Background: Oxidative stress plays a significant role in inflammatory bowel disease (IBD), yet the clinical relevance of specific lipid peroxidation markers remains insufficiently defined. This study evaluated serum levels of 8-epi-prostaglandin F2α (8-epi-PGF2α), an isoprostane generated through non-enzymatic lipid oxidation, and examined its relationship with antioxidant enzymes and clinical disease activity in ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Eighty-seven patients (55 UC and 32 CD) were assessed for serum 8-epi-PGF2α, superoxide dismutase 1 (SOD1), and glutathione peroxidase 1 (GPX1), and classified as having mild, moderate, or severe disease. Statistical analyses included comparative analysis, two-way ANOVA, multiple linear regression, and Ridge logistic regression. To address potential dietary confounding, total energy intake, Mediterranean Diet Score (MDS), and antioxidant supplement use were incorporated into the regression models. Results: Serum levels of 8-epi-PGF2α and GPX1 were significantly higher in UC than in CD (ρ = 0.001 and p = 0.042), and both increased with greater disease severity (p < 0.001 and p = 0.001). In UC, 8-epi-PGF2α positively correlated with high-sensitivity C-reactive protein (hs-CRP), white blood cells (WBC), and Truelove–Witts Index (TWI), and negatively with hemoglobin (False Discovery Rate (FDR)-adjusted q < 0.100). In CD, it correlated with the Harvey–Bradshaw Index (HBI) and disease duration (FDR-adjusted q < 0.050). Inter-biomarker analyses showed a strong association between 8-epi-PGF2α and GPX1 in UC (ρ = 0.677, p < 0.0001, FDR < 0.0001), suggesting coordinated activation of oxidative and antioxidant pathways. The observed associations remained consistent after adjustment for dietary factors, supporting the robustness of the findings. Because these results are cross-sectional, they cannot establish causality and should be interpreted with caution. Conclusions: Nevertheless, 8-epi-PGF2α emerges as a promising non-invasive biomarker for assessing oxidative stress and disease activity in IBD, with potential clinical applicability for patient monitoring and therapeutic evaluation.

Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and share a common cardiometabolic substrate through a shared cardiometabolic substrate. This narrative review critically appraises the epidemiological, experimental, and interventional evidence proposed to link chronic intermittent hypoxia (CIH) and sleep fragmentation to hepatic steatosis, steatohepatitis, and fibrosis. We summarize the candidate mechanisms, including mitochondrial oxidative stress, hypoxia-inducible factor 1-alpha signaling, sympathetically driven lipolysis, and Kupffer and stellate cell activation and then examine the limits of the evidence supporting them: hypoxia-induced hypophagia and the scarcity of pair-fed controls in rodent models, species differences in the physiological response to hypoxia, publication bias, common-cause confounding by age and systemic inflammation, and the rarity of progressive liver disease in lean patients with anatomically driven OSA. We further review non-invasive diagnostic tools, polysomnographic hypoxemia indices, transient elastography, METS-IR, FIB-4, and emerging biomarkers, such as omentin-1 and follistatin-like 1, that enable bidirectional screening between sleep and hepatology clinics. Finally, we discuss therapeutic strategies, including continuous positive airway pressure, structured weight loss, and incretin-based pharmacotherapy (GLP-1 and dual GIP/GLP-1 receptor agonists), highlighting recent phase 3 evidence for tirzepatide in OSA and semaglutide in metabolic dysfunction-associated steatohepatitis. Current evidence supports CIH as a context-dependent amplifier of liver injury in patients with pre-existing metabolic dysfunction rather than as an established independent cause of MASH. This interpretation still justifies integrated screening and treatment pathways, while identifying the study designs needed to test causality directly.

Colorectal cancer (CRC) is accompanied by substantial psychological, metabolic, inflammatory, and endocrine disturbances that may evolve throughout diagnosis, treatment, and disease progression. Psychological distress and circadian disruption can influence hypothalamic–pituitary–adrenal (HPA) axis activity, while systemic illness, inflammation, nutritional deterioration, and anticancer therapies may concurrently modify hypothalamic–pituitary–thyroid (HPT) axis function. This narrative review critically examines how these interconnected processes can be assessed and interpreted in patients with CRC, with particular attention to psychological stress, cortisol dynamics, allostatic load, systemic thyroid parameters, treatment-related endocrine dysfunction, and tumor-specific thyroid signaling. Structured PubMed/MEDLINE search prioritized evidence published between January 2020 and July 2026, supplemented by selected earlier landmark studies. Current evidence indicates that psychological distress is clinically relevant across the CRC trajectory, whereas altered cortisol rhythms and increased allostatic burden may provide complementary information on neuroendocrine and multisystem adaptation. Reduced FT3 concentrations and FT3/FT4 ratios have been associated with adverse clinical outcomes, but their interpretation is complicated by non-thyroidal illness syndrome, systemic inflammation, nutritional status, disease burden, and treatment exposure. Importantly, circulating thyroid parameters should not be considered direct surrogates of thyroid hormone activity within the tumor microenvironment, where deiodinases, thyroid hormone receptors, integrin αvβ3, WNT/β-catenin signaling, stromal metabolism, and local TSH–TSHR interactions may independently modify tumor behavior and antitumor immunity. Emerging evidence involving SP/NK-1R and CGRP/CRLR signaling further suggests that neuropeptide pathways may contribute to systemic–tumor communication in CRC. Overall, these findings support a multidimensional clinical framework rather than interpretation of isolated stress or endocrine biomarkers. Prospective longitudinal studies integrating validated psychometric assessment, circadian and endocrine profiling, inflammatory and nutritional status, treatment exposure, and matched tumor analyses are required to determine whether neuroendocrine phenotypes provide prognostic or predictive information beyond established clinicopathological factors.

