Journal of Personalized Medicine最新文献

Background: Treating depression and anxiety in adolescents can be challenging due to interindividual variability in medication response. With current trial-and-error prescribing practices, adolescents may undergo multiple medication changes over months or years before an effective and tolerated drug and dose are identified. Pharmacogenomic (PGx) testing can identify interindividual differences in drug metabolism, and evidence supporting PGx-guided prescribing in adults with mental disorders is growing. However, its impact on pediatric psychotropic prescribing remains underexplored. Methods: This is a protocol for a parallel-arm, multicentre, randomized controlled trial. Canadian adolescents aged 12-17 years who are initiating or switching a selective serotonin reuptake inhibitor (SSRI) for depression and/or an anxiety disorder under physician care are eligible. A total of 452 participants will be randomized 1:1 to PGx-guided SSRI prescribing (experimental) or SSRI prescribing based on current practice guidelines (control). Participants, caregivers, prescribing clinicians, outcome assessors, and investigators will be blinded to treatment allocation. Dual primary outcomes are symptom remission at 12 weeks, measured with the Quick Inventory of Depressive Symptomatology-Adolescent (QIDS-A17-SR) and the Screen for Child Anxiety Related Disorders (SCARED). Secondary outcomes, assessed at 4, 8, and 12 weeks, include participant- and physician-rated changes in depressive and anxiety symptoms, role functioning, health-related quality of life, health care utilization, cost-effectiveness, side-effect burden, medication burden, and adherence. Multiple testing will be addressed using the Hochberg method, and a parallel gated analysis will account for non-actionable genotypes. Secondary analysis will estimate minimal clinically important differences for symptom and role-functioning change with PGx-guided therapy. Discussion: At the time of writing, 36 participants have consented and been randomized to an intervention. This trial will evaluate whether PGx-guided prescribing improves symptom remission in adolescents treated with SSRIs. If efficacious, results should be interpreted with existing pediatric pharmacokinetic, observational, and adult trial data to inform PGx use in managing pediatric anxiety and depressive disorders.

Background/Objectives: The clinical superiority of rotating-bearing (RB) versus fixed-bearing (FB) total knee arthroplasty (TKA) remains controversial despite the proposed biomechanical advantages of mobile-bearing designs. Objective gait assessment with inertial measurement units (IMUs) provides a measurable view of functional recovery that may complement patient-reported outcome measures (PROMs). This study compared spatiotemporal gait parameters between FB and RB TKA over 24 months. Methods: This prospective longitudinal comparative study enrolled 57 patients undergoing primary unilateral TKA for end-stage knee osteoarthritis. Spatiotemporal gait parameters (gait velocity, cadence, and stance-phase duration) were measured using wireless IMUs (G-WALK system) at 6, 12, and 24 months post-surgery. WOMAC and the 10-point Geriatric Locomotive Function Scale (GLFS-10P) were assessed at 12 and 24 months. Group, time, and Group × Time effects were analyzed using linear mixed-effects models. Results: Both groups improved during follow-up, with performance largely plateauing between 12 and 24 months. At 24 months, there were no significant differences between groups in gait velocity (FB 1.17 vs. RB 1.16 m/s; p = 0.65), cadence (99.8 vs. 97.4 steps/min; p = 0.72), or stance-phase duration (59.3% vs. 59.0%; p = 0.82). Group × Time interactions were not significant across gait outcomes. WOMAC and GLFS-10P improved similarly in both groups (p > 0.05). Cadence was inversely correlated with the WOMAC function subscale at 24 months (rho = -0.563; p = 0.036). Conclusions: FB and RB bearing designs showed similar objective gait recovery trajectories and PROM improvements through 24 months after primary TKA, suggesting no intermediate-term functional advantage from bearing design.

