Knockdown of KCNQ1OT1 Alleviates the Activation of NLRP3 Inflammasome Through miR-17-5p/TXNIP Axis in Retinal Müller Cells.

PURPOSE: Diabetic retinopathy (DR) is one of the most severe and common complications caused by diabetic mellites. Inhibiting NLRP3 inflammasome activation displays a crucial therapeutic value in DR. Studies have shown that KCNQ1OT1 plays a critical role in regulating NLRP3 inflammasome activation and participates in the pathogenesis of diabetic complications. The present study aims to explore the role, and the potential mechanism of KCNQ1OT1 in regulating the activation of NLRP3 inflammasome in DR. METHODS: qRT-PCR was used to detect the expression of KCNQ1OT1, miR-17-5p, TXNIP, NLRP3, ASC, caspase-1 and IL-1ß. Western blot was performed to detect the expression of NLRP3, ASC, caspase-1, IL-1ß and TXNIP. Immunohistochemistry and immunostaining were performed to detect the expression of caspase-1. The levels of the inflammatory cytokine IL-1ß were determined by ELISA assay. FISH was used to detect the subcellular localisation of KCNQ1OT1. Bioinformatic analysis, luciferase reporter assay and in vitro studies were performed to elucidate the mechanism of KCNQ1OT1-mediated dysfunction. RESULTS: The expression of KCNQ1OT1 and the activation of NLRP3 inflammasome were increased in experimental DR models. KCNQ1OT1 knockdown alleviated NLRP3 inflammasome-associated molecules expression. In addition, KCNQ1OT1 was found to be localized mainly in the cytoplasm of Müller cells and facilitated TXNIP expression by acting as a miR-17-5p sponge. KCNQ1OT1 promoted the activation of NLRP3 inflammasome through miR-17-5p/TXNIP axis. CONCLUSIONS: In conclusion, it was found in this study that KCNQ1OT1 promoted the activation of NLRP3 inflammasome both in vitro and in vivo, which was mediated by miR-17-5p/TXNIP axis. KCNQ1OT1 might be an effective interference target for the prevention and treatment of DR.

Characteristic of myocardial work in mitral valve prolapse with versus without mitral annular disjunction: A propensity-matched study.

BACKGROUND: Mitral annular disjunction (MAD) tends to coexist with mitral valve prolapse (MVP) and mitral regurgitation (MR), and is also highly associated with arrhythmias. Myocardial work (MW) analysis is dedicated to estimate myocardial performance by integrating strain analysis and afterload. We aimed to use MW analysis to investigate the cardiac remodeling and dysfunction in MAD, particularly the damage of some segments, and to enhance the understanding of the correlations between MW parameters and VAs within MVP patients. METHODS: A total of 22 consecutive MVP patients with MAD (MAD+) and 44 consecutive MVP patients without MAD (MAD-) (50 ± 11yeas; 18% females) were screened by propensity score matching (PSM), and were divided into subgroups based on MR severity (MR+: Grade 2+; MR-: ≤1), GWI median (GWI ≤ 2079.5 mmHg%; GWI>2079.5 mmHg%), as well as the presence of VAs (VAs+; VAs-). MW parameters consist of global work efficiency (GWE), global work index (GWI), global constructive work (GCW) and global wasted work (GWW). RESULTS: The MAD+ patients had larger LVEDD and LAVI, as well as lower GWE, GWI, and GCW (all P<0.05) compared to the MAD- patients, regardless of similar GLS and regurgitant volume(both P>0.05). When categorized by MR severity, GWI (P = 0.049) and GCW (P = 0.040) were diminished in the MR-MAD+ group. The regional analysis showed MAD+ patients had decreased MW index in the basal (posterior and inferior) and mid (posterior and inferior) segments. Multivariate linear regression showed MAD phenotype, but not MR severity, was independently associated with diminished GWE, GWI, and GCW (all P<0.05). When divided by GWI median, MAD phenotype [OR (95%CI): 5.189 (1.193-22.572), P = 0.028] was an independent predictor of decreased GCW. The receiver-operating characteristic curve identified bileaflet prolapse [AUC (95%CI): 0.664 (0.502-0.825), P = 0.045], and GWI for basal inferior [(AUC (95%CI): 0.679 (0.538-0.819), P = 0.020] as the predictors of the VAs. CONCLUSION: MAD phenotype has the ability to compromise cardiac structure and function, irrespective of volume overload, as evidenced by dilated LV and impaired MW index in basal and mid segments. Excessively decreased regional MW index can identify patients with the high risk of VAs. MW analysis can be a valuable imaging marker for detecting myocardial impairment induced by MAD.

