Search Results (676)

Background/Objectives: Gastroesophageal reflux disease (GERD) seems to be a common complaint which persists or develops after metabolic bariatric surgery (MBS). Endoscopic evaluation is vital in both the preoperative and postoperative phases to ensure optimal patient outcomes. The aim of this study was to evaluate the prevalence of GERD after MBS in a 10-year follow-up and analyze the endoscopic outcomes. Methods: This retrospective, multicenter study included 368 patients who underwent single bariatric procedure. The data came from five bariatric centers in Poland, part of the BARI-10-POL project. Data on symptoms of GERD, endoscopic findings, demographics, and surgical outcomes were collected for a 10-year follow-up period. Surgical procedures included SG, Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). Results: Of the 305 patients without symptoms of GERD, 12.3% developed de novo GERD postoperatively. There was no statistical significance regarding the new-onset symptoms and the type of MBS (p = 0.074) and the presence of symptoms of GERD and the type of MBS (p = 0.208). However, SG was associated with a significantly lower likelihood of GERD remission after MBS (p = 0.005). Endoscopic evaluation showed abnormal findings in asymptomatic patients in both preoperative (35.8%) and postoperative (14.1%) examinations (p < 0.001). Conclusions: GERD may be a common issue after MBS. One-quarter of patients after MBS may experience symptoms of GERD, regardless of the type of MBS. SG appears to be associated with a higher risk of persistent symptoms of GERD and a lower likelihood of GERD remission after MBS. Asymptomatic patients both before and after MBS may have abnormal findings in gastroscopy. Full article

Background and Objectives: Implantation of cardiac implantable electronic devices (CIEDs) is increasingly performed in elderly and comorbid patients, for whom minimizing perioperative complications—including pain and systemic drug use—is critical. Traditional local infiltration often provides insufficient analgesia. The ultrasound-guided PECS II block, an interfascial regional technique, offers promising analgesic benefits in thoracic wall procedures but remains underutilized in cardiac electrophysiology. Materials and Methods: We conducted a prospective, controlled, non-randomized clinical study including 106 patients undergoing de novo CIED implantation. Patients were assigned to receive either a PECS II block (n = 53) or standard lidocaine-based local anesthesia (n = 53). Pain intensity was assessed using the numeric rating scale (NRS) intraoperatively and at 1, 6, and 12 h postoperatively. Secondary outcomes included the need for rescue analgesia, procedural duration, length of hospitalization, and patient satisfaction. Results: Patients in the PECS II group reported significantly lower NRS scores at all time points (mean intraoperative score: 2.1 ± 1.2 vs. 5.7 ± 1.6, p < 0.001; at 1 h: 2.5 ± 1.5 vs. 6.1 ± 1.7, p < 0.001). Rescue analgesia (metamizole sodium) was required in only four PECS II patients (7.5%) vs. 100% in the control group within 1 h. Hospital stay and procedural time were also modestly reduced in the PECS II group. Patient satisfaction scores were significantly higher in the intervention group. Conclusions: The ultrasound-guided PECS II block significantly reduces perioperative pain and the need for additional analgesia during CIED implantation, offering an effective, safe, and opioid-sparing alternative to conventional local infiltration. Its integration into clinical protocols for device implantation may enhance procedural comfort and recovery. Full article

Objectives: Patients with acute heart failure (AHF) often receive initial non-invasive ventilation (NIV). This study aimed to evaluate the prognostic role of NIV in patients hospitalized for AHF. Methods: This was a retrospective cohort study. We enrolled patients admitted to our cardiac intensive care unit with a diagnosis of AHF. Anthropometric, clinical, pharmacological, and instrumental assessments were collected. Both in-hospital and 180-day post-discharge mortality were evaluated. Results: Among 200 patients (mean age 81 ± 9 years; 52% male), NIV was applied in 80 cases (40%). These patients had more severe NYHA functional class, a higher prevalence of de novo AHF, required higher diuretic doses, and had longer hospital stays. In multivariate analysis, NIV remained significantly associated with length of stay (LOS) (r = 0.26; p = 0.0004). In-hospital mortality was 5% overall and significantly higher in the NIV group compared to non-NIV patients (10% vs. 1.6%, p < 0.001). At 180 days, mortality was also significantly higher in the NIV group [hazard ratio (HR) 1.84; 95% confidence interval (CI): 1.18–2.85; p = 0.006]. After adjusting for age, BNP, CRP, arterial blood gas parameters, renal function, and LVEF, NIV remained an independent predictor of 180-day mortality (HR 1.61; 95% CI: 1.01–2.54; p = 0.04). Conclusions: Patients with AHF who required NIV exhibited more severe disease and longer hospital stays. NIV use was independently associated with both in-hospital and post-discharge mortality, suggesting its potential role as a prognostic marker in AHF. Full article

