Aerosolized antibiotics are being increasingly used to treat respiratory infections, especially those caused by drug-resistant pathogens. Their use in the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in critically ill patients is especially significant. They are also used as an efficient alternative to overcome the issues caused by systemic administration of antibiotics, including the occurrence of drug-resistant strains, drug toxicity, and insufficient drug concentration at the target site. However, the rationale for the use of aerosolized antibiotics is limited owing to their insufficient efficacy and the potential for underestimated risks of developing side effects. Despite the lack of availability of high-quality evidence, the use of aerosolized antibiotics is considered as an attractive alternative treatment approach, especially in patients with multidrug-resistant pathogens. In this review, we have discussed the effectiveness and side effects of aerosolized antibiotics as well as the latest advancements in this field and usage in the Republic of Korea.

Metformin is a first-line therapeutic agent for type 2 diabetes. Apart from its glucose-lowering effect, metformin is attracting interest regarding possible therapeutic benefits in various other conditions. As metformin regulates cell metabolism, proliferation, growth, and autophagy, it may also modulate immune cell functions. Given that metformin acts on multiple intracellular signaling pathways, including adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation, and that AMPK and its downstream intracellular signaling control the activation and differentiation of T and B cells and inflammatory responses, metformin may exert immunomodulatory and anti-inflammatory effects. The efficacy of metformin has been investigated in preclinical and clinical studies on rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, ankylosing spondylitis, and gout. In this review, we discuss the potential mechanisms through which metformin exerts its therapeutic effects in these diseases, focusing particularly on rheumatoid arthritis and osteoarthritis.

Chronic pancreatitis (CP) is pathologically characterized by the loss of exocrine pancreatic parenchyma, irregular fibrosis, cellular infiltration, and ductal abnormalities. Diagnosing CP objectively is difficult because standard diagnostic criteria are insufficient. The change of parenchymal hardness is the key factor for the diagnosis and understanding of the severity of CP. The ultrasonography (US) or endoscopic ultrasonography (EUS) elastography have been used to diagnose pancreatic diseases. Both strain elastography (SE) and shear wave elastography are specific diagnostic techniques for measuring tissue hardness. Most previous studies were conducted with SE. There are three methods of interpreting SE; the method of recognizing the patterns in SE distribution images in the region of interest, the method of using strain ratio to compare the hardness of adipose tissue or connective tissue with that of the lesion, and the method of evaluating the hardness distribution of a target by histogram analysis. These former two methods have been used primarily for neoplastic diseases, and histograms analysis has been used to assess hardness distribution in the evaluation of CP. Since the hardness of the pancreas increases with aging, it is necessary to consider the age in the diagnosis of pancreatic disorders using US or EUS elastography.

The incidence and prevalence of heart failure (HF) is increasing worldwide, leading to high morbidity and mortality. The global management of HF involves lifestyle changes in addition to pharmacological treatments. Changes include exercise and dietary recommendations, mainly salt and fluid restriction, but without any clear evidence. We conducted a systematic review to analyse the degree of evidence for these dietary recommendations in HF. Only randomized controlled trials (RCT), and observational studies in humans were selected. Studies were considered eligible if they included participants with HF and sodium and/or fluid restriction. Publications in languages other than English or Spanish were excluded. We included 15 studies related to sodium or fluid restriction. Nine RCT and six observational studies showed some improvements in symptoms and quality of life and a degree of reduction in new hospitalizations, but the results are based on limited population groups, applying different methodologies, and with different restriction goals. We found a lack of clear evidence of the benefits of sodium/fluid restriction in chronic HF. The evidence is limited to few studies with conflicting results. Randomized clinical trials are needed to fill this gap in our knowledge.

Background/Aims: Patients with liver cirrhosis (LC) have low levels of branched-chain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti-fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs).
Methods: LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real-time quantitative polymerase chain reaction and Western blotting.
Results: The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively.
Conclusions: BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β- induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Background/Aims: The study aimed to investigate the current practice patterns in the management of pancreatic cystic neoplasms in Korea.
Methods: An electronic survey was systematically distributed by email to members of the Korean Pancreatobiliary Association from December 2019 to February 2020.
Results: In total, 115 (110 gastroenterologists, five surgeons) completed the survey, 72.2% of whom worked in a tertiary/ academic medical center. Most (65.2%) followed the 2012/2017 International Association of Pancreatology guidelines for the management of pancreatic cystic neoplasms. A gadolinium-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography was the most common first-line diagnostic modality (42.1%), but a contrast-enhanced computed tomography scan was preferred as a subsequent surveillance tool (58.3%). Seventy-four percent of respondents routinely performed endoscopic ultrasound-guided fine needle aspiration for pancreatic cystic neoplasms with suspicious mural nodules. Endoscopic ultrasound-guided fine needle aspiration cytology (94.8%) and cystic fluid carcinoembryonic antigen (95.7%) were used for cystic fluid analysis. Most (94%) typically recommended surgery in patients with high-risk stigmata, but 18.3% also considered proceeding with surgery in patients with worrisome features. Most (96.5%) would continue surveillance of pancreatic cystic neoplasms for more than 5 years.
Conclusions: According to this survey, there was variability in the management of pancreatic cystic neoplasms among the respondents. These results suggest that the development of evidence-based guidelines for pancreatic cystic neoplasms that fit the Korean practice is needed to create an optimal approach to the management of pancreatic cystic neoplasms.

Background/Aims: Data on the immunoprotective status against measles, mumps, rubella, varicella zoster virus (VZV), hepatitis A virus (HAV), and Epstein-Barr virus (EBV) infection in patients with inflammatory bowel disease (IBD) are still lacking. Therefore, we investigated the seropositivity rates for viral infectious diseases and the associated factors in Korean patients with IBD.
Methods: In this retrospective cohort study, serum immunoglobulin G antibody positivity rates against measles virus, mumps virus, rubella virus, VZV, HAV, and EBV viral capsid antigen (VCA) were measured in patients with Crohn's disease or ulcerative colitis (UC) who first visited the IBD clinic. Seropositivity rates and their associated factors were analyzed.
Results: Between January 2016 and December 2018, 263 patients were enrolled (male, 167 [67.3%]; UC, 134 [50.9%]). The median age at serological test was 30 years (interquartile range, 22 to 46). The seropositivity rates were 84.0%, 85.2%, 66.5%, 87.4%, 50.0%, and 93.7% for measles, mumps, rubella, VZV, HAV, and EBV, respectively. Younger age at serological test was associated with seronegative status for measles (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.88 to 0.96), VZV (aOR, 0.83; 95% CI, 0.74 to 0.93), and HAV (aOR, 0.93; 95% CI, 0.91 to 0.95). Furthermore, IBD type-UC was associated with seronegative status against VZV (aOR, 0.33; 95% CI, 0.11 to 0.99).
Conclusions: Seropositivity rates for common viral infectious diseases in Korean patients with IBD were similar to those of the general population. In the younger age group, protective immunity against measles, VZV, and HAV is required, with proper vaccination, as necessary.

Background/Aims: Extracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs.
Methods: LpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance.
Results: The isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner.
Conclusions: EVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.