Association of Mitral Valve Geometry at CT with Secondary Mitral Regurgitation after Transcatheter Aortic Valve Replacement in Patients with Aortic Regurgitation.

Background: The improvement rate and predictors of secondary mitral regurgitation in patients with aortic regurgitation undergoing transcatheter aortic valve replacement (TAVR) remain unclear. This study aimed to identify predictors of persistent moderate to severe secondary mitral regurgitation after TAVR in patients with aortic regurgitation by assessing mitral valve geometry with computed tomography (CT). Methods: This retrospective cohort study reviewed 242 consecutive patients with aortic regurgitation who underwent TAVR between May 2014 and December 2022. Patients with primary or less than moderate mitral regurgitation were excluded. Mitral annular dimensions (area, perimeter, anteroposterior, intercommissural, and trigone-to-trigone diameter), mitral valve tenting geometry (mitral valve tenting area [MVTA] and mitral valve tenting height [MVTH]), and papillary muscle displacement were systematically measured at CT. Mitral regurgitation improvement was assessed at 3 months after TAVR by echocardiography. Logistic regression was performed to explore the association of mitral valve geometry with mitral regurgitation improvement after TAVR. Results: A total of 75 patients (mean age, 74 ± 7 years; 32.0% female) with moderate to severe secondary mitral regurgitation were included in the final analysis. Mitral regurgitation improved in 49 patients and remained unchanged in 26 patients. Mitral annular dimensions, including area, perimeter, anteroposterior, and intercommissural diameter, were associated with mitral regurgitation improvement. MVTA and MVTH were risk factors for sustained mitral regurgitation. In addition, QRS duration > 120 ms and atrial fibrillation had an impact on the mitral regurgitation improvement. Mitral annular area (odds ratio [OR], 1.41; 95% confidence interval [CI]: 1.05, 1.90; p = 0.02) and MVTA (OR, 7.24; 95% CI: 1.72, 30.44; p = 0.007) were independent predictors of persistent secondary mitral regurgitation after TAVR. Conclusions: Mitral annular area and MVTA were independent predictors of persistent secondary mitral regurgitation after TAVR.

Triiodothyronine (T3) suppresses hepatic tumorigenesis and development by inhibiting the phosphorylation of ERK.

The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild-type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras-Tg and Kras-Tg)]) systems were used to investigate the effect of T3 on p-ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p-ERK in hepatoma cells within 30 min. However, p-ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p-ERK in liver tissues of WT. In Hras-Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p-ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p-MEK. Especially, the inhibitory effect of T3 on p-ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p-MEK was further confirmed in Kras-Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.

Circulation patterns and molecular characteristics of respiratory syncytial virus among hospitalized children in Tianjin, China, before and during the COVID-19 pandemic (2017-2022).

