Search Results (437)

Background/Objectives: Preoperative hypoalbuminemia is a known risk factor for adverse outcomes in cardiac surgery, but its role in patients undergoing HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation is unclear. This study evaluated the association between albumin levels and postoperative outcomes, aiming to define a clinically meaningful cut-off for risk stratification. Methods: We retrospectively analyzed 205 adult patients who underwent HM3 implantation at a single center from June 2014 to December 2023. Receiver operating characteristic (ROC) analysis identified an optimal pre-implant albumin cut-off of <32 g/L. This threshold, derived using the maximal Youden Index, provided a sensitivity of 52.1%, specificity of 71.6%, and an AUC of 0.64 (95% CI 0.56–0.71), with internal bootstrapping validation confirming model stability, and calibration demonstrating good agreement between predicted and observed outcomes. Kaplan–Meier analysis assessed freedom from hemocompatibility-related adverse events (HRAEs) and survival. Cox proportional hazards models evaluated albumin and other variables as independent risk factors for HRAEs. Results: Patients with pre-implant albumin <32 g/L had higher rates of HRAEs, including stroke (24.9% vs. 8.4%, p = 0.004) and bleeding (38.1% vs. 23.2%, p = 0.012). Freedom from HRAEs was significantly lower in the hypoalbuminemia group (45.2% vs. 69.8%, p < 0.001) and competing risk-adjusted cumulative incidence for HRAE was higher, but did not reach statistical significance (p = 0.11), one-year HRAE-free survival was also reduced (68.5% vs. 85.7%, p = 0.03). In multivariable analysis, low albumin (HR 0.56, 95% CI 0.33–0.93, p = 0.026) and temporary right ventricular assist device (RVAD) support (HR 3.32, 95% CI 2.05–5.39, p < 0.001) were independent predictors of HRAEs. Conclusions: Low preoperative albumin is independently associated with increased HRAEs and reduced one-year survival after HM3 implantation. Compared with the traditional 35 g/L threshold, the ROC-derived 32 g/L cut-off offered superior balance between sensitivity and specificity, underscoring its clinical utility. Albumin may serve as a simple, pragmatic, and cost-effective biomarker for preoperative risk assessment and optimization. Full article

Retinoblastoma is a rare but malignant pediatric retinal tumor, affecting 1 in 15,000–20,000 live births annually. It arises from biallelic mutations in the RB1 tumor suppressor gene (chromosome 13q14.2), leading to uncontrolled cell cycle progression. Clinically, it presents as unilateral (60%) or bilateral (40%) disease, with leukocoria and strabismus as hallmark signs. Untreated, retinoblastoma is fatal due to metastatic spread. The disease follows Knudson’s two-hit model: heritable forms (30–40% of cases) involve a germline RB1 mutation (M1) and a somatic second hit (M2), predisposing to bilateral/multifocal tumors and secondary cancers. Non-heritable cases (60–70%) result from somatic RB1 mutations or, rarely, MYCN amplification (2%). Genetic testing is critical to classify risk (H0, H1, and HX categories), guide surveillance, and inform family counseling. Bilateral cases almost always harbor germline mutations, while 15% of unilateral cases may carry germline/mosaic RB1 defects. Advanced techniques (Sanger/NGS sequencing for mutation detection, NGS for copy number alterations, and methylation assays) detect RB1 mutations, CNVs, and epigenetic silencing. Tumor DNA analysis resolves ambiguous cases. H1 patients require intensive ocular and brain MRI surveillance, while H0 cases need no follow-up. Prenatal/preimplantation genetic diagnosis (PGD) can prevent transmission in high-risk families. Emerging research explores additional genes (BCOR, CREBBP) and MYCN-amplified subtypes. Genetic counseling addresses recurrence risks, reproductive options, and long-term cancer monitoring. Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies. Full article

