Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), exert a wide range of beneficial effects beyond glycemic control, largely mediated by their anti-inflammatory properties. Chronic low-grade inflammation is a common pathological mechanism underlying metabolic, cardiovascular, hepatic, and neurodegenerative diseases. GLP-1RAs reduce systemic and tissue-specific inflammation through both direct and indirect mechanisms, including inhibition of nuclear factor kappa B signaling, reduction of proinflammatory cytokines, and modulation of immune cell activity, such as that of macrophages and microglia. In type 2 diabetes and obesity, GLP-1RAs improve insulin sensitivity and endothelial function by attenuating inflammation. In metabolic dysfunction-associated steatotic liver disease, GLP-1RAs reduce hepatic steatosis and fibrosis by modulating inflammation in hepatocytes and Kupffer cells. In cardiovascular disease, they mitigate atherosclerosis progression and improve vascular health. GLP-1RAs also exert direct nephroprotective effects by reducing renal inflammation, oxidative stress, and glomerular hyperfiltration in both diabetic and nondiabetic models. GLP-RAs have been also associated with the preservation of cognitive and motor function. Preclinical studies suggest that these neuroprotective effects may involve the attenuation of neuroinflammation and reduced aggregation of pathological proteins. Overall, these pleiotropic actions position incretin-based therapies as promising tools for the management of complex chronic diseases with an inflammatory component.

Background/Objectives: The presence of distant metastases is the main cause of death in medullary thyroid carcinoma (MTC). However, due to the rarity of this cancer, few studies have thoroughly analyzed the variables influencing the development of distant metastases. The objective of this study was to evaluate, in patients with MTC, the factors associated with the occurrence of synchronous and metachronous distant metastases. Methods: An analytical, observational, retrospective cohort study was conducted at a tertiary hospital. Patients with histologically confirmed MTC, both sporadic and familial (MEN2 syndrome), were included. The influence of epidemiological variables, heredity, complementary tests, surgical factors, histological features, staging, and disease progression was assessed. A univariate comparative analysis was first performed, followed by a multivariate analysis using logistic regression. Results: This study included 146 patients, of whom 75% (n = 109) had familial MTC. Lymph node involvement at diagnosis was observed in 36% (n = 52). During follow-up, distant metastases developed in 14% (n = 21) of patients, including five cases present at the time of diagnosis. The median follow-up was 214 months (IQR 106–289). The presence of distant metastases was associated with an increased risk of mortality. Factors associated with distant metastases included age, calcitonin level, hereditary status, lymph node involvement, and overall stage. In multivariate analysis, the lymph node ratio (LNR) remained the only significant predictor (OR 29.124). Conclusions: Several variables were related to the presence of distant metastases. Among them, the LNR emerged as the independent predictor of both synchronous and metachronous distant metastases.

Background/Objectives: Obesity is an increasingly concerning public health issue due to its high prevalence and its association with multiple comorbidities. A significant proportion of patients with obesity who undergo bariatric surgery could exhibit suboptimal mid-term outcomes. This study aims to comprehensively assess anthropometric, clinical, biochemical, nutritional, and quality of life parameters in patients with severe obesity undergoing bariatric surgery, with a particular focus on outcomes at 24 months post-surgery to capture mid-term effects that may not be apparent during the first year of follow-up. Methods: A prospective study was conducted in 95 patients with obesity undergoing bariatric surgery (Roux-en Y gastric bypass; RYGB) at the Virgen de la Arrixaca University Clinical Hospital (Murcia, Spain) between 2020 and 2023. Participants were followed up at 6, 12, and 24 months after RYGB. The study incorporated anthropometric assessments (BMI, body composition via bioelectrical impedance), full biochemical profiling, dietary analysis (using a validated food frequency questionnaire), and quality of life assessment (SF-36 questionnaire). Results: Our results showed significant weight loss after the intervention, accompanied by improvements in metabolic parameters, and dietary habits. Regarding quality of life, significant improvements were observed in both the physical (baseline: 39.62%; 6 months: 52.40%; 12 months: 53.12%) and mental components (baseline: 42.08; 6 months: 53.40; 12 months: 52.14%) at 6 and 12 months post-surgery. However, our prospective 24-month follow-up revealed that, despite these initial benefits, mental health significantly declined compared with the 12-month follow-up (24 months: 46.85%). In contrast, the physical component remained relatively stable at 24 months (24 months: 50.91%). However, our prospective 24-month follow-up revealed that, despite these initial benefits, there was a decline in mental health compared to the 12-month follow-up. Conclusions: While bariatric surgery is associated with improvements in anthropometric measures and some aspects of quality of life, our findings underscore the need for continued mid-term support to address emerging challenges in mental well-being.

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Case report: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: This case illustrates the diagnostic value of chronic hypophosphatemia as an early biochemical clue to PHPT, preceding hypercalcemia by nearly a decade. Recognition of this underappreciated marker may prevent delays in diagnosis and treatment.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic liver disease with increasing prevalence worldwide. Increasing evidence suggests that short-chain fatty acids (SCFAs) play an important role in MASLD. Medium-chain fatty acids (MCFAs), although less studied, may also contribute to MASLD pathogenesis. The aim of this study was to evaluate plasma SCFA and MCFA profiles across the MASLD histological spectrum and their associations with clinical, biochemical, and histopathological features of disease severity. Methods: We included 115 adults with obesity undergoing bariatric surgery. Intraoperative liver biopsies were assessed using the Steatosis, Activity, Fibrosis (SAF) score. Participants were classified as no MASLD (n = 26), metabolic dysfunction-associated steatotic liver (MASL; n = 42), or metabolic dysfunction-associated steatohepatitis (MASH; n = 47). Six SCFAs and two MCFAs were quantified in plasma by liquid chromatography–mass spectrometry. Results: Patients with MASH showed lower acetate and higher hexanoate plasma levels than those without MASLD. Acetate was inversely associated with ALT, AST, GGT, glucose, HbA1c, cytokeratin-18, SAF score, steatosis and lobular inflammation, whereas hexanoate was positively associated with SAF score and lobular inflammation. Higher acetate concentrations were independently associated with lower odds of MASH (OR 0.973; p = 0.040), while ALT levels were independently associated with increased odds of MASH (OR 1.083, p = 0.001). Conclusions: MASH in patients with obesity is characterized by a distinct circulating fatty acid profile, with reduced acetate and increased hexanoate. Lower acetate levels were independently associated with MASH and markers of metabolic and histological disease severity.

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Methods: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Results: Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: Hypophosphatemia may serve as a complementary biomarker in the diagnostic and therapeutic approach to PHPT, but only after other potential causes of low phosphate levels have been excluded, as illustrated in this case. Its consideration could facilitate the early identification of PHPT and improve clinical decision-making, particularly in patients who do not meet classical surgical indications.