Cristian David Castro Hernandez

Pharmacogenomic variability represents an increasingly relevant determinant of therapeutic response, drug toxicity, and treatment failure in emergency and internal medicine. This study analyzed the clinical applicability of actionable gene–drug interactions associated with acute pharmacological decision-making, severe adverse drug reactions, and the potential integration of genomic information into emergency-care workflows. A structured integrative review based on the Scientific Method was conducted using pharmacogenomic guidelines, implementation studies, regulatory resources, and clinically oriented evidence. Particular attention was given to associations involving CYP2D6, CYP2C19, CYP2C9, VKORC1, G6PD, RYR1, CACNA1S, HLA-B, SLCO1B1, TPMT, and NUDT15. The evidence demonstrated that pharmacogenomic-guided prescribing can be associated with measurable differences in medication safety. In the PREPARE study, clinically relevant adverse drug reactions occurred in 21.0% of patients managed with genotype-guided treatment compared with 27.7% receiving standard care. In an emergency department cohort, actionable pharmacogenomic variants were identified in 99% of patients, while clinically relevant gene–drug pairs were detected in 53%. The analyzed interactions were mainly associated with altered drug metabolism, modified pharmacological sensitivity, severe genetically mediated adverse reactions, and delayed toxicities capable of producing acute-care presentations. Pharmacogenomic information showed potential utility for medication selection, dose modification, drug avoidance, risk stratification, and prevention of recurrent adverse events. Nevertheless, its clinical value depends on integration with renal and hepatic function, comorbidities, drug interactions, disease severity, and conventional emergency assessment. Preemptive testing integrated into electronic health records appears to be one of the most feasible models for emergency implementation because it allows actionable results to be available before time-sensitive treatment decisions. Pharmacogenomics may therefore contribute to a more preventive, individualized, and precise approach to medication safety in acute care, although prospective emergency-specific studies, interoperable systems, population-diverse validation, and equitable access remain necessary for broader implementation.

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.

Antimicrobial resistance represents a growing challenge in the management of community-acquired sepsis because it reduces the effectiveness of conventional empirical therapy and increases the complexity of initial clinical decision-making. This study analyzed the relationship between antimicrobial resistance, epidemiological surveillance, empirical antimicrobial treatment, and antimicrobial stewardship in adult patients with community-acquired sepsis. A structured integrative review based on the Scientific Method was conducted using scientific literature, clinical guidelines, and international surveillance reports. The evidence showed that resistant microorganisms are increasingly relevant in community-onset infections and that both inadequate initial antimicrobial coverage and unnecessarily broad-spectrum therapy may be associated with unfavorable clinical outcomes. Previous antimicrobial exposure, history of resistant organisms, prior Gram-negative infections, infection source, and local susceptibility patterns were identified as important variables for estimating the probability of resistance. Epidemiological surveillance and local antibiograms were essential for guiding empirical therapy, while microbiological reassessment and antimicrobial de-escalation contributed to reducing unnecessary exposure. Procalcitonin-guided strategies were also associated with shorter antibiotic treatment duration when integrated with clinical judgment. Overall, the findings support an individualized approach based on early recognition of sepsis, appropriate empirical treatment, assessment of resistance risk, microbiological diagnosis, and systematic therapeutic reassessment. Integrating clinical management with surveillance and antimicrobial stewardship may improve therapeutic precision while contributing to the preservation of antimicrobial effectiveness.