Controlled release of hydrogel-encapsulated mesenchymal stem cells-conditioned medium promotes functional liver regeneration after hepatectomy in metabolic dysfunction-associated steatotic liver disease.

Background: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk.

Can the QRS morphology of outflow tract ventricular arrhythmia change when right bundle branch block emerges during sinus rhythm?

Background: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB).

Methods: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application.

Difference in radiofrequency ablation profile between during sinus rhythm and atrial fibrillation: Considerations in this era of high-power short-duration strategy.

Background: The concept of ablation index (AI) was introduced to evaluate radiofrequency (RF) ablation lesions. It is calculated from power, contact force (CF), and RF duration. However, other factors may also affect the quality of ablation lesions.

Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients.

The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes and evaluate how much dysregulation is associated with levodopa dose. Furthermore, to evaluate the effect of Opicapone, a catechol-o-methyl-transferase inhibitor, on vitamin B6 levels by monitoring the AST and ALT levels in patients treated with Levodopa-Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum vitamin B6 levels were measured (PD, n = 72 and controls, n = 31).

Conduction time around the mitral valve annulus has the potential to rule out postablation perimitral atrial tachycardia.

Introduction: It would be helpful in determining ablation strategy if the occurrence of perimitral atrial tachycardia (PMAT) could be predicted in advance. We investigated whether estimated perimitral conduction time (E-PMCT), namely, twice the time between coronary sinus (CS) pacing and the ensuing wave-front collision at the opposite side of the mitral annulus, correlated with the cycle length of PMAT and could predict future PMAT.

Methods And Results: We retrospectively (retrospective cohort) and prospectively (validation cohort) investigated atrial fibrillation patients who had received pulmonary vein isolation (PVI) and in whom left atrial maps had been created during CS pacing.

Effect of the Interfacial Tension on the Stability of Silica Stabilized Pickering Emulsions near the Lower Critical Solution Temperature of 2,6-Lutidine - Water Mixtures.

In this paper, the kinetic stability of Pickering emulsions stabilized by spherical silica particles (100 nm in diameter) was examined in the water - 2,6-lutidine mixture. In the close vicinity of the lower critical solution temperature, Pickering emulsions were unstable due to the ultra-low liquid-liquid interfacial tension but increased their stability with increasing the temperature. In this system, the interfacial tension obeys universal scale law and can be tuned by temperature without adding any surface-active agents.

Differences between typical and reverse typical atrial flutter identified by ultrahigh resolution mapping.

Background: Although atrial flutter (AFL) is a common arrhythmia that is based on a macro-reentrant tachycardia around the tricuspid annulus, the factors giving rise to typical AFL (t-AFL) versus reverse typical AFL (rt-AFL) are unknown. To investigate the difference between t-AFL and rt-AFL circuits using ultrahigh resolution mapping of the right atrium.

Methods: We investigated 30 isthmus-dependent AFL patients (mean age 71, 28 male) who underwent first-time cavo-tricuspid isthmus (CTI) ablation guided by Boston Scientific's Rhythmia mapping system and divided them into two groups: t-AFL (22 patients) and rt-AFL (8 patients).

Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson's disease-related fibril polymorphism.

Lipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson's disease (PD). However, it has not been fully determined which lipids are involved in the initiation of αSyn aggregation in PD. Here exploiting genetic understanding associating the loss-of-function mutation in Synaptojanin 1 (SYNJ1), a phosphoinositide phosphatase, with familial PD and analysis of postmortem PD brains, we identified a novel lipid molecule involved in the toxic conversion of αSyn and its relation to PD.

Sequential hypothermic and normothermic perfusion preservation and transplantation of expanded criteria donor livers.

Background: The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation.

Methods: With the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion using our institutionally developed perfusion device.

Results: Expanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries.

Treatment of atrial tachycardia arising after superior transseptal approach mitral valve surgery: Insights from ultra-high-density mapping to prevent atrioventricular block.

Introduction: Mitral valve surgery employing a superior transseptal approach (STA) is associated with arrhythmogenicity and intra-atrial conduction delay, despite being optimal for visualization of the surgical field. It is sometimes difficult to treat atrial tachycardias (AT) that arise after STA. To investigate AT circuits that arise after STA in detail in order to identify the optimal ablation line, using ultra-high-resolution mapping (UHRM).

A Phase 2 Trial of Afatinib in Patients with Solid Tumors that Harbor Genomic Aberrations in the HER family: The MOBILITY3 Basket Study.

