Does COVID-19 vaccination increase the risk of interstitial lung disease at a population level?

This study showed a significantly lower incidence of ILD among COVID-19 vaccinated individuals compared to unvaccinated, suggesting that the risk of COVID-19 vaccine-related ILD is not as high as previously reported https://bit.ly/3TWzzxP.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

Anti-Inflammatory Effects of Zinc Oxide and Berberine in Rats with Dextran Sulfate Sodium (DSS)-Induced Colitis.

Zinc oxide (ZnO) is frequently used in high concentrations to prevent diarrhea in weaning pigs. However, it can produce environmental pollution, because it is not absorbed by the intestines and is excreted in the feces. In studies to identify an alternative substance to ZnO, we used a model of colitis induced by dextran sulfate sodium (DSS) in rats to compare the anti-inflammatory effects of berberine with ZnO. DSS-treated rats displayed weight loss, shortening of the colon, increased fecal water content, and an increase in the disease activity index (DAI). In contrast, DSS + ZnO- and DSS + berberine-treated rats exhibited reduced colon shortening, decreased fecal water content, and a decrease in the DAI. Histological analysis revealed that both ZnO and berberine treatment reduced epithelial cell damage, crypt destruction, and infiltration of inflammatory cells. Moreover, the liver damage index was not significantly different between ZnO and berberine-treated rats. This study indicated that both ZnO and berberine can improve DSS-induced colitis in rats and suggests berberine as an alternative treatment to ZnO that would not cause environmental pollution.

Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis.

Backgrounds/Aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC. Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. Results: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Chronic periodontitis and risk of lung cancer: a nationwide cohort study.

Background: The impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset. Methods: This study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort). Results: During the median follow-up period of 5.1 (interquartile range, 2.8-8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94-2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40-59 age group, females, and never-smokers than their counterparts. Conclusion: We demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations.

Therapeutic effect of Nepenthes kampotiana Lecomte ethanol extract (Nk-EE) on androgenic alopecia through the inhibition of apoptosis and 5α-reductase activity.

There is increasing interest in hair loss treatment because a growing number of people affected. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE had a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has potential as an effective treatment for androgenic alopecia.

Characterization of Salmonella species from poultry slaughterhouses in South Korea: carry-over transmission of Salmonella Thompson ST292 in slaughtering process.

IMPORTANCE: Salmonella outbreaks linked to poultry meat have been reported continuously worldwide. Therefore, Salmonella contamination of poultry meats in slaughterhouses is one of the critical control points for reducing disease outbreaks in humans. OBJECTIVE: This study examined the carry-over contamination of Salmonella species through the entire slaughtering process in South Korea. METHODS: From 2018 to 2019, 1,097 samples were collected from the nine slaughterhouses distributed nationwide. One hundred and seventeen isolates of Salmonella species were identified using the invA gene-specific polymerase chain reaction, as described previously. The serotype, phylogeny, and antimicrobial resistance of isolates were examined. RESULTS: Among the 117 isolates, 93 were serotyped into Salmonella Mbandaka (n = 36 isolates, 30.8%), Salmonella Thompson (n = 33, 28.2%), and Salmonella Infantis (n = 24, 20.5%). Interestingly, allelic profiling showed that all S. Mbandaka isolates belonged to the lineage of the sequence type (ST) 413, whereas all S. Thompson isolates were ST292. Moreover, almost all S. Thompson isolates (97.0%, 32/33 isolates) belonging to ST292 were multidrug-resistant and possessed the major virulence genes whose products are required for full virulence. Both serotypes were distributed widely throughout the slaughtering process. Pulsed-field gel electrophoretic analysis demonstrated that seven S. Infantis showed 100% identities in their phylogenetic relatedness, indicating that they were sequentially transmitted along the slaughtering processes. CONCLUSIONS AND RELEVANCE: This study provides more evidence of the carry-over transmission of Salmonella species during the slaughtering processes. ST292 S. Thompson is a potential pathogenic clone of Salmonella species possibly associated with foodborne outbreaks in South Korea.

Protective Effects of the Postbiotic Levilactobacillus brevis BK3 against H2O2- Induced Oxidative Damage in Skin Cells.

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and antiobesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3- ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H2O2 and reduces intracellular ROS production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

Corrigendum: Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2024.1368926.].

Association Between Risk Perceptions of COVID-19, Political Ideology, and Mask-Wearing Behavior After the Outbreak: A Cross-Sectional Survey in South Korea.

