Successful Implantation Research Articles

Transcriptomic Analysis and Finding of Potential Key mRNA Expression Profile in Human Cumulus Cells During in Vitro Culture and Different Passages Based on Integrated Bioinformatics Analysis.

This study leveraged microarray datasets to investigate differentially expressed genes (DEGs) in cumulus cells and their relevance in predicting the successful implantation of embryos in human in-vitro fertilization procedures. The microarray data were obtained from the GEO database, encompassing samples of cumulus cells during in vitro culture and different passages. To ensure data consistency, inter-batch normalization was performed, and Principal Component Analysis (PCA) was applied to assess the impact of normalization on sample group clustering. The integrated dataset included samples from cumulus cells during in vitro culture, comprising 17,662 genes. Utilizing the "limma" software package, 1906 DEGs were identified, with 437 genes downregulated and 589 genes upregulated in the cumulus cells of infertility cases, while 748 genes were upregulated, and 1317 genes were downregulated in cumulus cells of successful implantation cases. Functional enrichment analysis utilized Gene Ontology, Metascape, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment tools. Biological processes and molecular functions were enriched, including protein targeting, mRNA processing, and molecular binding among the identified DEGs. Furthermore, target prediction and functional enrichment analysis of microRNAs (miRNAs) revealed 25 key genes and 13 relevant miRNAs were identified. Notably, hsa-miR-149, hsa-miR23b, hsa-miR-877, hsa-miR593, hsa-miR-18a, hsa-miR25, hsa-miR185, mmu-miR-207, hsa-miR425, hsa-miR214, hsa-miR-129, hsa-miR-629, and hsa-miR-194 emerged as the most prominent miRNAs with potential regulatory roles in successful embryo implantation. This comprehensive analysis provides valuable insights into the molecular mechanisms underlying embryo implantation, offering potential targets for further research and therapeutic interventions in assisted reproductive technologies.

Kidney disease, diabetes, and diameter stenosis predict Rotablation bailout in modified balloon application for severely calcified coronary lesions.

Modified balloon (MB) treatment in severely calcified coronary artery lesions is an established technique. However, some lesions require Rotablation (RA) as bailout strategy. This study aimed to assess predictors of switch from MB to RA and its impact on procedural and midterm outcomes. Four hundred and eighty-three consecutive patients were included undergoing MB treatment (n = 204) with a scoring or cutting balloon, or upfront RA treatment (n = 279) serving as control cohort. Strategy switch from MB to RA was performed in 19 of 204 patients. Procedural success was defined as successful stent implantation and TIMI III flow. In the MB cohort, median age was 72 [63-78] years, 75.5% were male and 42.1% had acute coronary syndrome. Procedure success was achieved in 89.4% of the switch group versus 98.4% of the MB only group (p < 0.001) and in 96.4% of the RA cohort. In the switch group, periprocedural complications (31.6% vs. 8.1% vs. 11.8%, p = 0.007), radiation dose (149 [126-252] vs. 59 [30-97] vs. 102 [59-156] Gcm2; p < 0.001) and contrast volume (250 [190-250] vs. 190 [150-250] vs. 195 [190--250] mL; p < 0.001) were significantly higher. Diabetes (OR 3.8, 95%CI 1.1-13.9, p = 0.042), chronic kidney disease stage 4 or 5 (OR 19.0, 95%CI 3.3-108.6, p < 0.001) and pronounced calcification resulting in higher angiographic diameter stenosis (OR 1.13, 95%CI 1.1-1.2, p = 0.001) independently predicted strategy switch. Midterm results were not affected by strategy switch regarding 1-year target lesion revascularization rates (86% vs. 89% vs. 89%; log-rank p = 0.95). Primary RA strategy might be considered in patients with severely calcified coronary artery lesions with high angiographic diameter stenosis, diabetes or impaired renal function due to increased periprocedural complication rates, radiation dose, and contrast volume following strategy switch.

