Publications

Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated a reduction in heart failure (HF) hospitalizations in HF patients and decreased recurrence of atrial fibrillation (AF), including in those who have undergone catheter ablation (CA). The effects of SGLT2i are likely due to suppression of the renin-angiotensin-aldosterone system, reduction in oxidative stress with subsequent improvement in myocardial efficiency, and attenuation of cardiac remodeling. We aim to present the effects of SGLT2i on AF recurrence in patients who have undergone CA for AF. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective studies evaluating the effect of SGLT2i on AF recurrence following CA compared with non-SGLT2i. The primary outcome was the recurrence of AF by the final follow-up reported in each study. Secondary outcomes include AF recurrence by the first follow-up within 12 to 24 months and follow-up intervals (6, 12, 18, 24, and 36 to 42 months) post-ablation, multivariate risk of AF recurrence, and the effect on left atrial diameter (LAD) (less than 45 mm vs. greater than or equal to 45 mm). For risk of bias (ROB) analysis, the NIH ROB and Cochrane ROB2 tool were used. All statistical, heterogeneity, and sensitivity analyses were conducted using Cochrane Review Manager. A random-effect model was employed for all pooled statistical analyses. Results: A total of nine studies, two RCTs and seven retrospective studies, were included (N = 6874) for the primary outcome. Compared to non-SGLT2i (N = 3693), SGLT2i (N = 3181) significantly decreased AF recurrence by the final follow-up (OR = 0.62; 95% CI: 0.45-0.85; p = 0.008). For secondary outcomes, SGLT2i significantly reduced AF recurrence by the first follow-up within 12 to 24 months post-ablation (OR = 0.58; p = 0.0001) and by the different follow-up periods, 6-month (OR = 0.53; p = 0.02), 12-month (OR = 0.56; p = 0.0001), 18-month (OR = 0.55; p = 0.01), and 24-month (OR = 0.60; p = 0.12) follow-up periods. On the other hand, by 36 to 42 months, SGLT2i was associated with increased risk of AF recurrence (OR = 1.41; p = 0.004). Conclusions: We conclude that SGLT2i demonstrated a reduction in AF recurrence following CA, particularly by 12 to 18 months post-ablation.

Background/Objectives: Immortality and anti-aging research is accelerating, with implications across medicine. This narrative review explores the biological principles, translational innovations, and ethical considerations at the intersection of aging and plastic surgery, reframed for a broad clinical audience. Methods: A narrative review of the literature from PubMed, clinical trials, and translational studies was conducted, with emphasis on regenerative medicine, stem cells, tissue engineering, gene editing, and longevity pharmacologics within the field of plastic and reconstructive surgery. Results: Key themes include (1) the biology of aging and epigenetic reprogramming, (2) esthetic and regenerative innovations with broader clinical significance, (3) emerging genetic and pharmacologic longevity strategies, (4) ethical and regulatory challenges, and (5) future directions such as nanotechnology, artificial intelligence, and digital immortality. Conclusions: Immortality remains an aspirational frontier, but innovations in regenerative science and longevity research offer opportunities for improving healthspans. Medicine as a whole must balance innovation with ethics, equity, and safety in translating these discoveries to patient care.

Inflammatory bowel disease, encompassing ulcerative colitis and Crohn's disease, is characterised by chronic immune-mediated inflammation and variable treatment response. Loss of drug efficacy due to underexposure, pharmacokinetic variability, and immunogenicity remains a key challenge. Therapeutic drug monitoring, using drug levels and anti-drug antibody measurements, is an important strategy for optimising the treatment of inflammatory bowel disease. It helps ensure adequate dosing and can distinguish between pharmacokinetic and mechanistic drug failure. Most evidence pertains to infliximab and adalimumab. Multiple factors influence drug pharmacokinetics, affecting both target drug levels and the doses required to achieve them. These include inflammatory burden, bodyweight, age, disease phenotype, and route of administration, all of which are important considerations for individualising treatment in inflammatory bowel disease. This narrative review explores how special clinical situations-acute severe ulcerative colitis, perianal fistulising Crohn's disease, hypoalbuminaemia, extremes of body composition, pregnancy, paediatrics, and advanced age-alter drug pharmacokinetics and influence the utility and interpretation of therapeutic drug monitoring in inflammatory bowel disease.

