Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Background: Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). Methods: This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. Results: After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. Conclusion Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

Purpose: This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs. Materials and Methods: Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included. Results: The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS. Conclusion The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Background and Objectives: We reviewed the long-term outcomes after tetralogy of Fallot (TOF) repair with trans-annular incision; and evaluated the effectiveness of pulmonary valve replacement (PVR) on outcomes. Methods: This was a retrospective review of clinical outcomes of 180 of 196 TOF patients who underwent total correction with trans-annular incision from 1991 to 1997 (PVR group: 81; non-PVR group: 99). Results: The median age of the patients was 14.0 months (interquartile range [IQR], 10.7–19.8 months) at TOF repair. Ten in-hospital deaths (5.1%) occurred. During the followup, 81 patients underwent PVR at the median age of 13.5 years (IQR, 11.2–17.1 years). The patients in PVR group showed better outcomes than non-PVR group in overall survival rate (100% in PVR vs. 88.7% in non-PVR, p=0.007), in all adverse events (arrhythmia, neurologic complications, 95.5% in PVR vs. 74.6% in non-PVR, p=0.024) at 20 years. Age at TOF repair younger than 1 year (hazard ratio [HR], 2.265; p=0.01) and previous shunt history (HR, 2.195; p=0.008) were predictive for requiring PVR. During follow-up, 10 late deaths (5 sudden deaths) occurred in the non-PVR group, mainly due to ventricular arrhythmia and right ventricular failure; there was 1 late death (not a sudden death) in the PVR group. Conclusions Long-term survival after repair of TOF with trans-annular incision were acceptable. However, arrhythmias were frequently observed during 20 years of follow-up. The patient age <1 year at the time of TOF repair and shunt implantation prior to TOF repair were predictive factors for requiring PVR.

Background and Objectives: We reviewed the long-term outcomes after tetralogy of Fallot (TOF) repair with trans-annular incision; and evaluated the effectiveness of pulmonary valve replacement (PVR) on outcomes. Methods: This was a retrospective review of clinical outcomes of 180 of 196 TOF patients who underwent total correction with trans-annular incision from 1991 to 1997 (PVR group: 81; non-PVR group: 99). Results: The median age of the patients was 14.0 months (interquartile range [IQR], 10.7–19.8 months) at TOF repair. Ten in-hospital deaths (5.1%) occurred. During the followup, 81 patients underwent PVR at the median age of 13.5 years (IQR, 11.2–17.1 years). The patients in PVR group showed better outcomes than non-PVR group in overall survival rate (100% in PVR vs. 88.7% in non-PVR, p=0.007), in all adverse events (arrhythmia, neurologic complications, 95.5% in PVR vs. 74.6% in non-PVR, p=0.024) at 20 years. Age at TOF repair younger than 1 year (hazard ratio [HR], 2.265; p=0.01) and previous shunt history (HR, 2.195; p=0.008) were predictive for requiring PVR. During follow-up, 10 late deaths (5 sudden deaths) occurred in the non-PVR group, mainly due to ventricular arrhythmia and right ventricular failure; there was 1 late death (not a sudden death) in the PVR group. Conclusions Long-term survival after repair of TOF with trans-annular incision were acceptable. However, arrhythmias were frequently observed during 20 years of follow-up. The patient age <1 year at the time of TOF repair and shunt implantation prior to TOF repair were predictive factors for requiring PVR.

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

BACKGROUND: Recently, the number of lung transplants in South Korea has increased. However, the long-term outcome data is limited. In this study, we aimed to investigate the long-term outcomes of adult lung transplantation recipients. METHODS: Among the patients that underwent lung transplantation at a tertiary referral center in South Korea between 2008 and 2017, adults patient who underwent deceased-donor lung transplantation with available follow-up data were enrolled. Their medical records were retrospectively reviewed. RESULTS: Through eligibility screening, we identified 60 adult patients that underwent lung (n=51) or heart-lung transplantation (n=9) during the observation period. Idiopathic pulmonary fibrosis (46.7%, 28/60) was the most frequent cause of lung transplantation. For all the 60 patients, the median follow-up duration for post-transplantation was 2.6 years (range, 0.01–7.6). During the post-transplantation follow-up period, 19 patients (31.7%) died at a median duration of 194 days. The survival rates were 75.5%, 67.6%, and 61.8% at 1 year, 3 years, and 5 years, respectively. Out of the 60 patients, 8 (13.3%) were diagnosed with chronic lung allograft dysfunction (CLAD), after a mean duration of 3.3±2.8 years post-transplantation. The CLAD development rate was 0%, 17.7%, and 25.8% at 1 year, 3 years, and 5 years, respectively. The most common newly developed post-transplantation comorbidity was the chronic kidney disease (CKD; 54.0%), followed by diabetes mellitus (25.9%). CONCLUSION: Among the adult lung transplantation recipients at a South Korea tertiary referral center, the long-term survival rates were favorable. The proportion of patients who developed CLAD was not substantial. CKD was the most common post-transplantation comorbidity.
Adult ; Allografts ; Comorbidity ; Diabetes Mellitus ; Follow-Up Studies ; Heart-Lung Transplantation ; Humans ; Idiopathic Pulmonary Fibrosis ; Korea ; Lung Transplantation ; Lung ; Mass Screening ; Medical Records ; Renal Insufficiency, Chronic ; Retrospective Studies ; Survival Rate ; Tertiary Care Centers