A novel balloon-expandable transcatheter aortic valve bioprosthesis: Myval and Myval Octacor.

INTRODUCTION: Over the past two decades, transcatheter aortic valve replacement (TAVR) has expanded its application across all surgical risk levels, including low-risk patients, where, due to longer life expectancy, reducing common pitfalls of TAVR is essential. To address these needs, many technological advancements have been developed. Myval and the new generation Myval Octacor (Meril Life Sciences Pvt. Ltd) are novel balloon-expandable (BE) transcatheter heart valve (THV) systems designed for the treatment of severe aortic stenosis. AREAS COVERED: This review aims to illustrate the design features of these novel THVs and the main evidence from available studies. Furthermore, we provide evidence of these THVs' performance in challenging scenarios such as extra-large aortic annuli, bicuspid aortic valves, and valve-in-valve/valve-in-ring procedures. EXPERT OPINION: Myval and Myval Octacor have demonstrated comparable early safety and clinical efficacy to the leading contemporary THVs, exhibiting remarkably low rates of moderate to severe paravalvular leak (PVL) and permanent pacemaker implantation (PPI). The wide range of sizes offered by the Myval family may minimize the risk of under-/oversizing, potentially explaining the lower rates of the aforementioned phenomena. Moreover, the presence of both internal skirt and external reinforced cuff may also explain the low rate of moderate to severe PVL.

Roles of lipid mediators in early pregnancy events.

Background: Early pregnancy events, including embryo implantation, are critical for maintaining a healthy pregnancy and facilitating childbirth. Despite numerous signaling pathways implicated in establishing early pregnancy, a comprehensive understanding of implantation remains elusive. Methods: This paper provides a comprehensive review of the current research on lipids in the context of early pregnancy, with a particular focus on feto-maternal communications. Main Findings: Embryo implantation entails direct interaction between uterine tissues and embryos. Introducing embryos triggers significant changes in uterine epithelial morphology and stromal differentiation, facilitating embryo implantation through communication with uterine tissue. Studies employing genetic models and chemical compounds targeting enzymes and receptors have elucidated the crucial roles of lipid mediators-prostaglandins, lysophosphatidic acid, sphingosine-1-phosphate, and cannabinoids-in early pregnancy events. Conclusion: Given the high conservation of lipid synthases and receptors across species, lipid mediators likely play pivotal roles in rodents and humans. Further investigations into lipids hold promise for developing novel diagnostic and therapeutic approaches for infertility in humans.

Pulmonary congestion assessed by lung ultrasound in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: Prevalence and prognostic implications.

AIMS: Lung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS-PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS-PC in patients with severe AS before and after TAVI. METHODS AND RESULTS: We designed a single-centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8-zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all-cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12-month follow-up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre-TAVI LUS-PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS-PC significantly decreased as compared to pre-TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B-lines score of 4 (interquartile range [IQR] 0-11) versus 11 (IQR 6-19) pre-TAVI (p < 0.001). During a median follow-up of 12 (12-17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre-TAVI LUS-PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114-6.857; p = 0.028). CONCLUSIONS: Lung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre-TAVI PC, measured by LUS, is an independent predictor of 1-year clinical outcome.

Importance of pseudoaneurysms after TAVI - a retrospective analysis of 2063 patients.

Background: Bifemoral arterial access is common in patients undergoing transcatheter aortic valve implantation (TAVI), with a primary treatment access (TAVI access) and a secondary non-TAVI access. Pseudoaneurysm (PSA) is an important complication of femoral arterial puncture. Major vascular complications after TAVI are well described, but little is known about PSA. Patients and methods: A total of 2063 patients underwent transfemoral TAVI between January 2014 and January 2020. Vascular ultrasound of the common femoral artery was assessed before and after TAVI. We compared patient characteristics, periprocedural risk scores, procedural characteristics, and access site bleeding events according to Valve Academic Research Consortium 3 (VARC-3) criteria, length of stay (LOS), and all-cause mortality at one year between patients with (46) and without (2017) PSA. Results: The incidence of PSA after TAVI was 2.2% (46/2063). All PSA were successfully treated with ultrasound-guided manual compression (UGMC) or thrombin injection (UGTI) without complications. Patients with PSA had lower platelet counts (210×1000/µl vs. 234×1000/µl; p<0.05), more heart failure symptoms on admission (91% vs. 25%; p<0.05), were more often treated with (N)OACs for atrial fibrillation (AF; 54% vs. 38%; p <0.05), and were less often treated with aspirin (35% vs. 51%; p<0.03). Multivariate analysis identified secondary access site (odds ratio [OR] 8.11; p<0.001) and (N)OAC therapy (OR 1.31; p = 0.037) as risk factors for PSA development. PSA is associated with VARC-3 type 1-3 access site bleeding and longer LOS (15.2 ± 11.3 d vs. 11.6 ± 8.9 d; p<0.01), but this did not affect one year mortality (17% vs. 14%; p = 0.53). Conclusions: Pseudoaneurysms are an important complication after TAVI and are associated with access site bleeding and prolonged hospital stay. (N)OAC therapy and secondary access are important risk factors. Pseudoaneurysms can be safely and effectively treated with thrombin injection and do not affect one-year mortality.