Purpose: After the declaration by the World Health Organization signaling the conclusion of the COVID-19 pandemic, most countries lifted mandatory mask-wearing regulations. This study aimed to investigate factors such as risk perception and political ideology associated with continued adherence to mask-wearing among specific populations, particularly when it is no longer deemed necessary. Methods: We conducted a cross-sectional study including a sample of 1001 respondents stratified by sex, age (≥ 18 years), and region from January 31 to February 2, 2023, after the mandatory mask regulation was lifted in South Korea. Multivariate logistic regression models were applied to estimate the relationships between risk perceptions, political ideology, and mask-wearing maintenance, adjusting for factors such as sex, age, occupation, and trust in the government. Results: Our results indicated significant associations between age, self-reported household economic status, political ideology, affective risk perception, and perceived effectiveness of the government's COVID-related measures with indoor mask-wearing. Specifically, liberals were more likely to keep mask-wearing indoors than conservatives (adjusted odds ratio [aOR]: 2.19; 95% confidence interval [CI]: 1.33-3.59); and those who perceived a greater affective risk of COVID-19 (aOR: 2.47; 95% CI: 1.96-3.10), along with those who perceived the government's countermeasures as inadequate, were more inclined to maintain the habit of wearing masks indoors (aOR: 1.90; 95% CI: 1.19-3.03). Conclusion: Our study highlighted the multifaceted factors influencing mask-wearing behavior in the post-COVID-19 era. Even after adjusting for various confounding factors, such as age, sex, and trust in the government, an association remained between affective risk perception, political ideology, and mask-wearing behavior. However, further research for psychological mechanisms is needed to foster a culture of preventive behaviors proportional to the risk of infection.

Free-standing two-dimensional ferro-ionic memristor.

Two-dimensional (2D) ferroelectric materials have emerged as significant platforms for multi-functional three-dimensional (3D) integrated electronic devices. Among 2D ferroelectric materials, ferro-ionic CuInP2S6 has the potential to achieve the versatile advances in neuromorphic computing systems due to its phase tunability and ferro-ionic characteristics. As CuInP2S6 exhibits a ferroelectric phase with insulating properties at room temperature, the external temperature and electrical field should be required to activate the ferro-ionic conduction. Nevertheless, such external conditions inevitably facilitate stochastic ionic conduction, which completely limits the practical applications of 2D ferro-ionic materials. Herein, free-standing 2D ferroelectric heterostructure is mechanically manipulated for nano-confined conductive filaments growth in free-standing 2D ferro-ionic memristor. The ultra-high mechanical bending is selectively facilitated at the free-standing area to spatially activate the ferro-ionic conduction, which allows the deterministic local positioning of Cu+ ion transport. According to the local flexoelectric engineering, 5.76×102-fold increased maximum current is observed within vertical shear strain 720 nN, which is theoretically supported by the 3D flexoelectric simulation. In conclusion, we envision that our universal free-standing platform can provide the extendable geometric solution for ultra-efficient self-powered system and reliable neuromorphic device.

The Impact of Bronchiectasis on the Clinical Characteristics of Non-Severe Asthma.

Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting ß2-agonists (P = 0.074) and mucolytics (P < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, P = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, P = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, P = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe.

Association of maternal ultra-processed food consumption during pregnancy with atopic dermatitis in infancy: Korean Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: Maternal diet during pregnancy might influence the development of childhood allergic disorders. There are few studies on the association between processed food intake and infant atopic dermatitis (AD) during pregnancy. The aim of the present study was to investigate the association of ultra-processed food (UPF) intake during pregnancy with infantile AD. METHODS: This study involved 861 pairs of pregnant women and their offspring from the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Dietary intake was estimated using a 24-h recall method at 12-28 weeks gestation. The NOVA classification was used to identify UPF, and UPF intake was calculated as the percentage of total energy consumption and categorized into quartiles. Infantile AD was assessed based on medical history and the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations were assessed by logistic regression with adjustment for confounding factors. RESULTS: Children born to mothers in the highest quartile of UPF consumption (15.5% or more of the total energy) compared to the lowest quartile (6.8% or less) showed a higher risk of AD within 12 months [odds ratio (OR) = 1.69; 95% confidence interval (CI): 1.07-2.66, P for trend 0.0436]. After adjustment for the confounding factors under study, the association was strengthened; the adjusted OR between extreme quartiles was 2.19 (95% CI: 1.11-4.32, P for trend = 0.0418). This association was maintained even after an additional adjustment based on the Korean Healthy Eating Index (KHEI), an indicator of diet quality. CONCLUSIONS: Higher maternal consumption of UPF during pregnancy was associated with a greater risk of infantile AD within the first year of life.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

The Association between Family History of Lung Cancer and Development of Lung Cancer: Analysis from the KoGES Data in Korea.

Comprehensive analyses of the association between a family history of lung cancer and lung cancer risk are limited, especially in the Korean population. We used baseline data from the Korean Genome and Epidemiology Study, conducted between 2001 and 2013. This study enrolled 198,980 individuals. Lung cancer diagnoses and family histories were determined using questionnaires. Multivariable logistic regression analysis was performed to evaluate the effect of family history on the risk of lung cancer. Of 198,980 individuals, 6296 (3.2%) and 140 (0.1%) had a family history of lung cancer and lung cancer, respectively. Individuals with a family history of lung cancer in first-degree relatives (FDRs) had a higher risk of lung cancer development than those without (adjusted odds ratio [aOR] = 2.28, 95% confidence interval [CI] = 1.11-4.66). This was more pronounced in young individuals (<60 years) who had affected relatives diagnosed with lung cancer before the age of 60 years (aOR = 3.77, 95% CI = 1.19-11.88). In subgroup analyses, this association was more evident in women, never smokers, and young individuals. A family history of lung cancer, especially in FDRs, is a significant risk factor for lung cancer development in Korea.

Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.