Influence of process parameters on the organization and properties of 316L-SCBCC bracket formed by selective zone laser melting

Abstract 316L porous skeletal scaffolds prepared by selective laser melting (SLM) technology are currently widely used in bone injuries. Its successful implantation is predicated on having properties that match those of natural bone. The process parameters significantly influence the performance of SLM-316L porous scaffold. In this study, the nine-group shaping process parameters were determined by orthogonal method. The 316L porous scaffolds were tested in compression, electrochemistry, XRD and microstructure. The influence of process parameters on the performance of body-centered cubic peripheral square structure bracket was investigated. The influence laws of process parameters on microstructure, mechanical properties and corrosion resistance were obtained. The results show that process parameters have a significant effect on the microstructure, properties and defect distribution. The reduction of defects and grain refinement in the stent is conducive to the improvement of compressive properties and hardness of the stent. The magnitude of the hardness is inversely related to the grain size. The corrosion current density of porous scaffolds are also affected by their microscopic defects and grain size. At an energy density of 78.70 J mm−3 presents the least defects and obtains smaller grains, resulting in the best mechanical properties and corrosion resistance.

Relationship of different left bundle branch pacing sites and clinical outcomes in patients with heart failure

BackgroundLeft bundle branch pacing (LBBP) is a novel physiological pacing modality. However, whether it delivers comparable efficacy with different capture sites in patients with heart failure remains unclear. ObjectiveThis study aimed to assess the association between different pacing sites and the response of LBBP. MethodsForty-three consecutive patients with heart failure, referred for successful LBBP implantation, were prospectively recruited in this study. Patients were assigned to 3 subgroups according to the paced QRS complex morphology (left bundle branch trunk pacing [LBTP], left posterior fascicular pacing, or left anterior fascicular pacing groups). Echocardiograms and electrocardiograms were recorded and analyzed at baseline and 6-month follow-up. ResultsThe response rate was 95.0%, 88.2%, and 83.3% in LBTP, left posterior fascicular pacing, and left anterior fascicular pacing groups, respectively. All subgroups were efficient in narrowing the QRS complex (QRS complex narrowing: 38.1 ± 10.8 ms, 36.4 ± 12.6 ms, and 40.8 ± 10.8 ms) and improving cardiac function (LVEF improvement： 25.7% ± 8.1%, 15.3% ± 8.1%, and 18.8% ± 4.4%). Compared with left fascicular pacing, LBTP resulted in longer peak left ventricular activation time (76.5 ± 10.2 ms vs 82.3 ± 6.5 ms; P = .037) and shorter duration from intrinsicoid deflection in V1 or V2 to QRS end (128.0 ± 6.0 ms vs 113.3 ± 5.2 ms; P＜.0001), along with better improvement in septal systolic longitudinal strain (P = .007) and lateral-septal myocardial loading inhomogeneity (P = .036). Linear regression analysis further revealed that left bundle branch capture sites were strongly associated with the improvement in peak strain dispersion (model R2 = 0.586; P = .042) and LVEF (model R2 = 0.425; P < .0001). ConclusionDifferent left bundle branch capture sites led to a subtle difference in mechanical synchrony, which may, in turn, affect LVEF improvement in patients with heart failure.

Sir Harold Ridley as the Pioneer of Intraocular Lenses: His Inspiration Drawn From World War II Pilots.

This article underscores the monumental contributions of Sir Harold Ridley to the development of intraocular lenses (IOLs), which have revolutionized cataract surgery. Sir Harold Ridley, a British ophthalmologist and medical scientist, drew inspiration from the injuries of World War II pilots to pioneer the first successful IOL implantation in 1949 at St. Thomas's Hospital. The lens, made from Perspex CQ, marked the inception of modern cataract surgery. Despite facing considerable skepticism and resistance from the medical community throughout the 1950s and 60s, Ridley's perseverance led to the gradual acceptance of IOLs by the 1970s. Today, Ridley is rightfully recognized as the "father of the intraocular lens," with his groundbreaking work having profoundly impacted the field of ophthalmology and improved the quality of life for millions globally.

Long-Term Results of the Atrial Septal Defect Occluder ASSURED Trial for Combined Pivotal/Continued Access Cohorts

