Simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction: initial experience.

BACKGROUND: Simultaneous transcatheter mitral valve in valve (VIV) replacement and aortic valve replacement experience is limited. We report our initial experience with simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction. METHODS: A total of 8 patients had simultaneous transcatheter heart valve implants for severe mitral bioprosthesis failure (VIV), with a second valve procedure that included native aortic regurgitation (n = 3) or degenerated bioprostheses in the aortic position (n = 5). All patients were treated with a self-expandable J-valve transcatheter valve, using the transapical approach. RESULTS: The mean age of the patients was 73.1 ± 6.2 years. The mean Society of Thoracic Surgeons score was 13.8 ± 6.3%. Device success was 100% according to Valve Academic Research Consortium-2 criteria. No other procedure-associated complications occurred, including left ventricular outflow tract obstruction and valve migration. The mean hospital lengths of stay after the procedure were 11.5 ± 8.0 days. No deaths occurred at 30 days. At a median follow-up period of 28.7 ± 22.3 months, no patients died. All patients were in New York Heart Association functional classes I-II. Echocardiographic parameters at follow-up showed a normofunctioning J valve in the mitral position and a mean max mitral flow velocity of 2.0 ± 0.5 m/s; the J valve in the aortic position was also normofunctioning, and the mean max aortic flow velocity was 2.3 ± 0.5 m/s. CONCLUSION: Simultaneous transapical transcatheter aortic and mitral valve replacement using the self-expandable J valve appears to be a feasible and effective alternative to redo surgery.

Lower incidence of new-onset severe conduction disturbances after transcatheter aortic valve implantation with bicuspid aortic valve in patients with no baseline conduction abnormality: a cross-sectional investigation in a single center in China.

Background: With technological advancements, the incidence of most transcatheter aortic valve implantation (TAVI)-related complications, with the exception of conduction disturbances, has decreased. Bicuspid aortic valve (BAV) is also no longer considered a contraindication to TAVI; however, the effect of BAV on postoperative conduction disturbances after TAVI is unknown. Methods: We collected information on patients who met the indications for TAVI and successfully underwent TAVI at our center between January 2018 and January 2021. Patients with preoperative pacemaker implantation status or conduction disturbances (atrioventricular block, bundle branch block, and intraventricular block) were excluded. Based on imaging data, the patients were categorized into the BAV group and the tricuspid aortic valve (TAV) group. The incidence of new perioperative conduction disturbances was compared between the two groups. Results: A total of 187 patients were included in this study, 64 (34.2%) of whom had BAV. The incidence of third-degree block in the BAV group was 1.6%, which was lower than that (13.0%) in the TAV group (P < 0.05). Multivariate logistic regression results showed that the risk of third-degree conduction disturbances was 15-fold smaller in the BAV group than that in the TAV group [relative risk (RR) = 0.067, 95% CI = 0.008-0.596, P < 0.05]. The risk of other blocks in the BAV group was about half of that in the TAV group (RR = 0.498, 95% CI = 0.240-1.032); however, the difference was not statistically significant (P > 0.05). Conclusion: The present study found that patients with BAV had a lower rate of third-degree conduction disturbances after TAVI than patients with TAV.

Innovative use of a self-expanding valve for valve-in-valve transcatheter mitral valve replacement: experience from a four-year single-center study.

Background: Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) is a minimally invasive option for patients with bioprosthetic mitral valve failure. Since January 2019, our center has been using a new innovative option, J-Valve, to treat patients with bioprosthetic mitral valve failure who were at high risk for open heart surgery. The aim of this study is to explore the effectiveness and safety of J-Valve and report the results from the four-year follow-up period of the innovative application of the transcatheter valve. Methods: Patients who underwent the ViV-TMVR procedure between January 2019 and September 2022 in our center were included in the study. J-Valve™ system (JC Medical Inc., Suzhou, China) with three U-shape grippers was used for ViV-TMVR via transapical approach. Data on survival, complications, transthoracic echocardiographic results, New York Heart Association functional class in heart failure, and patient-reported health-related quality of life according to the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were collected during the four-year follow up. Results: Thirty-three patients (mean age 70.1 ± 1.1 years, 13 men) were included and received ViV-TMVR. The surgery success rate was 97%: only one patient was converted to open-heart surgery due to intraoperative valve embolization to the left ventricle. During the first 30 days all-cause mortality was 0%, risk of stroke 2.5% and risk of mild paravalvular leak 15.2%; mitral valve hemodynamics improved (179.7 ± 8.9 at 30 days vs. 269 ± 49 cm/s at baseline, p < 0.0001). Median time from operation to discharge was six days, and there were no readmissions within 30 days from operation. The median and maximum follow-up durations were 28 and 47 months, respectively; during the entire follow-up, all-cause mortality was 6.1%, and the risk of cerebral infarction 6.1%. Cox regression analysis did not identify any variables significantly associated with survival. The New York Heart Association functional class and the KCCQ-12 score improved significantly compared with their preoperative values. Conclusion: The use of J-Valve for ViV-TMVR is safe and effective with a high success rate, low mortality and very few associated complications, representing an alternative surgical strategy for the elderly, high-risk patients with bioprosthetic mitral valve failure.