Respiratory syncytial virus (RSV) is the main pathogen that causes hospitalization for acute lower respiratory tract infections (ALRIs) in children. With the reopening of communities and schools, the resurgence of RSV in the COVID-19 post-pandemic era has become a major concern. To understand the circulation patterns and genotype variability of RSV in Tianjin before and during the COVID-19 pandemic, a total of 19,531 nasopharyngeal aspirate samples from hospitalized children in Tianjin from July 2017 to June 2022 were evaluated. Direct immunofluorescence and polymerase chain reaction (PCR) were used for screening RSV-positive samples and subtyping, respectively. Further analysis of mutations in the second hypervariable region (HVR2) of the G gene was performed through Sanger sequencing. Our results showed that 16.46% (3,215/19,531) samples were RSV positive and a delayed increase in the RSV infection rates occurred in the winter season from December 2020 to February 2021, with the average RSV-positive rate of 35.77% (519/1,451). The ON1, with H258Q and H266L substitutions, and the BA9, with T290I and T312I substitutions, are dominant strains that alternately circulate every 1-2 years in Tianjin, China, from July 2017 to June 2022. In addition, novel substitutions, such as N296Y, K221T, N230K, V251A in the BA9 genotype, and L226I in the ON1 genotype, emerged during the COVID-19 pandemic. Analysis of clinical characteristics indicated no significant differences between RSV-A and RSV-B groups. This study provides a theoretical basis for clinical prevention and treatment. However, further studies are needed to explore the regulatory mechanism of host immune responses to different lineages of ON1 and BA9 in the future.

Transcatheter aortic valve replacement in China - a review of the available evidence.

This paper discusses aortic stenosis (AS) in China, emphasising the role of transcatheter aortic valve replacement (TAVR) in treating AS in an ageing population. AS characteristics, its treatment and the clinical outcomes of transfemoral TAVR in Chinese patients are described via a systematic review. AS affects >1% of the Chinese population aged ≥65 years, with degenerative AS predominating over rheumatic AS among this age group. Chinese patients often have high aortic valve (AV) calcification with bicuspid AV morphology. In 2021, 38,000 surgical aortic valve replacements (SAVR) were reported in China, while the number of TAVR increased from 293 in 2017 to 7,357 in 2021. There are four self-expanding valves and one balloon-expandable SAPIEN 3 valve available in China. Among them, the Venus A-Valve is the most studied and widely used, whereas limited data are available for VitaFlow, TaurusOne, and SAPIEN 3. Notably, 10.0-16.5% of Venus A-Valve recipients and 0.2% of SAPIEN 3 recipients required multiple valve implantations. The rates of 30-day paravalvular leakage were 0-11.7%/0% for Venus A-Valve, 2.0%/0% for VitaFlow, and 0%/0% for SAPIEN 3, for moderate and severe leakage, respectively. Thirty-day all-cause mortality rates were 3.7-10.0% for Venus A-Valve, 0.9% for VitaFlow, and 0-3.2% for SAPIEN 3. One-year all-cause mortality rates were 5.9-13.6% for Venus A-Valve, 0-4.5% for VitaFlow, 6.7% for TaurusOne, and 6.2% for SAPIEN 3. The Venus A-Valve indicated lower 30-day permanent pacemaker implantation (PPI) rates (7.4-20.5%) than VitaFlow and TaurusOne. Outcomes for patients with bicuspid or tricuspid aortic valves were similar. AS is rising among the elderly Chinese population; SAVR is common, and TAVR is increasing. Limited device comparisons exist, but the Venus A-Valve seems to have lower PPI rates, and SAPIEN 3 has low 30-day mortality in China.

Pro-angiogenic cytokine features of left ventricular remodeling in patients with bicuspid aortic valve.