In this study, we aimed to correlate embryonic ploidy status studied with non-invasive preimplantation genetic testing for aneuploidy with the basic patient characteristics of the infertile couple to gain insight into the effects of parental physical health on embryo ploidy. We recruited 131 couples, who were stratified into 4 groups based on female age. We gathered general patient characteristics of the couple and determined the female’s hormonal status. We included 316 embryos in our study. Embryos were either transferred in the uterus in a fresh cycle or vitrified for later use. We collected spent embryo culture medium on either day 5 or 6 and performed whole genome amplification before using Next Generation Sequencing. Pregnancy outcomes were noted and cross-referenced with patient characteristics and the embryo’s ploidy status in a retrospective manner. While we have indirectly observed a level of maternal contamination, we nevertheless found a significant correlation between embryo ploidy status and cell free deoxyribonucleic acid concentration in spent embryo culture, as well a correlation between female age and embryo ploidy status. We observed a significant correlation between male body mass index and cell free deoxyribonucleic acid concentration in spent embryo culture medium and between male body mass index and pregnancy outcome. We illustrated a connection between male body mass index and cell free deoxyribonucleic acid, independent of female markers. This is the first study to observe not only female but male parameters in correlation to cell free deoxyribonucleic acid. Full article

Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis in the context of assisted reproductive technology, emphasizing transcriptional and epigenetic regulation. Essential transcription factors for cardiac development, including NKX2-5, GATA4, TBX5, ISL1, MEF2C, and HAND1/2, play a crucial role in mesodermal specification, heart tube formation, and chamber morphogenesis. Animal models and human preimplantation embryos have demonstrated that ART-related procedures, including gamete micromanipulation, supraphysiological hormone exposure, and extended in vitro culture, can alter the expression or epigenetic programming of these genes. Subsequent to ART, researchers have identified anomalous patterns of DNA methylation, alterations in histones, and modifications in chromatin accessibility in cardiogenic loci. These alterations indicate that errors occurred during the initial reprogramming process, potentially resulting in structural congenital heart abnormalities (CHDs) or modifications in cardiac function later in life. Analysis of the placental epigenome in babies conceived using assisted reproductive technology reveals that imprinted and developmental genes critical for cardiac development remain dysfunctional. This review proposes a mechanistic theory about the potential subtle alterations in the cardiogenic gene network induced by ART, synthesizing findings from molecular embryology, transcriptomics, and epigenomics. Understanding these molecular issues is crucial not only for enhancing ART protocols but also for evaluating the cardiovascular risk of children conceived by ART postnatally and for early intervention. Full article

Zygotic genome activation (ZGA) represents one of the most vulnerable periods to environmental perturbations. The objective of this study was to investigate the formation of stress granules in mouse embryos in response to temperature reduction during ZGA, preimplantation embryo mortality, and long-term phenotypic outcomes. These outcomes included the evaluation of expression noise in bilateral right/left limbs of offspring as an indicator of developmental instability, behavioral deviation, hippocampal volume, and metabolomics profiling in adult offspring. Exposure to hypothermia during ZGA was associated with an increased number and inter-blastomere variability of stress granules, extended duration of the second embryonic division, and elevated embryonic mortality during the second and third cleavage stages. The embryonic response to hypothermic stress correlated with phenotypic traits indicative of increased pathology risk. Expression noise, serving as an indicator of developmental instability, was reduced in adult offspring derived from two-cell embryos incubated at 35 °C compared to those at 37 °C, while showing no significant difference relative to the control group. These results suggest that embryos surviving hypothermic exposure (35 °C) possess enhanced resilience to the adverse effects commonly associated with embryo transfer procedures. Furthermore, increased hippocampal volume and augmented auditory startle reflex observed in offspring that endured hypothermia during ZGA imply reduced risks of cognitive-related pathologies and reduced risks of pathologies associated with cognitive functions. Full article

