European Journal of Clinical Investigation最新文献

Background: Diabetes mellitus is a leading global health concern. The parallel rise in obesity has exacerbated this burden, with projections suggesting over half of the adult population will be overweight or obese by 2050. Incretin-based therapies have emerged as cornerstone treatments for type 2 diabetes (T2DM), offering glycemic control alongside promising cardiovascular and renal benefits.

Results: This review consolidates current evidence regarding the cardiovascular effects of incretin-based medications. GLP-1 receptor agonists (GLP-1RAs) have demonstrated protective effects in preclinical models. Clinical trials show modest but consistent reductions in major adverse cardiovascular events (MACE), with additional renal benefits. Conversely, DPP-4 inhibitors display cardiovascular neutrality. Real-world studies largely support the superiority of GLP-1RAs over other glucose-lowering agents (e.g. DPP-4 inhibitors, insulin) in reducing MACE, though their benefits in heart failure (HF) with reduced ejection fraction remain limited. Recent trials in patients with obesity-related HFpEF demonstrate that GLP-1RAs and dual GIP/GLP-1 agonists significantly improve symptoms, functional status, and reduce HF events.

Conclusions: While incretin therapies represent a transformative advancement in cardiometabolic care, challenges remain-including gastrointestinal side effects, adherence issues, lean mass loss and cost. As next-generation agents (e.g. triple agonists) advance, lifestyle interventions remain essential for durable, management of diabetes, obesity and associated cardiovascular conditions.

Introduction: While hyperammonemia is traditionally associated with decompensated cirrhosis, emerging evidence suggests that disturbances in nitrogen homeostasis contribute to disease progression in earlier stages of steatohepatitis and fibrosis. L-ornithine L-aspartate (LOLA), an established ammonia scavenger, targets key pathophysiological mechanisms shared by metabolic dysfunction-associated steatotic liver disease (MASLD), including oxidative stress, mitochondrial dysfunction and hepatic stellate cell activation. This systematic review synthesizes current experimental and clinical research to evaluate the potential therapeutic role of LOLA in MASLD.

Methods: A systematic search of PubMed, Embase and SCOPUS was conducted up to December 1, 2025, following PRISMA 2020 guidelines. Eligible studies included experimental (in vivo/in vitro) and clinical trials evaluating the effects of LOLA or L-aspartate on hepatic steatosis, inflammation, or fibrosis in the context of MASLD. Data extraction and quality assessment were performed independently by two reviewers using appropriate tools for animal and human studies.

Results: Nineteen studies were included, comprising 10 experimental pre-clinical models (9 in vivo animal studies and 1 in vitro study) and 9 clinical studies involving approximately 1671 participants. Experimental studies consistently demonstrated that LOLA intervention ameliorates hepatic steatosis, inflammation and collagen deposition. Identified molecular mechanisms included the activation of the LKB1-AMPK axis, restoration of mitochondrial bioenergetics and modulation of the gut-liver-muscle axis. In clinical studies, results from three randomized controlled trials (RCTs) indicated significant improvements in liver enzymes (ALT, AST) and lipid profiles, with reductions in hepatic steatosis. Evidence from six observational and open-label studies corroborated these biochemical improvements and further demonstrated significant reductions in blood ammonia levels, improved intrahepatic microcirculation and reduced liver stiffness and patient-reported fatigue. However, clinical evidence remains limited by study heterogeneity and a lack of large-scale randomized trials using specific MASLD criteria.

Conclusions: Preclinical evidence suggests that LOLA exerts pleiotropic hepatoprotective effects in MASLD by targeting hyperammonemia-induced fibrosis and metabolic dysregulation. While growing clinical data indicate benefits in biochemical normalization, structural improvement and symptom relief, further robust clinical research is required to validate these findings and establish LOLA as a standard therapeutic option for MASLD patients.

Background: Integrating end-of-life (EoL) care in cardiac intensive care units (CICUs) is particularly complex because it requires a shift from a purely curative approach to one that emphasizes symptom management, emotional and spiritual support and patient-centered care. Moreover, this transition is challenging due to the need to balance life-sustaining treatments with the goals of comfort and dignity. The concept of EoL care varies across countries and is influenced by cultural, ethical and legal factors.

Methods: This narrative review examines palliative and EoL care in critically ill cardiac patients, including those with advanced heart failure, cardiogenic shock and other acute or chronic cardiac conditions, with a focus on models of care, multidisciplinary team involvement, ethical challenges and barriers to implementation in the CICU setting.

Results: Key candidates for palliative care (PC) in heart disease include patients with advanced heart failure, cardiogenic shock and other acute or chronic cardiac conditions; however, its implementation remains limited compared to other disciplines, such as oncology. In EoL care, multidisciplinary teams, including cardiologists, nurses, PC specialists and social workers, play a crucial role in providing holistic care. Effective communication with patients and their families is essential for aligning treatment with individual values and goals. Ethical dilemmas, such as the withdrawal of life-sustaining treatments and the deactivation of implanted cardiac devices, require compassionate and transparent decision-making. Unlike previous reviews, this work specifically highlights the timing of palliative care integration as the main factor influencing patient outcomes and family experience.

Conclusions: Timely integration of palliative care in the CICU remains a major challenge. Significant gaps persist in training, resource allocation and quality indicators for palliative and EoL care. Addressing these shortcomings through enhanced education, standardized protocols and rigorous research is essential to ensure the effective delivery of PC in the CICU setting.