Risks of KD and MIS-C in pediatric patients with COVID-19 infection: A TriNetX based cohort study.

BACKGROUND: The associations of COVID-19 with Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) remain unclear. Few large-scale studies have estimated the cumulative incidence of MIS-C and KD after COVID-19 in children. METHODS: Data were obtained from TriNetX. After propensity score matching was completed, data from 258,645 patients with COVID-19 (COVID-19 group) and 258,645 patients without COVID-19 (non-COVID-19 group) were analyzed using Cox regression. Hazard ratio (HR), 95% confidence interval (CI), and cumulative incidence of MIS-C and KD were calculated for both groups. Stratified analysis was performed to validate the results. RESULTS: After matching for age at baseline and sex, the risks of MIS-C and KD were higher in the COVID-19 group than in the non-COVID-19 group (HR: 3.023 [95% CI: 2.323 to 3.933] and 1.736 [95% CI: 1.273 to 2.369], respectively). After matching for age at baseline, sex, race, ethnicity, and comorbidities, the risks of MIS-C and KD remained significantly higher in the COVID-19 group than in the non-COVID-19group (HR: 2.899 [95% CI: 2.173 to 3.868] and 1.435 [95% CI: 1.030 to 2.000]). When stratified by age, the risk of MIS-C was higher in the COVID-19 group-for patients aged > 5 years and ≤ 5 years (HR: 2.399 [95% CI: 1.683 to 3.418] and 2.673 [95% CI: 1.737 to 4.112], respectively)-than in the non-COVID-19 group. However, the risk of KD was elevated only in patients aged ≤ 5 years (HR: 1.808; 95% CI: 1.203 to 2.716). When stratified by COVID-19 vaccination status, the risks of MIS-C and KD were elevated in unvaccinated patients with COVID-19 (HR: 2.406 and 1.835, respectively). CONCLUSION: Patients with COVID-19 who are aged < 18 and ≤ 5 years have increased risks of MIS-C and KD, respectively. Further studies are required to confirm the role of COVID-19 in the pathogenesis of MIS-C and KD.

Corrigendum: Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

[This corrects the article DOI: 10.3389/fimmu.2024.1384623.].

Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

Electron Dynamics in Alkane C-H Activation Mediated by Transition Metal Complexes.

Alkanes, ideal raw materials for industrial chemical production, typically exhibit limited reactivity due to their robust and weakly polarized C-H bonds. The challenge lies in selectively activating these C-H bonds under mild conditions. To address this challenge, various C-H activation mechanisms have been developed. Yet, classifying these mechanisms depends on the overall stoichiometry, which can be ambiguous and sometimes problematic. In this study, we utilized density functional theory calculations combined with intrinsic bond orbital (IBO) analysis to examine electron flow in the four primary alkane C-H activation mechanisms: oxidative addition, σ-bond metathesis, 1,2-addition, and electrophilic activation. Methane was selected as the representative alkane molecule to undergo C-H heterolytic cleavage in these reactions. Across all mechanisms studied, we find that the CH3 moiety in methane consistently uses an electron pair from the cleaved C-H bond to form a σ-bond with the metal. Yet, the electron pair that accepts the proton differs with each mechanism: in oxidative addition, it is derived from the d-orbitals; in σ-bond metathesis, it resulted from the metal-ligand σ-bonds; in 1,2-addition, it arose from the π-orbital of the metal-ligand multiple bonds; and in electrophilic activation, it came from the lone pairs on ligands. This detailed analysis not only provides a clear visual understanding of these reactions but also showcases the ability of the IBO method to differentiate between mechanisms. The electron flow discerned from IBO analysis is further corroborated by results from absolutely localized molecular orbital energy decomposition analysis, which also helps to quantify the two predominant interactions in each process. Our findings offer profound insights into the electron dynamics at play in alkane C-H activation, enhancing our understanding of these critical reactions.

Is Staged Surgery Always Necessary for Schatzker Type IV-VI Tibial Plateau Fractures? A Comparison Study.

