Early Implantation Research Articles

Risk factors for non-benefit of implantable cardioverter defibrillator therapy

Studies have demonstrated overall prognostic benefits of ICD implantation in patients at increased risk of sudden cardiac death. However, results are inconsistent in certain subgroups. This study aims to evaluate the prognostic implications of comorbidities on ICD outcomes and compare trends in patient selection and outcomes over a decade-long inclusion period. This study analysed 422 patients undergoing ICD implantation between 2011 and 2020. The study endpoint “no-benefit” was characterized by death from any cause occurring without prior appropriate ICD therapy. Benefit of ICD implantation was defined as either receiving appropriate ICD therapy before death or surviving until the end of the observation period. During a mean follow-up of 4.2 ± 3.0 years, no-benefit of ICD implantation was observed in 84 patients (20%). Independent risk factors for no-benefit were age ≥ 68 years (HR 4.599, p < 0.001), anemia (HR 2.549, p < 0.001), peripheral artery disease (HR 2.066, p = 0.007), and chronic obstructive pulmonary disease (HR 1.939, p = 0.014). Subgroup analysis by age < 68 years and ≥ 68 years demonstrated that the risk of no-benefit increases with age and comorbidities. When comparing patients with ICD implantation in 2011–2015 with those in 2016–2020, there were no significant differences in one-, two- and three-year-no-benefit rates. Different comorbidities were associated with no-benefit in the early and late implantation groups. Risk factors such as older age and specific comorbidities are associated with a higher likelihood of no-benefit from ICD implantation. A careful patient selection and consideration of individual risk factors besides advanced age is important.

Fluorinated Porcine Bone-Derived Hydroxyapatite Promotes Vascularized Osteogenesis by Coordinating Human Bone Marrow Mesenchymal Stem Cell/Human Umbilical Vein Endothelial Cell Complexes.

Biogenic hydroxyapatite is known for its osteoinductive potential due to its similarity to human bone and biocompatibility, but insufficient vascularization compared to autogenous bone during early implantation limits bone integration and osteogenesis. Fluorine has been shown to improve hydroxyapatite's mechanical properties and the coupling of osteogenic and angiogenic cells. In this study, fluorine-modified biogenic hydroxyapatite (FPHA) with varying fluorine concentrations was prepared and tested for its ability to promote vascularized osteogenesis. FPHA prepared in this study retained the natural porous structure of biological cancellous bone and released F- ions when immersed in cell culture medium. The extraction solutions of FPHA0.25 and FPHA0.50 promoted the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs), with FPHA0.25 significantly upregulating vegf mRNA and VEGF protein levels in co-cultured human bone marrow mesenchymal stem cells (HBMSCs). Additionally, FPHA0.25 and FPHA0.50 upregulated pdgf-bb mRNA and PDGF-BB protein levels in HUVECs. In vivo experiments using a rabbit cranial defect model demonstrated that FPHA0.25 promoted early bone formation and angiogenesis in the defect area, enhanced VEGF secretion, and increased PDGFR-β expression in endothelial and mesenchymal cells. These findings suggest that fluorine-modified biogenic hydroxyapatite with an optimal fluorine concentration (FPHA0.25) may offer a promising strategy to enhance the body's innate bone-healing potential by accelerating vascularization.

Identifying Significant SNPs of the Total Number of Piglets Born and Their Relationship with Leg Bumps in Pigs.

The aim of this study was to identify genetic variants and pathways associated with the total number of piglets born and to investigate the potential negative consequences of the intensive selection for reproductive traits, particularly the formation of bumps on the legs of pigs. We used genome-wide association analysis and methods for identifying selection signatures. As a result, 47 SNPs were identified, localized in genes that play a significant role during sow pregnancy. These genes are involved in follicle growth and development (SGC), early embryonic development (CCDC3, LRRC8C, LRFN3, TNFRSF19), endometrial receptivity and implantation (NEBL), placentation, and embryonic development (ESRRG, GHRHR, TUSC3, NBAS). Several genes are associated with disorders of the nervous system and brain development (BCL11B, CDNF, ULK4, CC2D2A, KCNK2). Additionally, six SNPs are associated with the formation of bumps on the legs of pigs. These variants include intronic variants in the CCDC3, ULK4, and MINDY4 genes, as well as intergenic variants, regulatory region variants, and variants in the exons of non-coding transcripts. The results suggest important biological pathways and genetic variants associated with sow fertility and highlight the potential negative impacts on the health and physical condition of pigs.

