Journal of Personalized Medicine最新文献

Background: The growing use of Emergency Departments (EDs) by older adults highlights the need for early and accurate identification of clinical deterioration. Early Warning Scores (EWSs) are widely implemented tools based on standardized vital sign thresholds; however, their performance in elderly patients is inconsistent, likely reflecting the biological heterogeneity, multimorbidity, and reduced physiological reserve typical of this population. Objectives: This narrative review aims to summarize current evidence on the use of EWSs in adults aged ≥ 65 years presenting to the ED, with a specific focus on mortality and intensive care unit (ICU) admission, and to discuss their role within the evolving framework of personalized medicine. Sources: A narrative review of 36 clinical studies published between 2014 and 2025 was conducted. Content: Traditional scores such as National Early Warning Score (NEWS), National Early Warning Score 2 (NEWS2), Modified Early Warning Score (MEWS), VitalPAC Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS) show variable and often reduced prognostic accuracy in older and frail patients. Evidence consistently suggests that applying uniform cut-off values fails to capture individual vulnerability in elderly patients. The integration of age, frailty, comorbidities, and baseline physiological status improves risk stratification. Second-generation tools-including Copeptin-NEWS, NEWS-L, suPAR-NEWS, OPERA, and RISE UP-as well as artificial intelligence-based models, represent emerging personalized approaches to clinical deterioration prediction. Implications: No single score currently provides reliable early risk prediction for all elderly ED patients. Moving beyond "one-size-fits-all" EWSs toward adaptive, person-centered models may better reflect the complexity of geriatric emergency care and improve prognostic accuracy.

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut-testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood-testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence.

Mucins are high-molecular-weight glycoproteins that form the main structural component of the mucus covering epithelial surfaces in the gastrointestinal, respiratory, and urogenital tracts. They support epithelial integrity by protecting against microbial invasion, dehydration, and mechanical or chemical insults, while facilitating the transit of luminal contents. Beyond their structural function, mucins play key roles in molecular recognition. Their extensive glycosylation enables interactions with a wide range of molecules and allows the discrimination between pathogenic and commensal microorganisms at mucosal surfaces. Mucins help maintain mucosal homeostasis by preventing pathogen adhesion and colonization, while simultaneously providing nutrients to commensal species, supporting their stability, and maintaining spatial segregation from epithelial surfaces. Aberrant expression of mucin subtypes or alterations in their glycosylation patterns are associated with numerous diseases, including a wide spectrum of cancers and inflammatory disorders. The immunological relevance of the esophageal mucosa has only recently been recognized. Advances in the study of the esophageal mucosa-associated immune surveillance system and its interactions with structural components of this organ's surface, including mucins, have shed light on unique pathological processes in the esophagus, such as Barrett's esophagus, gastroesophageal reflux disease, and eosinophilic esophagitis. This review focuses on the role of esophageal mucins in inflammation, compiling current evidence to provide an integrated overview of mucin-driven inflammatory mechanisms.

Background: Acquired cholesteatoma is a chronic inflammatory middle ear disease characterized by keratinizing squamous epithelium overgrowth and bone erosion. While the upregulation of pattern-recognition receptor (PRR) signaling has been consistently observed, it remains unclear whether this reflects a secondary response to microbial infection or a primary dysfunction driven by genetic predisposition. Methods: Using the UK Biobank, we analyzed 678 individuals with cholesteatoma (ICD-10: H71) among 502,164 participants. Candidate genes implicated in cholesteatoma-related inflammatory pathways (n = 17) were selected, and 147 polymorphisms were studied. Gene-specific genetic risk scores (GRSs) were calculated for cholesteatoma patients (GRSchol) and the general UK Biobank population (GRSpop). The difference (ΔGRSchol-GRSpop) was used to assess the relative contribution of each gene. Results: Genes with the highest ΔGRS were IL6, TREM1, IL1R1, IL1A, HIF1A, ID1, RAGE, and TNFA. These genes represent key downstream mediators and amplifiers of PRR signaling rather than the receptors themselves. Variants in cytokine genes (IL6, IL1R1, IL1A, and TNFA) may enhance inflammatory signaling and bone resorption; Trem1 amplifies TLR responses; RAGE sustains sterile DAMP-driven inflammation, while HIF1A and ID1 implicate hypoxia, tissue remodeling, and keratinocyte proliferation in disease persistence. Conclusions: Our findings suggest that cholesteatoma pathogenesis may not be driven solely by microbial activation of PRRs but rather by genetic variants that amplify and sustain downstream inflammatory responses. This supports a model of cholesteatoma as a disease of self-perpetuating inflammation triggered by diverse stressors, including microbial and non-microbial insults. These insights may inform preventive strategies targeting environmental stressors, as well as therapeutic approaches using biologics to interrupt chronic inflammatory amplification in cholesteatoma.