AIMS: This study aims to compare the outcomes of immediate (followed by closed-incision negative-pressure therapy use) versus delayed ORIF in patients with Schatzker type IV-VI TPFs. PATIENTS AND METHODS: A prospective study of patients undergoing ORIF between January 2018 and December 2019 was performed. The inclusion criteria were patients (>18 years) with a closed fracture sent to the emergency room (ER) within 24 h of injury. All the patients underwent preoperative image evaluation. Two senior orthopedic trauma surgeons evaluated the soft tissue condition in the ER by 5P's of the compartment syndrome, judging the timing of the operation of definitive ORIF. Group 1 (n = 16) received delayed ORIF. Group 2 (n = 16) received immediate ORIF and ciNPT use. Patient follow-up occurred after 2 and 6 weeks and 3, 6, and 12 months after surgery. The assessments included the time to definitive fixation, the length of hospital stay, the time to bone union, surgical site complications, and reoperation within 12 months. A universal goniometer was used to measure the postoperative 3 m, 6 m, and 12 m ROM. RESULTS: The patient demographics were similar between the groups (p > 0.05). Group 2 displayed significantly a shorter time to definitive fixation (5.94 ± 2.02 vs. 0.61 ± 0.28, p < 0.0001) and hospital stay (14.90 ± 8/78 vs. 10.30 ± 6.78, p = 0.0016). No significant difference was observed in the time to bone union, surgical site complication incidence, and reoperation rates (p > 0.05). Flexion and flexion-extension knee ROM were demonstrated to be significantly improved in Group 2, 3, 6, and 12 months postoperatively (p < 0.0001). CONCLUSIONS: In this study, early ORIF and ciNPT use resulted in a shorter hospital length of stay, a reduced time to early active motion of the knee, and improved knee ROM. These results suggest that early ORIF with ciNPT for Schatzker type IV-VI TPFs is safe and effective in some patients. However, further research to confirm these findings across larger and more diverse populations is needed.

The Role of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Predicting Complicated Appendicitis in Children.

BACKGROUND: Acute appendicitis is a common abdominal emergency observed in emergency departments (ED). Distinguishing between uncomplicated and complicated appendicitis is important in determining a treatment strategy. Serum soluble vascular cell adhesion molecule-1 (VCAM-1) is an inflammatory biomarker. We aimed to determine the role of VCAM-1 in predicting complicated appendicitis in children. METHODS: Pediatric patients with suspected appendicitis admitted to the ED were enrolled in this prospective study. Pre-surgical serum VCAM-1 was tested in children with acute appendicitis within 72 h of symptoms (from day 1 to day 3). Serum VCAM-1 levels were further analyzed and compared between patients with and without complicated appendicitis. RESULTS: Among the 226 pediatric appendicitis patients, 70 had uncomplicated appendicitis, 138 had complicated appendicitis, and 18 had normal appendices. The mean serum VCAM-1 levels in patients with perforated appendicitis were higher than in those with simple appendicitis (p < 0.001). On day 1 to day 3, the mean VCAM-1 levels in patients with complicated appendicitis were all significantly higher than in those with uncomplicated appendicitis (all p < 0.001). CONCLUSION: Serum VCAM-1 levels may be helpful in differentiating uncomplicated and complicated appendicitis in children and could predict appendiceal perforation.

Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

Transcriptome-wide identification of ARF gene family in medicinal plant Polygonatum kingianum and expression analysis of PkARF members in different tissues.

BACKGROUND: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. METHODS AND RESULTS: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. CONCLUSION: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources.

Different Splice Isoforms of Peripheral Triggering Receptor Expressed on Myeloid Cells 2 mRNA Expressions are Associated With Cognitive Decline in Mild Dementia Due to Alzheimer's Disease and Reflect Central Neuroinflammation.

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation.

Effects of mitral valve disease etiology on the outcomes of mechanical and biological valve replacement: retrospective cohort study.

INTRODUCTION: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. METHODS: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation. RESULTS: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation. CONCLUSION: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.

Treatment of Undifferentiated Embryonal Sarcoma of the Liver in Children.

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children.

Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript spread throughout the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing immunosuppressive macrophages and stimulating granzyme expression in infiltrating T and NK cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Epitaxial Growth of Surface Perforations on Parallel Cylinders in Terraced Films of Block Copolymer/Homopolymer Blends.

Due to incommensurability between initial thickness and interdomain distance, thermal annealing inevitably produces relief surface terraces (islands and holes) of various morphologies in thin films of block copolymers. We have demonstrated three kinds of surface terraces in blend films: polygrain terraces with diffuse edges, polygrain terraces with step edges, and pseudo-monograin terraces with island coarsening. The three morphologies were obtained by three different thermal histories, respectively. The thermal histories were imposed on blend films, which were prepared by mixing a homopolystyrene (hPS, 6.1 kg/mol) with a weakly segregated, symmetry polystyrene-block poly(methyl methacrylate) (PS-b-PMMA, 42 kg/mol) followed by spin coating. At a given weight-fraction ratio of PS-b-PMMA/hPS = 75/25, the interior of the blend films forms parallel cylinders. Nevertheless, the surface of the blend films is always dominated by a skin layer of perforations, which epitaxially grow on top of parallel cylinders. By oxygen plasma etching at various time intervals to probe interior nanodomains, the epitaxial relationship between surface perforations and parallel cylinders has been identified by a scanning electron microscope.

Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.

The ability to target the native production site of factor VIII (FVIII)-liver sinusoidal endothelial cells (LSECs)-can improve the outcome of hemophilia A (HA) gene therapy. By testing a matrix of ultrasound-mediated gene delivery (UMGD) parameters for delivering a GFP plasmid into the livers of HA mice, we were able to define specific conditions for targeted gene delivery to different cell types in the liver. Subsequently, two conditions were selected for experiments to treat HA mice via UMGD of an endothelial-specific human FVIII plasmid: low energy (LE; 50 W/cm2, 150 µs pulse duration) to predominantly target endothelial cells or high energy (HE; 110 W/cm2, 150 µs pulse duration) to predominantly target hepatocytes. Both groups of UMGD-treated mice achieved persistent FVIII activity levels of ∼10% over 84 days post treatment; however, half of the HE-treated mice developed low-titer inhibitors while none of the LE mice did. Plasma transaminase levels and histological liver examinations revealed minimal transient liver damage that was lower in the LE group than in the HE group. These results indicate that UMGD can safely target LSECs with a lower-energy condition to achieve persistent FVIII gene expression, demonstrating that this novel technology is highly promising for therapeutic correction of HA.

Long-term impacts of endocrine-disrupting chemicals exposure on kidney function: A community-based cohort study.

This study explores the extended renal effects of endocrine-disrupting chemicals (EDCs) exposure, a linkage already established with adverse health outcomes, notably chronic kidney disease. To delve deeper, the Chang Gung Community Research Center conducted a longitudinal study with 887 participants. Among them, 120 individuals were scrutinized based on EDC scores, analyzing 17 urinary EDCs and renal function. Findings revealed elevated mono-(2-ethylhexyl) phthalate (MEHP) and bisphenol A levels in higher EDC exposure cases. MEHP notably correlated with increased urinary albumin-to-creatinine ratio (UACR), predicting a > 15% decline in estimated glomerular filtration rate. Higher MEHP levels also hinted at declining renal function. UACR escalation linked significantly with specific EDCs: MEHP, methylparaben, nonylphenol, and 4-tert-octylphenol. This research underscores enduring renal hazards tied to environmental EDC exposure, particularly MEHP, emphasizing the urgent call for robust preventive public health strategies.

The Modulation of Phospho-Extracellular Signal-Regulated Kinase and Phospho-Protein Kinase B Signaling Pathways plus Activity of Macrophage-Stimulating Protein Contribute to the Protective Effect of Stachydrine on Acetaminophen-Induced Liver Injury.