BackgroundThe GORE CARDIOFORM ASD Occluder (GCA, W. L. Gore & Associates) was approved in 2019 for ostium secundum atrial septal defect (ASD) closure. ObjectivesThis study sought to report the combined pivotal and continued access cohorts of the ASSURED (Safety and Efficacy Study of Transcatheter Closure of Ostium Secundum ASDs) trial results through 36 months. MethodsThis prospective, multicenter, single-arm trial evaluated procedural and clinical outcomes of ASD closure with the GCA. The primary endpoints were 6-month closure success following device implantation and composite clinical success (deployment/retention of device, safety, and closure). Technical and procedure success, safety, clinically significant new arrhythmia (CSNA) secondary endpoints, and wire frame fracture (WFF, with fluoroscopy) at 6 and 36 months were evaluated. ResultsOf 569 patients (median age of 10.4 years and median weight of 35.0 kg) who underwent attempted secundum ASD closure, 526 were technical successes. The mean stop-flow ASD diameter was 17.6 ± 5.3 mm. All 478 patients with 6-month imaging achieved closure success. Composite clinical success at 6 and 36 months was achieved in 87.6% (468/534) and 84.0% (351/418) of patients, respectively. Technical failure occurred in 8.1% (43/548), 30-day device- or procedure-related serious adverse event in 3.9% (21/534), and 6-month device events in 2.8% (15/534) of patients. At 30 days, 21 of 569 patients (3.7%) had CSNA. At 6 months, 138 of 436 (31.7%) patients had WFFs and 105 of 185 (56.8%) at 36 months (without sequelae). ConclusionsIn this large congenital ASD device trial, the GCA had acceptable results. WFFs, although common, did not result in any clinical sequelae. The unique features, size range, and safety profile expand the options for secundum ASD closure. (Safety and Efficacy Study of Transcatheter Closure of Ostium Secundum ASDs [ASSURED]; NCT02985684)

Outcomes With the WATCHMAN FLX in Everyday Clinical Practice From the NCDR Left Atrial Appendage Occlusion Registry.

PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States. The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022. The key safety end point was defined as all-cause death, ischemic stroke, systemic embolism, or device or procedure-related events requiring open cardiac surgery or major endovascular intervention between device implantation and hospital discharge. Major adverse events were reported at hospital discharge, 45 days, and 1 year. Among 97 185 patients in the Left Atrial Appendage Occlusion registry undergoing WATCHMAN FLX, successful implantation occurred in 97.5% (n=94 784) of patients. The key safety end point occurred in 0.45% of patients. At 45 days post-procedure, all-cause death occurred in 0.81% patients, ischemic stroke in 0.23%, major bleeding in 3.1%, pericardial effusion requiring intervention in 0.50%, device-related thrombus in 0.44%, and device embolism in 0.04% patients. No peri-device leak was observed in 83.1% of patients at 45 days. At 1 year, the rate of all-cause death was 8.2%, the rate of any stroke was 1.5% (ischemic stroke, 1.2%), and major bleeding occurred in 6.4% of patients. In a large contemporary cohort of patients with the WATCHMAN FLX device, the rates of implant success and clinical outcomes through 1 year were comparable with the PINNACLE FLX study, demonstrating that favorable outcomes achieved in the pivotal approval study can be replicated in routine clinical practice.

Single Nucleotide Polymorphism (SNP) rs2229569 with L Selectin Gene Expression in Iraqi Female during in vitro Fertilization Program.

يُعرف العقم بأنه أحد مشاكل الصحة الإنجابية الرائدة في مناطق مختلفة من العالم. يعتبر الإخصاب في المختبرأحد أكثر علاجات العقم فعالية. في الدراسة الحالية ، تم تحديد دور جين SELL ، وخاصة تعدد الأشكال rs2229569 ، من حيث الانغراس ومستوى التعبير. اشتملت الدراسة على 67 انثى خضعن لدورة إخصاب في المختبر ، مقسمة إلى مجموعتين رئيسيتين: مجموعة الإناث التي فشلت عملية الزرع ومجموعة الإناث الناجحة في عملية الزرع. تم جمع عينات الدم من مجموعتي الاناث. بعد استخلاص الدنا من الدم وتضخيم الحمض النووي عن طريق تفاعل البلمرة المتسلسل ، تم إرسال العينات لتحليل التسلسل ، وتم تحديد SNP rs2229569 التي اظهرت ثلاثة أنماط وراثية. كانت مجموعة الفشل منحرفه عن H.W.E. ، وكانت مجموعة النجاح في اتفاق مع H.W.E. وفقًا لقيم مربع كاي ((X2 = 11.60 1.58، تشير الفروق المعنوية في مجموعة الفشل إلى تأثير العقم في مجتمع الدراسة. تُظهر نسبة الأرجحية لـ rs2229569 أن أليل T كان (2.09) ، لذلك قد يمثل T allele أليل المخاطرة لعمليةفشل الزرع .أخيرًا ، أظهر جين SELL مستوى تعبيرًا منخفضًا لدى الاناث المصابات بفشل الزرع مقارنة بالاناث في مجموعات الزرع الناجحة.

