Journal of Personalized Medicine最新文献

Interleukin-23 (IL-23) is a pivotal cytokine driving intestinal inflammation in inflammatory bowel disease (IBD). The development of monoclonal antibodies selectively targeting the p19 subunit of IL-23, including risankizumab, mirikizumab and guselkumab, has significantly expanded the therapeutic landscape of IBD. Landmark phase 3 trials in Crohn's disease (CD) and ulcerative colitis (UC) have demonstrated high efficacy and durable responses, followed by recent regulatory approvals across both indications. Notably, the SEQUENCE trial established the superiority of risankizumab over ustekinumab in achieving endoscopic and clinical endpoints in CD, underscoring the therapeutic value of IL-23p19 blockade and its differentiation from prior p40 inhibition. With additional agents in advanced development, IL-23p19 inhibitors are now emerging as a bona fide treatment class in IBD. Furthermore, IL-23p19 inhibitors display favorable safety profiles and convenient subcutaneous administration regimens, which broaden their applicability across diverse patient populations. However, key knowledge gaps remain regarding optimal treatment positioning, comparative effectiveness, and long-term disease outcomes. Precision medicine approaches will be crucial to fully exploit the potential of this drug class. For instance, early biomarkers can help monitor response, while future integration of serological and multi-omics biomarkers may enable the prediction of treatment success and guide personalized selection. This review summarizes the current knowledge base regarding IL-23p19 inhibitors in IBD, highlights their class effects and unique clinical value, and outlines a research agenda towards biomarker-driven and precision-guided use. Ultimately, IL-23p19-inhibition exemplifies how targeted immunotherapy and precision medicine can converge in order to reshape IBD management.

Background: Obstructive sleep apnea (OSA) is associated with slower response speed, yet conventional severity classification based on the apnea-hypopnea index (AHI) shows limited ability to predict cognitive outcomes. The AHI aggregates distinct pathophysiological processes, including intermittent hypoxemia and sleep fragmentation. Within emerging precision sleep medicine frameworks, disentangling these mechanisms is critical for improved phenotyping and personalized risk assessment. This study aimed to replicate prior findings using a Go/No-Go Continuous Visual Attention Test (CVAT) and to identify the most informative polysomnographic predictor of attentional performance in OSA. Methods: In this cross-sectional study, participants underwent full-night type I polysomnography and the CVAT. After exclusions, 84 patients with OSA and 22 polysomnographically normal controls were analyzed. The sample sizes for mean differences and correlational analyses were adequate. Attentional performance was indexed by standardized reaction time (RT), referenced to a normative database (n = 1244). Within the OSA group, linear regression with backward elimination evaluated hypoxemia and sleep fragmentation metrics. Results: Patients with OSA demonstrated significantly slower RTs than controls (p = 0.005). Within OSA, the AHI was not associated with attentional performance (p = 0.398). In the final regression model, sleep stage shifts-reflecting sleep-wake instability-emerged as the sole independent predictor of attentional slowing (β = 0.27, p = 0.013), whereas all hypoxemia indices were excluded. Conclusions: Sleep stage instability represents a cognitive vulnerability marker in OSA, independent of respiratory events. Integrating fragmentation metrics into precision sleep medicine models may enhance individualized phenotyping, identify patients at higher neurocognitive risk, and inform targeted interventions focused on stabilizing sleep architecture rather than relying solely on the AHI.

The kynurenine pathway (KP) is the primary route of tryptophan metabolism and a key interface linking immune activation, metabolic state, and neurochemical signaling. Although KP biomarkers are widely studied in psychiatric disorders, their interpretation remains inconsistent, in part due to biological context and compartmentalization. In this narrative review, we integrate evidence across peripheral and central systems to clarify how age, sex hormones, metabolic health, inflammation, and behavioral factors systematically bias KP flux and shape biomarker readouts. We re-examine the interpretation of the kynurenine/tryptophan ratio in light of differential IDO1 and TDO2 regulation, blood-brain barrier constraints, and cell-specific downstream metabolism that governs neuroprotective and neurotoxic outputs. We further synthesize clinical evidence linking KP alterations to symptom severity, cognitive dysfunction, treatment resistance, and suicidality, highlighting quinolinic acid as a mechanistic node connecting immune activation to glutamatergic dysregulation. Together, this framework reframes the kynurenine pathway not as a static biomarker of disease, but as a context-sensitive metabolic system with direct implications for study design, risk stratification, and personalized approaches in psychiatry.