Background: Spectrin proteins are critical cytoskeleton components that maintain cellular structure and mediate intracellular transport. Pathogenic variants in SPTBN1, encoding βII-spectrin, have been associated with various neurodevelopmental disorders, including developmental delay, intellectual disability, autism spectrum disorder, and epilepsy. Here we report a Korean infant with infantile epileptic spasms syndrome (IESS) and an SPTBN1 mutation and provide a review of this mutation. Methods: The genomic data of the patient were analyzed by whole exome sequencing. A comprehensive literature review was conducted to identify and analyze all reported SPTBN1 variants, resulting in a dataset of 60 unique mutations associated with neurodevelopmental phenotypes. Case Presentation: A 10-month-old Korean female presented with IESS associated with a de novo heterozygous SPTBN1 mutation (c.785A>T; p.Asp262Val). The patient exhibited global developmental delay, microcephaly, hypotonia, spasticity, and MRI findings of diffuse cerebral atrophy and corpus callosum hypoplasia. Electroencephalography revealed hypsarrhythmia, confirming the diagnosis of IESS. Seizures persisted despite initial treatment with vigabatrin and steroids. Genetic analysis identified a likely pathogenic variant within the calponin homology 2 (CH2) domain of SPTBN1. Conclusions: This is the first report of an association between IESS and an SPTBN1 CH2 domain mutation in a Korean infant. This finding expands the clinical spectrum of SPTBN1-related disorders and suggests domain-specific effects may critically influence phenotypic severity. Further functional studies are warranted to elucidate the pathogenic mechanisms of domain-specific variants. Full article

Background/Objectives: This study aimed to evaluate myocardial scar burden and distribution, as well as other nuclear imaging parameters, in predicting cardiac resynchronization therapy (CRT) responses and long-term outcomes in patients selected for CRT with ischemic HF etiology. Methods: Seventy-one patients were prospectively included. They all had NYHA class II/III despite optimal medical therapy, LVEF ≤ 35%, wide QRS complexes, and ischemic HF etiology. All were indicated for de novo CRT implantation and underwent a SPECT MPI viability test prior to CRT implantation. Two-dimensional echocardiography was performed one day before CRT implantation and 6 months after the intervention. The follow-up examination was conducted six months after the CRT implantation and, after 5 years, patients underwent a telephone follow-up to assess survival. Results: Most patients (85%) were male, with an average age of 66.26 ± 9.25 yrs. SPECT MPI revealed large myocardial scars (44.53 ± 20.94%) with high summed rest scores (SRSs) of 25.02 ± 11.29 and low EFs of 26.67 ± 7.71%. At the 6-month follow-up, after the CRT implantation, the NYHA class significantly changed and 35% of the patients were classified as CRT responders. The only difference between responders and non-responders was in the SRS and myocardial scar size (p < 0.001). A scar size of 19.5% was an optimal cutoff for the prediction of CRT response (AUC 0.853, Sn 85% and 1-sp 94%). Conclusions: SPECT MPI parameters are valuable in predicting responses and long-term survival in patients with CRT. Patients with myocardial scars of less than 19.5% may be suited to CRT and experience better cardiovascular survival. Full article

Background: Long-term right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony, resulting in adverse outcomes. Recently, left bundle branch area pacing (LBBAP) has emerged as a physiological pacing modality and is considered a promising alternative. To date, the long-term outcomes of LBBAP compared with RVP, particularly with respect to sex differences, remain unclear. Methods: Between January 2017 and July 2024, 1211 patients who underwent de novo pacemaker implantation were enrolled and categorized into RVP (n = 789) and LBBAP (n = 422). The primary outcome was a composite of all-cause mortality, heart failure hospitalization (HFH), and pacing-induced cardiomyopathy (PICM). Propensity score matching (PSM) was employed to minimize the selection bias and achieve comparability among the study population. A post hoc power analysis based on the observed effect size and sample size showed a power of 80%, confirming sufficient sensitivity to detect group differences. Results: After PSM, 764 patients were analyzed. The mean age of the patients was 74.6 ± 10.5 years in RVP and 74.5 ± 9.8 years in LBBAP, respectively, and 52.3% patients were male. Patients with LBBAP had a lower incidence of the primary outcome (8.6% vs. 24.6%, p < 0.001), HFH (2.6% vs. 13.6%, p < 0.001), and all-cause mortality (6.5% vs. 13.9%, p < 0.001) compared with RVP. There were no significant differences in the clinical outcomes, including the primary outcome, HFH and all-cause mortality, between the sexes in the group with either RVP or LBBAP. However, during a 2-year follow-up period for survival analysis, male patients with LBBAP had a significant lower incidence of all the endpoints, whereas female patients with LBBAP had a lower incidence of HFH [HR 0.14 (95% CI 0.06–0.32), p = 0.001] compared with those with RVP. Conclusions: Regardless of sex, patients with LBBAP had a lower risk of poor clinical outcomes, including HFH and all-cause mortality, compared to those with RVP. Moreover, compared with RVP, LBBAP decreased the risks of all the major endpoints in male patients and the risk of HFH particularly in female patients. Further research is needed to establish the sex-specific responses to LBBAP. Full article

