Cristóbal Washington Franco Lucas

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent metabolic disorder characterized by substantial clinical heterogeneity and frequent association with obesity, insulin resistance, type 2 diabetes mellitus, dyslipidemia, visceral adiposity, and alterations in body composition. This study analyzed the principal clinical phenotypes of MASLD and their relationship with personalized nutritional interventions through a structured analytical review of clinical guidelines, systematic reviews, meta-analyses, randomized controlled trials, and observational studies. The evidence showed marked differences in disease prevalence and metabolic characteristics across lean, overweight, obese, and diabetic populations. Sustained weight loss was associated with progressive hepatic improvement, with reductions of approximately 5% linked to decreased liver fat, 7–10% to improvement in inflammatory activity, and reductions of 10% or greater to greater probability of fibrosis improvement. Dietary quality was also relevant independently of absolute weight reduction, particularly through Mediterranean-style patterns, reduced intake of added sugars and ultra-processed foods, and replacement of saturated fats with unsaturated sources. Lean MASLD represented a distinct phenotype in which metabolic dysfunction may persist despite normal body mass index, requiring greater emphasis on body composition, visceral adiposity, physical activity, and preservation of lean mass rather than aggressive caloric restriction. Overall, the findings support a phenotype-oriented model of nutritional management in which common evidence-based lifestyle principles are maintained while the intensity and priority of specific interventions are adapted to individual metabolic, hepatic, anthropometric, and behavioral characteristics. Further prospective studies are required to determine whether personalized nutritional strategies improve long-term fibrosis progression, cardiovascular outcomes, liver-related complications, and mortality.

Cardiorenal syndrome represents a complex clinical condition resulting from bidirectional interactions between cardiac and renal dysfunction and is particularly relevant in patients with multimorbidity, in whom heart failure, chronic kidney disease, diabetes mellitus, hypertension, obesity, and vascular disease frequently coexist. This study analyzed current evidence regarding emerging biomarkers, prognostic stratification, and integrated therapeutic approaches in adult patients with cardiorenal syndrome and multimorbidity. A structured integrative review based on the Scientific Method was conducted using contemporary clinical guidelines, scientific statements, randomized controlled trials, observational studies, and biomarker investigations. The analysis focused on conventional parameters and emerging biomarkers associated with glomerular filtration, tubular injury, myocardial stress, inflammation, and fibrosis. Cystatin C showed its greatest relevance as a complementary marker of glomerular function, while NGAL and KIM-1 were predominantly associated with tubular injury. NT-proBNP was mainly related to myocardial stress and congestion, whereas sST2 and galectin-3 provided additional information regarding inflammatory and fibrotic remodeling. Prognostic assessment demonstrated that declining estimated glomerular filtration rate, increased albuminuria, persistent congestion, recurrent heart failure decompensation, biomarker abnormalities, and greater multimorbidity burden were consistently associated with adverse cardiorenal outcomes. Therapeutic evidence from major randomized trials showed that sodium–glucose cotransporter-2 inhibitors significantly reduced major kidney and cardiovascular events across broad chronic kidney disease populations, while finerenone demonstrated complementary renal and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease. The findings support a transition from isolated organ-based evaluation toward a multidimensional cardiorenal framework integrating renal function, cardiovascular status, metabolic disease, biomarker profiles, and therapeutic response. Emerging biomarkers may improve biological phenotyping but should currently complement rather than replace established clinical variables. Integrated, multidisciplinary management involving internal medicine, cardiology, and nephrology may provide a more coherent approach to risk stratification and individualized treatment in patients with complex cardiorenal disease.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as one of the most prevalent chronic liver diseases worldwide and represents a growing challenge for healthcare systems due to its close relationship with obesity, insulin resistance, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. This review aimed to integrate current scientific evidence regarding the epidemiology, pathophysiology, clinical progression, diagnosis, treatment, and emerging role of precision medicine in MASLD. International scientific literature was reviewed through recognized biomedical databases, incorporating original studies, systematic reviews, meta-analyses, clinical practice guidelines, and international consensus statements relevant to the disease. The evidence demonstrates a substantial global burden of MASLD, with particularly high prevalence estimates reported in Latin America and other regions experiencing rapid growth in cardiometabolic disorders. Disease progression is heterogeneous, ranging from hepatic steatosis to metabolic dysfunction-associated steatohepatitis, advanced fibrosis, cirrhosis, and hepatocellular carcinoma, with fibrosis representing one of the most important predictors of adverse clinical outcomes. Advances in non-invasive biomarkers, serum-based fibrosis scores, transient elastography, and magnetic resonance-based techniques have improved risk stratification and reduced dependence on liver biopsy. Lifestyle modification remains fundamental to treatment, while emerging pharmacological therapies provide additional opportunities for patients with specific metabolic and hepatic profiles. The integration of clinical characteristics, metabolic phenotype, fibrosis stage, imaging findings, and biological markers supports the transition toward precision medicine. MASLD should therefore be approached as a multisystem metabolic disease requiring early identification, multidisciplinary management, comprehensive cardiometabolic control, and individualized therapeutic strategies to reduce progression and long-term complications.

