Transplantation and Surgical Strategies in Patients With Neuroendocrine Liver Metastases: Protocol of Four Systematic Reviews

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition linked to obesity, diabetes, and metabolic syndrome, and can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Current diagnostic standards such as liver biopsy are invasive and unsuitable for routine screening. Liquid biopsy, particularly through analysis of extracellular RNAs (exRNAs), including microRNAs (e.g., miR-122, miR-21, miR-34a), long non-coding RNAs, and tRNA-derived fragments, offers a promising non-invasive alternative. These exRNAs, released from hepatocytes and carried in blood via extracellular vesicles or protein complexes, can be detected using techniques like RNA sequencing, qRT-PCR, and droplet digital PCR. These biomarkers correlate with histologic severity, fibrosis stage, and treatment response, and have shown promising diagnostic utility; however, their performance may differ across various populations and disease stages. Despite their potential, clinical translation is limited by a lack of standardization and large-scale validation. This review outlines recent advances in exRNA-based diagnostics for MASLD and MASH, emphasizing their role in early detection, disease monitoring, and the shift toward personalized hepatology.

Mitochondria are crucial for cellular functioning, serving as both an intracellular energy source and a signaling organelle. Recent evidence also highlights their existence outside of cells, where they participate in cell-to-cell communication. Cardiometabolic disease (CMD) has a complex pathogenesis closely associated with mitochondrial dysregulation, inflammation, and metabolic abnormalities. This review explores the roles of circulating extracellular mitochondria (CEMI) in CMD, detailing how their various forms, whether as intact structures or within vesicles, contribute to CMD pathogenesis. We classify different forms of CEMIs and discuss their potential as biomarkers and therapeutic agents in CMDs. We also describe mitochondrial transplantation as an emerging therapy for restoring cellular function in damaged tissues. Finally, to standardize CEMI assessment, we propose the Universal CEMI Assessment Protocol (UCAP), a framework aimed at enhancing comparability and reproducibility across studies.

Purpose of Review: Recently developed once-weekly basal insulin analogs, including insulin icodec and insulin efsitora alpha (efsitora), aim to improve treatment adherence and patient convenience compared with daily basal insulin. This systematic review and meta-analysis evaluated the efficacy and safety of once-weekly basal insulin analogs compared with daily basal insulin analogs in adults with type 2 diabetes mellitus (T2DM) and included 14 randomized controlled trials (RCTs), comprising 8,487 subjects. Recent Findings: Evidence supports that once-weekly basal insulin analogs achieve comparable glycemic control to daily basal insulin analogs in adults with T2DM, offering greater reductions in HbA1c and improvements in time in range, with a safety profile similar to that of daily insulin regimens. In our analysis, once-weekly basal insulin resulted in a greater reduction in HbA1c compared with daily basal insulin (mean difference [MD] -0.09%, 95% CI -0.15 to -0.03), greater improvements in time in range (TIR) (MD 1.86%, 95% CI 0.73 to 2.98) and higher odds of attaining an HbA1c < 7.0% (OR 1.32, 95% CI 1.07 to 1.63, I2 64.9%). Rates of level 2 or 3 hypoglycemia did not differ significantly. Summary: Once-weekly basal insulin provides glycemic control comparable to daily basal insulin, with modest improvements in glycemic outcomes and similar hypoglycemia risk. Its primary advantage lies in treatment simplification and reduced injection burden, supporting its role as a convenient alternative to daily basal insulin in adults with T2DM.

We describe a case of euglycemic diabetic ketoacidosis (EDKA) in a 30-year-old man with no known diabetes on tirzepatide, intermittent fasting (IF), and a low-carbohydrate diet for weight loss. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combined GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs), like tirzepatide, are effective for weight loss and diabetes management, their unsupervised use, especially alongside ketosis-inducing diets, may lead to serious risks such as EDKA. This report emphasizes the need for medical supervision in weight management, particularly when combining medications such as tirzepatide with dietary interventions, like IF and low-carbohydrate diets.