Prediction of Male Coronary Artery Bypass Grafting Outcomes Using Body Surface Area Weighted Left Ventricular End-diastolic Diameter: Multicenter Retrospective Cohort Study.

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

Upregulation of FOXA2 in uterine luminal epithelium and vaginal basal epithelium of epiERα-/- (Esr1fl/flWnt7aCre/+) mice†.

Forkhead box protein A2 (FOXA2) is a pioneer transcription factor important for epithelial budding and morphogenesis in different organs. It has been used as a specific marker for uterine glandular epithelial cells (GE). FOXA2 has close interactions with estrogen receptor α (ERα). ERα binding to Foxa2 gene in the uterus indicates its regulation of Foxa2. The intimate interactions between ERα and FOXA2 and their essential roles in early pregnancy led us to investigate the expression of FOXA2 in the female reproductive tract of pre-implantation epiERα-/- (Esr1fl/flWnt7aCre/+) mice, in which ERα is conditionally deleted in the epithelium of reproductive tract. In the oviduct, FOXA2 is detected in the ciliated epithelial cells of ampulla but absent in the isthmus of day 3.5 post-coitum (D3.5) Esr1fl/fl control and epiERα-/- mice. In the uterus, FOXA2 expression in the GE appears to be comparable between Esr1fl/fl and epiERα-/- mice. However, FOXA2 is upregulated in the D0.5 and D3.5 but not PND25-28 epiERα-/- uterine luminal epithelial cells (LE). In the vagina, FOXA2 expression is low in the basal layer and increases toward the superficial layer of the D3.5 Esr1fl/fl vaginal epithelium, but FOXA2 is detected in the basal, intermediate, and superficial layers, with the strongest FOXA2 expression in the intermediate layers of the D3.5 epiERα-/- vaginal epithelium. This study demonstrates that loss of ERα in LE and vaginal basal layer upregulates FOXA2 expression in these epithelial cells during early pregnancy. The mechanisms for epithelial cell-type specific regulation of FOXA2 by ERα remain to be elucidated.

Visualization of preimplantation uterine fluid absorption in mice using Alexa Fluor™ 488 Hydrazide†.

Uterine fluid plays important roles in supporting early pregnancy events and its timely absorption is critical for embryo implantation. In mice, its volume is maximum on day 0.5 post-coitum (D0.5) and approaches minimum upon embryo attachment ~D4.0. Its secretion and absorption in ovariectomized rodents were shown to be promoted by estrogen and progesterone (P4), respectively. The temporal mechanisms in preimplantation uterine fluid absorption remain to be elucidated. We have established an approach using intraluminally injected Alexa Fluor™ 488 Hydrazide (AH) in preimplantation control (RhoAf/f) and P4-deficient RhoAf/fPgrCre/+ mice. In control mice, bulk entry (seen as smeared cellular staining) via uterine luminal epithelium (LE) decreases from D0.5 to D3.5. In P4-deficient RhoAf/fPgrCre/+ mice, bulk entry on D0.5 and D3.5 is impaired. Exogenous P4 treatment on D1.5 and D2.5 increases bulk entry in D3.5 P4-deficient RhoAf/fPgrCre/+ LE, while progesterone receptor (PR) antagonist RU486 treatment on D1.5 and D2.5 diminishes bulk entry in D3.5 control LE. The abundance of autofluorescent apical fine dots, presumptively endocytic vesicles to reflect endocytosis, in the LE cells is generally increased from D0.5 to D3.5 but its regulation by exogenous P4 or RU486 is not obvious under our experimental setting. In the glandular epithelium (GE), bulk entry is rarely observed and green cellular dots do not show any consistent differences among all the investigated conditions. This study demonstrates the dominant role of LE but not GE, the temporal mechanisms of bulk entry and endocytosis in the LE, and the inhibitory effects of P4-deficiency and RU486 on bulk entry in the LE in preimplantation uterine fluid absorption.