Background: The use of augmented reality (AR) in orthopaedics is growing rapidly but is mainly limited to pre-operative planning and teaching. This study is one of the first to describe the intraoperative application within revision arthroplasty for the positioning of customised partial pelvic replacements. Methods: In a proof-of-concept study an AR environment was used during surgery in 11 cases to enhance implant positioning. Postoperatively, a voxel-based CT deviation analysis was carried out to determine the COR deviation and the cup plane deviation angle. Additionally, digital implant superimposition was conducted. Results: Implantation was possible in all cases with a mean COR deviation vector of 4.2 (SD 2.5; 1.2-9.3) mm and a cup plane deviation angle of 4.4 (SD 2.5; 0.7-8.1)°. The implant analysis showed a superimposition of 0.69 (SD 0.15; 0.38-0.88) (Dice-Score calculation). Conclusions: This study is able to report promising results for AR in orthopaedic surgery, showing improved intraoperative feedback in complex operations, resulting in increased accuracy. However, the integration of AR poses a new challenge to the surgical team, especially because the AR users are facing a significantly increased level of intraoperative stress. Further development of this auspicious tool, as well as a conceivable combination with navigation, is necessary to facilitate broader usage.

Background: Extranodal extension (ENE) is a critical prognostic factor in head and neck squamous cell carcinoma (HNSCC) and was incorporated into the AJCC eighth-edition staging system. However, the concordance between clinical (cENE) and pathological (pENE) ENE remains poorly understood in real-world practice. Methods: We conducted a retrospective analysis using Taiwan Cancer Registry (TCR) long-form data from 2018 to 2022, focusing on four major HNSCC sites (oral cavity, oropharynx, hypopharynx, and larynx). The diagnostic gap was defined as the difference between pENE and cENE positivity rates. Results: Among 29,830 patients, a persistent diagnostic gap was observed across all sites: laryngeal (20.8%), hypopharyngeal (20.4%), oropharyngeal (11.5%), and oral cavity (9.9%). For oral cavity cancer, the gap did not narrow over the 5-year period (p = 0.9788). Furthermore, in oral cavity cancer, medical centers demonstrated a larger gap than non-medical centers (10.5% vs. 8.4%), a phenomenon we term the "Quality-Gap Paradox". Conclusions: A significant diagnostic gap persists in HNSCC, highlighting the limitations of current imaging. The Quality-Gap Paradox, observed in oral cavity cancer, suggests this is driven by a complex interplay of factors including superior pathological detection in high-volume centers. Our findings underscore the need for advanced, personalized risk-stratification tools to bridge this gap and improve patient management.

Background/Objectives: One key objective in temporomandibular joint replacement is to precisely position the implant according to the virtual surgical plan, utilizing drilling and osteotomy guides for accuracy. However, implementing this process can be challenging, as-even though the drilling and osteotomy guides should only fit in one position-there often are still multiple potential positions for both guides and implants on smooth bony surfaces. Even minor deviations in the implant's placement can affect wear, influence biomechanical behavior, and lead to adverse outcomes. Intraoperative navigation has emerged to verify the alignment of implants with the preoperatively planned ideal position. While the use of navigation systems in TMJ surgery is well documented for certain procedures, its application in TMJ replacement cases has been limited. Methods: In this study, two methods to improve the accuracy of TMJ replacement are introduced: a new marker-based navigation workflow and the use of orientation screws in two patients. Results: Unlike conventional navigation methods, the marker-based system provides a more intuitive method for assessing the 3D orientation of the TMJ implant concerning the planned position, enhancing surgical accuracy. The addition of a guiding screw provides a reference point to enhance the accuracy of guide placement. Conclusions: The accurate placement of the prosthesis largely relies on the precise positioning of the guides. Even slight inaccuracies in the position of the TMJ prosthesis, resulting from suboptimal guide placement, can lead to significant negative clinical outcomes. Marker-based navigation and the use of guiding screws may potentially improve the precision of TMJ replacement procedures.

The aspiration to personalize psychiatric care has long accompanied the field's scientific development, yet its realization has often lagged behind advances seen in other areas of medicine [...].