Background/Objectives: In recent decades, free flaps have emerged as the gold standard for head and neck reconstruction. However, their use is contraindicated in some cases due to advanced age and/or comorbidities. In such patients, a pedicled flap may be considered. The aim of this observational study was to evaluate strategies for head and neck reconstruction using pedicled flaps in the era of free flaps. Furthermore, the complication rate was analyzed. Methods: Patients who underwent head and neck reconstruction with pedicled flaps were included. The following flaps were considered: the pectoralis major (PMF), deltopectoral, platysma, frontal, temporal, nasolabial, supraclavicular artery island (SCAIF), infrahyoid, sternocleidomastoid, buccal fat pad, and facial artery myomucosal flap (FAMM). Patients' characteristics, flap type, recipient sites, and flap-related complications were systematically recorded. Results: A total of 112 pedicled flaps were analyzed. A PMF was most commonly used for tongue and hypopharyngeal reconstruction. Partial and complete flap necrosis occurred in 11.6% and 1.8% of cases, respectively. Wound dehiscence was reported in 12.5% of cases, while pharyngo-/oro-cutaneous fistulas developed in 6.3% of patients. Hemorrhage from the donor site or flap occurred in 3.6% of cases, and pharyngeal stenosis in 0.9%. Conclusions: Each reconstructive strategy depends on the site and extent of tissue loss. Given the low complication rates, pedicled flaps remain a valid option for head and neck reconstruction in selected patients.

Background/Objectives: Janus Kinase inhibitors (JAKi) are an effective treatment option for rheumatoid arthritis (RA); however, emerging concerns regarding cardiovascular and thromboembolic risk have prompted further investigation. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in patients receiving JAKi versus other disease-modifying anti-rheumatic drugs (DMARDs). Methods: Following PRISMA 2020 guidelines and a preregistered protocol, we systematically searched PubMed, Embase, and the Cochrane Library. Observational studies and randomized controlled trials (RCTs) reporting MACE or VTE among adults with RA treated with JAKi or comparator DMARDs were included. Hazard ratios (HRs) from observational studies and odds ratios (ORs) from RCTs were pooled using fixed- or random-effects models depending on heterogeneity. A sensitivity analysis was conducted for participants aged ≥ 65 years. Results: Twenty-five observational studies and eight RCTs were included. Across observational studies, the pooled HRs for MACE showed no significant difference between JAKi and other DMARDs, HR = 0.98, 95% CI = 0.85-1.13. This finding remained consistent in individuals aged ≥ 65 years. No increase in MACE risk was observed across RCTs, OR = 1.27, 95% CI = 0.89-1.81. In contrast, JAKi use was associated with a significantly higher risk of VTE in the observational studies (HR = 1.32, 95% CI = 1.08-1.61) but not in the RCTs (OR = 1.69, 95% CI = 0.94-3.02). Conclusions: JAKi use does not appear to increase the risk of MACE compared to DMARDs, including in older adults, but may be associated with a higher risk of VTE. These findings highlight the importance of a personalized approach when considering JAKi therapy, incorporating structured cardiovascular and thrombotic risk assessment, patient preferences, and mitigation of modifiable risk factors.

Background: Although traditional rehabilitation methods are effective in promoting recovery for patients with disabilities, some approaches can involve repetitive tasks, making it challenging to maintain high patient engagement and adherence. This can impact the amount of therapy patients receive, which can sometimes limit their overall recovery potential, particularly given constraints in healthcare resources. Extended reality (XR) technologies, which include virtual reality (VR) and augmented reality (AR), offer promising benefits to personalize care and enhance rehabilitation and engagement by increasing motivation and engagement through interactive and immersive environments. Despite these promising advantages, their successful integration in clinical practice has remained limited, partly due to lack of early involvement of clinicians and end-users in the development process. Objective: We aim to provide recommendations for XR rehabilitation technology development, including researchers and industry professionals, to foster more personalized, adoptable and effective tools for patients with neuromusculoskeletal disorders in a clinical setting. Methods: Principles from motor control and game theory are used to describe key features and recommendations for XR rehabilitation technology development to optimize rehabilitation applications in a clinical setting. These recommendations stem from established motor learning and game design principles, a state-of-the-art narrative review of emerging XR rehabilitation literature (2015-2025) and insights from the Ensemble! Program, a living lab where clinicians, researchers, and patients collaborate to explore emerging technologies, including but not limited to serious games using XR technologies. Results: Key design recommendations include strategies for supporting patient motivation, adjusting game difficulty, providing feedback and handling data collection. Conclusions: Integrating motor control and game theory principles into XR rehabilitation technology can help optimize its therapeutic effectiveness and clinical applicability for patients with neuromusculoskeletal conditions. By addressing clinician and patient needs early in the development process, these technologies can be better tailored to meet therapeutic goals and facilitate broader adoption in clinical practice.