OBJECTIVE: Bicuspid aortic valve (BAV) is prone to promote left ventricular remodeling (LVR), which is associated with adverse clinical outcomes. Although the association between angiogenic activity and LVR has been established, pro-angiogenic cytokine features and potential biomarker candidates for LVR in patients with BAV remain to be clarified. METHODS: From November 2018 to May 2019, patients with BAV diagnosed by transthoracic echocardiography at our institution were included. LVR was diagnosed on the basis of echocardiographic calculations of relative wall thickness (RWT) and left ventricular mass index (LVMI). A multiplex ELISA array was used to measure the plasma levels of 60 angiogenesis-related cytokines. RESULTS: Among 103 patients with BAV, 71 were categorized into the LVR group and 32 into the normal left ventricular (LV) geometry group. BAV patients with LVR demonstrated increased LVMI, elevated prevalence of moderate to severe aortic stenosis and aortic regurgitation, and decreased LV ejection fraction (LVEF). Plasma levels of angiopoietin-1 were elevated in BAV patients with or without LVR compared with healthy controls (P = 0.001, P < 0.001, respectively), and were negatively correlated with RWT (r = -0.222, P = 0.027). Plasma levels of angiopoietin-2 were elevated in the LVR group (P = 0.001) compared with the normal LV geometry group, and were negatively correlated with LVEF (r = -0.330, P = 0.002). CONCLUSION: Decreased angiogenesis plays a crucial role in the occurrence and progression of LVR in patients with BAV. Disturbance in the pro- and anti-angiogenesis equilibrium in BAV patients with LVR may reflect the aggravation of endothelial injury and dysfunction.

Continuous 3D Myocardial Motion Tracking via Echocardiography.

Myocardial motion tracking stands as an essential clinical tool in the prevention and detection of cardiovascular diseases (CVDs), the foremost cause of death globally. However, current techniques suffer from incomplete and inaccurate motion estimation of the myocardium in both spatial and temporal dimensions, hindering the early identification of myocardial dysfunction. To address these challenges, this paper introduces the Neural Cardiac Motion Field (NeuralCMF). NeuralCMF leverages implicit neural representation (INR) to model the 3D structure and the comprehensive 6D forward/backward motion of the heart. This method surpasses pixel-wise limitations by offering the capability to continuously query the precise shape and motion of the myocardium at any specific point throughout the cardiac cycle, enhancing the detailed analysis of cardiac dynamics beyond traditional speckle tracking. Notably, NeuralCMF operates without the need for paired datasets, and its optimization is self-supervised through the physics knowledge priors in both space and time dimensions, ensuring compatibility with both 2D and 3D echocardiogram video inputs. Experimental validations across three representative datasets support the robustness and innovative nature of the NeuralCMF, marking significant advantages over existing state-of-the-art methods in cardiac imaging and motion tracking. Code is available at: https://njuvision.github.io/NeuralCMF.

Correlation of tuberculosis-related anemia severity with tuberculosis-induced inflammation in children: a six-year retrospective study.

BACKGROUND: Anemia is a common complication of tuberculosis (TB), and there is evidence that its prevalence is higher in patients with TB. Although TB is very important in epidemiology, careful investigation of TB-related anemia in children has not been carried out systematically. This study aimed to describe the details of anemia in children with TB and its association with clinical characteristics and the severity of inflammation. METHODS: In this retrospective study, we explored Hb levels in 103 children with pulmonary TB (PTB) and they were divided into anemic or non-anemic groups. Logistics regression analysis was used to study the associations between anemia and demographic characteristics. Spearman correlations analysis was performed to analyse the associations between the biochemical parameters and hemoglobin levels in blood. RESULTS: The prevalence of anemia in children with TB was 37.9% (48.7% showed microcytic hypochromic anemia, and 5.1% showed normal cell anemia). Compared with the anemia (n = 39) group, the non-anemic group (n = 64) had longer fever duration and increased respiratory rate (P < 0.05). In logistic regression analysis, anemia was associated with lower levels of Alb and higher levels of WBC, CRP, LDH, and ESR (P < 0.05). Spearman correlations analysis showed a significant negative correlation between hemoglobin (Hb) levels and inflammatory markers. After one month of antitubercular therapy (ATT), the Hb levels of 76.9% children returned to normal. CONCLUSIONS: Anemia is common among children with TB at diagnosis. The majority of children with TB-related anemia are mild to moderate microcytic hypochromic anemia. There is a strong correlation between the severity of anemia and the inflammation induced by TB. This suggests that anemia is a biomarker of the severity of TB in clinical practice among children.

Comparative genomic sequencing to characterize Mycoplasma pneumoniae genome, typing, and drug resistance.

