Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the skin. This congenital disease results from a mutation in the ABCA12 gene responsible for lipid transport, whereby healthy skin development is assured. Harlequin ichthyosis is an autosomal recessive condition that requires parents to carry a defective gene copy for the disorder to manifest in their offspring. Babies born with Harlequin ichthyosis have thick skin plates that crack and flake off; they easily become dehydrated, infected, and may suffer from respiratory complications. With new improvements in neonatal care and systemic therapy, notably retinoid therapy, infants’ survival rates have improved. This review provides an inclusive overview of the pathophysiology, clinical features, diagnostic methods, management, and potential future therapies for Harlequin ichthyosis. In addition, a discussion on genetic counseling and its importance in managing family risk factors is also included, as well as a look into cutting-edge research focused on gene therapy and potential curative treatments.

Neurodegenerative diseases (NDs) represent a major global health challenge in aging populations, with their incidence continuing to rise worldwide. Although substantial progress has been made in elucidating the clinical features and molecular underpinnings of these disorders, the precise mechanisms driving neurodegeneration remain incompletely understood. This review examines the increasing significance of the gut–brain–immune triad in the pathogenesis of NDs, with particular attention to Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. It explores how disruptions in gut microbiota composition and function influence neuroinflammation, blood–brain barrier integrity, and immune modulation through microbial-derived metabolites, including short-chain fatty acids, lipopolysaccharides, and bacterial amyloids. In both Alzheimer’s and Parkinson’s diseases, a reduced abundance of short-chain fatty acid-producing bacterial taxa has been consistently associated with heightened pro-inflammatory signaling, thereby facilitating disease progression. Although detailed mechanistic understanding remains limited, experimental evidence—primarily from rodent models—indicates that microbial metabolites derived from a dysbiotic gut may initiate or aggravate central nervous system dysfunctions, such as neuroinflammation, synaptic dysregulation, neuronal degeneration, and disruptions in neurotransmitter signaling via vagal, humoral, and immune-mediated pathways. The review further highlights how gut microbiota alterations in amyotrophic lateral sclerosis and multiple sclerosis contribute to dysregulated T cell polarization, glial cell activation, and central nervous system inflammation, implicating microbial factors in disease pathophysiology. In addition to identifying critical knowledge gaps, the review emphasizes the need for sustained, multifactorial research efforts, including the development of physiologically relevant brain–gut organoid models and the implementation of standardized experimental protocols. A major limitation in the field remains the difficulty of establishing causality, as clinical manifestations often arise after extended preclinical phases—lasting years or decades—during which aging, dietary patterns, pharmacological exposures, environmental factors, and comorbidities collectively modulate the gut microbiome. Finally, the review discusses how microbial influences on host epigenetic regulation may offer innovative avenues for modulating neuroimmune dynamics, underscoring the therapeutic potential of targeted microbiome-based interventions in neurodegenerative diseases.

Celiac disease is a chronic, immune-mediated enteropathy precipitated by gluten exposure in genetically predisposed individuals, with a global prevalence of approximately 1%. Though diagnostic workflows incorporate serologic techniques with both histologic and genetic evaluation, each approach carries key pitfalls that contribute to diagnostic inaccuracy. Serology testing is limited by selective immunoglobulin A deficiency and low-titer antibodies, in addition to interlaboratory variability of calibration standards and specimen concentrations. While duodenal biopsy is considered the gold standard for celiac diagnosis, patchy villous atrophy (e.g., ultrashort celiac disease) mimics other enteropathies, and the inherent subjectivity of histologic interpretation can compromise accuracy. Furthermore, celiac predisposition is highly correlated with two human leukocyte antigen (HLA) alleles, HLA-DQ2 and HLA-DQ8. However, nearly 30–40% of the general population expresses one of these alleles, thus introducing the risk of overdiagnosis and limiting the practical implications of genetic testing. There exist special celiac presentations, such as seronegative or potential celiac disease, overlap syndromes, and enteropathy-associated T-cell lymphoma, that introduce additional challenges to diagnostic success. The serologic-histologic discordance and nonspecific symptoms associated with these cases may require divergence from the traditional workflow, as well as supplemental investigations, such as a gluten challenge or breath testing, to confirm a celiac diagnosis. These challenges in celiac diagnosis have driven research into novel biomarkers and molecular assays that can not only enable earlier, more accurate detection but also provide longitudinal disease monitoring. Such markers include intestinal fatty acid-binding proteins, specific microRNA expression, and microbiome signatures that are strongly linked to celiac disease, which may one day serve as adjunctive screening tools to optimize diagnostic yield. This narrative review identifies the key pitfalls in adult celiac disease diagnosis — from pre-analytic serology issues to patchy histology and overinterpretation of HLA — and proposes a guideline-aligned, stepwise algorithm (with emerging biomarkers) to enhance accuracy and reduce missed or delayed cases. Ultimately, continued refinement of a comprehensive, multimodal diagnostic strategy that can integrate with emerging molecular tools is necessary for overcoming the current limitations of individual approaches to celiac diagnosis.

