Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background: s/Aims: In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy. Methods: CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns. Results: Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR). Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Purpose: This study aimed to evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiotherapy (RT). Materials and Methods: A total of 229 patients who received RT in 10 tertiary hospitals between 2010 and 2019 were included in this multicenter analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS), and overall survival (OS) were evaluated. Results: After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 patients (99.6%) achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a poor prognostic factor for LRFS (hazard ratio, 3.72; confidence interval, 1.38 to 10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 patients (30.1%). Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 patients (4.8%) after RT. Conclusion Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for RT to the stomach is not high.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.