Effects of implantation height on the performance of a redo transcatheter aortic valve replacement using a balloon-expandable valve.

Objective: The use of the transcatheter aortic valve in low-risk patients might lead to a second intervention due to the deterioration of the first 1. Understanding the implantation height is key to an effective redo transcatheter aortic valve replacement treatment. Methods: The effects of implantation height on the performance of a balloon-expandable valve within a self-expandable valve were assessed using hemodynamic testing and particle image velocimetry. The hemodynamic performances, leaflet kinematics, and turbulent shear stresses were measured and compared. Results: When a second balloon-expandable valve was positioned at varying heights relative to the first self-expandable valve, the leaflet motion of the first valve transitioned from free opening and closing to overhanging, and eventually to being entirely pinned to the stent, forming a neo-skirt. When the leaflets of the self-expandable valve could move freely, a decrease in regurgitation fraction was observed, but with an increased pressure gradient across the valve. Flow visualization indicated that the overhanging leaflets disrupted the flow, generating a higher level of turbulence. Conclusions: This study suggests that the overhanging leaflets should be avoided, whereas the other 2 scenarios should be carefully evaluated based on an individual patient's anatomy and the cause of failure of the first valve.

Effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following cardiac stent implantation.

BACKGROUND: Coronary stent implantation is usually used to treat unstable angina to alleviate stenosis or occlusion, promoting blood flow restoration and alleviating symptoms such as myocardial ischemia. And postoperative cardiac rehabilitation is essential for enhancing recovery and prognosis. Nevertheless, conventional rehabilitation lacks specificity, particularly for elderly patients with multiple comorbidities and poor compliance, rendering it less effective. AIM: To investigate the effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following coronary stenting intervention. METHODS: A retrospective enrollment was conducted comprising fifty-four elderly patients with unstable angina pectoris who underwent systematic cardiac rehabilitation training after receiving coronary intervention as the rehabilitation group, while fifty-three elderly patients who received basic nursing and rehabilitation guidance measures after coronary intervention were assigned to the control group. Differences in Seattle Angina Questionnaire scores, survival quality (SF-36) scores, cardiopulmonary exercise function assessment index, echocardiographic cardiac function index, and adverse cardiovascular events were compared between the two groups. RESULTS: After intervention, the rehabilitation group observed greater VO2 Max, maximum metabolic equivalent, eft ventricular ejection fraction, left ventricular end-diastolic diameter and smaller left ventricular end-systolic diameter. And the rehabilitation group observed greater scores of physical activity limitation, stable angina pectoris, treatment satisfaction, and SF-36 score. The incidence of adverse cardiovascular events in the two groups, showed no significant difference. CONCLUSION: Systematic cardiac rehabilitation following coronary stenting in elderly patients with unstable angina pectoris can enhance cardiac function recovery, consequently enhancing both quality of life and cardiopulmonary exercise tolerance.

Role of imaging in third aortic valve implantation: TAV-in-TAV-in-SAV.

Coronary obstruction remains a primary concern for redo transcatheter aortic valve implantation (TAVI) due to supra-annular leaflets. Hereby, we present two valve-in-valve-in-valve cases, initially incorporating a surgical valve implanted to clarify our concept that the surgical valve serves to safeguard against the coronary ostium obstruction.

Duration of cochlear implant use in children with prelingual single-sided deafness is a predictor of word perception in the CI ear.