Polypharmacology, the rational design of small molecules that act on multiple therapeutic targets, offers a transformative approach to overcome biological redundancy, network compensation, and drug resistance. This review outlines the scientific rationale for polypharmacology, highlighting its success across oncology, neurodegeneration, metabolic disorders, and infectious diseases. Emphasis is placed on how polypharmacological agents can synergize therapeutic effects, reduce adverse events, and improve patient compliance compared to combination therapies. We also explore how computational methods—spanning ligand-based modeling, structure-based docking, network pharmacology, and systems biology—enable target selection and multi-target ligand prediction. Recent advances in artificial intelligence (AI), particularly deep learning, reinforcement learning, and generative models, have further accelerated the discovery and optimization of multi-target agents. These AI-driven platforms are capable of de novo design of dual and multi-target compounds, some of which have demonstrated biological efficacy in vitro. Finally, we discuss the integration of omics data, CRISPR functional screens, and pathway simulations in guiding multi-target design, as well as the challenges and limitations of current AI approaches. Looking ahead, AI-enabled polypharmacology is poised to become a cornerstone of next-generation drug discovery, with potential to deliver more effective therapies tailored to the complexity of human disease. Full article

Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual MRI scales. Methods: Eighty-one de novo PD patients (≤36 months from diagnosis) and twenty healthy controls underwent 3T MRI with visual atrophy ratings and completed an extensive neuropsychological battery. Results: Using a mixed a priori–a posteriori approach, we defined eight anatomocognitive subtypes reflecting distinct patterns of regional vulnerability: frontosubcortical, posterior cortical, left/right hippocampal, global, and preserved cognition. Specific MRI markers correlated with cognitive deficits in executive, visuospatial, memory, and language domains. Cluster analyses supported subtype validity (AUC range: 0.68–0.95). Conclusions: These results support a practical classification model linking cognitive performance to brain structural changes in early PD. This scalable approach may improve early patient stratification and guide personalized management strategies. Longitudinal studies are needed to assess progression patterns and therapeutic implications. Full article

As tumor research has deepened, the deregulation of cellular metabolism has emerged as yet another recognized hallmark of cancer. Tumor cells adapt different biochemical pathways to support their rapid growth, proliferation, and invasion, resulting in distinct anabolic and catabolic activities compared with healthy tissues. Certain metabolic shifts, such as altered glucose and glutamine utilization and increased de novo fatty acid synthesis, are critical early on, while others may become essential only during metastasis. These metabolic adaptations are closely shaped by, and in turn remodel, the tumor microenvironment, creating favorable conditions for their spread. Anticancer metabolic strategies should integrate pharmacological approaches aimed at inhibiting specific biochemical pathways with well-defined dietary interventions as adjunctive therapies, considering also the role of gut microbiota in modulating diet and treatment responses. Given the established link between the consumption of foods rich in saturated fatty acids and sugars and an increased cancer risk, the effects of diet cannot be ignored. However, current evidence from controlled and multicenter clinical trials remains insufficient to provide definitive clinical recommendations. Further research using modern omics methods, such as metabolomics, proteomics, and lipidomics, is necessary to understand the changes in the metabolic profiles of various cancers at different stages of their development and to determine the potential for modifying these profiles through pharmacological agents and dietary modifications. Therefore, clinical trials should combine standard treatments with novel approaches targeting metabolic reprogramming, such as inhibition of specific enzymes and transporters or binding proteins, alongside the implementation of dietary restrictions that limit nutrient availability for tumor growth. However, to optimize therapeutic efficacy, a precision medicine approach should be adopted that balances the destruction of cancer cells with the protection of healthy ones. This approach, among others, should be based on cell type-specific metabolic profiling, which is crucial for personalizing oncology treatment. Full article