Working Memory, Attention Skills, and Language Proficiency in Children with Unilateral and Bilateral Cochlear Implants.

Previous studies observed that children with cochlear implants (CIs) have poor language, working memory, and attention skills. The ability to perform cognitive tasks, such as attention and memory, plays a crucial role in the academic achievement and everyday life of children with hearing impairment. This study aimed to evaluate and compare the effects of age at the time of implantation and bilateral hearing on cognitive skills, such as language development, working memory, and selective attention, among children with CIs. Language skills were assessed using the Test of Language Development-Primary: Fourth Edition (TOLD-P:4), working memory using the Visual-Aural Digit Span Test-Revised Form (VADS-R), and selective attention skills using the Stroop Test TBAG Form. A total of 58 participants, comprised of 21 children with early unilateral CIs (before 2 years), 18 children with late unilateral CIs (after 2 years), and 19 children with bilateral CIs, between the ages of 6 and 9 years, were included in the study. According to the age at the time of implantation and whether or not the participant was unilaterally or bilaterally implanted, the mean scores, percentage values, and resultant scores of the participants were calculated using the Mann-Whitney U test. The number of repeated backward digit spans for the VADS-R test, completion times, number of errors and corrections for the Stroop test, raw scores, scaled scores corresponding to raw scores at the relevant age, descriptive terms for the TOLD-P:4 test, and within-group comparisons for all tests were examined. There were significant differences in language, working memory, and attention skills between individuals with early and late unilateral cochlear implantation, whereas there were no significant differences in many subtests between individuals with early unilateral and bilateral cochlear implantation. These findings demonstrate the importance of early cochlear implantation and bilateral hearing on the development of cognitive processes, such as language development, selective attention, and memory skills, which are important factors that may contribute to children's academic performance and overall success.

Endometrial extracellular vesicles regulate processes related to embryo development and implantation in human blastocysts.