Ab-Externo XEN Gel stent implantation effectively treated refractory glaucoma with prior failed shunt tube

PurposeTo assess the efficacy of a gelatin stent (XEN 45 Gel Stent; Allergan) implant in advanced glaucoma eyes that have failed prior aqueous shunt implantation.MethodsWe retrospectively reviewed 6 patients with refractory glaucoma, defined as persistently high IOP (> 21 mmHg) despite taking at least 3 IOP-lowering medications subsequent to undergoing a glaucoma drainage device (GDD) with or without a second GDD or cilioablative procedure. Eyes with previous failed GDD underwent subconjunctival 0.3 cc (0.4 mg/ml) mitomycin C, tenonectomy, and placement of an ab- externo XEN stent. The outcome measures included change in IOP and the number of glaucoma medications. Success was defined as patients achieving an IOP ≤ 18 mmHg with a percentage reduction of 25% or 15 mmHg and 40% mean IOP reduction from baseline while taking the same number or fewer medications.ResultsAll six eyes with age of 77.6 ± 7.82 years who underwent XEN implantation following previous GDD surgery had primary open-angle glaucoma. The IOP decreased significantly from 32.33 ± 5.99 to 12.67 ± 3.27 mmHg (p < 0.001) with a follow-up of 13.9 ± 2 (11.7–16.7) months. Visual acuity and visual field remained stable after XEN placement. Compared to the baseline number of medications of 4.2 ± 0.8, all medication was discontinued except in one eye on two drops at the end of the follow-up. The overall surgical success rate was 100%. No complications, needling, or additional procedures were required.ConclusionThis study described successful implantation of the XEN stent following failed GDD. XEN Gel stent implantation associated with mitomycin C and tenonectomy can be considered a viable surgical option for patients with a history of previously failed tube shunt requiring further IOP lowering.

Vaginal and endometrial microbiome dysbiosis associated with adverse embryo transfer outcomes

BackgroundAssisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured.PurposeThis study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis.MethodsWe compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women.ResultsOur study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance.ConclusionsThis study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.

Influence of Bridging Stent Graft Implantation into the Renal Artery during Complex Endovascular Aortic Procedures on the Renal Resistance Index.

Comparative sonographic examination of the renal resistance index (RRI) can provide evidence of renal artery stenosis. The extent to which the RRI is changed after stent graft implantation is not known. The aim of this study was to investigate the influence of stent graft implantation into non-diseased renal arteries during endovascular treatment of pararenal aortic aneurysms on the RRI. Sonographic examinations of the kidneys were conducted using a GE ultrasound system. The evaluation was performed according to the European Society for Vascular Surgery (ESVS) 2D standard criteria. RRI values were determined in consecutive patients on the day before and after stent graft implantation and compared for each kidney. A total of 32 consecutive patients (73.9 ± 8.2 years, 5 females, 27 males) were treated with a fenestrated or branched aortic stent graft including bridging stent graft implantations into both renal arteries and received pre- and postinterventional examinations. Sonomorphologically, the examined kidneys were inconspicuous. The arborisation of the renal perfusion was preserved pre- and post-implantation. The RRI did not differ (0.66 ± 0.06 versus 0.67 ± 0.07; p = ns). Successful stent graft implantation into non-stenosed renal arteries did not lead to a relevant change in RRI. Therefore, the RRI is a suitable tool for assessing renal perfusion after fenestrated or branched endovascular aortic therapy.

A Comprehensive Review of the Endometrial Receptivity Array in Embryo Transfer: Advancements, Applications, and Clinical Outcomes.

Embryo transfer is a pivotal procedure in assisted reproductive technologies (ART). Yet, the success of this process hinges on multiple factors, with endometrial receptivity playing a critical role in determining the likelihood of successful implantation. The endometrial receptivity array (ERA) is an advanced diagnostic tool designed to personalize embryo transfer timing by assessing the endometrium's receptivity. This review comprehensively examines the ERA, exploring its biological foundation, technological development, and clinical applications. The ERA's ability to analyze the expression of genes associated with endometrial receptivity offers a tailored approach to identifying the optimal window of implantation (WOI), particularly benefiting patients with recurrent implantation failure (RIF) or repeated unsuccessful in vitro fertilization (IVF) cycles. Clinical outcomes from ERA-guided embryo transfers indicate improvements in implantation rates and overall pregnancy success, although challenges such as result variability and cost-effectiveness persist. This review also discusses the latest advancements in ERA technology, including integrating genomic and transcriptomic analyses, non-invasive techniques, and using artificial intelligence (AI). Controversies regarding the widespread application of ERA and its necessity in all IVF cases are critically examined. By summarizing the current state of ERA in embryo transfer, this review aims to inform clinicians, researchers, and patients about its potential to enhance ART outcomes and to highlight areas for future research and innovation.