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that belong to genetic and epigenetic mechanism. Despite the recent advantages in next-generation sequencing (NGS) technology, ASD etiology is still unclear. Materials and Methods: In this study, we tested a customized target genetic panel consisting of 74 genes in a cohort of 53 ASD individuals. The tested panel was designed from the SFARI database. Results: Among 53 patients analyzed using a targeted genetic panel, 102 rare variants were identified, with nine individuals carrying likely pathogenic or pathogenic variants considered genetically “positive.” We identified six de novo variants across five genes (POGZ 2 variants, NCOR1, CHD2, ADNP, and GRIN2B), including two variants of uncertain significance in POGZ p.Thr451Met and NCOR1 p.Glu1137Lys, one likely pathogenic variant in GRIN2B p.Leu714Gln, and three pathogenic variants in POGZ p.Leu775Valfs32, CHD2 p.Thr1108Metfs8, and ADNP p.Pro5Argfs*2. Conclusions: This study presents a comprehensive characterization of the targeted gene panel used for genetic analysis, while critically evaluating its diagnostic limitations within the context of contemporary genomic approaches. A pivotal accomplishment of this study was the ClinVar submission of novel de novo variants which expands the documented mutational spectrum of ASD-associated genes and enhances future diagnostic interpretation. Full article

The domesticated species currently available in the market have been developed through the breeding of wild relatives. Breeding strategies using wild relatives with high genetic diversity are attracting attention as an important approach for addressing climate change and ensuring sustainable food supply. However, studies examining gene expression variation in multiple wild and domesticated species are limited. Therefore, we aimed to investigate the changes in gene expression associated with domestication. We performed a meta-analysis of public gene expression data of domesticated species of rice, tomato, and soybean and their presumed ancestral species using 21 pairs for rice, 36 pairs for tomato, and 56 pairs for soybean. In wild relatives, the expression of genes involved in osmotic, drought, and wound stress tolerance was upregulated, with 18 genes included in the top 5% of DW scores. In domesticated species, upregulated expression was observed in genes related to auxin and those involved in the efflux of heavy metals and harmful substances, with 36 genes included in the top 5% of DW scores. These findings provide insights into how domestication influences changes in crop traits. Thus, our findings may contribute to rapid breeding and the development of new varieties capable of growing in harsh natural environments. Hence, a new cultivation method called “de novo domestication” has been proposed, which combines the genetic diversity of currently unused wild relatives and wild relatives with genome editing technologies that enable rapid breeding. Full article

Background and Objectives: To evaluate the feasibility and clinical outcomes of a novel non-mesh robot-assisted sacrocolpopexy (RSC) using autologous round ligament (ARL) grafts in patients with pelvic organ prolapse (POP). Materials and Methods: This retrospective study included 92 patients who underwent non-mesh RSC with ARL grafts at Kagoshima University Hospital between August 2020 and June 2024. All patients met the inclusion criteria for symptomatic POP-Q stage II or higher and elected to undergo non-mesh RSC. The procedures were performed using the da Vinci^® Xi or the hinotori™ Surgical Robot System. The clinical characteristics, operative data, complications, and recurrence rates were analyzed. Results: ARL harvesting was feasible in all patients, and the non-mesh RSC procedure was completed without conversion to open surgery or any intraoperative complications. The median operative time was 251 min, and the median blood loss was 30 mL. Postoperative complications of Clavien-Dindo grade ≥ 2 occurred in five patients (5%), all of whom developed pelvic infections. De novo stress urinary incontinence was observed in one patient (1%). POP recurrence occurred in seven patients (8%) during a median follow-up of 3 months (range, 3–18 months), all of whom presented with cystocele. Five patients underwent reoperation, and two were managed conservatively. All patients experienced postoperative symptomatic improvement. A higher BMI and advanced POP-Q stage were significant predictors of recurrence. Conclusions: This is the first report of non-mesh RSC using an ARL graft. The procedure is feasible and effective, avoids the use of synthetic mesh, and offers short-term outcomes comparable to those of mesh-based RSC. ARL-based RSC represents a promising alternative, especially for patients at risk of mesh-related complications. Long-term follow-up is required to confirm durability. Full article

Horizontal trafficking of subcellular components, such as nucleic acids, proteins, and membrane fragments, is utilized by tumor cells to facilitate tumor cell proliferation and survival. Conventionally, tumor cells have been known to undergo long-range transfer through the import and export of extracellular vesicles and exosomes. However, other means of intercellular transfer are also employed by tumor cells. These trafficking methods can facilitate changes in anti-tumor immunity and distribute oncogenic protein variants to nearby cells to provide a hospitable tumor microenvironment. The molecular mechanisms that drive many of these cell trafficking mechanisms are conserved, relying on de novo synthesis of filamentous actin. However, the delineation between these processes is not yet known. This review will highlight four recently characterized and underappreciated contact-dependent intercellular trafficking mechanisms: (i) trogocytosis, (ii) entosis, (iii) cell fusion, and (iv) tunneling nanotubes/microtubes utilized by tumor cells to promote a hospitable microenvironment. Full article