This review explores the dual regenerative and antimicrobial properties of platelet- and marrow-derived biologics, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), autologous protein solutions, and plasma fractions. These biologics, widely used in regeneration and tissue repair, offer multiplex bioactivity through growth factors, cytokines, and cellular components that promote healing while reducing infection risk. PRP and BMAC demonstrate significant regenerative effects in musculoskeletal conditions, wound healing, and cartilage repair, with platelets and leukocytes contributing antimicrobial peptides and immune modulation for more indirect regenerative mechanisms. Preparation methods, patient factors, and lack of standardization impact clinical outcomes and efficacy. While promising for reducing reliance on chronic pain medications and improving function, these therapies face limitations including inconsistent preparation and utilization protocols, limited long-term safety data, and regulatory challenges. Here, we review the need for consensus-building, standardized procedures, and robust research to optimize clinical integration and realize the full potential of biologic regenerative therapies in pain medicine.

Background: We recently generated T cell receptor (TCR) transgenic (Tg) mice specific to cardiac myosin heavy chain-α (Myhc-α 334-352) on both myocarditis-resistant (C57BL/6) and susceptible (A/J) genetic backgrounds. We noted that the antigen-specific TCRs were expressed in CD4+ and CD8+ T cells in both strains, but their responses differed. While the T cells from naïve Tg C57BL/6 mice do not respond to Myhc-α 334-352, whereas those from A/J mice spontaneously respond to the antigen, suggesting their underlying molecular mechanisms might differ. Methods: To investigate the mechanisms of differences in the antigen-responsiveness between the Tg C57BL/6 and A/J mice, we performed bulk RNA sequencing on CD4⁺ and CD8⁺ T cells sorted by flow cytometry. Differentially expressed genes, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, gene set enrichment analysis (GSEA) of GO and KEGG, and transcription factor (TF) network analyses were performed to identify pathways and regulators of immune responses. Results: First, the principal component analysis of the transcriptomic profiles distinguished CD4+ from CD8+ T cells, which also differed between the two strains. Second, the differentially expressed cytokine and cytotoxicity genes revealed similar patterns between CD4+ and CD8+ T cells. Importantly, KEGG enrichment analysis revealed downregulated pathways in both CD4+ and CD8+ T cells that are associated with viral myocarditis, and various autoimmune conditions in C57BL/6 as compared to A/J mice. Similarly, the GSEA of GO revealed negative regulation of heart contraction and positive regulation of cardiac muscle hypertrophy processes were negatively enriched in CD4+ T cells of C57BL/6 mice. Finally, by generating the transcription factor (TF) networks, 22 TFs were found common to both CD4+ and CD8+ T cells, whereas eight TFs were unique to CD4+ or CD8+ T cells that have a role in T cell activation, tolerance, and T regulatory cells. Conclusions: Our data provide new insights into the transcriptomic profiles that may contribute to the genetic resistance mechanisms for developing cardiac autoimmunity.

Solid tumors collectively drive the global cancer burden, with profound molecular heterogeneity demanding precision and molecularly informed management. Advances in sequencing technologies have established molecular taxonomy as a cornerstone of clinical oncology, progressively superseding traditional histopathological classifications. Sanger sequencing remains the gold standard for validating guideline mandated actionable variants. Next-generation sequencing (NGS) has revolutionized early cancer detection through liquid biopsy applications and enabled the reclassification of diagnostically challenging tumor subtypes. Emerging long-read platforms offer unique capabilities to resolve complex genomic rearrangements, structural variants, and therapy-induced epigenetic remodeling. Consequently, therapeutic strategies are shifting from organ-centric approaches to mutation-specific interventions, exemplified by non-small-cell lung cancer, where molecular stratification drives substantial improvements in treatment response. Nevertheless, temporal tumor heterogeneity, biological contamination, and computational limitations highlight the urgent need for robust, integrated verification systems. Collectively, this evolution positions sequencing as the operational backbone of adaptive precision oncology across solid tumors. Here, we synthesize our laboratory findings with the current literature to comprehensively review the diagnostic, therapeutic, and prognostic applications of first- through fourth-generation sequencing technologies and discuss future directions in this rapidly evolving field.

Magnetic Particle Imaging (MPI) is a new type of tracer-based imaging that has great spatial and temporal resolution, does not require ionizing radiation, and can see deep into tissues by directly measuring the nonlinear magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs). Unlike Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), MPI has very high contrast and quantitative accuracy, which makes it perfect for use in dynamic cardiovascular applications. This study presents a full picture of the most recent changes in cardiac MPI, such as the physics behind Field-Free Point (FFP) and Field-Free Line (FFL) encoding, new ideas for tracer design, and important steps in the evolution of scanner hardware. We discuss the clinical relevance of cardiac MPI in visualizing myocardial perfusion, quantifying blood flow, and guiding real-time interventions. A hybrid imaging workflow, which improves anatomical detail and functional assessment, is utilized to explore the integration of MPI with complementary modalities, particularly MRI. By consolidating recent preclinical breakthroughs and highlighting the roadmap toward human-scale implementation, this article underscores the transformative potential of MPI in cardiac diagnostics and image-guided therapy.