Background: Embryo selection in in vitro fertilization (IVF) aims to prioritize embryos with the highest reproductive potential. While preimplantation genetic testing for aneuploidy (PGT-A) remains the gold standard for identifying euploid embryos, it is invasive and not universally applicable. Deep learning (DL)-based models, such as the intelligent data analysis (iDA) score, have emerged as non-invasive alternatives for embryo assessment. This review critically evaluates the relationship between iDAScore (versions 1.0 and 2.0), embryo euploidy, and clinical outcomes, including live birth and miscarriage rates. Methods: A narrative review was performed using PubMed and Google Scholar, covering studies published from January 2020 to May 2025. The search included terms such as “iDAScore,” “deep learning,” “euploidy,” and “live birth.” Only English-language full-text studies assessing the predictive performance of iDAScore relative to chromosomal status or reproductive outcomes were included. Results: Six retrospective studies met the inclusion criteria. All reported a statistically significant association between higher iDAScore values and embryo euploidy. AUC values for euploidy prediction ranged from 0.60 to 0.68. In several studies, iDAScore was also positively associated with live birth rates and negatively with miscarriage rates. However, the predictive accuracy was moderate when restricted to euploid embryo cohorts, indicating that iDAScore may be more effective in broader populations where chromosomal status is unknown. Conclusions: iDAScore represents a promising adjunct to traditional embryo assessment. Although it cannot replace PGT-A, it may aid in embryo prioritization when genetic testing is not feasible. Larger prospective studies are warranted to further validate its clinical utility. Full article

Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) rat offspring, partially through epigenomic and transcriptomic programming. Primordial germ cells, which become the second generation (F2), are also exposed, which could incite generational risk. This study aimed to determine whether the F2 transcriptome already has genomic variation at the preimplantation embryo stage, and whether variations normalize, persist or compound in the third generation (F3). Methods: F0 female rats were fed a control or HF diet, then DM was induced in HF-fed dams on gestational day (GD)14, exposing F1 offspring and F2 primordial germ cells to hyperlipidemia, hyperglycemia and fetal hyperinsulinemia during the last third of pregnancy. F1 pups were reared by healthy dams and bred to produce F2 embryos (F2e) and F2 pups. F2 offspring were bred to produce F3 embryos (F3e). Embryos were assessed by a novel grading method, live cell imaging, and single-cell RNA sequencing. Results: Embryo grades were not different, but HF+DM F2e had more cells while F3e had fewer cells and overall fewer embryos. HF+DM F2e had similar mitochondria quantity but a downregulation of genes involved in lipid metabolism and more oxidative stress, consistent with mitochondrial dysfunction. They also had an upregulation of chromatin-remodeling genes. The predicted developmental effect is accelerated embryo aging and epigenetic drift. In contrast, HF+DM F3e had an adaptive stress response leading to increased mitochondria quantity and an upregulation of genes involved in mitochondrial respiration, metabolism, and genomic repair that led to a predicted developmental effect of delayed embryo maturation. Conclusions: Although pathways vary, both generations have metabolically linked differentially expressed genes that influence cell fate and developmental pathways. In conclusion, HF+DM pregnancy can program the early embryonic transcriptome for three generations, despite an intergenerational healthy diet. Full article

Background: Preimplantation genetic testing for aneuploidy (PGT-A) is a popular approach in assisted reproductive technology that improves embryo selection and implantation rates. Traditional approaches rely on trophectoderm (TE) biopsy, which is an invasive procedure that might jeopardize embryo integrity and create technical constraints such as mosaicism-related misclassification. Non-invasive preimplantation genetic testing (niPGT) has emerged as a possible alternative, using embryonic cell-free DNA (cfDNA) extracted from wasted culture media or blastocoel fluid to assess chromosomal status without requiring direct embryo manipulation. Methods: This systematic study investigates the molecular mechanisms behind cfDNA release, its biological properties, and the technological concerns that influence its utilization in niPGT. We look at recent advances in next-generation sequencing (NGS), whole-genome amplification (WGA), and bioinformatic techniques that improve cfDNA-based aneuploidy detection. In addition, we compare the sensitivity, specificity, and concordance rates of niPGT to conventional TE biopsy, highlighting the major aspects impacting its diagnostic performance. Results: The release of cfDNA from embryos is influenced by apoptotic and necrotic processes, active DNA shedding, and extracellular vesicle secretion, which results in fragmented chromosomal material of different qualities and quantities. While niPGT has shown promise as a noninvasive screening approach, significant variability in cfDNA yield, maternal DNA contamination, and sequencing biases all have an impact on test accuracy. Studies show that niPGT and TE biopsies have moderate-to-high concordance, although there are still issues in detecting mosaicism, segmental aneuploidies, and DNA degradation artifacts. Conclusions: NiPGT is a safer and less intrusive alternative to TE biopsy, with potential clinical benefits. However, technical advancements are required to improve cfDNA collecting procedures, reduce contamination, and improve sequencing accuracy. Additional large-scale validation studies are needed to create standardized methodologies and ensure that niPGT achieves the diagnostic reliability requirements required for widespread clinical deployment in IVF programs. Full article