Clinical incidence and relevance of incomplete endothelialization in atrial fibrillation patients with Left Atrial Appendage Closure

BackgroundThe objective of this study is to investigate the incidence, potential risk factors, and clinical outcomes of incomplete device endothelialization (IDE) in atrial fibrillation (AF) patients undergoing Watchman left atrial appendage closure (LAAC).MethodsIn this study, 68 AF patients who underwent successful implantation of the Watchman device without peri-device leak (PDL) during follow-up were included. The endothelialization status was assessed using Transesophageal echocardiography (TEE) and LAA computed tomography angiography (CTA) at 6 weeks and 6 months post-implantation. Adverse cerebro-cardiac events were documented at one-year follow-up. Baseline characteristics, including age, device sizes, and clinical indicators, were analyzed as potential predictors for IDE.ResultsIDE was observed in 70.6% and 67.6% of patients at 6 weeks and 6 months after implantation, respectively. Higher levels of high-density lipoprotein cholesterol (HDL-C) [odds ratio (OR): 15.109, 95% confidence interval (CI): 1.637-139.478, p = 0.017 and OR: 11.015, 95% CI: 1.365–88.896, p = 0.024] and lower aspartate aminotransferase (AST) (OR 0.924, 95% CI: 0.865–0.986, p = 0.017 and OR: 0.930, 95% CI: 0.874–0.990, p = 0.023) at baseline were found to be significantly associated with IDE at 6 weeks and 6 months, respectively, although no significant difference in adverse cerebro-cardiac events was noted between incomplete and complete DE groups during 1-year follow-upConclusionsIDE is found to be a prevalent occurrence in humans following LAAC. Elevated HDL-C and reduced AST levels are shown to be linked to an increased risk of IDE after LAAC

Angiogenesis and full thickness wound repair in a cell sheet-based vascularized skin substitute

Skin tissue engineering is undergoing tremendous expansion as a result from clinical needs, mandatory replacement of animal models and development of new technologies. Many approaches have been used to produce vascularized skin substitutes for grafting purposes showing the presence of capillary-like structures but with limited analysis of their in vitro maturation and plasticity. Such knowledge is however important for the development of tissue substitutes with improved implantation success as well as for validation of vascularization in vitro models, including as a readout in pharmacological analyses. For optimal interactions of cells with microenvironment and vasculature, we here used a cell sheet approach consisting in the sole production of matrix by the cells. In this context, we limited the density of endothelial cells seeded for self-assembly and rather relied on the stimulation of angiogenesis for the development of an extensive connected microvascular-like network. After detailed characterization of this network, we challenged its plasticity both during and after establishment of the skin substitute. We show that fine tuning of VEGF concentration and time of application differentially affects formation of capillary-like structures and their perivascular coverage. Furthermore, we performed a deep wound assay that displayed tissue repair and angiogenesis with unique characteristics of the physiological process. These studies demonstrate the importance of cell-derived microenvironment for the establishment of mature yet dynamic vascularized skin models allowing a wide range of pharmacological and basic investigations. Statement of significanceThe significant advancements in organ-on-chips and tissue engineering call for more relevant models including microvascularization with remodeling potential. While vascularized skin substitutes have been developed for years, focus has primarily been on the impact of microvascularization on implantation rather than on its in vitro characterization. We here developed a cell sheet-based vascularized skin substitute relying on angiogenesis, i.e. growth of vessel-like structures within the 3D model, rather than solely on endothelial cell self-assembly. We then characterized :1/ vascularization after modulation of angiogenic factor VEGF during the substitute construction; -2/ angiogenesis associated to tissue repair after deep mechanical wounding. These studies establish a solid physiologically relevant model for further investigation of skin cell interactions and in vitro wound healing.

Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report

IntroductionCardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case reportA 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. DiscussionCA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. ConclusionsVarious diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.