Background: Epidermal growth factor receptor (EGFR)- and human epidermal growth factor receptor (HER)2-targeted therapies are approved for the treatment of breast, gastric/gastrointestinal junction (GEJ), and non-small cell lung cancer (NSCLC) with specific molecular aberrations affecting HER family members. Over 10 % of other cancers harbor genomic aberrations affecting HER family members, but their role remains undefined.

Objective: The MOBILITY3 trial evaluated the antitumor activity of afatinib, an oral pan-HER tyrosine kinase inhibitor (TKI) in HER-aberrant tumors outside of the licensed indications.

Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson's disease.

Parkinson's disease is a neurodegenerative disease characterized by the formation of neuronal inclusions of α-synuclein in patient brains. As the disease progresses, toxic α-synuclein aggregates transmit throughout the nervous system. No effective disease-modifying therapy has been established, and preventing α-synuclein aggregation is thought to be one of the most promising approaches to ameliorate the disease.

Association of Early Bifurcation of Hepatic Artery With Arterial Injury in Right-Sided Living-Donor Hepatectomy: Retrospective Analysis of 500 Cases.

Objective: The aim of this study was to explore the incidence of early bifurcation of the right hepatic artery (RHA) and the right posterior hepatic artery (RPHA), which is crucial in right lobe graft (RLG) and right posterior sector graft (RPSG) procurement for living-donor liver transplantation.

Summary Background Data: Early bifurcation of the hepatic artery tends to induce oversight of one of the bifurcated arteries and its injury in RLG/RPSG procurement. Unrecognizable on conventional 3-dimensional (3-D) images, its significance is underestimated.

Angiogenesis Inhibitors as Anti-Cancer Therapy Following Renal Transplantation: A Case Report and Review of the Literature.

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation.

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT).

Alternative mitochondrial quality control mediated by extracellular release.

Mitochondrial quality control, which is crucial for maintaining cellular homeostasis, has been considered to be achieved exclusively through mitophagy. Here we report an alternative mitochondrial quality control pathway mediated by extracellular mitochondria release. By performing time-lapse confocal imaging on a stable cell line with fluorescent-labeled mitochondria, we observed release of mitochondria from cells into the extracellular space.

Novel strategies in immune checkpoint inhibitor drug development: How far are we from the paradigm shift?

The development of immune checkpoint inhibitors (ICI) represents a major milestone in immune-oncology. Over the years these agents have demonstrated efficacy in an increasing array of malignancies. Despite this success however, significant challenges remain.

Structure and Optimization of Checkpoint Inhibitors.

With the advent of checkpoint inhibitor treatment for various cancer types, the optimization of drug selection, pharmacokinetics and biomarker assays is an urgent and as yet unresolved dilemma for clinicians, pharmaceutical companies and researchers. Drugs which inhibit cytotoxic T-lymphocyte associated protein-4 (CTLA-4), such as ipilimumab and tremelimumab, programmed cell death protein-1 (PD-1), such as nivolumab and pembrolizumab, and programmed cell death ligand-1 (PD-L1), such as atezolizumab, durvalumab and avelumab, each appear to have varying pharmacokinetics and clinical activity in different cancer types. Each drug differs in terms of dosing, which becomes an issue when drug comparisons are attempted.

Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody-positive or ABO blood-type incompatible (ABOi) organ transplantation. Rituximab dramatically improved the outcome of ABOi living-donor liver transplantation (LDLT); however, an effective treatment for posttransplant AMR, once occurred, is yet to be established. A 44-year-old woman with biliary cirrhosis underwent ABOi-LDLT from her sister (AB-to-A).

Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats.

Background: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models.

Urinary Liver-Type Fatty Acid-Binding Protein Level as a Predictive Biomarker of Acute Kidney Injury in Patients with Acute Decompensated Heart Failure.

Background: There are no biological markers to predict the onset of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF). Liver-type fatty acid-binding protein (L-FABP) levels are markedly upregulated in the proximal tubules after renal ischemia. We investigated whether urinary L-FABP is a suitable marker to predict AKI in ADHF patients.

Usefulness of Lipoprotein(a) for Predicting Clinical Outcomes After Endovascular Therapy for Aortoiliac Atherosclerotic Lesions.

Purpose: To evaluate the usefulness of serum lipoprotein(a) as a biomarker of clinical outcomes after endovascular therapy (EVT) for atherosclerotic aortoiliac lesions.

Methods: Serum lipoprotein(a) concentrations were measured at admission in 189 consecutive patients (median age 72 years; 160 men) with peripheral artery disease who underwent EVT for aortoiliac occlusive disease. The patients were dichotomized into 2 groups based on serum lipoprotein(a) levels ≤40 mg/dL (LOW; n=135) or >40 mg/dL (HIGH; n=54).