Chronic kidney disease (CKD) without diabetes mellitus has become an increasingly recognized clinical entity whose progression cannot be explained exclusively by traditional hemodynamic mechanisms. Growing evidence indicates that endocrine dysregulation, metabolic remodeling, mitochondrial dysfunction, chronic inflammation, oxidative stress, and altered communication between the kidney and other organ systems play fundamental roles throughout disease development and progression. The present review critically analyzes current scientific evidence regarding the endocrine and metabolic mechanisms involved in non-diabetic CKD, integrating findings from nephrology, endocrinology, and internal medicine while incorporating information relevant to Latin American populations. A narrative review based on the Scientific Method was conducted using high-quality publications retrieved from internationally recognized databases and clinical practice guidelines. The available evidence demonstrates that persistent activation of the renin–angiotensin–aldosterone system, disruption of the fibroblast growth factor 23–Klotho axis, impaired vitamin D metabolism, insulin resistance, obesity-related endocrine alterations, mitochondrial dysfunction, and gut–kidney interactions contribute substantially to renal fibrosis, progressive loss of kidney function, and cardiovascular complications. Contemporary therapeutic approaches, particularly sodium–glucose cotransporter-2 inhibitors, have significantly modified disease management by providing nephroprotective effects beyond glycemic control. Emerging biomarkers and precision medicine strategies also show considerable potential for improving early diagnosis, individualized risk assessment, and targeted therapeutic interventions. Nevertheless, additional multicenter studies, particularly involving underrepresented regions such as Latin America, remain necessary to strengthen the current evidence base. Overall, non-diabetic CKD should be regarded as a complex multisystem disorder requiring an integrated clinical approach that combines endocrine, metabolic, cardiovascular, and nephrological perspectives to optimize patient outcomes.

Cardiorenal syndrome associated with type 2 diabetes mellitus has emerged as a major global health challenge due to its increasing prevalence, complex pathophysiology, and significant impact on morbidity and mortality. The interaction between cardiovascular disease, chronic kidney disease, and metabolic dysfunction creates a bidirectional cycle of organ damage mediated by inflammation, oxidative stress, endothelial dysfunction, neurohormonal activation, and fibrosis. This review analyzes current evidence regarding the mechanisms linking diabetes with cardiovascular and renal deterioration, emphasizing the concept of the cardiorenal-metabolic continuum. A comprehensive review of contemporary literature was conducted using international scientific databases and clinical practice guidelines. The findings indicate that recent therapeutic advances, particularly sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists, have significantly improved cardiovascular and renal outcomes while reducing disease progression and hospitalization rates. Despite these advances, substantial challenges remain regarding early diagnosis, treatment accessibility, therapeutic implementation, and healthcare disparities. These challenges are especially relevant in Latin American countries, including Mexico, Colombia, and Ecuador, where the burden of diabetes and chronic kidney disease continues to rise. Current evidence supports the adoption of integrated multidisciplinary approaches focused on early detection, comprehensive risk assessment, and evidence-based therapeutic interventions. The transition from organ-centered management toward a cardiorenal-metabolic model represents a fundamental paradigm shift that may contribute to improved patient survival, preservation of organ function, and enhanced quality of life.

