recruited with informed consent. Peripheral blood was collected from healthy controls and IgG4-RD patients, and three blood samples from IgG4-RD patients were re-collected two months after the last rituximab (RTX) treatment. The various immune cells and cytokine productions were measured by flow cytometry.
RESULTS Blood CD14+ monocytes and steady-state follicular helper T cells were increased in patients with IgG4-RD. However, there were no changes in other immune cell populations, including B cells, CD4 T cells, CD8 T cells, and innate lymphoid cells. Also, the TGF-β-producing CD14+ monocytes were significantly augmented in patients with IgG4-RD. Two months after RTX treatment, total B cells (CD19+) were depleted; however, the expressions of TGF-β from CD14+ monocytes remained unchanged.
CONCLUSION These findings showed that IgG4-RD is related to the increment of CD14+ monocytes. Besides, controlling increased TGF-β-producing CD14+ monocytes with RTX treatment might be a conducive way to regulate IgG4-RD.
PubMed IF 2.3 알레르기내과
31232020

제1저자 박소영, 김정희 · 교신저자 조남한

, , , , , , ,
Longitudinal changes in bone mineral density and trabecular bone score in Korean adults: a community-based prospective study.
Arch Osteoporos. 2020;15(1):100.

Abstract
UNLABELLED The bone mineral densities (BMDs) of the femoral neck and total hip, and the lumbar spine trabecular bone score (TBS), tended to decrease with age in both men and women, whereas the lumbar spine BMD tended to increase. Lumbar spine BMD is thus inappropriate for evaluating longitudinal changes in bone loss; the lumbar spine TBS is an alternative measure.
PURPOSE Aging is associated with a decrease in bone mass and quality. This community-based prospective cohort study investigated longitudinal changes in bone phenotype in Korean adults.
METHODS We analyzed data from a prospective community-based cohort study, the Korean Genome and Epidemiology Study. Postmenopausal women and men who underwent dual-energy X-ray absorptiometry at least twice from 2007 to 2014 were included. Longitudinal changes in bone mineral density (BMD) and trabecular bone score (TBS) over 6 years were analyzed by sex, age, and body mass index.
RESULTS A total of 1895 subjects were enrolled (men 965; postmenopausal women 929). The femoral neck (FN) BMD, total hip (TH) BMD, and lumbar spine (LS) TBS decreased significantly over time, but the LS BMD increased significantly. In men, the average annual changes were 0.3% in LS BMD (p < 0.001), - 0.33% in FN BMD (p < 0.001), - 0.26% in TH BMD (p = 0.001), and - 0.27% in LS TBS (p < 0.001). In women, the average annual changes were 0.27% in LS BMD (p < 0.001), - 0.67% in FN BMD (p < 0.001), - 0.66% in TH BMD (p < 0.001), and - 0.27% in LS TBS (p < 0.001). The longitudinal decrease in TH BMD over time was significantly greater in women (versus men) and those who were older (versus younger).
CONCLUSION The FN and TH BMDs decreased with aging. But, the LS BMD was inappropriate to evaluate longitudinal changes of bone loss. The LS TBS could be alterative.
PubMed IF 2.7 내분비대사내과
31222020

제1저자 강민규 · 교신저자 박흥우

, , ,
Genetic Signatures of Acute Asthma Exacerbation Related With Ineffective Response to Corticosteroid.
Allergy Asthma Immunol Res. 2020;12(4):626-640.

Abstract
PURPOSE Acute exacerbation (AE) is an important domain of asthma management and may be related with ineffective response to corticosteroid. This study aimed to find mechanisms of AE using genome-wide gene expression profiles of blood cells from asthmatics and its perturbation by in vitro dexamethasone (Dex)-treatment.
METHODS We utilized lymphoblastoid B cells from 107 childhood asthmatics and peripheral blood mononuclear cells from 29 adult asthmatics who were treated with inhaled corticosteroids. We searched for a preserved co-expression gene module significantly associated with the AE rate in both cohorts and measured expression changes of genes belong to this module after Dex-treatment.
RESULTS We identified a preserved module composed of 77 genes. Among them, expressions of 2 genes (EIF2AK2 and NOL11) decreased significantly after Dex-treatment in both cohorts. EIF2AK2, a key gene acting antiviral defense mechanism, showed significantly higher expressions in asthmatics with AE. The protein repair pathway was enriched significantly in 64 genes which belong to the preserved module but showed no expression differences after Dex-treatment in both cohorts. Among them, MSRA and MSRB2 may play key roles by controlling oxidative stress.
CONCLUSIONS Many genes belong to the AE rate-associated and preserved module identified in blood cells from childhood and adults asthmatics showed no expression changes after in vitro Dex-treatment. These findings suggest that we may need alternative treatment options to corticosteroids to prevent AE. EIF2AK2, MSRA and MSRB2 expressions on blood cells may help us select AE-susceptible asthmatics and adjust treatments to prevent AE.
PubMed IF 4.3 알레르기내과
31212020

제1저자 이철형, 이윤빈 · 교신저자 김윤준

, , , , , , , , , , , ,
Effectiveness of nivolumab versus regorafenib in hepatocellular carcinoma patients who failed sorafenib treatment.
Clin Mol Hepatol. 2020;26(3):328-339.

Abstract
BACKGROUND/AIMS Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients.
METHODS Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias.
RESULTS Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0-10.8) months for regorafenib and 5.9 (95% CI, 3.7-8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30-0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51-1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04).
CONCLUSION After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.
PubMed IF 21.7 소화기내과
31202020

제1저자 김연욱 · 교신저자 박종선

, , , , , , , ,
Diagnostic value of bronchoalveolar lavage and bronchial washing in sputum-scarce or smear-negative cases with suspected pulmonary tuberculosis: a randomized study.
Clin Microbiol Infect. 2020;26(7):911-916.

Abstract
OBJECTIVES Bronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients.
METHODS We enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications.
RESULTS A total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group.
DISCUSSION As long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.
PubMed IF 8.7 호흡기내과
31192020

제1저자 김수환 · 교신저자 임윤정

, , , , , , , , ,
Changes in performance of small bowel capsule endoscopy based on nationwide data from a Korean Capsule Endoscopy Registry.
Korean J Intern Med. 2020;35(4):889-896.

Abstract
BACKGROUND/AIMS Capsule endoscopy (CE) is widely used for the diagnosis of small bowel diseases. The clinical performance and complications of small bowel CE, including completion rate, capsule retention rate, and indications, have been previously described in Korea. This study aimed at estimating the recent changes in clinical performance and complications of small bowel CE based on 17-year data from a Korean Capsule Endoscopy Registry.
METHODS CE registry data from 35 hospitals were retrospectively analyzed. Clinical information, including completion rate, capsule retention rate, and indications, was collected and analyzed. In addition, the most recent 5-year data for CE examinations were compared with the previous 12-year data.
RESULTS A total of 4,650 CE examinations were analyzed. The most common indication for CE was obscure gastrointestinal bleeding (OGIB). The overall incomplete examination rate was 16% and the capsule retention rate was 3%. Crohn's disease was a risk factor for capsule retention. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination. An indication other than OGIB was a risk factor for incomplete examination. A recent increasing trend of CE diagnosis of Crohn's disease was observed. The most recent 5-year incomplete examination rate for CE examinations decreased compared with that of the previous 12 years.
CONCLUSION The 17-year data suggested that CE is a useful and safe tool for diagnosing small bowel diseases. The incomplete examination rate of CE decreased with time, and OGIB was consistently the main indication for CE. Inadequate bowel preparation was significantly associated with capsule retention and incomplete examination.
PubMed IF 2.2 소화기내과

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