Background/Objectives: Vitamin D deficiency and obesity are prevalent public health concerns among older adults, with potential impacts on metabolic health. Despite high deficiency rates reported globally, data on their relationship in Chilean older populations remain limited. This study investigates the relationship between 25(OH)D status, obesity, and metabolic parameters in Chilean older adults using data from the 2016-2017 National Health Survey (ENS). Methods: A cross-sectional analysis was conducted in 1252 individuals aged ≥ 65 years with complete 25(OH)D and anthropometric measurements. Plasma levels of 25(OH)D were classified as optimal ≥ 30 ng/mL, insufficiency 20-29.9 ng/mL, deficiency 12-19.9 ng/mL, and severe deficiency < 12 ng/mL. Logistic regression models adjusted for age, sex, education, comorbidities, and environmental factors were used to assess associations. Results: The results demonstrated that 88.3% of older adults had 25(OH)D ≤ 30 ng/mL, with 58.3% presenting deficiency. Obesity was an independent risk factor for vitamin D deficiency across all models. Geographic location, female sex, and smoking also influenced deficiency risk, while no significant associations emerged with type 2 diabetes or hypertension. Conclusions: These findings highlight the need for targeted strategies addressing vitamin D insufficiency in older adults, considering regional and lifestyle factors, to improve health outcomes in this vulnerable population.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder most commonly caused by pathogenic variants in sarcomeric genes, yet many patients remain genotype-negative and the mechanisms linking genetic alterations to disease pathology are not fully understood. Traditional bulk analyses have provided limited insight into the cellular and molecular changes that drive disease progression. Recent advances in single-cell and spatial multi-omics technologies now allow detailed characterization of cell type-specific transcriptional programs, signaling pathways, and tissue remodeling within the human myocardium. These approaches have begun to redefine HCM as a complex, multicellular disease rather than a purely sarcomeric disorder. This review summarizes current single-cell and spatial transcriptomic studies of human septal myectomy tissue, outlines their major findings and limitations, and discusses how these data may inform the development of precision medicine strategies in obstructive HCM.

Restenosis after carotid endarterectomy and carotid artery stenting remains the main complication after both surgical and endovascular treatment of carotid stenosis, with a 2-year restenosis rate of 6-12%. Complex inflammation processes are the cause of early (<2 years) and late (>2 years) restenosis and principal systemic risk factors are female gender, hypertension, diabetes, dyslipidemia, and smoking. Non-procedural treatment includes lifestyle modifications and best medical therapy. The procedural treatment, considered mostly for symptomatic patients, includes different open and endovascular techniques. The management should be personalized according to patient and plaque characteristics.

Frailty is a multidomain reduction in physiologic reserve that impacts recovery and can contribute to poor outcomes following trauma beyond what chronological age, comorbidities, or injury severity predicts. In geriatric trauma patients, a large proportion are frail or prefrail on initial encounter in the emergency department, and because there are opportunities for actionable management plans, major trauma guidelines endorse systematic screening integrated into coordinated geriatric trauma care. We reviewed the literature and identified practical instruments used in the acute trauma setting for risk stratification. Additionally, we highlight the feasibility of using these instruments, as some can be completed via patient report, proxy input, or chart review when cognition, language, or caregiver availability limits history-taking. Implementation efforts succeed when shared mental models are leveraged and screening is embedded in the electronic health record system, linked to order sets and trigger-based pathways that offer downstream goal-directed care management, such as early mobility, delirium prevention, nutrition, medication review, and comprehensive geriatric assessment. Additionally, we highlight the importance of initiating early goals-of-care discussions and coordinating care with palliative care services. Resource-limited systems can preserve the same architecture by using nurse-led or allied staff-led screening, tele-geriatric consultation, and virtual interdisciplinary huddles. Lastly, we expand upon opportunities for longitudinal post-discharge follow-up. We describe how targeted initiatives translate research into practice, improve outcomes, and support longitudinal reassessment through in-person and telehealth follow-up visits.

Background: Outcomes after critical illness vary markedly despite similar diagnoses and severity scores, underscoring the limitations of chronological age and conventional Intensive Care Unit (ICU) prognostic tools. Personalization of critical care is increasingly essential to improve not only short-term survival but also long-term post-discharge outcomes. Biological aging clocks provide a quantitative framework to capture physiological reserve, immune competence, and vulnerability to stress. Methods: We conducted a scoping review of original human studies published between January 2015 and October 2025 that evaluated biological aging biomarkers in adult ICU populations. PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched, with backward citation screening. Results: Across epigenetic, telomere-based, cfDNA, proteomic, metabolomic, and phenotypic aging measures, accelerated biological aging was consistently associated with increased mortality, organ dysfunction, and post-ICU vulnerability. Despite substantial methodological heterogeneity, a convergent signal emerged linking inflammation-weighted and stress-responsive deep biological clocks to clinically meaningful outcomes in critically ill patients. Conclusions: Biological aging biomarkers represent a mechanistically grounded approach to personalized prognostication in critical care. From a translational perspective, deep biological clocks hold promise for personalized risk stratification, prognostication, and the identification of high-risk recovery phenotypes, although prospective validation and implementation studies are required.

Cardiovascular health and depression influence each other bidirectionally and negatively, leading to high comorbidity rates, and favouring higher morbidity and mortality. Heart rate variability (HRV) has received much attention as a "biomarker" for major depressive disorder, with studies suggesting its potential both as a diagnostic and as a predictive biomarker. This narrative review offers a first orientation to the evidence base for researchers entering the field. We present and discuss the state-of-the-art evidence of cross-sectional and longitudinal studies (including observational, pharmacological interventions, and non-pharmacological interventions) linking depression and/or depressive symptoms to HRV by highlighting meta-analyses and key studies in the field. We briefly discuss the physiological context for interpretation of HRV and important confounders to consider, including the influence of genetics, age, sex, antidepressant medication, and lifestyle factors. Finally, with this information at hand, we discuss and provide guidance for factors to consider when using HRV in designing a study. Our literature review indicates that while there is potential for vagally mediated HRV to be of value in predicting future depression, more in-depth and stratified research of HRV is beneficial to the field and the understanding of what HRV can mean for depression research.