The gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Between the 1990s and early 2000s, GIST was identified as a tumor characterized by KIT or PDGFRA mutations, resulting in imatinib being established as an effective targeted therapy. However, with advances in molecular diagnostics, approximately 10%–15% of GISTs have been reported to harbor alternative mutations, such as those in the succinate dehydrogenase subunit genes and BRAF, leading to the development of additional targeted therapies. GISTs exhibit a wide spectrum of clinical behaviors, ranging from indolent to highly aggressive, prompting the development of diverse risk classification systems. However, multiple systems remain in use, leading to inconsistent pathologic reports. Moreover, the mitotic counting method—a key factor in risk stratification—has become a major source of confusion among pathologists owing to the adoption of digital pathology and discrepancies between updated international guidelines and outdated reimbursement requirements. These inconsistencies have hindered pathologic reporting and communication between pathologists and clinicians. This review comprehensively overviews the historical background, molecular subtypes, and risk classification systems of GIST, focusing on evolving issues in mitotic rate evaluation and the application of risk classification systems in clinical practice.

Purpose: Food sensitization to egg white (EW) peaks during early childhood, after which some children with sensitization to EW outgrow food sensitization, while others develop an increased degree of sensitization to EW. We investigated factors determining changes in EW-specific IgE in children under 2 years of age. Methods: Among children under 2 years of age with atopic dermatitis or food allergy who visited Asan Medical Center from March 2018 to September 2021, a total of 172 sensitized to EW were enrolled. Serum specific IgE to EW, ovalbumin and ovomucoid, and specific IgG4 to EW and ovomucoid were measured at 0, 6, and 12 months. An increase in EW-specific IgE was defined as an increased level of EW-specific IgE after 12 months from baseline. Multiple logistic regression analysis was performed to identify factors determining an increase in EW-specific IgE. Results: Of the 172 children, 85 had complete data on serum specific IgE and specific IgG4 during a period of 12 months. The levels of EW-specific IgE were decreased in 51 subjects (60.0%), while they were increased in 34 subjects (40.0%). Introduction of baked eggs had a protective effect against an increase in EW-specific IgE levels during a period of 12 months (adjusted odds ratio, 0.148; 95% confidence interval, 0.022–0.983). Conclusion Introduction of the baked egg can prevent an increase in EW-specific IgE during early childhood. Further studies are needed for the long-term effect of baked egg on the natural course of EW sensitization.

Purpose: Sixty to eighty percent of children with egg allergy are able to tolerate eggs in baked form. The purpose of this study was to evaluate the clinical usefulness and diagnostic value of measurements of IgE specific to egg white, ovalbumin, and ovomucoid for reactivity to baked egg in children with sensitivity to egg. Methods: Two hundred seventeen children with suspected egg allergy underwent open food challenges with baked egg (in the form of muffins). The outcomes of the challenges were compared to the serum concentrations of IgE specific to egg white, ovalbumin, and ovomucoid by using ImmunoCAP. Results: There were no statistically significant differences in levels of IgE specific to egg white, ovalbumin, and ovomucoid between the baked egg challenge positive and negative groups younger than 2 years (n = 163). However, significant differences were observed between the challenge positive and negative groups in 54 subjects aged 2 to 5 years (all P < 0.05). The optimal cutoff points of egg white, ovalbumin, and ovomucoid specific IgE levels among children aged 2 to 5 years were 12.40 kU A/L (sensitivity 79%, specificity 66%), 4.07 kU A/L (sensitivity 88%, specificity 58%), and 3.65 kU A/L (sensitivity 77%, specificity 62%), respectively. Conclusion The level of IgE specific to egg white and its components can predict the reactivity to baked egg in children aged 2 to 5years.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). Methods: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. Results: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. Conclusions Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Abnormal inflammatory responses are closely associated with intestinal microbial dysbiosis. Oral administration of Qmatrix-diabetes-mellitus complex (QDMC), an Aloe gel-based formula, has been reported to improve inflammation in type 2 diabetic mice; however, the role of the gut microbiota in ameliorating efficacy of QDMC remains unclear. We investigated the effect of QDMC on the gut microbiota in a type 2 diabetic aged mouse model that was administered a high-fat diet. Proinflammatory (TNF-α and IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine levels in the fat were normalized via oral administration of QDMC, and relative abundances of Bacteroides, Butyricimonas, Ruminococcus, and Mucispirillum were simultaneously significantly increased. The abundance of these bacteria was correlated to the expression levels of cytokines. Our findings suggest that the immunomodulatory activity of QDMC is partly mediated by the altered gut microbiota composition.

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). Methods: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. Results: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. Conclusions Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.
Air Filters ; Air Pollution ; Animals ; Asthma ; Child ; Dander ; Dogs ; Education ; Environmental Exposure ; Humans ; Logistic Models ; Odds Ratio ; Ownership ; Risk Factors ; Smoke ; Social Change ; Tobacco

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.
Animals ; Bacteroides ; Diet, High-Fat ; Down-Regulation ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Hyperglycemia ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-18 ; Metformin ; Mice ; Toll-Like Receptors

BACKGROUND: Depression is considered as a risk factor for cardiovascular disease (CVD) and associated with changes in individuals' health status that might influence CVD risk. However, most studies have scrutinized this relationship on a rather narrower and specific study population. By focusing on general population of Korea, we sought to inspect the association of depression with CVD risk and cardiovascular risk factors. METHODS: The data from the first year (2016) of the 7th Korea National Health and Nutrition Examination Survey was used. Participants were classified by the Patient Health Questionnaire-9 (PHQ-9) score as such: normal group (PHQ-9 score 0–4), mild depression (MD) group (PHQ-9 score 5–9) and moderate and severe depression (MSD) group (PHQ-9 score 10–27). General linear model was used to analyze differences and the trend of mean CVD risk according to depression level. Adjusted odds ratios (AORs) were calculated by logistic regression to identify the association between depression and cardiovascular risk factors after adjusting for age. RESULTS: Mean CVD risk of MSD group was higher than that of normal group (p < 0.05). There was a tendency of CVD risk to increase as depression worsened (p < 0.01). Among men, MSD group was associated with current smoking (AOR, 2.97; 95% confidence interval [CI], 1.78–4.97), taking antihypertensive medications (AOR, 2.42; 95% CI, 1.26–4.66), increased fasting blood sugar (> 125 mg/dL; AOR, 2.37; 95% CI, 1.25–4.50) and taking diabetes medications (AOR, 3.08; 95% CI, 1.65–5.72). MD group was associated with current smoking (AOR, 1.60; 95% CI, 1.18–2.17). Among women, MSD group was associated with high body mass index (≥ 25 kg/m2; AOR, 1.61; 95% CI, 1.11–2.32), large waist circumference (≥ 85 cm; AOR, 1.63; 95% CI, 1.12–2.37), current smoking (AOR, 5.11; 95% CI, 3.07–8.52) and taking diabetes medications (AOR, 2.62; 95% CI, 1.68–4.08). MD group was associated with current smoking (AOR, 1.86; 95% CI, 1.18–2.93). CONCLUSIONS: We suggest that depression is associated with increased risk for CVD occurrence in general population of Korea.
Blood Glucose ; Body Mass Index ; Cardiovascular Diseases ; Depression ; Fasting ; Female ; Humans ; Korea ; Linear Models ; Logistic Models ; Male ; Nutrition Surveys ; Odds Ratio ; Risk Factors ; Smoke ; Smoking ; Waist Circumference