Stachydrine, a prominent bioactive alkaloid derived from Leonurus heterophyllus, is a significant herb in traditional medicine. It has been noted for its anti-inflammatory and antioxidant characteristics. Consequently, we conducted a study of its hepatoprotective effect and the fundamental mechanisms involved in acetaminophen (APAP)-induced liver injury, utilizing a mouse model. Mice were intraperitoneally administered a hepatotoxic dose of APAP (300 mg/kg). Thirty minutes after APAP administration, mice were treated with different concentrations of stachydrine (0, 2.5, 5, and 10 mg/kg). Animals were sacrificed 16 h after APAP injection for serum and liver tissue assays. APAP overdose significantly elevated the serum alanine transferase levels, hepatic pro-inflammatory cytokines, malondialdehyde activity, phospho-extracellular signal-regulated kinase (ERK), phospho-protein kinase B (AKT), and macrophage-stimulating protein expression. Stachydrine treatment significantly decreased these parameters in mice with APAP-induced liver damage. Our results suggest that stachydrine may be a promising beneficial target in the prevention of APAP-induced liver damage through attenuation of the inflammatory response, inhibition of the ERK and AKT pathways, and expression of macrophage-stimulating proteins.

Presentations of Children with Suspected Sepsis Caused by Acute Infectious Diarrhea in the Pediatric Emergency Department.

BACKGROUND: Acute infectious diarrhea is a common cause of hospitalization in children. Hence, early identification of acute bacterial gastroenteritis with suspected sepsis in pediatric emergency departments (EDs) is important. This study aimed to describe the clinical spectrum and initial characteristics of children who were presented to a pediatric ED with acute infectious diarrhea and suspected sepsis. METHODS: Between April 2020 to March 2021, children with clinical diagnoses of acute bacterial colitis and suspected sepsis who were admitted to the pediatric ED were prospectively enrolled. The following data were obtained and compared between different age groups of children: including demographics, presentation, laboratory tests, culture results, treatment modalities, complications, and short-term outcomes. RESULTS: A total of 105 patients (70 males and 35 females; mean age: 3.75 ± 3.52 years) were enrolled in this study. Of them, 89 (84.8%) patients were <6 years of age, and 80 (76.2%) patients required hospitalization for a duration of 4.7 ± 2.08 days. C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher in the admission (both p < 0.001) and anti-biotic treatment groups (both p < 0.001). Salmonella enteritidis was the most common organism cultured from the stool and blood samples (39 of 91 (38.5%) and 2 of 105 (1.9%), respectively). CONCLUSIONS: The primary causative organism of acute infectious diarrhea identified in this study was S. enteritidis. Age and elevated serum CRP or PCT levels could be important factors in the decisions of emergency physicians regarding hospitalization and antibiotic therapies for pediatric acute infectious diarrhea.

Risk Factors for Urinary Tract Infections in Children with Hematuria in the Emergency Department.

INTRODUCTION: Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED). METHODS: We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated. RESULTS: A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria. CONCLUSIONS: Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.

Sex Differences in Epidemiological Distribution and Outcomes of Surgical Mitral Valve Disease.

BACKGROUND: Mitral valve (MV) disease is the most common form of valvular heart disease. Findings that indicate women have a higher risk for unfavorable outcomes than men remain controversial. This study aimed to determine the sex-based differences in epidemiological distributions and outcomes of surgery for MV disease.Methods and Results: Overall, 18,572 patients (45.3% women) who underwent MV surgery between 2001 and 2018 were included. Outcomes included in-hospital death and all-cause mortality during follow up. Subgroup analysis was conducted across different etiologies, including infective endocarditis (IE), degenerative, ischemic, and rheumatic mitral pathology. The overall MV repair rate was lower in women than in men (20.5% vs. 30.6%). After matching, 6,362 pairs (woman : man=1 : 1) of patients were analyzed. Women had a slightly higher risk for in-hospital death than men (10.8% vs. 9.8%; odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.99-1.24; P=0.075). Women tended to have a higher incidence of de novo dialysis (9.8% vs. 8.6%; P=0.022) and longer intensive care unit stay (8 days vs. 7.1 days; P<0.001). Women with IE had poorer in-hospital outcomes than men; however, there were no sex differences in terms of all-cause mortality. CONCLUSIONS: Sex-based differences of MV intervention still persist. Although long-term outcomes were comparable between sexes, women, especially those with IE, had worse perioperative outcomes than men.