3DMOUSEneST: a volumetric label-free imaging method evaluating embryo-uterine interaction and decidualization efficacy.

Effective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth. We demonstrate that decidual nest volume is a measurable indicator of decidualization efficacy and correlates with the probability of early pregnancy progression based on a logistic regression analysis using Smad1/5 and Smad2/3 conditional knockout mice with known implantation defects. 3DMOUSEneST has great potential to become a principal method for studying decidual fibrillar collagen and characterizing mouse models associated with early embryonic lethality and fertility issues.

The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells

Embryo implantation failures are a major challenge in reproductive medicine, but the underlying mechanism remains poorly understood. Successful implantation requires dynamic remodeling of the endometrium through integrated proliferation and differentiation of endometrial cells including luminal epithelial, glandular epithelial, and stromal cells. Conversely, their disruption causes infertility. Spatiotemporal control of transcription is required for these processes; however, the underlying epigenetic regulation is largely unknown. In this study, we examined expression data from the human endometrium during implantation and discovered that expression of the histone lysine methyltransferase KMT2D was significantly suppressed in patients with recurrent implantation failure. Further study revealed that uterine deletion of Kmt2d in mice caused infertility due to implantation failure. Morphological analysis discovered a reduction in the number of uterine glands and aberrant differentiation of the luminal and glandular epithelium into stratified phenotypes in Kmt2d knockout uteri. Administration of leukemia inhibitory factor protein, which is expressed in uterine glands and is essential for implantation, did not rescue implantation failure in Kmt2d knockout mice, suggesting that infertility was not solely due to uterine gland dysfunction. RNA sequencing analysis revealed that Kmt2d knockout uteri displayed suppressed expression of genes involved in ion homeostasis, which may affect the uterine luminal morphology. Our study suggests that KMT2D plays an essential role in facilitating successful embryo implantation by regulating the coordinated differentiation of endometrial cells, providing valuable insights into unexplained implantation failures in women.

Transcriptomic Analysis of Vitrified-Warmed vs. Fresh Mouse Blastocysts: Cryo-Induced Physiological Mechanisms and Implantation Impact.

Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes' effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified-warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2, and decreased expression of genes such as Dkk3 and Mapk10. Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes.

Association between BMI and success of transaxillary venous port implantation: A retrospective cohort study.

Totally implanted venous access device are widely used for long-term chemotherapy in cancer patients. Previous studies have only focused on the analysis of complications associated with infusion port implantation, ignoring the causes of unsuccessful infusion port implantation. The purpose of this study was to investigate the association between body mass index (BMI) and the success rate of transaxillary intravenous port implantation in breast cancer patients. To review 361 breast cancer patients who underwent intravenous port implantation from January 2021 to September 2021. Baseline data, and surgical data were collected from the patients, and the success rate of puncture of the axillary vein was recorded. The logistic regression analysis and smoothed curve fitting were used to assess the relationship between BMI and the success rate of axillary venipuncture. In addition, subgroup analyses were performed to explore potential interactions. Under ultrasound guidance, 67.3% of patients (243/361) had an infusion port implanted by axillary vein puncture. There was a roughly linear relationship between BMI and the success rate of axillary venipuncture. In the multiple regression equation, BMI was significantly and negatively associated with the success rate of axillary venipuncture (OR = 0.83; 95% CI = 0.77-0.89; p < 0.001). Stratified analysis showed that the relationship between BMI and the success rate of axillary venipuncture was stable and unaffected by other variables. The higher the patient's BMI, the higher the chance of difficult axillary venipuncture or failed cannulation.

Exploring Optimal Strategies for Surgical Access in Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) has revolutionised the management of severe aortic stenosis, particularly for patients deemed high risk or inoperable for traditional surgical aortic valve replacement. The transfemoral approach is the preferred route whenever feasible, attributed to its minimally invasive nature, reduced procedural morbidity, and shorter recovery times. In total, 80-90% of TAVI procedures are performed via the transfemoral route. However, anatomical constraints such as severe peripheral arterial disease, small vessel diameter, or significant vessel tortuosity can preclude the use of this access site. In such cases, alternative access strategies must be considered to ensure the successful implantation of the valve. This review aims to provide a comprehensive summary of the various surgical techniques available for TAVI access, exploring the rationale, technical aspects, and challenges associated with each method. We will explore alternative routes, including the transapical, transaortic, transaxillary, and transcarotid approaches, highlighting their respective benefits and limitations.