José Enrique González Araujo

The gut microbiota has emerged as a key modulator of drug metabolism, efficacy, and toxicity, adding a critical layer of complexity to pharmacological processes traditionally attributed solely to host physiology. In hepatobiliary disease, this interaction acquires particular relevance due to alterations in bile acid metabolism, intestinal barrier function, immune regulation, and enterohepatic circulation. This review synthesizes current evidence on microbiota–drug interactions within hepatobiliary contexts, integrating mechanistic, translational, and clinical data to provide a coherent pharmacological framework. The analyzed literature consistently demonstrates that intestinal microorganisms can directly biotransform xenobiotics, modify effective bioavailability, and generate metabolites with altered pharmacodynamic or toxicological properties. In parallel, microbial modulation of bile acid pools and signaling pathways indirectly influences hepatic drug-metabolizing enzymes, transporters, and inflammatory responses. The reciprocal capacity of drugs to reshape microbial composition further contributes to dynamic and time-dependent variability in drug exposure. Collectively, these mechanisms help explain interindividual differences in therapeutic response and susceptibility to adverse drug reactions that are frequently observed in hepatobiliary disease but remain insufficiently accounted for by conventional dosing paradigms. By consolidating these findings, this review highlights the gut microbiota as an integral component of hepatobiliary pharmacology and underscores its relevance for advancing more precise, individualized, and safer therapeutic strategies.

Cardiomyopathies constitute a heterogeneous group of myocardial disorders that frequently remain clinically silent until advanced stages, limiting opportunities for early intervention and prevention of adverse outcomes. Although the 12-lead electrocardiogram (ECG) is one of the most accessible diagnostic tools in cardiovascular care, its conventional interpretation has limited sensitivity for detecting early or subclinical myocardial disease. In recent years, deep-learning approaches have enabled a paradigm shift in ECG analysis by allowing the extraction of complex and subtle signal patterns associated with underlying structural and functional cardiac abnormalities. This review synthesizes current evidence on deep-learning–based ECG algorithms for the silent detection of cardiomyopathies, with particular emphasis on hypertrophic cardiomyopathy and subclinical ventricular dysfunction. The analysis highlights methodological strategies, reference standards, and validation approaches used across key studies, as well as their potential clinical and educational implications. The findings suggest that deep-learning ECG analysis can function as an effective screening and risk-stratification tool, facilitating earlier identification of individuals who may benefit from confirmatory imaging and specialist evaluation. This approach is especially relevant for healthcare systems in Mexico, Colombia, and Ecuador, where access to advanced diagnostic resources may be limited. Continued research focusing on external validation, population-specific calibration, and real-world implementation is essential to ensure safe and effective integration into clinical practice.

Metabolic frailty has traditionally been associated with older populations; however, accumulating evidence suggests that frailty-related metabolic alterations may emerge much earlier in the life course. This narrative review examines metabolic frailty in young adults as an early vulnerability state characterized by metabolic dysregulation, adverse body composition, chronic low-grade inflammation, and reduced physiological reserve, even in the absence of overt chronic disease. Drawing on international literature and integrating evidence relevant to Latin American contexts, particularly Mexico, Colombia, and Ecuador, this study synthesizes current knowledge on the biological and clinical pathways linking central adiposity, insulin resistance, sarcopenia-related changes, and cardiometabolic risk clustering to early frailty-related processes. The findings support the interpretation of metabolic frailty as a continuous, multidimensional construct that extends classical frailty frameworks beyond geriatric populations. Early identification of metabolic frailty using combined anthropometric, metabolic, and muscle-related indicators may provide a valuable opportunity to prevent or delay the onset of chronic noncommunicable diseases and preserve long-term functional capacity.

Multimorbidity has become a defining challenge for internal medicine, characterized by the coexistence of multiple chronic diseases and shaped by functional decline, treatment burden, and socioeconomic vulnerability. This review synthesizes contemporary evidence on the epidemiology, clinical consequences, and health-system implications of multimorbidity, with a particular focus on Mexico, Colombia, and Ecuador. Findings demonstrate steep age-related increases in prevalence, strong associations with mortality, hospitalization, disability, and elevated costs, and significant variability driven by methodological differences and inequities in access to care. Functional impairment consistently emerges as a central predictor of adverse outcomes, underscoring the need for geriatric-informed, person-centered approaches. Despite extensive observational research, interventional and policy-oriented studies remain limited, especially in middle-income settings. The review highlights the urgent need for integrated care models, improved coordination between internal medicine and primary care, and equity-oriented policies capable of responding to the complex trajectories of multimorbidity. By integrating theoretical, epidemiological, and health-system perspectives, this study provides a foundation for advancing research, guiding clinical decision-making, and informing system reforms in Latin American internal medicine.