As part of a longitudinal study regarding the benefit of early cochlear implantation for children with single-sided deafness, the current work explored the children's daily device use, potential barriers to full-time device use, and the children's ability to understand speech with the cochlear implant (CI). Data were collected from 20 children with prelingual SSD who received a CI before the age of 2.5 years, from the initial activation of the sound processor until the children were 4.8 to 11.0 years old. Daily device use was extracted from the CI's data logging, while word perception in quiet was assessed using direct audio input to the children's sound processor. The children's caregivers completed a questionnaire about habits, motivations, and barriers to device use. The children with SSD and a CI used their device on average 8.3 h per day, corresponding to 63 % of their time spent awake. All children except one could understand speech through the CI, with an average score of 59 % on a closed-set test and 73 % on an open-set test. More device use was associated with higher speech perception scores. Parents were happy with their decision to pursue a CI for their child. Certain habits, like taking off the sound processor during illness, were associated with lower device use. Providing timely counselling to the children's parents, focused on SSD-specific challenges, may be helpful to improve daily device use in these children.

Emerging Cases of Cat-Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Northeast Brazil.

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ2 = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment.

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

Modern advances in spinal cord regeneration: hydrogel combined with neural stem cells.

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

Effect of capsule treatment on visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataract.

BACKGROUND: Cataracts pose a significant clinical burden due to their complex pathogenesis. In recent years, an increase in cataracts coexisting with myopia has heightened the incidence of retinopathy and posterior vitreous detachment. Additionally, symptoms of ocular axis elongation, lens nucleus hardening, and vitreous liquefaction have become more prevalent. While conventional extracapsular cataract extraction is commonly employed, it often yields suboptimal visual outcomes. Subsequent advancements in cataract phacoemulsification and lens implantation surgeries have gained widespread acceptance for their ability to improve refraction and significantly improve uncorrected visual acuity. AIM: To investigate the effect of capsular treatment after phacoemulsification lens implantation in myopic patients with cataract. METHODS: We selected 110 patients (with 134 eyes) with myopia and cataracts treated. These patients were categorized into two groups: an observation group (57 patients with 70 eyes) and a control group (53 patients with 64 eyes). The control group underwent cataract phacoemulsification and lens implantation, while the observation group received a refined capsular treatment based on the control group's procedure. We assessed the differences in visual acuity and quality between the two groups before and after surgery. RESULTS: At six months post-operation, the observation group exhibited significantly improved far vision, intermediate vision, near vision, lower objective scattering index, higher Modulation transfer function cut-off frequency, and overall vision metrics at different contrast levels (100%, 20% and 9%) compared to the control group (P < 0.05). The total score of the National Eye Institute Visual Function Questionnaire in the observation group at 6 months after operation was significantly higher than that in the control group (P < 0.05). No significant difference in the incidence of adverse reactions was observed between the observation group and control group (P > 0.05). CONCLUSION: Capsular treatment demonstrates efficacy in improving visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataracts, warranting its clinical application.

Diagnostic Value and Molecular Function of MicroRNAs in Endometrial Diseases: A Systematic Review.

The human endometrium experiences significant cyclic morphological and biochemical changes throughout the menstrual cycle to prepare for embryo implantation. These processes are meticulously regulated by ovarian steroids and various locally expressed genes, encompassing inflammatory reactions, apoptosis, cell proliferation, angiogenesis, differentiation (tissue formation), and tissue remodeling. MicroRNAs (miRNAs) have been recognized as crucial regulators of gene expression, with their altered expression being linked to the onset and progression of various disorders, including cancer. This review examines the expression of miRNAs in the endometrium and their potential regulatory roles under pathological conditions such as endometriosis, recurrent implantation failure and endometrial cancer. Given miRNAs' critical role in maintaining gene expression stability, understanding the regulatory mechanisms of endometrial miRNAs and identifying their specific target genes could pave the way for developing preventive and therapeutic strategies targeting specific genes associated with these reproductive disorders.

Long-Term Outcomes of Mechanical versus Bioprosthetic Aortic Valve Replacement in Patients Under 50 Years Old: Meta-Analysis of Reconstructed Time-to-Event Data.

To compare long-term outcomes of mechanical versus bioprosthetic aortic valve replacement (AVR) in patients under the age of 50, we performed a study-level meta-analysis with reconstructed time-to-event data including studies published by December of 2023. The primary outcome was overall survival. Secondary outcomes included reoperation, major bleeding, and stroke. Five studies met our inclusion criteria with a total of 4245 patients (2311 mechanical, 1934 bioprosthetic). All studies were observational and the mean age of groups across the studies ranged from 38.2 to 43.0 years. The median follow-up time was 11.4 years (IQR, 6.9-15.0). Bioprosthetic AVR was associated with reduced overall survival and higher risk of all-cause death (HR, 1.170 [95% CI, 1.002-1.364], P=0.046), increased risk of reoperation over time (HR, 2.581, [95% CI, 2.102-3.168], P<0.001), decreased risk of major bleeding (HR, 0.500, [95% CI, 0.367-0.682], P<0.001), and decreased risk of stroke (HR, 0.751, [95% CI, 0.565-0.998], P=0.049) compared to mechanical AVR in patients under 50. In conclusion, for patients under the age of 50, bioprosthetic AVR is associated with increased mortality and risk of reoperation compared to mechanical valves. On the other hand, mechanical AVR is associated with an increased risk of major bleeding events and stroke. These aspects should be carefully considered during the selection of valve type in this age group; however, we should keep in mind that the statistically significant differences in the risk of all-cause death and stroke might not be clinically relevant (due to marginal statistical significance).