Case report: Transapical transcatheter double valve-in-valve replacement of degenerated aortic and mitral bioprosthetic valves with limited radiopaque landmarks.

A 67-year-old male patient who had undergone double valve replacement 11 years before presented with severe dyspnea to our department. The bioprosthetic aortic and mitral valves have failed. Because of the high risk of redo surgery. We perform a simultaneous transapical transcatheter valve-in-valve replacement of degenerated aortic and mitral bioprosthetic valves with limited radiopaque landmarks using the second-generation self-expanding J-valve. The post-operative course was stable and the patient was discharged on post-operative day eight.

Core Outcome Sets in Child Health: A Systematic Review.

Importance: Developing core outcome sets is essential to ensure that results of clinical trials are comparable and useful. A number of core outcome sets in pediatrics have been published, but a comprehensive in-depth understanding of core outcome sets in this field is lacking. Objective: To systematically identify core outcome sets in child health, collate the diseases to which core outcome sets have been applied, describe the methods used for development and stakeholder participation, and evaluate the methodological quality of existing core outcome sets. Evidence Review: MEDLINE, SCOPUS, Cochrane Library, and CINAHL were searched using relevant search terms, such as clinical trials, core outcome, and children, along with relevant websites, such as Core Outcome Measures in Effectiveness Trials (COMET). Four researchers worked in teams of 2, performed literature screening and data extraction, and evaluated the methodological quality of core outcome sets using the Core Outcome Set-Standards for Development (COS-STAD). Findings: A total of 77 pediatric core outcome sets were identified, mainly developed by organizations or researchers in Europe, North America, and Australia and mostly from the UK (22 [29%]) and the US (22 [29%]). A total of 77 conditions were addressed; the most frequent International Classification of Diseases, 11th Revision category was diseases of the digestive system (14 [18%]). Most of the outcomes in pediatric core outcome sets were unordered (34 [44%]) or presented in custom classifications (29 [38%]). Core outcome sets used 1 or more of 8 development methods; the most frequent combination of methods was systematic review/literature review/scoping review, together with the Delphi approach and consensus for decision-making (10 [14%]). Among the 6 main types of stakeholders, clinical experts were the most frequently involved (74 [100%]), while industry representatives were rarely involved (4 [5%]). Only 6 core outcome sets (8%) met the 12 criteria of COS-STAD. Conclusions and Relevance: Future quality of pediatric core outcome sets should be improved based on the standards proposed by the COMET initiative, while core outcome sets methodology and reporting standards should be extended to pediatric populations to help improve the quality of core outcome sets in child health. In addition, the COMET outcome taxonomy should also add items applicable to children.

Fabrication of a donkey spleen ferritin-pectin complex to reduce iron release and enhance the iron supplementation efficacy.

Iron deficiency is a global issue, influencing more than one-third of the population in the world. Ferritin as a natural iron-containing protein is considered a marvelous iron supplement due to its biocompatibility, biodegradability and bioavailability. However, foodstuffs contain plenty of reductants which could induce iron release from the cavity of ferritin and cause oxidative damage. In this study, we aimed to prevent the iron release from donkey spleen ferritin (DSF) by pectin encapsulation driven by the electrostatic interaction and evaluated the iron supplementation of the DSF-pectin complex (DPC). After DSF was purified, we fabricated the DPC and the iron release was decreased by 53.68% after 60 min when DSF : pectin was 1 : 10 (w/w). TEM analysis showed that ferritin in the DPC is clustered in a linear pattern, and the cell viability assay indicated that the DPC has no toxicity towards Caco-2 cells. In the mouse experiment, the DPC increased the content of serum iron and serum ferritin with no significant difference from the control check. Furthermore, the DPC increased the iron content in the liver, suppressed the expression of hepcidin and increased the expression of ferroportin. These results suggested that the DPC could prevent the interactions between food components and ferritin and is a promising iron supplement to ameliorate iron deficiency.

Quality appraisal of clinical practice guidelines on physical restraints in ICU: a systematic review.