Background: Although contemporary stent technology has significantly evolved, a substantial number of patients present with stent failure (SF), the clinical expression of which is either in-stent restenosis (ISR) or stent thrombosis (ST). Methods: In this observational, single-center study, we aimed to compare the clinical characteristics, clinical presentation, angiographic findings and subsequent management of patients who underwent percutaneous coronary intervention (PCI) for SF, either ISR or ST, with patients who had PCI for de novo lesions. Results: Over a period of two years (September 2022–October 2024), 1120 patients underwent PCI, of whom 9% had SF. Of the 101 SF cases, the majority (76 cases, 75%) had ISR, while the rest (25 cases, 25%) had ST. Regarding baseline characteristics, patients who underwent PCI for SF had a higher incidence of diabetes mellitus (53% vs. 29%; p < 0.001), dyslipidemia (88% vs. 50%; p < 0.001) as well as prior coronary artery bypass grafting surgery (7.9% vs. 3.7%; p = 0.043), while they were less likely to be current smokers (33% vs. 52%; p < 0.001). SF PCI patients presented more frequently with unstable angina (17% vs. 8.9%; p = 0.010). A new stent was implanted in less than half of SF cases (i.e., stent implantation, 44% vs. 91%; p < 0.001). On the other hand, in the clinical setting of SF, drug-coated balloons (44% vs. 5.3%; p < 0.001) and plain balloon angioplasty (8.9% vs. 0.7%; p < 0.001) was applied more frequently compared with de novo lesions. Furthermore, the usage of cutting/scoring balloons and lithotripsy was significantly higher in the SF group (8.9% vs. 0.4% and 12% vs. 3%, respectively; p < 0.001 for both). Intracoronary imaging guidance was more commonly used in the SF group (33% vs. 13%; p < 0.001). Stent malapposition (44%) and neoatherosclerosis (67%) were the most common mechanisms of ST and ISR, respectively, as identified by intravascular imaging modalities. Finally, the success rates were comparable (96% vs. 98%; p = 0.150) between the two groups. Conclusions: Approximately one of ten patients underwent PCI because of the failure of a previously implanted stent. Use of intracoronary imaging is significantly higher in the clinical context of SF. While DES implantation remains the standard of practice for de novo lesions, DCBs are a popular alternative, especially for ISR cases. Interventional cardiologists who are involved in the treatment of SF cases should be familiar with interpreting intravascular imaging to guide the use of the adjunctive device required to ensure that optimal procedural results in SF cases are obtained. Full article

Bombax ceiba is an important medicinal and ornamental tree widely distributed in tropical and subtropical areas. However, its seeds lose viability rapidly after harvest, which has created hurdles in large-scale propagation. Here, we describe the development of a rapid and efficient de novo organogenesis system for Bombax ceiba, incorporating both indirect and direct regeneration pathways. The optimal basal medium used throughout the protocol was ½ MS supplemented with 30 g/L glucose, with all cultures maintained at 26–28 °C. For the indirect pathway, callus was induced from both ends of each hypocotyl on basal medium supplemented with 0.2 mg·L⁻¹ 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg·L⁻¹ 6-Benzylaminopurine (6-BA) under dark conditions. The induced calluses were subsequently differentiated into adventitious shoots on basal media containing 0.5 mg·L⁻¹ Indole-3-butyric acid (IBA), 0.15 mg·L⁻¹ Kinetin (KIN), and 1 mg·L⁻¹ 6-BA under a 16 h photoperiod, resulting in a callus induction rate of 140% and a differentiation rate of 51%. For the direct regeneration pathway, shoot buds cultured on medium with 0.5 mg·L⁻¹ IBA and 1 mg·L⁻¹ 6-BA achieved a 100% sprouting rate with a regeneration coefficient of approximately 3.2. The regenerated adventitious shoots rooted successfully on medium supplemented with 0.5 mg·L⁻¹ Naphthylacetic acid (NAA) and were acclimatized under greenhouse conditions to produce viable plantlets. This regeneration system efficiently utilizes sterile seedling explants, is not limited by seasonal or environmental factors, and significantly improves the propagation efficiency of Bombax ceiba. These optimized micropropagation methods also provide a robust platform for future genetic transformation studies using hypocotyls and shoot buds as explants. Full article