Antithrombotic Therapy in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

A Neuronal Network-Based Score Predicting Survival in Patients Undergoing Aortic Valve Intervention: The ABC-AS Score.

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention.

Reducing Left Ventricular Wall Stress through Aortic Valve Enlargement via Transcatheter Aortic Valve Implantation in Severe Aortic Stenosis.

Background: In aortic stenosis, the left ventricle exerts additional force to pump blood through the narrowed aortic valve into the downstream arterial vasculature. Adaptive hypertrophy helps to maintain wall stress homeostasis but at the expense of impaired compliance. Advanced ventricular deformation impacts the extent of functional recovery benefits achieved through transcatheter aortic valve implantation. Methods and Results: Subgroups were stratified based on output, with low-flow severe aortic stenosis defined as stroke volume index <35 mL· m-2. Before intervention, the low-flow subgroup exhibited worse effective orifice area index and arterial and global impedance, along with thinner wall thickness and larger chamber volume marginally. LV performance, including stroke volume index, ventricular elastance, and ventricular-arterial coupling, were notably inferior, consistent with worse adverse remodeling. Although the effective orifice area index was similarly augmented after TAVI, inferior recovery benefits were noted. Persistently higher wall stress and energy consumption were observed, along with poorer ventricular-arterial coupling. These changes in wall stress showed an inverse relationship with alterations in wall thickness and were proportional to changes in dimension and volume. Additionally, they were proportional to changes in left ventricular end-systolic pressure, pressure-volume area, and ventricular-arterial coupling but inversely related to ventricular end-systolic elastance. Conclusions: The study revealed that aortic valve enlargement through transcatheter aortic valve implantation reduces left ventricular wall stress in severe aortic stenosis. The reduced recovery benefits in the low-flow subgroup were evident. Wall stress could serve as a marker of mechanical benefit after the intervention.

Changes in Global Longitudinal Strain after TAVI: Additional Prognostic Value over Cardiac Damage in Patients with Severe Aortic Stenosis.

Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31-71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152-1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

The Extremely-Low-Frequency Electromagnetic Field Affects Apoptosis and Oxidative-Stress-Related Genes and Proteins in the Porcine Endometrium-An In Vitro Study.

Nowadays, the extremely-low-frequency electromagnetic field (ELF-EMF) is recognized as environmental pollution. The data indicate that the ELF-EMF may affect factors related to epigenetic regulation and alter important biological processes in the uterus. The impact of the ELF-EMF on apoptosis and oxidative-stress-related genes has not been documented in porcine endometrium. This raises the question of whether the exposure to the ELF-EMF can induce apoptosis and/or oxidative stress in the endometrium of pigs during the peri-implantation period. Porcine endometrial slices (100 ± 5 mg) collected (n = 5) during the peri-implantation period were treated in vitro with ELF-EMF at a frequency of 50 Hz and flux density of 8 × 104 mG for 2 h. To determine the effect of ELF-EMF on apoptosis and oxidative stress in the endometrium, CASP3, CASP7, CIDEB, GADD45G, NOS1, NOS2, NOS3, and TP53I3 mRNA transcript were analyzed using real-time PCR, and protein abundance of CASP3, CASP7 using Western blot, and eNOS using ELISA were determined. Moreover, CASP3/7 and NOS activity was analyzed using flow cytometry and colorimetry, respectively. The decreased CASP7 and increased NOS3 mRNA transcript and protein abundance in ELF-EMF-treated endometrium were observed. Moreover, CIDEB, GADD45G, and TP53I3 mRNA transcript abundance was increased. Only p ≤ 0.05 was considered a statistically significant difference. The documented alterations indicate the potential of the ELF-EMF to affect apoptosis and generate oxidative stress in the endometrium. The insight into observed consequences documents for the first time the fact that the ELF-EMF may influence endometrial cell proliferation, angiogenesis, and/or tissue receptivity during peri-implantation.