What is the transcriptomic response of human blastocysts following internalization of extracellular vesicles (EVs) secreted by the human endometrium? EVs secreted by the maternal endometrium induce a transcriptomic response in human embryos that modulates molecular mechanisms related to embryo development and implantation. EVs mediate intercellular communication by transporting various molecules, and endometrial EVs have been postulated to be involved in the molecular regulation of embryo implantation. Our previous studies showed that endometrial EVs carry miRNAs and proteins associated with implantation events that can be taken up by human blastocysts; however, no studies have yet investigated the transcriptomic response of human embryos to this EV uptake, which is crucial to demonstrate the functional significance of this communication system. A prospective descriptive study was performed. Primary human endometrial epithelial cells (pHEECs), derived from endometrial biopsies collected from fertile oocyte donors (n = 20), were cultured in vitro to isolate secreted EVs. Following EV characterization, Day 5 human blastocysts (n = 24) were cultured in the presence or absence of the EVs for 24 h and evaluated by RNA-sequencing. EVs were isolated from the conditioned culture media using ultracentrifugation, and characterization was performed using western blot, nanoparticle tracking analysis, and transmission electron microscopy. Human blastocysts were devitrified, divided into two groups (n = 12/group), and cultured in vitro for 24 h with or without previously isolated EVs. RNA-sequencing analysis was performed, and DESeq2 was used to identify differentially expressed genes (DEGs) (FDR < 0.05). QIAGEN Ingenuity Pathway Analysis was used to perform the functional enrichment analysis and integration with our recently published data from the pHEECs' EV-miRNA cargo. Characterization confirmed the isolation of EVs from pHEECs' conditioned culture media. Among the DEGs in blastocysts co-cultured with EVs, we found 519 were significantly upregulated and 395 were significantly downregulated. These DEGs were significantly enriched in upregulated functions related to embryonic development, cellular invasion and migration, cell cycle, cellular organization and assembly, gene expression, and cell viability; and downregulated functions related to cell death and DNA fragmentation. Further, the intracellular signaling pathways regulated by the internalization of endometrial EVs were previously related to early embryo development and implantation potential, for their role in pluripotency, cellular homeostasis, early embryogenesis, and implantation-related processes. Finally, integrating data from miRNA cargo of EVs, we found that the miRNAs carried by endometrial EVs targeted nearly 80% of the DEGs in human blastocysts. This is an in vitro study in which conditions of endometrial cell culture could not mimic the intrauterine environment. This study provides novel insights into the functional relevance of EVs secreted by the human endometrium, and particularly the role of EV-miRNA regulation on global transcriptome behavior of human blastocysts during early embryogenesis and embryo implantation. It provides potential biomarkers that could become useful diagnostic targets for predicting implantation success. This study was supported by the Spanish Ministry of Education through FPU awarded to M.S.-B. (FPU18/03735), Generalitat Valenciana through VALi+d Programme awarded to M.C.C.-G. (ACIF/2019/139), and Instituto de Salud Carlos III and cofounded by the European Social Fund (ESF) "Investing in your future" through the Miguel Servet Program (CP20/00120 [H.F.]; CP19/00149 [I.C.]). The authors have no conflicts of interest to disclose. N/A.

GPRC5A promotes lung colonization of esophageal squamous cell carcinoma

Emerging evidence suggests that cancer cells may disseminate early, prior to the formation of traditional macro-metastases. However, the mechanisms underlying the seeding and transition of early disseminated cancer cells (DCCs) into metastatic tumors remain poorly understood. Through single-cell RNA sequencing, we show that early lung DCCs from esophageal squamous cell carcinoma (ESCC) exhibit a trophoblast-like ‘tumor implantation’ phenotype, which enhances their dissemination and supports metastatic growth. Notably, ESCC cells overexpressing GPRC5A demonstrate improved implantation and persistence, resulting in macro-metastases in the lungs. Clinically, elevated GPRC5A level is associated with poorer outcomes in a cohort of 148 ESCC patients. Mechanistically, GPRC5A is found to potentially interact with WWP1, facilitating the polyubiquitination and degradation of LATS1, thereby activating YAP1 signaling pathways essential for metastasis. Importantly, targeting YAP1 axis with CA3 or TED-347 significantly diminishes early implantation and macro-metastases. Thus, the GPRC5A/WWP1/LATS1/YAP1 pathway represents a crucial target for therapeutic intervention in ESCC lung metastases.

Mechanisms and timing of carbonaceous chondrite delivery to the Earth

The nucleosynthetic isotope signatures of meteorites and the bulk silicate Earth (BSE) indicate that Earth consists of a mixture of “carbonaceous” (CC) and “non-carbonaceous” (NC) materials. We show that the fraction of CC material recorded in the isotopic composition of the BSE varies for different elements, and depends on the element's tendency to partition into metal and its volatility. The observed behavior indicates that the majority of material accreted to the Earth was NC-dominated, but that CC-dominated material enriched in moderately volatile elements by a factor of ∼10 was delivered during the last ∼2–10% of Earth's accretion. The late delivery of CC material to Earth contrasts with dynamical evidence for the early implantation of CC objects into the inner solar system during the growth and migration of the giant planets. This, together with the NC-dominated nature of both Earth's late veneer and bulk Mars, suggests that material scattered inwards had the bulk of its mass concentrated in a few, large CC embryos rather than in smaller planetesimals. We propose that Earth accreted a few of these CC embryos while Mars did not, and that at least one of the CC embryos impacted Earth relatively late (when accretion was 90–98% complete). This scenario is consistent with the subsequent Moon-forming impact of a large NC body, as long as this impact did not re-homogenize the entire Earth's mantle.