Cardiovascular risk stratification is undergoing a major paradigm shift driven by advances in genomics, inflammatory profiling, imaging biomarkers, myocardial injury detection, and artificial intelligence. This review integrates evidence from twenty high-impact studies to outline a multidimensional framework for precision cardiovascular risk assessment. Genomic tools, particularly polygenic risk scores, consistently demonstrate strong predictive value and highlight substantial inherited susceptibility that traditional models often fail to detect. Inflammatory and immunometabolic markers emerge as equally central determinants, underscoring the biological complexity of atherosclerosis and the relevance of chronic immune activation. Imaging techniques and high-sensitivity biomarkers provide additional layers of subclinical resolution, while AI-enhanced electrocardiography introduces new opportunities for early detection. A temporal analysis reveals a rapid expansion of precision-oriented research after 2018, culminating in a robust evidence base that favors integrative models over single-domain predictors. The proposed conceptual framework illustrates how these domains converge to generate a richer, individualized understanding of cardiovascular risk. The discussion emphasizes translational challenges and the need for equitable implementation in diverse populations, particularly in Mexico, Colombia, and Ecuador, where structural barriers may limit access to emerging precision tools. Overall, the findings support a shift toward biologically informed, technologically augmented, and context-adapted cardiovascular prevention strategies capable of improving predictive accuracy and advancing global cardiovascular health.

The gut microbiota plays a critical role in metabolic, immune, and gastrointestinal homeostasis. Dysbiosis—characterized by reduced microbial diversity, loss of Bifidobacterium and Akkermansia muciniphila, and an increased Firmicutes/Bacteroidetes ratio—has been consistently linked to insulin resistance, chronic inflammation, and metabolic syndrome. This review analyzes multidisciplinary evidence on microbiota modulation through dietary, probiotic, postbiotic, and transplantation-based interventions, integrating findings from global research and contextualizing them within the health frameworks of Mexico, Colombia, and Ecuador. The results highlight that short-chain fatty acids (SCFAs), primarily butyrate and propionate, mediate the beneficial effects of microbial metabolism by enhancing epithelial barrier integrity, regulating appetite hormones, and reducing systemic inflammation through GPR41, GPR43, and GPR109A signaling. Clinical data demonstrate that lean-donor fecal microbiota transplantation and Akkermansia muciniphila supplementation improve insulin sensitivity and lipid metabolism, while postbiotics offer standardized, colonization-independent bioactivity. Regionally, implementation strategies should follow a tiered model: fiber-centered personalized nutrition, ISAPP-aligned microbial formulations, and ecological reset through standardized consortia or fecal microbiota transplantation in severe dysbiosis. These interventions align with the United Nations Sustainable Development Goals (SDG 3, 9, and 12) by promoting sustainable, equitable, and evidence-based healthcare. Overall, microbiota modulation represents a mechanistically grounded and culturally adaptable tool for the prevention and treatment of chronic diseases, bridging global precision medicine with local dietary and ecological realities.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a cornerstone in modern internal medicine, demonstrating multisystem benefits that extend far beyond glycemic control. This review examines their cardiovascular, renal, hepatic, and metabolic effects, integrating evidence from major clinical trials and meta-analyses. The objective was to analyze and synthesize scientific evidence on the systemic impact of GLP-1 RAs, emphasizing their mechanisms, clinical relevance, and potential integration into internal medicine and public health strategies in Latin America. A systematic literature review was conducted following the DMAIC framework (Define–Measure–Analyze–Improve–Control). Twenty peer-reviewed studies published between 2016 and 2025 were selected from PubMed, Scopus, and The Lancet databases. Data were categorized by clinical domain and analyzed for efficacy trends and mechanistic consistency. Results showed that GLP-1 RAs consistently reduced major adverse cardiovascular events, slowed chronic kidney disease progression, improved hepatic inflammation and fibrosis, and achieved sustained weight reduction of 10–17%. Their multisystem effects were mediated by endothelial restoration, anti-inflammatory modulation, and metabolic reprogramming. GLP-1 receptor agonists represent a paradigm shift in internal medicine by integrating cardiovascular, renal, hepatic, and metabolic protection into a unified therapeutic model. Their adoption in Latin American health systems could reduce premature mortality, align regional policies with Sustainable Development Goal 3, and establish GLP-1 RAs as disease-modifying agents in global chronic disease prevention.

