Journal of Personalized Medicine最新文献

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.

Background: Psychological services within hospitals are essential to delivering integrated, patient-centred care, yet in many health systems they remain fragmented, variably organised, or confined to specific medical specialties. The Clinical Psychology Unit of the Fondazione Policlinico Universitario Agostino Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), represents one of the few examples of a hospital-wide psychological governance model in Italy, but its organisational structure and longitudinal activity have not previously been systematically described. Objective: This study (I) describes the organisational design and operational components of the Gemelli Unit; (II) compares it with international organisational models using a typological framework; and (III) examines its resilience and adaptive capacity during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A descriptive-narrative approach was adopted, integrating institutional documentation, routinely collected service data (2019-2024), anonymised case vignettes, and a structured comparison with national and international psychological care structures. The analysis was informed by theoretical models of integrated health-care delivery and by Donabedian's structure-process-outcome framework. Results: Between 2019 and 2024, psychological interventions increased from 28,878 to 47,076 (+63%), with a post-pandemic average of 41,868 annual interventions. In 2024, the Unit supported 2150 patients and 340 healthcare professionals, with psycho-oncology accounting for approximately one-third of all activities. The model integrates clinical activity, staff support, conflict management, research, and training under a centralised governance structure, ensuring hospital-wide coverage and coordinated referral pathways. The comparative analysis identified four international organisational types-department-based, liaison/specialty-based, structured health-system, and academic-clinical hybrid-highlighting the hybrid and transversal nature of the Gemelli Unit and its capacity to maintain and adapt services during the COVID-19 emergency. Conclusions: The Gemelli Unit represents a distinctive hospital-wide organisational model that combines centralised governance, transversal deployment, personalised care, and structured support for healthcare professionals. These characteristics position it as a potentially transferable benchmark for health systems seeking to integrate psychological care into core organisational and clinical processes. Future work should prioritise the development of standardised outcome indicators and national frameworks to support the evaluation and harmonisation of hospital-based psychological services.

Objective: Asthma is a complex and heterogeneous syndrome, making it hard to predict disease progression and suitable treatments. One strategy for reducing this uncertainty is to define genetic subtypes, or endophenotypes, that capture shared biological mechanisms. Most genome-wide studies, however, compare one subgroup against all others within a single cohort and rarely replicate their findings. We aimed to determine whether simultaneously modeling all asthma endophenotypes improves the discovery and replication of genetic associations compared with the standard one-versus-rest approach. Methods: We analyzed common single-nucleotide polymorphisms (SNPs) in the Childhood Asthma Management Program (CAMP) using an analysis of covariance (ANCOVA) across all severity-related endophenotypes, adjusting for age, sex, and ancestry principal components. SNPs showing genome-wide significance were tested for replication in the Genetics of Asthma in Costa Rican Children Study (GACRS). For comparison, we performed traditional one-versus-rest logistic regression analyses within each cohort, using identical covariates and endophenotype labels. Results: The ANCOVA identified 244 genome-wide significant SNPs in CAMP, of which six unique loci replicated in GACRS. In contrast, logistic regression recovered only four significant contrasts from those six loci in CAMP and replicated just one in GACRS. Conclusions: Our findings highlight genetic variants that are associated with asthma severity endophenotypes and demonstrate that modeling all clinical subtypes simultaneously can reveal biologically meaningful signals that are missed by standard pairwise design.

Background: Osteoarthritisof the first trapeziometacarpal (TMC) joint (rhizarthrosis) is a degenerative condition causing pain, reduced mobility, and functional limitations, particularly in older adults and postmenopausal women. Though conservative treatments offer symptomatic relief, advanced cases often require trapeziectomy or total joint replacement. The choice of prosthesis is tailored to patient-specific factors such as age, functional demands, and comorbidities. Despite the benefits of TMC joint replacements, prosthetic infections remain underexplored. Materials and Methods: This systematic review (covering 2000-2024) adhered to PRISMA guidelines, searching Medline, Cochrane, and Google Scholar for randomized controlled trials and case series. Data on demographics, prosthesis types, infection rates, and management strategies were extracted and analyzed. Results: Among 4165 TMC joint procedures reported in 63 studies, 15 cases (0.36%) involved superficial or deep infections, with Staphylococcus aureus identified in two instances. Management ranged from antibiotic therapy and debridement to prosthesis removal with or without reimplantation. Conclusions: Variability in diagnostic criteria and reporting limited uniform conclusions. Although infections are infrequent, they pose significant management challenges due to inconsistent diagnostic criteria and treatments. Early identification and tailored interventions remain critical. This review underscores the need for standardized protocols and highlights gaps in current research. Future studies should focus on multicenter trials and robust methodologies to improve outcomes and advance infection management in TMC prosthesis surgery.

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways-such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)-and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the "treatable traits" approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation.