Minimizing the risk of disease transmission, disseminating superior genetics, and reducing transportation costs are recognized advantages of embryo biotechnologies. These advantages make the development of a minimally invasive and repeatable procedure in pigs enticing, but simultaneously magnify the anatomical constraints. For decades, the swine industry has struggled to establish a universal procedure to collect pre-implantation embryos from pigs due to their long and convoluted uterine horns (UHs). Thus, the objectives were to evaluate the benefits of employing a transitional surgical model by shortening UH tissue using a 40 cm ipsilateral resection and assess the compensatory ovulatory response following an ovariectomy. The surgery was deemed successful as the UH was resected and the contralateral UH was fully ligated. The dam- and sire-line gilts exhibited ovarian hypertrophy between surgery and slaughter on the remaining ovary, illustrated by an increase in the number of corpora lutea (13.4 and 3.0 vs. 27.2 and 12; p < 0.05, respectively) and intact ovary weight (11.9 and 7.7 vs. 25.9 vs. 38.7 g; p < 0.05, respectively). This research is a vital step in assessing whether this interim surgical approach serves as a valuable method to advance the development of non-surgical techniques to collect pre-implantation embryos in pigs. Full article

Chromosomal structural rearrangements (SR) can impair gametogenesis, increasing the risk of embryos carrying unbalanced chromosomal content (i.e., with a gain or loss of chromosomal material). In such cases, assisted reproduction technologies (ARTs) with preimplantation genetic testing for structural rearrangements (PGT-SR) is recommended to identify embryos with a normal or balanced karyotype. However, data on IVF laboratory outcomes in this context remain limited. This retrospective cohort study analyzed 548 ART cycles, comprising 129 with PGT-SR and 419 with PGT-A, conducted at a single university-affiliated center. Following propensity score matching, laboratory outcomes were compared using logistic regression. The fertilization rate was comparable between groups, but the PGT-SR group had significantly lower blastocyst development (36.7% vs. 47.1%) and top-quality blastocyst development rates (9.6% vs. 21.1%). No significant differences were found either in the blastocyst development rate on days 5, 6, 7, or in euploidy rates. In the PGT-SR cohort, the generalized linear mixed-effects model indicated no significant effect of carrier gender on the normal/balanced blastocyst rate, while the type of SR was strongly associated with it: non-reciprocal SRs yielded a higher rate of normal/balanced blastocysts (89.9%) compared to reciprocal translocations (45.7%). These findings indicate that patients undergoing PGT-SR generate fewer blastocysts available for biopsy, and that in cases involving reciprocal translocations, the proportion of normal/balanced blastocysts suitable for transfer is significantly reduced. These results underscore the importance of personalized counseling in managing expectations and supporting informed clinical decision-making. Full article

Background: Patients presented for complicated redo surgery after previous aortic valve replacement with the indication for aortic root repair due to dilatation or aneurysm. In those cases where the prosthetic aortic valve is in good condition, a valve-sparing procedure might simplify the complicated surgery. The aim of this case series paper is to describe a technique and to show the results of repairing the aortic root without compromising the previously inserted, well-functioning mechanical aortic valve. Methods: Between March 2017 and May 2017, 11 patients underwent re-sternotomy with placement on cardiopulmonary bypass with cardiac arrest and exposure of the aortic root. After the aortotomy, the aortic valve was inspected. Subsequently, the aortic sinuses were resected, sparing the coronary ostia buttons. A prosthetic tube was implanted above the preexisting valve. Finally, the coronary ostia were reattached to the tube, turning this procedure into a complete Bentall. Results: Echocardiography demonstrated fully functional valves and well-implanted aortic prosthesis. All patients were discharged within ten days post-surgery without any adverse events. Conclusions: The delayed two-stage Bentall procedure is a feasible and safe technique that preserves pre-implanted valves and does not cause any distortion of the aortic annulus. Full article