Hypoxia is a complex multisystemic condition characterized by insufficient oxygen availability at the tissue level, producing progressive dysfunction involving the pulmonary, cardiovascular, and neurological systems. Although traditionally associated with respiratory failure, contemporary evidence demonstrates that hypoxia activates interconnected physiological, inflammatory, vascular, metabolic, and neurological pathways capable of generating widespread systemic injury. The objective of this review was to analyze the principal mechanisms through which hypoxia contributes to pulmonary, cardiovascular, and neurological dysfunction, emphasizing the integrated interactions between these systems and their clinical implications in modern medicine. This review was developed using a structured narrative methodology based on scientific literature indexed in international databases including PubMed, Scopus, Google Scholar, Europe PMC, Elsevier, and SpringerLink. The investigation integrated evidence from pulmonology, cardiology, neurology, critical care medicine, and vascular physiology in order to evaluate the systemic consequences of acute, chronic, and intermittent hypoxia. Special attention was given to molecular mechanisms such as hypoxia-inducible factor activation, oxidative stress, endothelial dysfunction, autonomic imbalance, mitochondrial injury, inflammatory cytokine release, and vascular remodeling. The findings demonstrate that pulmonary dysfunction initiates hypoxemia through mechanisms including ventilation-perfusion mismatch, diffusion impairment, hypoventilation, and shunt physiology. Cardiovascular adaptation initially attempts to preserve oxygen delivery through sympathetic activation and pulmonary vasoconstriction; however, prolonged hypoxic exposure contributes to pulmonary hypertension, right ventricular overload, endothelial dysfunction, arrhythmogenic instability, and impaired systemic perfusion. Neurological consequences include neuroinflammation, excitotoxicity, cognitive impairment, cerebral autoregulatory dysfunction, and hypoxic-ischemic injury due to the high metabolic vulnerability of neuronal tissue. Intermittent hypoxia, particularly in obstructive sleep apnea, was associated with substantial cardiovascular and neurocognitive consequences related to oxidative stress and autonomic dysregulation.

Cardiorenal syndrome (CRS) represents a complex bidirectional interaction between the cardiovascular and renal systems in which dysfunction of one organ may induce or worsen dysfunction of the other. The increasing global prevalence of heart failure, chronic kidney disease, hypertension, obesity, and diabetes mellitus has significantly contributed to the growing clinical and epidemiological burden of CRS. This review aimed to analyze the principal pathophysiological mechanisms, diagnostic approaches, and contemporary therapeutic strategies associated with cardiorenal syndrome through an evidence-based analysis of current scientific literature. The study was developed as a narrative and analytical review using scientific evidence obtained from internationally recognized databases, including PubMed, Scopus, Web of Science, and high-impact journals in nephrology, cardiology, and internal medicine. The analysis focused on hemodynamic alterations, neurohormonal activation, venous congestion, inflammatory pathways, endothelial dysfunction, oxidative stress, diagnostic biomarkers, pharmacological therapies, and multidisciplinary management approaches. The reviewed evidence demonstrated that CRS is a multifactorial systemic condition involving complex interactions between cardiac and renal dysfunction. Venous congestion, activation of the renin–angiotensin–aldosterone system, sympathetic nervous system stimulation, chronic inflammation, and endothelial injury were identified as major contributors to disease progression. Biomarkers such as NT-proBNP, cystatin C, NGAL, and KIM-1 showed important diagnostic and prognostic value, although integrated clinical evaluation remains essential. Contemporary therapeutic strategies, particularly sodium-glucose cotransporter-2 inhibitors, demonstrated substantial cardiovascular and renal protective effects. Multidisciplinary care models were also associated with improved patient outcomes and optimization of long-term management. In conclusion, cardiorenal syndrome should be understood as a highly dynamic and multisystemic condition requiring integrated cardiovascular and renal assessment. Early diagnosis, evidence-based therapy, preventive medicine, and multidisciplinary collaboration remain fundamental for improving prognosis and reducing the global burden associated with CRS.