Background: Cutaneous melanoma is an aggressive malignancy driven by complex interactions between tumor cells and the host immune system. Tumor progression is shaped not only by intrinsic tumor characteristics but also by immune-mediated processes within the tumor microenvironment. Cytokines, particularly interleukins, are key regulators of inflammation, immune cell recruitment, and tumor behavior. Cytokine profiling provides an integrated assessment of soluble immune mediators from tumor and stromal cells, reflecting both local and systemic immune responses. Methods: This narrative review summarizes and synthesizes the current literature addressing the biological and clinical relevance of selected interleukins, including IL-6, IL-8, IL-10, IL-2, IL-17, and IL-18, in cutaneous melanoma. Published data were evaluated with a focus on their immunomodulatory functions and potential implications for prognostic assessment. Results: Interleukins demonstrated distinct and context-dependent prognostic and predictive relevance in cutaneous melanoma. Elevated IL-2 levels correlated with sentinel lymph node positivity, supporting its prognostic value in early disease. Increased circulating IL-6 and IL-8 were consistently associated with tumor burden, advanced disease, and reduced survival. IL-10 expression reflected tumor progression and immune modulation. IL-17 signatures predicted response to combined immune checkpoint inhibition, particularly in BRAFV600-mutant melanoma. IL-18 exhibited dual roles, associating with both immune activation and favorable outcomes depending on tumor context. Conclusions: Interleukin profiling offers a biologically relevant framework for understanding immune regulation in cutaneous melanoma. Integrating interleukin signatures into prognostic models may support more refined risk stratification and advance the implementation of personalized medicine approaches in melanoma management.

Background: In the Americas, the number of people living with diabetes is expected to rise from 92 million in 2024 to 120 million by 2050. Indigenous populations may experience distinct biological, environmental, and sociocultural risk factors; however, they are often treated as a homogeneous group in epidemiological research, and consolidated evidence on diabetes prevalence across diverse Indigenous populations remains limited. This scoping review examines the prevalence of diabetes among Indigenous populations in the Americas. Methods: Following PRISMA-ScR guidelines, we conducted a systematic scoping review of population-based studies reporting the prevalence of diabetes among Indigenous adult populations in the Americas. Searches were performed in PubMed and Scopus. Collected data included study location, Indigenous group, population characteristics, diagnostic criteria, and test used and reported prevalence estimates. Results: Sixty documents encompassing 73 studies met the inclusion criteria, representing 45,503 individuals from 16 countries between 1975 and 2025. The total number of ethnic groups represented was 111, and 12 studies did not identify a specific ethnic group. Fasting blood glucose (FBG) was the most frequently used diagnostic method, followed by the oral glucose tolerance test (OGTT). Estimates of the prevalence of diabetes varied widely across populations, regions, and time periods. Five studies-from Brazil, Chile, Colombia, Mexico, and Paraguay-did not identify any cases of diabetes. Among studies reporting cases, prevalence ranged from 1 to 70% in North America, 5 to 14% in Central America, and 1 to 29% in South America. Conclusions: The prevalence of diabetes among Indigenous populations varied widely across the region, with substantially higher estimates reported in North America than in Central and South America. The decline in published studies in recent years suggests reduced research attention to this topic. The marked heterogeneity identified in this review underscores the need for standardized measurement approaches to support population-specific strategies aligned with personalized care and precision public health.

Objective: Exposure to rotenone, a naturally occurring pesticide, has been linked to an increased risk of developing Parkinson's disease (PD). Rotenone strongly inhibits complex I of the mitochondrial respiratory chain, inducing oxidative stress both in vitro and in vivo, ultimately leading to cell death. The objective of this study was to evaluate the cytoprotective effects of the multifunctional agonist D-512 against rotenone-induced toxicity in neuronal PC12 and dopaminergic MN9D cell lines. Methods: Various cell-based assays, including cell viability, antioxidant activity, caspase-mediated apoptosis, and other related assays, were performed. Results: Rotenone was found to be toxic to both dopaminergic MN9D cells and neuronal PC12 cells. However, treatment with D-512 protected both cell types from rotenone-induced toxicity in a dose-dependent manner. Rotenone-induced impairment of mitochondrial membrane potential and increased production of reactive oxygen species were reversed by D-512 treatment. Furthermore, rotenone-induced caspase-mediated apoptotic signaling in MN9D cells was inhibited by D-512. In addition, D-512 restored levels of phosphorylated tyrosine hydroxylase in rotenone-exposed cells across various doses, indicating protection of the dopaminergic system. Finally, rotenone-induced activation of phosphorylated ERK was reversed by D-512 treatment, further supporting its neuroprotective potential. Conclusions: This study demonstrates the ability of D-512 to reverse the toxic effects of rotenone across multiple experimental models. The data presented here are consistent with previously reported neuroprotective properties of D-512. The multifunctional nature of D-512, which combines potent dopamine agonist activity with neuroprotective and other beneficial properties, may address therapeutic needs in PD beyond symptomatic relief and could have potential application across PD subgroups as part of a personalized therapeutic approach.

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