Background: Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort. Methods: We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age:38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment. Results: Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV1 %) and forced vital capacity (FVC%) after controlling for covariates (P < 0.001). However, FEV1 /FVC ratio was not significantly different among the four quartiles (P = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV1 % < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094–1.351), 1.293 (1.156–1.448), and 1.481 (1.311– 1.672) (P for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090–1.348), 1.283 (1.147–1.436), and 1.502 (1.331–1.695) with increasing quartiles (P for trend < 0.001). However, the aORs for FEV1 /FVC < LLN were not significantly different among groups (P for trend = 0.273). Conclusion High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN. Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups. Conclusions We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Background/Aims: Standard triple therapy, including a proton pump inhibitor, clarithromycin, and amoxicillin, has been recommended as the first-line for Helicobacter pylori infection. However, the eradication rate of standard triple therapy has declined over the past years because of the increasing resistance to clarithromycin in Korea. We analyzed the eradication rates and the 10-year change in the eradication rates in Korea. Methods: PubMed, EMBASE, the Cochrane Library, and KoreaMed were searched for studies published between January 2007 and June 2018. The pooled eradication rates and their 95% CIs were estimated using a random-effect logistic regression model. Results: Twenty-six randomized controlled studies on standard triple therapy conducted in Korea were selected. The intention-to-treat (ITT) and per protocol analyses showed pooled eradication rates of standard triple therapy of 71.6% (95% CI, 69.9~73.3%) and 79.6% (95% CI, 76.6~82.2%), respectively. The eradication rate decreased with time. The ITT analysis showed that the 14-day therapy (78.1% [95% CI, 75.2~80.7%]) had significantly higher eradication rates than the 7-day therapy (70.0% [95% CI, 68.5~71.4%]) (P<0.01). Conclusions These results suggest that the eradication rate of standard triple therapy, as the first-line therapy, has shown an unacceptable decrease. The eradication rate increased when the duration of therapy was increased to 14 days, but it was not satisfactory. Therefore, other treatment regimens or therapies based on susceptibility tests should be considered for the first-line therapy.

Background/Aims: The eradication rate of the first-line standard triple therapy (STT) for Helicobacter pylori (H. pylori) infection has decreased since 2000; therefore, other first-line therapies are required. This study was aimed at investigating the efficacy of bismuth-containing quadruple therapy (PBMT) for first-line H. pylori eradication compared to STT, sequential therapy (SQT), and concomitant therapy (CT). Materials and Methods: The Ovid-MEDLINE, Koreamed, EMBASE, KMBASE, and Cochrane Library databases were searched from January 2008 to July 2018. All identified randomized controlled trials (RCTs) comparing PBMT and non-PBMT for first-line H. pylori eradication therapy were included in the final analysis. Results: A total of 3,653 patients from seven RCTs were enrolled. The pooled eradication rates of PBMT by intention-to-treat (ITT) and per-protocol (PP) analyses were 82.1% (95% CI, 68.2~90.8%) and 88.8% (95% CI, 77.1~94.9%), respectively. However, no statistically significant difference was observed in eradication rates of the 10- or 14-day PBMT as compared to 14-day STT, 10-day SQT, and 10-day CT in ITT and PP analyses. PBMT was significantly higher in adverse events than in the other eradication regimens (RR, 1.64; 95% CI, 1.11~2.44). Considerable heterogeneity in adverse events was observed among studies (χ2=88.7; P<0.001, I2=93%). Conclusions PBMT can be the first-line treatment for H. pylori eradication in Korea when other first-line options, including STT, SQT, or CT, are unavailable due to their high adverse event rates.

Background/Aims: As antibiotic resistance increases and new first-line therapies emerge, salvage therapies for Helicobacter pylori (H. pylori) eradication failures are becoming more common and complicated. This study aimed to systematically review overall salvage regimens after previous failure of H. pylori eradication. Materials and Methods: A systematic review of randomized clinical trials evaluating salvage therapies after previous H. pylori eradication failure was performed. A meta-analysis was conducted when an adequate number of studies suitable for grouping was found. Results: Overall, 36 studies with 77 treatment arms were identified, and they were highly heterogeneous regarding previously failed regimens and salvage regimens under comparison. Bismuth quadruple therapy after failure of standard triple therapy showed a pooled intention-to-treat (ITT) eradication rate of 75.5% (95% CI, 71.6~79.1%), and the rates were significantly higher with 14-day therapy than 7-day therapy by 9% (95% CI, 2~15%). Levofloxacin triple therapy after failure of standard triple therapy demonstrated a pooled ITT eradication rate of 73.3% (95% CI, 68.4~77.3%). In direct comparison, the two regimens were not significantly different in eradication rates. No study evaluated salvage regimens after the failure of bismuth or non-bismuth quadruple therapy. Conclusions The current studies regarding salvage regimens are highly heterogeneous. Bismuth quadruple therapy and levofloxacin triple therapy may be a reliable option after failure of standard triple therapy, but the regional profile of antibiotic resistance should be considered. Further studies are needed for salvage regimens after failure of non-bismuth or bismuth quadruple therapy.

Helicobacter pylori infection is one of the most common infectious diseases worldwide. H. pylori is responsible for substantial gastrointestinal morbidity with a high disease burden. Since the revision of the H. pylori Clinical Practice Guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin based triple therapy. According to a nationwide randomized controlled study by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance to clarithromycin. The clinical practice guidelines for treatment of H. pylori were updated based on evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines were designed to provide clinical evidence for the treatment of H. pylori to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards, and will be revised if more evidence emerges in the future.