To analyze the characteristics of Mycoplasma pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. Thirteen clinical strains isolated from 2003 to 2019 were selected, 10 of which were resistant to erythromycin (MIC >64 µg/mL), including 8 P1-type I and 2 P1-type II. Three were sensitive (<1 µg/mL) and P1-type II. One resistant strain had an A→G point mutation at position 2064 in region V of the 23S rRNA, the others had it at position 2063, while the three sensitive strains had no mutation here. Genome assembly and comparative genome analysis revealed a high level of genome consistency within the P1 type, and the primary differences in genome sequences concentrated in the region encoding the P1 protein. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. Clinical information showed seven cases were diagnosed with severe pneumonia, all of which were infected with drug-resistant strains. Notably, BS610A4 and CYM219A1 exhibited a gene multi-copy phenomenon and shared a conserved functional domain with the DUF31 protein family. Clinically, the patients had severe refractory pneumonia, with pleural effusion, necessitating treatment with glucocorticoids and bronchoalveolar lavage. The primary variations between strains occur among different P1-types, while there is a high level of genomic consistency within P1-types. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.IMPORTANCEMycoplasma pneumoniae is an important pathogen of community-acquired pneumonia, and macrolide resistance brings difficulties to clinical treatment. We analyzed the characteristics of M. pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. The work addressed primary variations between strains that occur among different P1-types, while there is a high level of genomic consistency within P1-types. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. All the strains isolated from severe pneumonia cases were drug-resistant, two of which exhibited a gene multi-copy phenomenon, sharing a conserved functional domain with the DUF31 protein family. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.

Remarkably Enhanced Phosphate Sequestration from Waters by Biochar with High-Density Quaternary Ammonium Groups.

A new biochar (N-BC) was fabricated by incorporating high-density positively charged quaternary ammonium groups into the pristine biochar without any adsorption for phosphate. N-BC can highly efficiently remove phosphate with an optimal pH of 5.0, a maximum experimental adsorption capacity of 30 mg of P/g, and an adsorption equilibrium time of 180 min. The predicted pore diffusion coefficient D (the diffused surface area of the adsorbate for unit time) for phosphate adsorption by N-BC was 5.3 × 10-9 cm2/s. N-BC can still capture phosphate in the copresence of anion Cl- with a molar concentration 50 times that of phosphate. The exhausted N-BC was completely regenerated using a 10 wt % NaOH solution and further reused without any observable loss in adsorption capacity. Moreover, N-BC yielded ∼324 bed volumes (BV) of wastewater containing 1 mg P/L phosphate and 50 mg/L Cl- before breakthrough occurring (<0.1 mg P/L in effluent) in a fixed-bed column operation system. The introduced quaternary ammonium groups covalently bound to biochar played a dominant role in phosphate sequestration by N-BC through forming the out-sphere complexation with phosphate. All results imply that it is of promising prospect for N-BC practical application for phosphate purification from waters. The present study provided a new strategy to expand the application of biochar, usually serving as an adsorbent for cationic pollutants, to the purification of anionic pollutants such as phosphate from waters.

General reversal of N-decomposition relationship during long-term decomposition in boreal and temperate forests.

Decomposition of dead organic matter is fundamental to carbon (C) and nutrient cycling in terrestrial ecosystems, influencing C fluxes from the biosphere to the atmosphere. Theory predicts and evidence strongly supports that the availability of nitrogen (N) limits litter decomposition. Positive relationships between substrate N concentrations and decomposition have been embedded into ecosystem models. This decomposition paradigm, however, relies on data mostly from short-term studies analyzing controls on early-stage decomposition. We present evidence from three independent long-term decomposition investigations demonstrating that the positive N-decomposition relationship is reversed and becomes negative during later stages of decomposition. First, in a 10-y decomposition experiment across 62 woody species in a temperate forest, leaf litter with higher N concentrations exhibited faster initial decomposition rates but ended up a larger recalcitrant fraction decomposing at a near-zero rate. Second, in a 5-y N-enrichment experiment of two tree species, leaves with experimentally enriched N concentrations had faster decomposition initial rates but ultimately accumulated large slowly decomposing fractions. Measures of amino sugars on harvested litter in two experiments indicated that greater accumulation of microbial residues in N-rich substrates likely contributed to larger slowly decomposing fractions. Finally, a database of 437 measurements from 120 species in 45 boreal and temperate forest sites confirmed that higher N concentrations were associated with a larger slowly decomposing fraction. These results challenge the current treatment of interactions between N and decomposition in many ecosystems and Earth system models and suggest that even the best-supported short-term controls of biogeochemical processes might not predict long-term controls.