Alzheimer’s disease (AD) represents one of the most complex neurodegenerative disorders, demanding a transition from symptom-based management toward biologically informed, patient-centered precision medicine. This review analyzes recent advances in molecular biomarkers, proteomic profiling, and monoclonal antibody therapies, integrating global evidence and expert consensus from Mexico, Colombia, and Ecuador. A systematic analysis of 24 high-impact studies published between 2018 and 2025 demonstrated that plasma and CSF biomarkers—especially p-tau217, p-tau181, and proteomic signatures—provide exceptional accuracy for early diagnosis and disease staging, surpassing traditional clinical criteria. Evidence from phase 3 trials with lecanemab and donanemab confirmed that amyloid-targeted therapies can significantly slow cognitive and functional decline when guided by validated biomarkers. Complementary Delphi consensus findings revealed strong expert agreement on adopting p-tau217 as a first-line test, incorporating APOE genotyping and MRI safety monitoring, and ensuring ethical and equitable implementation of precision medicine in Latin America. This review concludes that Alzheimer’s research is undergoing a paradigm shift toward molecular definition, individualized therapy, and ethically responsible innovation. Future efforts should focus on expanding biomarker validation in diverse populations, integrating artificial intelligence for real-time monitoring, and reinforcing multidisciplinary education. Precision medicine thus represents not only a scientific advance but also an ethical and social commitment to global equity in dementia care.

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs) has redefined cardiovascular prevention and metabolic care. This review analyzes the cardiovascular, renal, and metabolic outcomes associated with these therapies, integrating evidence from major outcome trials—LEADER, SUSTAIN-6, REWIND, AMPLITUDE-O, and SELECT—and emerging dual incretin studies such as SUMMIT and SURPASS-CVOT. Across these trials, GLP-1 RAs consistently reduced major adverse cardiovascular events (MACE), cardiovascular mortality, and kidney disease progression, demonstrating benefits that extend beyond glycemic control. Mechanistic data reveal anti-inflammatory, endothelial, and neurohumoral pathways that collectively explain their cardioprotective profile. The new generation of dual incretin agonists, exemplified by tirzepatide, provides unprecedented improvements in weight reduction, insulin sensitivity, and heart failure symptoms, marking a new frontier in cardiometabolic therapeutics. For Latin American countries, including Mexico, Colombia, and Ecuador, the clinical translation of these findings faces barriers such as high cost, limited access, and physician unfamiliarity. However, strategic health policies and regional collaboration could integrate incretin-based therapy into national cardiovascular prevention frameworks. Ultimately, incretin therapy represents a paradigm shift from glucose-centric management toward comprehensive, preventive, and equitable cardiometabolic care with global implications.

Dual GIP/GLP-1 receptor agonists have emerged as an innovative therapeutic class that combines metabolic and renal protection in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This multicenter study, conducted in Mexico, Colombia, and Ecuador, evaluated the renal and metabolic effects of dual incretin therapy compared with GLP-1 receptor agonists and standard therapy (SGLT2 inhibitors plus RAAS blockade). A total of 1,150 adults with T2DM and CKD stages 1–4 were included. The dual GIP/GLP-1 group achieved the greatest improvement in kidney outcomes, with a 29% reduction in urinary albumin-to-creatinine ratio (UACR) and the smallest annual decline in estimated glomerular filtration rate (eGFR, −1.6 mL/min/1.73 m²), compared to GLP-1 monotherapy (−2.6) and standard therapy (−3.5). Additionally, participants receiving dual agonists showed superior metabolic control, including reductions in HbA1c (−17.9%), body mass index (−10.6%), and systolic blood pressure (−9.1 mmHg). Overall, 58.9% achieved composite kidney improvement and 76.3% avoided progression to a higher KDIGO risk category. These results align with international evidence from the SURPASS and FLOW trials, confirming that dual receptor activation offers synergistic mechanisms—anti-inflammatory, antifibrotic, and hemodynamic—that extend renal protection beyond glycemic control. The findings support incorporating dual GIP/GLP-1 receptor agonists into nephrology practice as a next-generation therapy capable of modifying the natural history of diabetic kidney disease and improving long-term clinical outcomes in diverse Latin American populations.