Extracellular particles (EPs), an umbrella term encompassing membrane-enclosed extracellular vesicles (EVs) and non-vesicular extracellular particles ([NVEPs], previously described as extracellular condensates [ECs]) contain a complex cargo of biomolecules, including DNA, RNA, proteins, and lipids, reflecting the physiological state of their cell of origin. Identifying proteins associated with EPs that regulate host responses to physiological and pathophysiological processes is of critical importance. Here, we report the findings of our study to gain insight into the proteins associated with NVEPs. We used samples from human semen, the rat brain, and the rhesus macaque (RM) brain and blood to assess the physical properties and proteome profiles of NVEPs from these specimens. The results show significant differences in the zeta potential, concentration, and size of NVEPs across different species. We identified 938, 51, and 509 total proteins from NVEPs isolated from rat brain tissues, RM blood, and human seminal plasma, respectively. The species-specific protein networks show distinct biological themes, while the species-conserved protein interactome was identified with six proteins (ALB, CST3, FIBA/FGA, GSTP1, PLMN/PLG, PPIA) associated with NVEPs in all samples. The six NVEP-associated proteins are prone to aggregation and formation of wide, insoluble, unbranched filaments with a cross-beta sheet quaternary structure, such as amyloid fibrils. Protein-to-function analysis indicates that the six identified proteins are linked to the release of dopamine, immune-mediated inflammatory disease, replication of RNA viruses, HIV-HCV co-infection, and inflammation. These interesting findings have created an opportunity to evaluate NVEPs for their potential use as biomarkers of health and disease. Additional in-depth studies are needed to clarify when and how these proteins sustain their physiological role or transition to pathogenic roles.

Excitation-contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel, dihydropyridine receptor (DHPR), and the ryanodine receptor (RyR1) Ca2+ release channel. Although the exact mode of communication that links these two membrane proteins remains to be fully resolved, both the α1s and β1a subunits of DHPR are two of a select number of critical proteins involved in this process. A detailed in vitro interaction study of these two proteins reveals that their association occurs between the β1a SH3 domain and the polyproline motifs located in a critical region of the α1s II-III loop. We demonstrate that subtle changes in the composition of the β1a SH3 domain influences the ability of β proteins to bind to II-III loop proteins and investigate the effect of these changes on EC skeletal coupling. Furthermore, investigation into the composition of the II-III loop shows that previously identified amino acids demonstrated to be important in EC coupling are implicated in in vitro binding. In summary, we ascribe a role for the DHPR β1a which involves the engagement of its SH3 domain with the α1s II-III loop and propose a scenario whereby this interaction may facilitate skeletal muscle EC coupling.

Background/Aims: Intravascular imaging during percutaneous coronary intervention (PCI) improves clinical outcomes; however, is dependent on accurate and rapid interpretation of the images generated. This study aimed to compare coronary artery calcification assessment using a novel automated artificial intelligence (AI) software algorithm with manual optical coherence tomography (OCT) image analysis. Methods and Results: A deep neural network based on a UNet-like architecture was developed and trained to identify calcified atherosclerotic plaque from an independent dataset of expert-annotated clinical intravascular OCT pullbacks. The AI network was subsequently validated on previously unseen clinical OCT pullbacks that were manually annotated for plaque calcium and used to quantify clinically relevant calcified plaque characteristics. Correlation and agreement between the expert-annotated images and the model predictions were evaluated. In total, 8259 cross-sectional images comprised the training and internal validation dataset. Pixel-based classification by the AI model performed best to identify calcified plaque (AUC = 0.96), with an overall diagnostic accuracy of 73.3%. During independent external validation, the model correctly identified 934 of the 1248 calcified plaques, corresponding to a diagnostic accuracy of 74.8%. The AI model performed well in assessing the calculated OCT-calcium score (ρ = 0.84; 95% confidence interval [CI], 0.81-0.87, p ≤ 0.001). Conclusions: Implementation of an automated AI software algorithm provides a rapid and efficient method to comprehensively map coronary calcium in intravascular OCT images. With further training and refinement, it is anticipated that the AI machine learning software will continue to improve, enabling new robust tools for clinical OCT calcium detection to better guide PCI procedures.