Background: Preimplantation genetic testing for polygenic diseases (PGT-P) is a reproductive technology that has made it possible to assign risk scores to embryos for various complex polygenic conditions such as diabetes, hypertension, breast cancer, and schizophrenia. Whether there is public interest in utilizing PGT-P and what public opinions are regarding this technology is unknown. Therefore, the objective of our study was to evaluate the opinion of the general United States (US) public regarding PGT-P. Methods: A web-based questionnaire consisting of 25 questions was administered to a nationally representative sample of adult US residents according to age and sex. The survey contained a description of PGT-P, followed by questions with Likert-scale responses ranging from strongly agree to strongly disagree. Results: Of the 715 respondents recruited, 673 (94%) completed the survey. Most respondents agreed that use of PGT-P is ethical (54%), and another 37% were neutral; however, approximately 9% of respondents disagreed and were opposed to the use of PGT-P. Those that opposed PGT-P cited that it was “unethical” (46%) or “not natural” (39%), believed children could be negatively affected (31%), or stated that it went against their religion (15%). The majority of respondents did not know whether PGT-P was safe for embryos (68%) or children (67%) and felt that anyone should be able to utilize it (53%). Conclusions: Participants who were younger, were Atheist, or were Democrats were more likely to agree that “PGT-P is ethical”. This study identified that more than half of respondents supported the use of PGT-P. However, concerns regarding its safety and ethical implications persist. Full article

Objectives: Torus mandibularis (TM) is a benign bony exostosis on the lingual surface of the mandible, typically developing from the third decade of life with slow progression; its etiology remains unclear. As TM excision causes no functional or aesthetic disadvantages, its use as autologous bone graft material (e.g., for pre-implant or sinus lift augmentation) has been suggested. In this study, we investigate the prevalence and expression of TM in a southern German population with regard to age and gender. Additionally, we examine whether TM undergoes dynamic changes over time, with the hypothesis that TM may show temporal growth. Material and Methods: A retrospective analysis of CBCT scans from 210 randomly selected patients (105 males, 105 females) was performed. Patients were divided into three age groups (≤40, 41–60, ≥61 years; 70 per group), and TM was measured using OsiriX MD. For the longitudinal study, 146 CBCTs from 73 patients were compared over intervals of 2–9 years. Surface changes were assessed via 3D overlay using GOM Inspect. Results: TM was found in 30.5% of patients, and its prevalence was significantly higher in males (38%) than females (23%), with no age-related differences identified. Most TMs measured <2 mm (n = 51); only five exceeded this size. No dynamic growth was observed over time. Conclusion and Clinical Implications: TM is a common anatomical variant, more frequently detected through 3D imaging than clinical examination. In most cases, size remains minimal (<2 mm), limiting its clinical use as augmentation material in rare individual cases. Full article

This study characterized collagen remodeling in an electron-beam-sterilized porcine acellular dermal matrix (E-PADM) by evaluating host response kinetics during wound healing. E-PADM (n = 6 lots/time point) was implanted in an abdominal wall bridging defect in nonhuman primates (N = 24). Histological, immunohistochemical, and biochemical assessments were conducted. Pro-inflammatory tissue cytokines peaked 1 month post-implantation and subsided to baseline by 6 months. E-PADM-specific serum immunoglobulin G antibodies increased by 213-fold from baseline at 1 month, then decreased to <10-fold by 6–9 months. The mean percentage tissue area staining positively for matrix metalloproteinase-1 plateaued at 3 months (40.3 ± 16.9%), then subsided by 6 months (16.3 ± 11.1%); tissue inhibitor matrix metalloproteinase-1 content plateaued at 1 month (39.0 ± 14.3%), then subsided by 9 months (13.0 ± 8.8%). Mean E-PADM thickness (1.7 ± 0.2 mm pre-implant) increased at 3 months (2.9 ± 1.5 mm), then decreased by 9 months (1.9 ± 1.1; equivalent to pre-implant). Histology demonstrated mild inflammation between 1–3 months, then a peak in host tissue deposition, with ≈75%–100% E-PADM collagen turnover, and fibroblast infiltration and neovascularization between 3–6 months. Picrosirius red staining revealed that mature E-PADM collagen was replaced by host-associated neo-collagen by 6 months. E-PADM implantation induced wound healing, which drove dermal E-PADM collagen remodeling to native, functional fascia-like tissue at the implant site. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article