BACKGROUND: Physical restraint has been regarded as a protective measure in the intensive care unit (ICU) in order to avoid unexpected events. But a great number of researches have proven that physical restraints can cause bad influences on patients' mental health, such as language delays of children, sense of uncertainty, loss of trust, etc. However, it is unclear whether there are currently high-quality clinical practice guidelines (CPGs) to guide clinical practice in physical restraints. So we aim to analyze available CPGs on physical restraints in ICU with Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluating methodological quality and Reporting Items for Practice Guidelines in Healthcare (RIGHT) evaluating reporting quality. METHODS: We systematically searched PubMed, Embase, Web of Science, CINAHL, CNKI (Chinese database), Wanfang data (Chinese database), relevant websites (GIN, NICE, SIGN, RNAO, AHRQ, AACN), and Google from their inception to Nov 21, 2021. Two reviewers independently use the AGREE II tool and RIGHT checklist to evaluate methodological and reporting quality of included guidelines on physical restraints in ICU. The number and proportion of reported items of RIGHT checklist and the scores of each domain of AGREE II were calculated. We also evaluated the consistency among the reviewers via use of the intragroup correlation coefficient. RESULTS: A total of six guidelines were included. The mean AGREE II score for the included guidelines was 39.56% with a range of 30.27-69.85%. No guideline was "high quality", and only one guideline was "moderate quality" with 69.85% mean AGREE II score. The mean RIGHT reporting score for guidelines was 41.0% with a range of 24.7-77.7%. Only one guideline was "moderate-reported" with a mean reporting score of 77.7%. DISCUSSION: In general, the methodological and reporting quality of physical restraints guidelines is low, and future development or updating of high-quality guidelines to guide clinical practice is needed.

Transcatheter mitral valve replacement versus redo surgery for mitral prosthesis failure: A systematic review and meta-analysis.

Background: Transcatheter mitral valve replacement (TMVR) has emerged as an alternative to redo surgery. TMVR compared with redo surgical mitral valve replacement (SMVR) in patients with mitral prosthesis failure remains limited. In this study, we performed a meta-analysis to assess the outcomes of TMVR (including valve-in-valve and valve-in-ring) versus redo surgery for mitral prosthesis failure. Methods: We comprehensively searched the PubMed, Embase, and Cochrane library databases according to predetermined inclusion and exclusion criteria, and then we extracted data. We compared the outcomes of TMVR and redo SMVR for mitral prosthesis failure in terms of the in-hospital mortality, stroke, renal dysfunction, vascular complication, pacemaker implantation, exploration for bleeding, paravalvular leak, mean mitral valve gradient, 30-day mortality, and 1-year mortality. Results: Nine retrospective cohort studies and a total of 3,038 patients were included in this analysis. Compared with redo SMVR for mitral prosthesis failure, TMVR was associated with lower in-hospital mortality [odds ratios (OR): 0.44; 95% confidence interval (CI): 0.30-0.64; P < 0.001], stroke (OR: 0.44; 95% CI: 0.29-0.67; P = 0.0001), renal dysfunction (OR: 0.52; 95% CI: 0.37-0.75; P = 0.0003), vascular complication (OR: 0.58; 95% CI: 0.43-0.78; P = 0.004), pacemaker implantation (OR: 0.23; 95% CI: 0.15-0.36; P < 0.00001), and exploration for bleeding (OR: 0.24; 95% CI: 0.06-0.96; P = 0.04). Conversely, redo SMVR had lower paravalvular leak (OR: 22.12; 95% CI: 2.81-174.16; P = 0.003). There was no difference in mean mitral valve gradient (MD: 0.04; 95% CI: -0.47 to 0.55; P = 0.87), 30-day mortality (OR: 0.65; 95% CI: 0.36-1.17; P = 0.15), and 1-year mortality (OR: 0.96; 95% CI: 0.63-1.45; P = 0.84). Conclusion: In patients with mitral prosthesis failure, TMVR is associated with lower in-hospital mortality and lower occurrence of postoperative complications, except for paravalvular leak. TMVR offers a viable alternative to the conventional redo surgery in selected patients.

Varied effects of doxorubicin (DOX) on the corpus luteum of C57BL/6 mice during early pregnancy†.

