Journal of Personalized Medicine最新文献

Background: Cirrhosis represents the final common pathway of chronic liver injury, arising from diverse etiologies such as metabolic, viral, autoimmune, and alcohol-related liver diseases. Despite similar exposures, disease progression varies considerably among individuals, suggesting a genetic contribution to susceptibility and outcome. Objective: This narrative review examines how specific genetic variants influence the risk, progression, and phenotypic expression of cirrhosis. It provides a structured synthesis of established and emerging gene associations, emphasizing their biological mechanisms and potential clinical relevance. Methods: This narrative review synthesizes evidence from all major biomedical and scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar, as well as reference lists of relevant articles, covering literature published between 2005 and 2025 on genetic polymorphisms associated with cirrhosis and its etiological subtypes. Content: Variants are categorized into four mechanistic domains-metabolic regulation, immune modulation, liver enzyme activity, and ancestry-linked expression patterns-representing a novel integrative framework for understanding genetic risk in cirrhosis. Well-characterized variants such as PNPLA3, TM6SF2, HSD17B13, and MBOAT7, along with less commonly studied loci and chromosomal alterations, are discussed in relation to major etiologies, including MASLD/MASH, viral hepatitis, alcohol-related liver disease, and autoimmune conditions. Conclusions: Genetic insights into cirrhosis offer pathways toward early risk stratification and personalized disease management. While polygenic risk scores and multi-omic integration show promise, their clinical translation remains exploratory and requires further validation through large-scale prospective studies.

Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune responses in genetically susceptible individuals. Sex-dependent genetic variations are associated with differences in phenotype and organ localization. Gender-related factors also influence the impact of sarcoidosis on quality of life and health perception, contributing to variability in disease burden and outcomes. Aim of the study: to provide an overview of sex- and gender-related differences in sarcoidosis, focusing on pathophysiological and clinical implications. Material and Methods: The systematic search was conducted on Medline database through Pubmed search engine. We included all clinical studies from 1992 to the present, and imposed language restrictions, accepting only English publications. Case reports, reviews, and pre-print studies were excluded. Results: A total of 35 studies were included. Sex differences significantly influenced both age of onset and clinical presentation of the disease. Women received a diagnosis of sarcoidosis at an older age and exhibited more frequently extrapulmonary localizations, with predominant involvement of the eyes, skin, and extra-thoracic lymph nodes. In contrast, men more commonly presented with limited pulmonary forms. Löfgren syndrome was more prevalent among women and appeared to be associated with sex-specific genetic variations, particularly within the MHC region. Gender differences also impacted quality of life and disease perception: women reported a lower quality of life and were more susceptible to anxiety and depression throughout the disease course. Conclusions: This report confirms that clinical presentation of sarcoidosis is significantly influenced by sex and gender. The identification of sex- and gender-specific clinical patterns supports a personalized medicine framework, in which diagnostic assessment, monitoring strategies, and therapeutic approaches may be tailored according to individual biological and gender-related characteristics.

Bladder cancer (BC) represents a major global health issue with high recurrence and significant mortality rates in cases of advanced disease. Currently, the development of molecular profiling, liquid biopsy technologies, and artificial intelligence (AI) software has resulted in unprecedented opportunities to improve diagnosis, prognostic assessment, and treatment selection. Recent multicenter studies have identified emerging metabolomic, proteomic, and genomic biomarkers with high sensitivity and specificity that may help replace or complement invasive approaches. AI-driven models that combine multi-omics datasets with radiomics and clinical parameters have demonstrated improved accuracy for predicting both therapeutic response and long-term outcomes, compared to standard approaches for risk stratification. Additionally, the incremental clinical usefulness of liquid biopsy platforms has been demonstrated for the monitoring of non-muscle-invasive bladder cancer and minimal disease detection. As these innovations converge, they herald the advent of a new era of personalized management of urothelial carcinoma; however, broad-based clinical implementation will require large-scale validation, standardization, regulatory harmonization, and economic analyses. Background: Bladder cancer continues to be a global health problem, particularly in the advanced disease setting where treatment options are limited, and mortality remains high. The exciting advances in precision medicine, including breakthrough molecular profiling techniques, liquid biopsy, and opportunities to apply AI to interpret these molecular data, hold unprecedented promise in improving the accuracy of diagnosis, prognostic stratification, and therapeutic decision-making.