Optimization of leaf area index measurement method and correction of green plot ratio formula based on regional plant characteristics-a study in Chongqing, China.

The quantification of green space green plot ratio (GPR) is mostly based on estimation formulas, and the leaf area index (LAI) estimation values in these estimation formulas have not been well verified by measured LAI values, resulting in errors and uncertainties in GPR quantification results. This study aims to address this gap by measuring the LAI of 113 regional plants in Chongqing, China, following a standardized measurement path for digital hemispherical photography (DHP). The results indicate that the optimal relative exposure value (REV) was - 1 under overcast conditions and - 2 under sunny and cloudy conditions. Among the threshold algorithms for hemispherical images, the Intermodes algorithm in ImageJ was the best. The LAI of regional plants is highest in summer, followed by spring and autumn, and lowest in winter. Tree height (h) and crown width (w) are key factors affecting LAI, but the LAI also varies with plant species. Overall, the LAI of evergreen trees is higher than that of deciduous trees. The LAI of evergreen trees and shrubs with a height shorter than 5 m is the largest, and that of deciduous trees and shrubs with a crown width larger than 8 m is the largest. The study further verified that the existing GPR estimation formula exhibited large errors in Chongqing, while there was a strong correlation (R2 = 0.973) between the GPR estimation value and the measured value. A conversion formula was developed to reduce estimation biases, and the corrected formula is capable of estimating GPR values more accurately when actual LAI measurements are insufficient. Overall, this study verifies the significance of measuring localized LAI values, promotes the understanding of LAI suitability for GPR calculations, and provides an empirical formula for GPR estimation in Chongqing, China.

One new species and two new records of the spider wasp genus Telostholus Haupt, 1929 in China, with a key to the world species.

The taxonomy of the genus Telostholus (Hymenoptera: Pompilidae: Pompilinae) from China is studied and one species is newly described and illustrated: T. venarectus Song & Ma, sp. nov. Additionally, two species, T. lao and T. malayensis are newly reported from China. A key to the world species of Telostholus is provided.

In vitro and clinical validation of different correction algorithms for the two-dimensional proximal isovelocity surface area method in a low-velocity flow field for quantifying tricuspid regurgitation.