Identifying patients at high risk for poor bowel preparation preceding a colonoscopy is critical to successful colorectal cancer screening. High-risk patients, such as those who are obese, diabetic, opioid users, or former smokers, often have comorbidity, medication, and sociodemographic factors that lead to suboptimal bowel preparation even when following protocol. Suboptimal preparation results in missed lesions, longer procedure times, and increased healthcare costs. Optimal visualization of the colon mucosa is achieved through effective bowel preparation. Polyethylene glycol (PEG) solutions are preferred for their safety, especially in patients with kidney or cardiac disease. Split-dose PEG regimens with a low-residue diet are recommended by the American Gastroenterological Association to promote cleansing and patient tolerance. Tailored regimens can be employed in high-risk patients, including those with chronic constipation, opioid dependence, or diabetes. Educational interventions, such as written and verbal instructions, patient navigators, and mobile device reminders, improve compliance. Medical strategies include split-dose PEG-electrolyte lavage solution with bisacodyl, additional purgatives for select patients, and avoidance of sodium phosphate in elderly or renally impaired individuals. Open-access colonoscopy services have expanded following the COVID-19 pandemic to manage backlogs and improve access. Improving education, simplifying regimens, and targeting interventions can reduce repeat procedures and enhance colorectal cancer detection. This narrative review summarizes patient-, medication-, and system-level risk factors for inadequate bowel preparation in high-risk populations and synthesizes practical, evidence-based strategies to optimize colonoscopy quality, including in open-access settings.

Nutrition plays a pivotal role in the prevention and management of gastrointestinal and hepatic diseases, yet dietary guidance remains generic, limiting its effectiveness. Conditions such as inflammatory bowel disease, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, celiac disease, and gastroesophageal reflux disease are significantly influenced by dietary factors. Personalized nutrition has emerged as a promising strategy to tailor interventions, but conventional approaches fail to account for individual metabolic, genetic, and microbiome variability, limiting their clinical impact. The rapid rise of artificial intelligence (AI) has transformed precision nutrition by integrating genomics, microbiome profiles, metabolic markers, and real-time dietary tracking to generate individualized recommendations. AI-driven systems are advancing dietary assessment, condition-specific nutrition optimization, and continuous monitoring through tools such as wearable devices and natural language processing-based diet analysis. These innovations hold transformative potential in gastroenterology and hepatology, offering dynamic, patient-specific strategies that may enhance clinical outcomes. However, challenges remain, including the lack of standardized AI-driven protocols, ethical concerns such as bias and data privacy, limited clinical validation, and the underrepresentation of nutrition in many current AI applications. Opportunities for progress include developing federated learning models, expanding real-world validation studies, and designing regulatory and ethical frameworks for safe implementation. This narrative review synthesizes literature published between 2015 and 2025 across five databases, highlighting key applications, limitations, and future directions of AI-driven personalized nutrition in gastroenterology and hepatology. It provides insights into how AI could reshape patient-centered care through more individualized, effective, and scalable dietary strategies.

Aging is characterized by a progressive decline in physiological function, an increased risk of chronic diseases, and multiple molecular and cellular alterations, including inflammation, oxidative stress, and mitochondrial dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, may modulate pathways associated with the hallmarks of aging. This review aims to summarize the mechanistic and therapeutic evidence for GLP-1 RAs in targeting key aging processes and their potential to restore cellular homeostasis and enhance healthspan. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025. Both preclinical and clinical studies were included if they evaluated the effects of GLP-1 RAs on the major biological processes encompassed by the 12 hallmarks of aging, such as mitochondrial dysfunction, insulin resistance, dysbiosis, inflammaging, autophagy, proteostasis, and genomic stability. Data were analyzed narratively to elucidate potential mechanisms and translational relevance. Evidence from animal and human studies demonstrates that GLP-1 RAs improve mitochondrial function, reduce oxidative stress, attenuate chronic inflammation, and enhance autophagic activity. Additionally, they modulate nutrient-sensing pathways and metabolic processes, thereby improving cellular resilience. Preclinical studies indicate neuroprotective, cardioprotective, and hepatoprotective effects, while emerging clinical data support improvements in metabolic and inflammatory profiles in older adults. Taken together, GLP-1 RAs exert pleiotropic effects across all 12 hallmarks of aging. Although long-term safety and efficacy require further evaluation, current evidence positions GLP-1 RAs as promising therapeutic agents in translational geroscience, with the potential to mitigate age-related physiological decline and promote a longer, healthier lifespan.