A Comparative Evaluation of the Genetic Variant Spectrum in the USH2A Gene in Russian Patients with Isolated and Syndromic Forms of Retinitis Pigmentosa.

Pathogenic variants in the USH2A gene are the primary cause of both non-syndromic autosomal recessive inherited retinitis pigmentosa (RP) and the syndromic form, characterized by retinal degeneration and sensorineural hearing loss. This study presents a comparative assessment of the genetic variant spectrum in the USH2A gene among Russian patients in two clinical groups. A retrospective analysis was conducted on massive parallel panel sequencing data from 2415 blood samples of unrelated patients suspected of having hereditary retinal diseases. The copy number of USH2A exons was determined using the quantitative MLPA method with the MRC-Holland SALSA MLPA kit. Biallelic pathogenic and likely pathogenic variants in the USH2A gene were identified in 69 patients (8.7%). In the group of patients with isolated hereditary RP (55 patients), the most frequent pathogenic variants were p.(Glu4445_Ser4449delinsAspLeu) (20.9%), p.(Trp3955*) (15.5%), and p.(Cys934Trp) (5.5%). In patients with the syndromic form (14 patients), the most frequent variants were p.(Trp3955*) (35.7%) and c.8682-9A>G (17.9%). It was found that patients with isolated vision impairment rarely had two "null" variants (17.8%), whereas this was common among patients with both hearing and vision impairment (71.4%) (p ≤ 0.05), explaining the severity of the disease and the earlier onset of clinical symptoms in the syndromic form of RP. Ten previously undescribed loss-of-function variants were identified. The estimated prevalence of USH2A-associated retinal dystrophy in Russia was 1.9 per 100,000 individuals. The obtained data on the differences in the spectra of genetic variants in the USH2A gene in the two studied groups highlight the importance of establishing genotype-phenotype correlations and predicting disease severity, aiming at potential early cochlear implantation and selection of target therapy.

Auditory Development of Young Children with Profound Hearing Loss, Cochlear Implants, and Congenital CMV Infection.

Background/Objectives: The aim of this study was to assess auditory development in young children with profound hearing loss, cochlear implants (CIs), and congenital cytomegalovirus (cCMV) infection and to determine the effect of comorbidities on their development. Methods: The study group (cCMV group) consisted of 47 CI children-18 girls and 29 boys-who had been diagnosed as having prelingual hearing loss due to cCMV infection (with or without comorbidities); the mean age at CI activation was 15.2 months (range: 9.7-23.8; SD = 3.5). The reference group (no cCMV) consisted of 117 similar children (57 girls and 60 boys) who had profound sensorineural hearing loss not caused by cCMV infection; they had no comorbidities. The mean age at CI activation in the second group was 14.3 months (range: 7.9-23.5; SD = 4.0). Auditory development in all children was assessed with the LittlEARS Auditory Questionnaire (LEAQ) at CI activation and at about 1, 5, 9, 14, and 24 months of CI use. Results: The mean LEAQ total score increased over a similar time frame from 9.8 pts to 28.9 pts in the cCMV group without comorbidities, from 4.5 pts to 18.5 pts in the cCMV group with comorbidities, and from 9.2 to 31.6 pts in the reference group with no cCMV infection. Conclusions: Early cochlear implantation in children with sensorineural hearing loss due to congenital CMV infection and no comorbidities promotes their early auditory development in a similar way to children without cCMV infection.