Background: The 2-dimensional proximal isovelocity surface area (2D PISA) method underestimates tricuspid regurgitation (TR) severity. Previously proposed correction algorithms should be further scrutinized. Methods: Two correction algorithms were tested. One approach involves dividing the 2D PISA effective regurgitant orifice area by a constant of 0.7 (EROA0.7). Another approach involves multiplying the unadjusted EROA by Vorifice/(Vorifice - Valiasing), where Vorifice denotes the TR jet velocity, and Valiasing represents the color aliasing velocity (EROAVo-Va). In vitro validation was performed on a commercially available multifunctional valve tester with different size orifices and peak pressure gradients. A true EROA was derived through the regurgitant volume (RVol) calculated from the tester. For clinical validation, RVol was calculated as the difference between the overall stroke volume and the forward stroke volume of the right ventricle. Volumetric EROA was derived by dividing the RVol by the TR velocity-time integral (VTI). The vena contracta area (VCA) was obtained through direct planimetry with 3D echocardiography. The mean of volumetric EROA and VCA served as the reference in clinical validation. Results: Excellent correlation between the calculated EROAs and the true EROA was observed in vitro (r=0.98, r=0.97, and r=0.98 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively; all P values <0.0001). EROAVo-Va underestimated the true EROA and averaged 33% (P=0.3163), while EROA0.7 overestimated the true EROA and averaged 8% (P=0.0032). Clinically, these methods consistently exhibited a notable underestimation that varied with the reference EROA. This systematic underestimation was mitigated by both algorithms when either the VCA (biases of 19.6, 15.1, and 11.8 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) or the volumetric EROA (biases of 10.1, 5.6, and 2.3 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) served as the reference. Their ability to distinguish severe TR was similar, with area under the curve values of 0.905, 0.903, and 0.893 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively. No statistically significant differences were observed for diagnostic accuracy (all P values >0.05). Conclusions: Using a correction factor of 0.7 in quantifying TR provides similar accuracy when compared to other techniques. This represents a valuable clinical tool for quickly correcting the underestimation of the 2D PISA method in TR. This simple method may increase the frequency of applying the correction and earlier recognition of patients with severe TR.

Feasibility Study of a Novel Transapical Chordal Implantation System in a Porcine Model.

Transapical beating-heart mitral repair with chordal implantation system has been considered as an alternative treatment for degenerative mitral regurgitation. This study aimed to assess the feasibility and safety of the E-Chord system (Med-Zenith Medical, Beijing, China) for transapical beating-heart mitral valve repair in a porcine model. Artificial chordae were transapically implanted on the mitral valves of 12 anesthetized pigs under epicardial echocardiographic guidance and secured outside the left ventricular apex. The study endpoints included procedural success, device durability, and tissue response to the device. The procedural success rate was 100% (12/12). All animals were implanted with E-Chord in the anterior and posterior leaflets, respectively, and survived uneventfully until euthanized as planned. During the 180-day follow-up, no animal had significant mitral valve dysfunction. The gross observation showed no evidence of anchor detachment and chordal rupture, and there was no obvious damage or changes to mitral leaflets. Microscopic evaluation revealed that the endothelialization of anchor and chordae was completed 90 days after implantation and there was no evidence of chordal rupture, thrombosis, or infection during the 180-day follow-up. The E-Chord system was found to be feasible and safe for heart-beating mitral chordal implantation in a porcine model. The findings of this study suggest that the E-Chord system may be a potential alternative for the treatment of degenerative mitral regurgitation in humans.

Transcatheter mitral valve replacement with Mi-thos system: First-in-human experience.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has become an alternative for high-risk patients with severe mitral regurgitation (MR). The aim of this study was to evaluate the safety and feasibility of the Mi-thos TMVR system (NewMed Medical) for high-risk patients with severe MR. METHODS: This was a prospective, two-center, single-arm early feasibility study. Baseline characteristics, procedural data and 30-day follow-up outcomes were collected and analyzed. The primary endpoint was intraoperative success rate of device implantation. The second endpoints were all-cause mortality and major post-procedural complications. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. RESULTS: Ten high-risk patients with severe MR were enrolled at two sites from August 2021 to November 2022. The median age was 70.5 years, and 60% of patients were female. The median Society of Thoracic Surgeons Predicted Risk of Mortality was 9.5%. The Mi-thos TMVR system was successfully implanted via transapical access in all patients. There was no pericedural mortality or major postpericedural complications during the 30-day follow-up. All implanted prosthetic valves had no or trace valvular or paravalvular MR, and the median mitral valve gradient at 30 days was 2.0 mmHg (IQR: 2.0-3.0 mmHg). There was one mild left ventricular outflow tract obstruction. CONCLUSIONS: The favorable short-term outcomes of the Mi-thos TMVR system demonstrated that it might be a feasible and safe therapeutic alternative for high-risk patients with severe MR. Nevertheless, further evaluation of the Mi-thos TMVR system is warranted.