Craniopharyngioma (CP), although histologically benign, is a surgically challenging sellar-region tumor for which stereotactic irradiation is increasingly used as an alternative or adjuvant strategy. This review summarizes the role of stereotactic radiosurgery (SRS) in managing CP, with a focus on treatment outcomes, technical advances, and emerging strategies to support evidence-based clinical practice. Literature reports indicate that Gamma Knife radiosurgery achieves variable tumor control rates (36–100%), with optimal outcomes (79.6–91.4%) when marginal doses ≥12 Gy are delivered and patients receive adequate follow-up. Smaller tumors (<5 cm3) and those with higher solid components show particularly favorable outcomes. SRS demonstrates a favorable safety profile, with visual impairment occurring in approximately 4% of cases and endocrine dysfunction in 6%. Compared to conventional radiotherapy, SRS significantly reduces the risk of hypothalamic obesity in pediatric patients. The identification of BRAF mutations in papillary CPs has created novel opportunities for combining targeted therapies with SRS. Collectively, these advances underscore the role of SRS as an essential component of multidisciplinary CP management, particularly in the treatment of residual or recurrent lesions. It offers a more favorable toxicity profile and may improve quality of life outcomes compared to conventional radiotherapy. Further studies are needed to optimize patient selection, dosing strategies, and integration with novel systemic therapies.

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China with a high hepatitis B virus prevalence. Early-stage diagnosis remains challenging due to its asymptomatic onset and the limited sensitivity of conventional biomarkers, which together contribute to delayed detection, suboptimal therapeutic outcomes, and poor prognosis. These limitations underscore the urgent need for reliable, sensitive, and specific biomarkers to enable timely detection and targeted intervention. Protein induced by vitamin K absence or antagonist-II, an abnormal prothrombin variant generated under vitamin K deficiency or antagonism, has emerged as a promising candidate with diagnostic and therapeutic relevance in HCC. This review critically examines the molecular and biological characteristics of protein induced by vitamin K absence or antagonist-II, evaluates its clinical utility in HCC diagnosis and management, and delineates the current limitations hindering its broader application. Furthermore, future perspectives are proposed to guide translational research and clinical implementation. Collectively, this review aims to provide a comprehensive theoretical framework to advance precision diagnosis and individualized treatment strategies for HCC.

Congenital portosystemic shunts (CPSS) are rare vascular anomalies characterized by abnormal communication between the portal and systemic venous systems, resulting in partial or complete diversion of portal blood away from the liver. These shunts can give rise to a broad spectrum of clinical manifestations, including hyperammonemia (with or without encephalopathy), hepatopulmonary syndrome, and portopulmonary hypertension. Notably, these complications often occur in the absence of portal hypertension. Advances in diagnostic imaging, particularly Doppler ultrasound, computed tomographic angiography, and magnetic resonance imaging, have enhanced the early detection and classification of CPSS. Treatment approaches vary depending on shunt type and clinical severity and may include interventional closure via embolization or surgical ligation. Most persistent or symptomatic shunts require immediate intervention. Recent studies have also identified potential genetic and embryological mechanisms contributing to CPSS development, offering new insights into their pathogenesis. This review aims to summarize current knowledge on the epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and management of CPSS, and to highlight their consideration in patients with hepatic encephalopathy or unexplained liver disease.

Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders that result in chronic, predominantly conjugated hyperbilirubinemia without cholestasis or hepatocellular injury. Although both conditions are benign and non-progressive, they reflect distinct molecular defects in hepatocellular transport pathways. DJS arises from mutations in the ABCC2 gene encoding the canalicular transporter multidrug resistance–associated protein 2, leading to impaired biliary excretion of conjugated bilirubin and organic anions. In contrast, RS results from combined deficiencies of the sinusoidal transporters OATP1B1 and OATP1B3, encoded by SLCO1B1 and SLCO1B3 genes, respectively, which mediate hepatic reuptake of conjugated bilirubin from the sinusoidal blood. These defects explain the characteristic biochemical and clinical distinctions between the syndromes, including the black hepatic pigmentation and markedly elevated urinary coproporphyrin I fraction in DJS, and the absence of pigmentation with moderate coproporphyrin I predominance in RS. Recent studies have expanded the understanding of how these transporters influence not only bilirubin handling but also the hepatic disposition of various drugs and endogenous metabolites. Recognition of DJS and RS is essential to prevent misdiagnosis of cholestatic or hepatocellular disease, avoid unnecessary investigations, and anticipate altered pharmacokinetics in affected individuals. This review synthesizes current evidence from molecular, biochemical, and clinical studies to highlight how these syndromes illuminate broader principles of hepatic transporter physiology and its relevance to inherited and acquired disorders of bilirubin metabolism.