Background/Objectives: Heart failure (HF) is a systemic syndrome in which congestion, hypoperfusion, inflammation and neurohormonal activation may affect the liver, splanchnic circulation, intestinal barrier, pancreas, biliary system and nutritional state. This systematic review synthesised clinical evidence on digestive-system involvement in adults with established HF and examined its diagnostic and prognostic implications within a cautious cardio-gastrointestinal syndrome (CGIS) framework. Methods: The structured synthesis was based on an audited historical review register. The original project record reported 815 records before deduplication, although source-specific yields and the citation-level deduplication trail could not be reconstructed from the preserved files. A reproducibility–validation rerun was executed on 8 August 2026 in PubMed/MEDLINE, Scopus and Web of Science Core Collection, targeting literature through 1 July 2026; exact day-level cutoff reproducibility differed by database. The rerun recovered all ten benchmark reference-set reports but was not used to redefine the historical corpus and does not establish search exhaustiveness. The final 29-report register was re-audited for eligibility, design, analysed sample, principal findings and cohort overlap. Owing to substantial heterogeneity, findings were synthesised narratively. Results: 29 eligible reports represented approximately 26 cohort families. Hepatic and splanchnic involvement was the most mature evidence cluster, followed by intestinal congestion/barrier dysfunction. Pancreatic, biliary, microbiota and nutritional findings were less independently replicated. Liver biochemistry, composite hepatic scores and venous Doppler phenotypes showed marker-specific prognostic associations. Intestinal oedema was associated with impaired oral diuretic response. Direct pancreatic exocrine-insufficiency evidence was limited to faecal-elastase assessment. Conclusions: Digestive involvement in HF is clinically coherent but unevenly evidenced. CGIS is best regarded as a hypothesis-generating framework rather than a validated diagnostic entity, and prospective standardised studies are required before organ-specific biomarkers or imaging thresholds enter routine algorithms.

Paraneoplastic endocrine syndromes (PESs) are hormonal disturbances associated with malignancies that result from tumor-related production of hormone-like substances, immune-mediated mechanisms, or dysregulated signaling pathways. While they are well recognized in lung and neuroendocrine cancers, their relevance in gastrointestinal tumors remains less clearly defined. This narrative review synthesizes current knowledge on paraneoplastic endocrine manifestations in gastrointestinal malignancies, based on a structured search of the literature in major databases, including PubMed, Scopus, and Web of Science. The analysis focuses on clinically relevant syndromes such as hypercalcemia, Cushing-like manifestations, disorders of water balance, hypoglycemia, and acromegaly, with emphasis on underlying mechanisms, associated tumor types, diagnostic approaches, and therapeutic considerations. Available evidence indicates that gastrointestinal tumors can produce a range of biologically active substances, leading to diverse endocrine manifestations that may precede tumor detection and influence disease course. Among these, hypercalcemia and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) are among the most frequently reported, while other syndromes, such as ectopic Cushing syndrome or tumor-related hypoglycemia, are less common but often associated with more severe clinical outcomes. Recognition of these manifestations has direct clinical implications, as they may support earlier diagnosis, contribute to prognostic assessment, and guide therapeutic management. Improved awareness and a multidisciplinary approach remain essential for optimizing outcomes in patients with gastrointestinal malignancies.

Obstructive sleep apnea (OSA) is strongly associated with hypertension, yet the apnea–hypopnea index (AHI), while it defines the presence and frequency of respiratory events, predicts cardiovascular risk less reliably in the individual patient than metrics that incorporate the depth and duration of hypoxic exposure. Patients with comparable AHI values can differ substantially in nocturnal hypoxemia, sympathetic activation, ambulatory blood pressure behavior, and target-organ damage, exposing a persistent gap between respiratory classification and cardiovascular prognosis. This review synthesizes current evidence on the mechanisms linking OSA to hypertension, intermittent hypoxia, chemoreflex-mediated sympathetic overactivity, renin–angiotensin–aldosterone system activation, hypoxia-associated insulin resistance and examines emerging metrics, including hypoxic burden, oxygen desaturation index, and ambulatory blood pressure monitoring, that capture cardiovascular risk more accurately than AHI alone. We describe six cardiovascular phenotypes of hypertension in OSA: resistant, nocturnal, non-dipping/reverse-dipping, masked, and morning-surge hypertension, alongside hypertension-mediated target-organ damage, each with distinct mechanisms, prognosis, and treatment response. Because intermittent hypoxia and sympathetic activation are also implicated in insulin resistance and MASLD, this shared metabolic pathway is integrated throughout rather than treated as an incidental comorbidity. Building on this evidence, we propose a phenotype-oriented clinical framework spanning cardiovascular screening, multidomain phenotyping, risk stratification, and personalized therapy intended to complement, not replace, AHI-based diagnosis and current hypertension guidelines. This framework is presented as a conceptual, expert-derived proposal intended to structure clinical reasoning, and it has not been derived from or validated in an independent cohort. We conclude with future directions, including digital biomarkers, multimodal imaging, and artificial intelligence-assisted phenotyping, as pathways toward precision cardiovascular medicine in hypertensive patients with OSA.