Vancomycin Powder vs Gentamycin Sheets, Beads &amp; Cement with Antibiotic in Early Implant Related Infection. A Comparative Study

Vancomycin Powder vs Gentamycin Sheets, Beads &amp; Cement with Antibiotic in Early Implant Related Infection. A Comparative Study

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

The effect of treatment srategy for acute myocardial infarction complicated by cardiac shock using Impella in accordance with institutional protocol

Abstract Backgrounds Team-based care for cardiogenic shock (CS) using mechanical circulatory support (MCS) including Impella in accordance with standardized protocol was reported to improve the prognosis of patients with CS. Methods Between February 2018 and September 2022, we performed percutaneous coronary intervention (PCI) in 63 patients with acute myocardial infarction (AMI) complicated by CS using Impella. We introduced institutional protocol (Figure 1) to standardize the treatment strategy for CS from June 2019, in which early Impella implantation preceding PCI was recommended. We retrospectively examined the incidence of Impella implantation preceding PCI, in-hospital outcomes including the rates of survival to Impella weaning and to discharge, and the incidence of major cardiovascular events (MACE) including all death, MI, and hospitalization for heart failure at 1-year before and after protocol introduction. Results The patients have a mean age of 67.1±13.2 years and 53 patients (84.1%) were male. The patients in preceding period were 16 cases, while 47 in latter period. The rate of Impella implantation preceding PCI was significantly higher in latter period than that in preceding period (61.7% vs. 25%, p=0.027) (Figure 2A). The rate of survival to Impella weaning was significantly higher in latter period than that in preceding period (83% vs. 56.3%. p=0.043). There was no difference in the rate of survival to discharge between each period (50% in preceding period vs. 68.1% in latter period, p=0.236). However, the cumulative MACE free survival rate was significantly higher in latter period than that in preceding period (56.9% vs. 31.3%, Log-rank p=0.020) (Figure 2B). Conclusion The introduction of institutional standardized protocol of MCS use might improve 1-year outcomes of patients with AMI complicated by CS treated with Impella.Figure 1Figure 2

Cost-Effectiveness of Hypoglossal Nerve Stimulation for Pediatric Severe Obstructive Sleep Apnea in Down Syndrome Patients.

To examine the cost-effectiveness of hypoglossal nerve stimulation (HGNS) implantation at an early age in simulated pediatric cohorts with Down Syndrome (DS) and severe obstructive sleep apnea (OSA). Cost-utility analysis. Hypothetical cohort. A Markov model simulated 3 pediatric cohorts with DS and OSA beginning at age 4 years until 21 years. Cohorts received HGNS implants in early childhood, late childhood, or adulthood at age 4, 13 (current FDA-approved age), or 18 years, respectively. Input model parameters were obtained from the literature and our institution. Outcomes were measured with an incremental cost-effectiveness ratio (ICER), measured in dollars per quality-adjusted life-year (QALY). Deterministic 1-way sensitivity analyses were conducted to evaluate the effects of parameter uncertainty. Results (total costs; total QALYs) across the time horizon were determined for each cohort: early implantation ($83,300.35; 15.79), late ($48,319.09; 14.98), and adult ($38,721.07; 14.55). ICERs were $48,892.47 per QALY for early vs late implantation, $43,471.15 per QALY for early vs adult implantation, and $30,959.58 per QALY for late vs adult implantation. All ICERs were below a willingness-to-pay threshold of $50,000 per QALY. Varying the discount rate and utility expectedly varied the ICERs and cost-effectiveness. Threshold analysis showed early implantation to be cost-effective for a HGNS implantation cost up to $62,230 compared to late implantation. The current study suggests HGNS is a cost-effective treatment strategy for pediatric patients with DS and severe OSA. Our findings also suggest cost-effectiveness at ages younger than 13, the current age of FDA approval.

Advances and challenges in the development of visual prostheses.

The past 20 years have witnessed significant advancements in the field of visual prostheses, with developments spanning from early retinal implants to recent cortical approaches. This Perspective looks at some of the remaining challenges to achieve the ambitious clinical goals that these technologies could enable.