Background/Objectives: Psychological stress is a common problem but hard to universally treat. Personalized (N-of-1) trials assess a participant's response to multiple specific interventions. Though personalized (N-of-1) trials have been used in select interventions, no prior research has examined whether N-of-1 designs provide superior stress reduction relative to standard of care. Methods: Participants were randomized to personalized N-of-1 (N = 106) or standard-of-care (N = 106) arms for three stress-management interventions (mindfulness meditation; yoga; brisk walking). All participants completed ecological momentary assessments (EMA) of stress three times daily for 18 weeks (2-week baseline, 12-week intervention, 2-week assessment, and 2-week follow-up). After the intervention, participants in the N-of-1 arms received a personalized report identifying which intervention worked best for them. All participants chose one intervention to manage their stress during follow-up. The primary outcome was change in perceived stress between baseline and follow-up. Results: Participants in the personalized (N-of-1) arms did not report significantly reduced EMA stress levels relative to standard-of-care (p = 0.496), though the effect was stronger among N-of-1 participants who chose the stress-management intervention recommended by their report [B(SE) = -0.67(0.34); p = 0.049]. Conclusions: Results show the potential of personalized (N-of-1) trials to provide individuals with information unique to them to help identify interventions for stress management. However, many participants in the personalized trial arms did not choose the intervention recommended by their trial. Additional research is required to refine how personalized (N-of-1) trials are conducted and how trial results are reported to participants to ensure the maximal benefit of these trial designs.

Background/Objectives: Endometriosis is a chronic inflammatory disease affecting up to 10-15% of women of reproductive age and is frequently associated with pelvic pain and infertility. Non-invasive biomarkers remain insufficient for accurate diagnosis, often necessitating laparoscopic confirmation. The fibrinogen-to-albumin ratio (FAR), a composite marker of systemic inflammation, has been proposed in both oncological and cardiovascular disease but has not yet been evaluated in endometriosis. Methods: We conducted a retrospective monocentric study including 390 women who underwent laparoscopy between January 2015 and December 2021 at the Medical University of Vienna. Of these, 218 had histologically confirmed endometriosis and 172 had benign ovarian cysts. Preoperative laboratory data was collected, and FAR was calculated. Group comparisons were performed using the Mann-Whitney U test. ANOVA was used to compare FAR across revised American Society for Reproductive Medicine (rASRM) stages, and Spearman's rank correlation assessed associations with disease severity. Subgroup analyses were performed for adenomyosis and deep infiltrating endometriosis (DIE). Results: FAR was significantly higher in women with endometriosis than in controls (median 0.0679, IQR 0.0588-0.0778 vs. 0.0641, IQR 0.0559-0.716; p = 0.0035). Across rASRM stages I-IV, FAR values were comparable (means 0.0691-0.0709) and did not differ significantly (p = 0.822, ANOVA). Spearman's correlation confirmed no significant association with disease stage (ρ = 0.085, p = 0.24). In exploratory analyses, women with adenomyosis (n = 35) showed a non-significant trend toward a higher median FAR compared to those without adenomyosis (0.0707 vs. 0.0669; p = 0.073, one-sided). No difference in FAR was observed between women with deep infiltrating endometriosis (DIE; n = 144) and those without (0.0680 vs. 0.0672; p = 0.389, one-sided). Conclusions: Although FAR alone cannot replace surgical confirmation, the difference observed between the groups may reflect the systemic inflammatory aspect of endometriosis and should be investigated further in future studies. Given its accessibility and cost-effectiveness, FAR may support the development of non-invasive, personalized diagnostic approaches when combined with other clinical and molecular markers.

Background: Prospective trials provide robust evidence for prostate cancer (PCa) treatment but often include highly selective populations, limiting generalizability. Real-world data (RWD) can address these gaps and inform personalized care. Objectives: This study aimed to evaluate treatment-free survival (TFS) and secondary treatment sequences after initial curative therapy for PCa using electronic health record (EHR) data and to analyze associated medication profiles. Methods: We studied 3024 patients treated with radical prostatectomy (RP), brachytherapy (BT), or curative radiotherapy (RT) at Erasmus MC (2009-2023), the Netherlands. Outcomes included TFS, treatment sequences, and medication patterns across treatment lines. Results: Median age at diagnosis was 65 years (IQR 61-69) for RP, 68 (62-73) for BT, and 72 (68-76) for RT. At 10 years, TFS was 89% (95% CI: 84.9-94.1) for BT, 85% (95% CI: 83-87) for RT, and 71% (95% CI: 65.7-75.8) for RP. Most patients remained treatment-free, but up to five treatment lines occurred, mainly in patients with low comorbidity scores. Medication profiles reflected treatment-related morbidity: alpha-blocker use increased after BT and RT, while bladder relaxants were common after RP. Comorbidity-related medication use remained low among patients undergoing multiple sequenced treatments. Conclusions: These findings highlight the real-world application of multiple secondary treatments after different primary curative therapy options for PCa and associated comorbidity and medication use patterns. They confirm the durability and long-term effectiveness of curative treatments in real-world PCa care. By combining treatment trajectories and medication profiles, RWD provides insights for personalized counseling, helping clinicians and patients anticipate long-term treatment needs, and enabling informed decisions aligned with health status and preferences.