Complex multimorbidity has become a defining feature of contemporary internal medicine, particularly within inflammatory–metabolic intersections such as dermatologic and endocrine disorders. As chronic conditions cluster in structured cardiometabolic networks, traditional disease-specific guideline approaches increasingly generate therapeutic conflict, polypharmacy, and reduced predictive accuracy in high-complexity patients. This study developed and evaluated an integrated precision decision-making framework designed to reconcile inflammatory burden, endocrine dysregulation, cardiovascular risk stratification, medication safety, and patient-centered prioritization within a unified clinical model. Multidimensional analysis demonstrated coherent cardiometabolic clustering with measurable inflammatory–metabolic overlap. As multimorbidity complexity increased, medication burden, adverse drug event risk, and guideline conflict rose progressively under traditional management approaches, while predictive discrimination declined. In contrast, the integrated precision framework showed lower conflict indices and improved predictive performance across escalating strata of complexity. Outcome prioritization analysis revealed a structured distribution balancing cardiovascular stabilization, metabolic control, inflammatory skin management, polypharmacy reduction, and quality-of-life considerations. These findings support the transition from fragmented, disease-centered optimization toward an integrated, value-based, and precision-guided model of internal medicine capable of addressing the biological and therapeutic interdependence characteristic of complex chronic disease networks.

Neuroimmune interactions have emerged as a central framework for understanding the complexity of gastrointestinal diseases, integrating immune regulation, neural signaling, and microbiota-driven mechanisms within the gut–brain axis. This review synthesizes current evidence on the role of neuroimmune pathways in both inflammatory and functional gastrointestinal disorders, with particular emphasis on inflammatory bowel disease and irritable bowel syndrome. The analyzed literature demonstrates that gastrointestinal symptom generation and disease expression result from dynamic interactions among immune cells, enteric and autonomic neural circuits, microbial signaling, and stress-related modulation rather than from isolated pathological processes. In inflammatory conditions, immune dysregulation and macrophage-mediated pathways predominate, while neural and autonomic mechanisms contribute to symptom persistence and variability. In functional disorders, immune–neural coupling, mast cell–nerve interactions, and visceral sensory sensitization emerge as key drivers of pain and altered bowel habits despite minimal structural abnormalities. Across both disease categories, the intestinal microbiota acts as a cross-cutting regulator influencing immune tone, barrier integrity, and neural responsiveness. From a clinical and diagnostic perspective, these findings support a mechanism-based approach that complements traditional inflammatory and structural assessments with neuroimmune-informed reasoning. This integrative framework has particular relevance for medical education and clinical practice in diverse healthcare settings, including Latin America, where resource variability necessitates strong pathophysiological interpretation. Overall, neuroimmune models provide a coherent and biologically grounded perspective for advancing diagnosis, teaching, and future translational strategies in gastroenterology.

Cardiovascular disease remains the leading cause of mortality worldwide, despite significant advances in prevention and treatment strategies. Increasing evidence indicates that traditional risk factors alone are insufficient to fully explain cardiovascular risk, highlighting the importance of inflammatory and metabolic mechanisms in the development and progression of atherosclerotic disease. This review synthesizes current scientific evidence on the role of chronic low-grade inflammation and metabolic dysregulation as interconnected determinants of cardiovascular risk. The analysis integrates mechanistic, clinical, and population-level data describing how immune activation, insulin resistance, obesity, metabolic syndrome, and endothelial dysfunction interact to promote atherosclerosis and related cardiovascular outcomes. Particular attention is given to inflammatory signaling pathways, immune cell involvement, and the concept of residual inflammatory risk, which persists even in the presence of optimal lipid control. Additionally, the review examines the contribution of lifestyle factors as upstream modulators of immunometabolic processes. By adopting an integrative immunometabolic perspective, this review provides a comprehensive framework for understanding cardiovascular risk beyond conventional models. This approach is especially relevant for educational and clinical contexts in regions undergoing epidemiological transition, including Mexico, Colombia, and Ecuador. The findings support the incorporation of inflammatory and metabolic determinants into cardiovascular risk assessment, prevention strategies, and future research agendas.