Certain chemotherapeutic drugs are toxic to ovarian follicles. The corpus luteum (CL) is normally developed from an ovulated follicle for producing progesterone (P4) to support early pregnancy. To fill in the knowledge gap about effects of chemotherapy on the CL, we tested the hypothesis that chemotherapy may target endothelial cells and/or luteal cells in the CL to impair CL function in P4 steroidogenesis using doxorubicin (DOX) as a representative chemotherapeutic drug in mice. In both mixed background mice and C57BL/6 mice, a single intraperitoneal injection of DOX (10 mg/kg) on 0.5-day postcoitum (D0.5, postovulation) led to ~58% D3.5 mice with serum P4 levels lower than the serum P4 range in the phosphate buffer saline-treated control mice. Further studies in the C57BL/6 ovaries revealed that CLs from DOX-treated mice with low P4 levels had less defined luteal cords and disrupted collagen IV expression pattern, indicating disrupted capillary, accompanied with less differentiated luteal cells that had smaller cytoplasm and reduced StAR expression. DOX-treated ovaries had increased granulosa cell death in the growing follicles, reduced proliferating cell nuclear antigen-positive endothelial cells in the CLs, enlarged lipid droplets, and disrupted F-actin in the luteal cells. These novel data suggest that the proliferating endothelial cells in the developing CL may be the primary target of DOX to impair the vascular support for luteal cell differentiation and subsequently P4 steroidogenesis. This study fills in the knowledge gap about the toxic effects of chemotherapy on the CL and provides critical information for risk assessment of chemotherapy in premenopausal patients.

New Internet-Based Warfarin Anticoagulation Management Approach After Mechanical Heart Valve Replacement: Prospective, Multicenter, Randomized Controlled Trial.

BACKGROUND: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. OBJECTIVE: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. METHODS: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. RESULTS: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). CONCLUSIONS: The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-032949.

The Effect of Minimally Invasive Thoracoscopic Left Atrial Appendage Excision on Cardiac Dynamic and Endocrine Function.

PURPOSE: Left atrial appendage (LAA) isolation is an effective surgical treatment for decreasing thromboembolic risk. We sought to evaluate the short-term effect of minimally invasive surgery with LAA excision on left atrial dynamic and endocrine function in atrial fibrillation (AF) patients. METHODS: A total of 52 patients with paroxysmal AF undergoing minimally invasive surgery with LAA excision in Anzhen Hospital from October 2012 to June 2014 were enrolled in the study. The natriuretic peptide plasma level was determined by enzyme-linked immunosorbent assay (ELISA), and left atrial dynamic function was measured preprocedure by real-time three-dimensional echocardiography and postprocedure after 7 days and 3 months. RESULTS: With the exception of six recurrences, 88.5% (46/52) of the patients were prospectively followed over 3 months in terms of their sinus rhythm postprocedure. No severe operative complications or embolism events occurred within those 3 months. Echocardiography showed a 3-6% decrease in left atrial volume postprocedure, and dynamic function was largely restored by 3 months. There was no significant change in natriuretic peptide levels, although a slight decrease was detected 7 days postprocedure, which gradually recovered by 3 months (P = 0.350). CONCLUSIONS: There are no significant differences in left atrial dynamics and natriuretic peptide secretion in AF patients after minimally invasive surgery with LAA excision.

New warfarin anticoagulation management model after heart valve surgery: rationale and design of a prospective, multicentre, randomised trial to compare an internet-based warfarin anticoagulation management model with the traditional warfarin management model.

INTRODUCTION: Warfarin is an effective anticoagulant and the only oral anticoagulant available for patients with mechanical heart valves. The prothrombin time and the associated international normalised ratio (INR) are routinely tested to monitor the response to anticoagulation therapy in patients. Patients who undergo mechanical heart valve replacement need lifelong anticoagulation therapy, and their INR is regularly measured to adjust the anticoagulation strength and the dose of anticoagulation drugs. Appropriate warfarin anticoagulation management can reduce patient complications, such as bleeding and thrombosis, and improve the long-term survival rate. We propose modern internet technology as a platform to build a warfarin anticoagulation follow-up system after valve replacement surgery. This system will provide doctors and patients with more standardised and safer follow-up methods as well as a method to further reduce the risk of warfarin anticoagulation-related complications and improve its therapeutic effects. METHODS AND ANALYSIS: A prospective, multicentre, randomised, controlled trial will be conducted. A total of 700 patients who require long-term warfarin anticoagulation monitoring after heart valve replacement will be enrolled and randomly divided at a 1:1 ratio into a traditional outpatient anticoagulation management group and a group undergoing a new method of management based on the internet technology with follow-up for 1 year. Differences in the percentage of time in the therapeutic range (TTR), drug dose adjustments, bleeding/thrombosis and other related complications will be observed. The primary endpoint is the difference in the TTR between the two groups. The purpose of this study is to explore a safer and more effective mode of doctor-patient interaction and communication in the internet era. As of 13 July 2019, 534 patients had been enrolled. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University. The results will be published in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: ChiCTR1800016204.