Background/Objectives: Patient-Controlled Analgesia (PCA) is a well-established strategy for managing postoperative pain, but its use in the Intensive Care Unit (ICU) remains poorly defined, poorly standardized, and fragmented. The aim of this scoping review is to map the extent, nature, and characteristics of the available evidence on the use of PCA in ICU patients, identifying key areas of uncertainty and knowledge gaps that require further study. Methods: Scoping review reported according to the PRISMA-ScR guidelines. Results: 12 relevant studies were identified. Available evidence suggests that PCA can provide pain control comparable to traditional techniques in post-cardiac surgery patients in the ICU, while data on its use in non-surgical patients are limited. The studies reported good feasibility and a generally favorable safety profile, with a low incidence of significant respiratory events thanks to intensive monitoring. Methodological variability prevents direct comparisons between studies. Conclusions: PCA supports personalized pain management based on patient-specific clinical conditions and response. However, more standardized studies are needed to define its role.

Background: Digital pulp reconstruction with toe-based flaps reliably restores sensibility and contour, yet the healing behavior of viable subcutaneous fat remains underexplored. Because adipose tissue exhibits patient-specific regenerative and volumetric responses, its preservation represents a key element of personalized fingertip reconstruction. This study evaluates the outcomes of toe pulp flaps with targeted fat preservation to assess how individual tissue biology influences contour and functional recovery. Methods: We retrospectively reviewed consecutive digital reconstructions performed with free toe flaps and several variations (pulp toe flap, chimeric pulp toe flap, trimmed great toe flap and chimeric pulp+ trimmed great toe). Particular attention was given to healthy subcutaneous fat that was deliberately maintained or exposed to help shape the final contour. All patients were followed clinically and photographically until complete healing occurred. Results: A total of 126 patients underwent a finger reconstruction with free toe flaps and several variations. The preserved fat layer was intentionally left exposed to promote healthy granulation and spontaneous epithelialization, contributing favorably to the final contour of the distal pulp as the nail advanced. All wounds healed without the need for skin grafts. All patients achieved good to excellent functional and esthetic outcomes with minimal donor-site morbidity. Conclusions: This large retrospective series confirms the reliability of a healthy flap to help shape the digital reconstruction, highlighting the regenerative potential of viable digital fat. Incorporating this concept into the flap design may reduce the need for grafting, minimize donor-site morbidity, and enhance reconstructive outcomes in hand surgery.

Objective: To evaluate the impact of recommendations issued by the Pharmacovigilance Risk Assessment Committee (PRAC) and endorsed by the European Medicines Agency (EMA) and the Italian Medicines Agency (AIFA) on rheumatologists' prescribing patterns of Janus kinase inhibitors (JAK inhibitors) and biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA), within a personalized, risk-adapted care framework. Methods: A brief survey was conducted across 21 Italian rheumatology centers. This retrospective multicenter study included 4421 RA patients assessed before PRAC recommendations (1 January 2022-1 January 2023) and 4376 patients evaluated afterward (2 January 2023-1 January 2024). Prescribing behaviors, cardiovascular risk management, and clinical outcomes were compared between cohorts. Results: Following PRAC recommendations, a more individualized cardiovascular risk management strategy was observed, with increased use of targeted treatments for hypercholesterolemia, hypertension, and diabetes. The post-PRAC cohort showed a significant reduction in myocardial infarction incidence (0.90% vs. 0.47%; p = 0.02) and increased statin use (8.25% vs. 11.1%; p = 0.05). No increase in cardiovascular risk was observed among JAK inhibitor users. Notably, upadacitinib utilization remained stable despite regulatory restrictions. Conclusions: PRAC recommendations promoted safer prescribing practices and improved cardiovascular risk stratification in RA. These findings support a shift toward precision medicine, integrating real-world evidence with advanced diagnostic and decision-support tools, including future artificial intelligence-based approaches, to optimize personalized therapeutic strategies in autoimmune diseases.

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder associated with significant cardiometabolic morbidity, impaired neurocognitive functioning, daytime sleepiness, and reduced quality of life. Although continuous positive airway pressure (CPAP) therapy remains the cornerstone of treatment for moderate-to-severe OSA, long-term adherence is frequently suboptimal, and a substantial proportion of patients experience residual symptoms despite adequate therapy. These limitations have driven increasing interest in non-CPAP treatment strategies and, more recently, in pharmacological approaches tailored to specific OSA pathophysiological mechanisms. This narrative review provides an updated overview of non-CPAP therapies for OSA, including oral appliances, surgical interventions, positional therapy, hypoglossal nerve stimulation, and behavioral strategies, with a particular focus on emerging and established pharmacological treatment and their role in endotype/phenotype-guided management of OSA. Overall, the expanding pharmacological landscape of OSA reflects a paradigm shift toward personalized, multimodal management. Integrating non-CPAP and pharmacological therapies with patient-specific pathophysiology may improve symptom control, adherence, and long-term outcomes in OSA.