A qualitative exploration of the assessment process to cochlear implantation for children with hearing loss

Objective To explore the process of paediatric cochlear implant assessment, from referral to implantation, from the perspective of parents, cochlear implant professionals, and through observations of clinics. Design Qualitative approach, using grounded theory methodology. Study sample Twelve families with children under 5 years with permanent hearing loss referred for a cochlear implant or received an implant in the past year, and six professionals who refer or assess children for cochlear implants. Data collection involved interviews and ethnographic observations of assessment clinics. Results The core theme derived from interview and observation data related to the work of the cochlear implant assessment for families. The relationship between the work generated by the assessment process and capacity of parents to do the work provides a model to examine access to early implantation, consistent with the Burden of Treatment theory. We identified variation in terms of workload, relating to factors such as a child’s additional needs or number of appointments required, and in terms of capacity, relating to factors such as social circumstances or health literacy. Social, peer and professional support and information helped families manage the workload. Conclusions Findings have implications for delivery of paediatric cochlear implant services.

Subjective and functional outcome measures to evaluate performance of pediatric cochlear implant

BackgroundThe majority of research on the effects of cochlear implants has been on clinical evaluations of efficacy (hearing and speech skills and auditory thresholds). But it is unclear how much clinical efficacy metrics (speech, hearing, and language tests) actually demonstrate how beneficial cochlear implants (CI) are in everyday circumstances. In this study, we aim to assess the performance of a child’s current CI with both subjective and functional outcomes measures. Also, we aimed to assess factors affecting these outcomes after CI.MethodsThe study group included 45 cochlear-implanted children, and their chronological age ranges between 4 and 12 years. Children were divided according to their language age into three groups: group 1 (G1) includes15 children with a language age of less than 2 years, group 2 (G2) includes 15 children with a language age of 2 to less than 4 years, and group 3 (G3) includes 15 children with language age 4 to 6 years. Assessment was done in two sessions: one for phoniatric evaluation and another for audiological evaluation.ResultsCI enabled children to develop speech perception in a closed manner evidenced by the early speech perception (ESP) test with pattern perception being the easiest and monosyllabic words being the most difficult and the least to develop. Most children with CI were able to control their voice, to a lesser extent to use speech in meaningful use in social situations and to develop communication strategies in oral situations which were the least to develop, and this was evident by Meaningful Use of Speech Scale. Children with CI were able to acquire language, and their receptive language was better than expressive language, but their language age was below their chronological age.ConclusionThe cochlear implant is an effective rehabilitative tool for the treatment of prelingually deafened children, and this was evident by our results. A hierarchal approach of speech assessment according to the language age of the child and selection of age-appropriate speech perception test is very important to assess cochlear-implanted children Speech recognition had a high degree of variability. Early implantation age and increased duration of implant experience were the most important factors associated with good performance with CI, better speech perception, and better language outcomes.

The long-term influence of lesion set in the surgical ablation of atrial fibrillation during mitral valve surgery: Multicenter propensity-score weighted study

ObjectiveThis study aimed to assess the effect of the lesion sets for surgical ablation of atrial fibrillation on long-term outcomes and identify the optimal lesion set. MethodsBetween 2005 and 2017, 1825 patients underwent surgical ablation concomitant to mitral valve surgery in the participating institutions. Of these, 529 underwent left atrial ablation, whereas the remainder had biatrial ablation. The clinical and rhythm outcomes were compared, considering death as a competing event. Inverse probability treatment weighting was used to mitigate the selection bias. ResultsThe patients undergoing left atrial ablation were younger and less frequently had long-standing atrial fibrillation with a shorter duration or required concomitant tricuspid valve surgery. Adjusted analysis showed that left atrial ablation was associated with a lower risk of early pacemaker implantation (odds ratio, 0.16; 95% CI, 0.07-0.38; P < .001) than biatrial ablation. Over a median follow-up of 70.4 months (interquartile range, 44.1-111.2 months), the left atrial ablation group presented a higher risk of atrial fibrillation recurrence (subdistribution hazard ratio, 1.26; 95% CI, 1.12-1.41; P < .001), with a 5-year cumulative incidence of 34.2% compared with 28.6% in the biatrial group. The risk of late mortality (subdistribution hazard ratio, 1.17; 95% CI, 0.74-1.86; P = .507) and stroke (subdistribution hazard ratio, 1.21; 95% CI, 0.82-1.79; P = .345) did not differ between the groups. ConclusionsIn patients undergoing surgical ablation concomitant to mitral valve surgery, both lesion sets provided comparable incidence of mortality and stroke. However, biatrial ablation was associated with a superior rhythm outcome at the expense of a higher risk of early pacemaker implantation.

Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation. The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation. Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re-implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were < 12 years old. The average number of failed ASMs prior to VNS implantation was 7.1, and 145 (17.7%) had undergone previous epilepsy-related surgery. Epilepsy was classified as focal in 47.7% of participants, generalized in 16.1% and combined focal and generalized in 34.2%. Many of the participants (40.9%) had epilepsy of unknown etiology. The median time from diagnosis to first implantation was 10.33 years and was significantly shorter in participants with combined focal and generalized epilepsy compared to those with focal epilepsy alone, and in participants with genetic and immune epilepsy compared to those with unknown etiologies. In people with DRE, VNS Therapy is provided after multiple failures of ASMs and after failure of epilepsy surgery in one in six individuals. Time from diagnosis to first implantation is associated with epilepsy type and etiology, likely reflecting variable treatment pathways. Clearer guidelines on when and how non-drug therapies should be deployed in people with DRE related to different epilepsy factors are needed. Neuromodulation can be a very helpful treatment in people who have seizures that do not respond to medications. The most widely utilized neuromodulation therapy is vagus nerve stimulation (VNS). We present data from a large, global study to show that people use an average of seven anti-seizure medications before attempting VNS Therapy and that it takes about 10 years for people to get their first VNS implant. We advocate for clearer treatment guidelines on how and when to consider VNS Therapy in people with seizures that are resistant to medication.

Chenodeoxycholic acid fortified diet drives ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor signaling pathway in rats

Infertility is a worldwide reproductive health problem influenced by the embryo implantation efficiency. We previously revealed that dietary chenodeoxycholic acid (CDCA) positively influence the early embryo implantation. But how CDCA regulate embryo implantation is largely unexplored. Herein, we investigated the mechanism behind CDCA's regulation on embryo implantation in rats. Results showed that CDCA promoted uterine receptivity, leading to increased number of implantation sites. Mechanistically, CDCA reshaped maternal amino acid metabolism and enhanced serum progesterone levels. CDCA enhanced ovarian progesterone synthesis by improving steroidogenesis-related protein (StAR and CYP11A1) expression via Takeda G-protein-coupled receptor 5. Elevated progesterone exaggerated uterine progesterone but weakened the estradiol signaling in the CDCA group, contributing to better uterine receptive for embryo implantation. Additionally, elevated transcription repressor Stat5b induced the down-regulation of progesterone-metabolizing enzyme 20-hydroxysteroid dehydrogenase 20α-HSD, complementally explained uterine progesterone signaling enhancement. Overall, our data revealed that CDCA drove ovarian steroidogenesis to improve embryo implantation through enhancing uterine receptivity via progesterone receptor pathway in rats. Therefore, CDCA diet may be a potential favorable nutritional strategy for infertility and pregnancy management.

Environmental high temperature affects pre-implantation embryo development by impairing the DNA repair ability

Environmental high temperature poses a significant threat to human health, however, limited information is available for understanding the relationship between the hot weather and infertility. This study aims to assess the adverse effect of the hot weather to early embryonic cells. Our results indicated that environmental high temperature exposure could cause the decline of early embryo quality and implantation ability. In detail, it led to early embryonic development retardation, embryo degeneration rate increased, the rate of blastocyst and hatching decreased, and reduced the number of implants. And the finding also the impairment of environmental high temperature on early embryonic cells may be due to oxidative damage of DNA caused by ROS, while BER repair ability is decreased, failing to repair oxidative damage of DNA in time, resulting in a large number of early embryonic apoptosis. The work underscored that pregnant women should stay away from high-temperature environments.