Transcatheter aortic valve implantation after previous mechanical mitral valve replacement in a patient with coexistent rheumatic aortic stenosis and regurgitation.

A 67-year-old female was referred to our center with rheumatic aortic stenosis (AS) and aortic regurgitation (AI). As the patient was a high-risk case for surgery, we chose transcatheter aortic valve implantation (TAVI) as the treatment of choice. However, the thickened, long, and mildly calcified aortic valve, and the very small distance (7 mm) between the aortic annulus and mechanical mitral valve (MMV) increased the risk of coronary artery occlusion and flap clamping of MMV. As the left ventricle was small in size, transfemoral TAVI, which causes lesser degree of trauma to the patient, was successfully performed eventually.

Association of luteal cell degeneration and progesterone deficiency with lysosomal storage disorder mucolipidosis type IV in Mcoln1-/- mouse model†.

Transient receptor potential cation channel, mucolipin subfamily, member 1 (TRPML1) (MCOLN1/Mcoln1) is a lysosomal counter ion channel. Mutations in MCOLN1 cause mucolipidosis type IV (MLIV), a progressive and severe lysosomal storage disorder with a slow onset. Mcoln1-/- mice recapitulate typical MLIV phenotypes but roles of TRPML1 in female reproduction are unknown. Despite normal mating activities, Mcoln1-/- female mice had reduced fertility at 2 months old and quickly became infertile at 5 months old. Progesterone deficiency was detected on 4.5 days post coitum/gestation day 4.5 (D4.5). Immunohistochemistry revealed TRPML1 expression in luteal cells of wild type corpus luteum (CL). Corpus luteum formation was not impaired in 5-6 months old Mcoln1-/- females indicated by comparable CL numbers in control and Mcoln1-/- ovaries on both D1.5 and D4.5. In the 5-6 months old Mcoln1-/- ovaries, histology revealed less defined corpus luteal cord formation, extensive luteal cell vacuolization and degeneration; immunofluorescence revealed disorganized staining of collagen IV, a basal lamina marker for endothelial cells; Nile Red staining detected lipid droplet accumulation, a typical phenotype of MLIV; immunofluorescence of heat shock protein 60 (HSP60, a mitochondrial marker) and in situ hybridization of steroidogenic acute regulatory protein (StAR, for the rate-limiting step of steroidogenesis) showed reduced expression of HSP60 and StAR, indicating impaired mitochondrial functions. Luteal cell degeneration and impaired mitochondrial functions can both contribute to progesterone deficiency in the Mcoln1-/- mice. This study demonstrates a novel function of TRPML1 in maintaining CL luteal cell integrity and function.

Structural analysis of the mitral valve in rheumatic and degenerative mitral valve diseases: implications for annuloplasty selection.

BACKGROUND: Mitral valve (MV) repair has been recommended for MV diseases. Good repair requires a full understanding of the three-dimensional (3D) structure of the MV, however, currently little is known about the 3D structure of the rheumatic MV. METHODS: A total of 82 cases underwent 3DTEE. Of these, 41 patients with rheumatic valvular disease (RVD) were studied intraoperatively (17 had severe mitral stenosis, 8 had severe mitral regurgitation, 16 had severe mitral stenosis coupled with regurgitation). There were 19 patients with degenerative MV disease (mitral valve prolapse [MVP] with severe regurgitation) and 22 cases with normal MV served as control subjects (CS). RESULTS: Compared with CS, the anteroposterior diameter, anterolateral posteromedial, annulus circumference, and annulus area of both pathological groups, i.e., the RVD and MVP groups, were understandably greater. Though the sphericity index was greater in the RVD group vis-à-vis CS, the MVP group had nearly the same sphericity index as CS. The mitral annulus of patients with RVD tended to be round. Annular unsaddling, defined as annular height to commissural width ratio (an indicator of saddle degree) less than 15%, was significantly more prevalent in the group with degenerative MV disease. Automatic dynamic analysis revealed that the parameters of annular maximum displacement and annulus area fraction (two-dimensional) were considerably decreased in the RVD group. CONCLUSIONS: Annular unsaddling was significantly more prevalent in the degenerative MV disease group. The mitral annulus of patients with RVD tended to be round and stiff.