Background/Objectives: Avascular necrosis (AVN) of the humeral head is a severe complication after intracapsular proximal humerus fractures in the elderly. Hertel's radiographic classification is widely used to estimate ischemic risk, yet its real-world accuracy remains debated. Methods: We retrospectively analyzed 204 patients aged ≥65 years treated between 2019 and 2022 for intracapsular proximal humerus fractures. Fractures were classified according to Hertel's criteria and the LEGO system. The incidence of AVN and its association with radiographic predictors were assessed. Diagnostic performance metrics (sensitivity, specificity, predictive values, accuracy) were calculated for Hertel's classification. Results: AVN developed in 22 patients (10.8%). High-risk fractures according to Hertel's criteria showed a 24.7% AVN rate versus 0.8% in low-risk fractures (p < 0.001; OR = 38.7). Hertel's model demonstrated high sensitivity (95.5%) and negative predictive value (99.2%) but low positive predictive value (24.7%). Medial hinge disruption and calcar extension < 8 mm were the strongest radiographic predictors (p < 0.001). Conclusions: Hertel's classification effectively identifies elderly patients at low risk for AVN, given its high sensitivity and NPV. However, its limited positive predictive value highlights the need for integrative models combining radiographic and clinical parameters to improve ischemic risk stratification.

Theranostic approaches employing radioactive materials have emerged as innovative strategies that integrate molecular imaging with targeted therapy using nanosystems, thereby advancing the paradigm of precision medicine in oncology. Each year, substantial research efforts are dedicated to developing molecular probes capable of detecting early-stage tumors, with improved efficacy and reduced toxicity to the surrounding healthy tissues. Radiopharmaceuticals based on vitamins and nanoparticles are among the most promising developments in this field, as they possess a high level of specificity and low toxicity. Vitamin B9 and vitamin B12 represent notable examples, as their targeting properties exploit the overexpression of corresponding receptors in tumor cells. In this context, future directions may include the radiolabeling of nanoparticles functionalized with these vitamins using isotopes such as [⁶⁸Ga] and [¹⁷⁷Lu], thereby enabling both diagnostic imaging and therapeutic applications. Despite the encouraging preclinical evidence, many in vitro and in vivo studies employing these strategies do not sufficiently address their translational applicability to radiotheranostics. This review highlights the most promising advances in the diagnostic and therapeutic potential of vitamin and nanoparticle-based systems. It aims to critically evaluate current findings and propose hypotheses for further study in the emerging field of radiopharmaceutical theranostics.

Background: Metabolic acidosis is a frequent and serious complication in critically ill neonates, particularly preterm infants, and is associated with an increased risk of mortality, intraventricular hemorrhage, and long-term neurodevelopmental impairment. Despite limited evidence, sodium bicarbonate (SB) is widely administered in neonatal intensive care units (NICUs) to correct acidosis, largely extrapolated from adult and pediatric practice. However, concerns have been raised about its potential adverse effects, including paradoxical intracellular acidosis, impaired cerebral autoregulation, and increased risk of neurological injury. Given the uncertainty regarding both its efficacy and safety, we conducted a systematic review and meta-analysis to evaluate the role of SB administration in the neonatal population. Methods: MEDLINE, Scopus, and the Cochrane Library were searched using specific medical subject headings and terms. We included all study published up to July 2025 that involved newborns treated with SB. The primary outcome was positive response to treatment, while secondary outcomes included mortality, morbidity, and long-term impairment. Results: We analyzed 10 studies (9 randomized and 1 unrandomized study, including 660 neonates). Pooled results from the randomized controlled studies showed no efficacy of SB in newborns. Data from one unrandomized study showed an increased risk for mortality (OR 13.1 p = 0.02), clinical seizures (OR 2.8, p = 0.01), and a combined outcome of death or neurological damage (OR 3.1 p < 0.01) for neonates treated with SB. Conclusions: Current evidence is insufficient to support the routine administration of SB in NICUs. Neonatologists have the responsibility to administer only drugs of proven efficacy, personalizing therapy on the basis of a pathology's etiology, in order to reduce risk and optimize benefits. In the absence of robust, statistically significant data, the indiscriminate use of SB should be discouraged in current clinical practice. PROSPERO registration number: CRD420251132502.

Background: Accurate characterization of complex renal cystic lesions is essential for individualized patient management, as enhancement patterns of septa and walls determine Bosniak classification, malignancy risk, and tailored follow-up strategies. While contrast-enhanced ultrasound (CEUS) is widely used to assess enhancement, Superb Microvascular Imaging (SMI) offers a non-contrast alternative that is capable of detecting slow-flow microvascular signals. This study aimed to evaluate the diagnostic concordance, accuracy, and reproducibility of SMI compared with CEUS in the Bosniak 2019 classification, and to explore its role in personalized imaging pathways for patients with contraindications to contrast media. Methods: Eighty patients (92 cystic renal lesions) who underwent both SMI and CEUS between January 2024 and July 2025 were retrospectively analyzed. Lesions were categorized using the Bosniak 2019 criteria. CEUS served as the reference standard. Concordance between modalities was evaluated using Cohen's κ, and diagnostic accuracy was determined by ROC analysis. Inter- and intra-reader agreement were assessed with κ and intraclass correlation coefficients (ICC), respectively. Histopathologic confirmation was available for resected Bosniak III-IV lesions. Results: SMI showed excellent concordance with CEUS (κ = 0.84, 95% CI 0.76-0.91; overall agreement 83.7%). Concordance was perfect for Bosniak I-II, good for IIF (85%), and moderate for III (68%) and IV (64%) categories. Using CEUS as the reference, SMI achieved a sensitivity of 88.5%, specificity of 90.0%, and AUC of 0.94 for distinguishing low- from high-risk lesions. Inter-reader (κ = 0.83) and intra-reader (ICC = 0.91) agreements were excellent. Among 18 surgically resected Bosniak III-IV lesions, 14 (77.8%) were malignant; SMI correctly identified 12/14 malignant and 3/4 benign cases. Conclusions: SMI shows high diagnostic accuracy and reproducibility in the assessment of complex renal cystic lesions, with strong concordance to CEUS within the Bosniak 2019 system. By providing vascular characterization without contrast administration, SMI supports more personalized renal cyst management, enabling safer imaging for patients at risk from contrast agents and potentially reducing unnecessary interventions. Further multicenter validation is warranted to define its integration into precision-oriented multiparametric renal ultrasound protocols.

Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ² = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ² = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population.

Background/Objectives: Sepsis heterogeneity limits advances in immunotherapy. Increasing use of artificial intelligence (AI) and machine learning (ML) attempts to turn multi-dimensional data into meaningful clusters, indicating biological mechanisms. We provide an overview of the existing evidence on AI-derived sepsis subtyping, exploring treatment response to available immune modulating therapies. Methods: On 1 October 2025, we conducted a structured search on all relative publications on MEDLINE and undertook a narrative review. Results: Multiple subphenotyping algorithms were identified, using clinical, biological, and omics data, across different cohorts, mainly through secondary analyses of randomized trials. The main classification was between hyper- and hypoinflammatory subphenotypes. Statins, corticosteroids, activated protein C, or thrombomodulin displayed differential effects on the outcome of these subphenotypes. Conclusions: Further research is required to prospectively validate findings and to offer pragmatic solutions to patients who need them the most. Issues of validity, equity, ethics, and feasibility are discussed.

Background/Objectives: Patients with moderate-to-severe psoriasis who experience inadequate response or loss of efficacy to multiple biologic agents ("multi-failure patients") represent a particularly challenging subgroup in clinical practice. Evidence regarding the efficacy of bimekizumab in this setting is still limited. This multicentre, real-life study aimed to evaluate the effectiveness, safety, and treatment persistence of bimekizumab in patients with moderate-to-severe psoriasis who had failed at least two previous biologic therapies. Methods: This multicentre, retrospective, real-life study across Italian referral centers retrospectively collected clinical data from 33 adult patients with plaque psoriasis treated with bimekizumab across Italian referral centers. Efficacy was assessed through changes in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores at weeks 4 and 16. Logistic regression was performed to identify predictors of treatment response, and Kaplan-Meier analysis evaluated drug survival up to 12 months. Results: The mean baseline PASI was 14.5 ± 7.1, decreasing to 1.5 ± 4.0 at week 16 (p < 0.001). PASI90 and PASI100 responses were achieved by 57.6% and 42.4% of patients at this timepoint, respectively, while mean DLQI improved by 84.2%. In this small cohort, no significant differences in efficacy were observed according to the number or class of prior biologic failures. Genital psoriasis was associated with a lower likelihood of achieving PASI100. Adverse events were generally mild to moderate in severity and manageable in routine clinical practice. No discontinuations occurred due to lack of efficacy; all withdrawals were related to mild adverse events or personal reasons. Twelve-month drug survival reached 85.4% (95% CI 63.8-100). Conclusions: Bimekizumab demonstrated rapid, marked, and sustained clinical improvements with a favorable safety profile in multi-failure psoriasis patients. These findings support its role as an effective and well-tolerated therapeutic option for individuals with highly refractory disease in real-life practice.