Journal of Personalized Medicine最新文献

Purpose: Lung resection surgery (LRS) induces a strong local and systemic inflammatory response that may extend to peripheral organs, including the liver. This study aimed to evaluate the potential effect of intravenous lidocaine on hepatic inflammatory and apoptotic responses during lung resection surgery with one-lung ventilation (OLV) in an experimental porcine model. Methods: Eighteen mini pigs were randomly assigned to three groups: lidocaine (LIDO), control (CON), and sham (SHAM). Animals underwent left caudal lobectomy. The LIDO group received a continuous intravenous infusion of lidocaine (1.5 mg/kg/h) during surgery. The CON group received the same volume of saline, and the SHAM group underwent thoracotomy without lobectomy or OLV. Different samples were collected at baseline, during surgery, and 24 h postoperatively to assess inflammatory cytokines and apoptosis-related proteins. Liver biopsy was taken 24 h after de surgery. Results: One-lung ventilation and lung resection surgery increased the expression of proinflammatory markers in the liver biopsy and enhanced apoptotic protein expression and iNOS production. Lidocaine administration attenuated these effects, showing lower levels of inflammatory mediators, a better balance between iNOS and eNOS, and reduced apoptotic activity compared with controls. Conclusions: Our findings suggest that intravenous lidocaine may serve as a personalized perioperative strategy to attenuate systemic inflammatory and apoptotic responses, contributing to improved hepatic protection during thoracic surgery.

The diagnosis and treatment of rheumatoid arthritis (RA) have been constantly evolving for decades, pointing towards early diagnostic and therapeutic interventions. Synovial biopsy has emerged as a pivotal tool in precision medicine, transitioning from a research procedure to a clinically feasible approach. Modern ultrasound-guided techniques allow safe, reproducible access to inflamed joints, enabling direct analysis of the synovial tissue, which reveals biological heterogeneity undetectable in peripheral blood. Histological scoring, including the Krenn synovitis score, discriminates inflammatory from non-inflammatory pathology, supporting targeted escalation of immunosuppressive therapy. Molecular and histological profiling has defined distinct synovial pathotypes-lympho-myeloid, diffuse-myeloid, and fibroid/pauci-immune-with reproducible associations to therapeutic responsiveness. Moreover, biopsy-driven trials, such as R4RA and STRAP, demonstrate that pathotype-guided strategies can predict outcomes: diffuse-myeloid synovitis responds to IL-6 receptor blockade, lympho-myeloid synovitis to B cell depletion, and fibroid synovitis exhibits multidrug resistance. In difficult-to-treat RA, synovial biopsy differentiates inflammatory from non-inflammatory drivers of persistent symptoms, providing a rational basis for therapy selection. Ongoing biomarker-driven initiatives, including PRECISion and 3TR Precis-The-RA, aim to embed biopsy findings into clinical decision-making. In this review, it is underscored that the integration of histology, molecular profiling, and clinical context positions synovial biopsy as a patient-centered precision approach, guiding individualized therapy and bridging RA stratification with clinical practice.

Background/Objectives: Patient interest in pharmacogenomics (PGx) is growing, yet literacy remains low. This study aims to evaluate patient perspectives on pharmacist-led PGx services, assessing community perceptions of PGx pharmacists, their perceived role in care, literacy levels, and willingness to pay for services. Methods: A brief survey was distributed via social media to participants in southern Ohio, northern Kentucky, and southeastern Indiana. This survey included the Minnesota Assessment of Pharmacogenomic Literacy (MAPL), Likert-style questions to assess preferences, and willingness to pay questions with open fields. Upon completion, 152 responses were received. After data cleaning, 82 responses were analyzed. Results: While 66% of participants preferred their primary care provider to order testing, 45% preferred a PGx pharmacist over their primary care provider to explain their results and medication implications. Conclusions: After being educated on the role of a PGx pharmacist, respondents preferred a PGx pharmacist to explain their PGx testing results and any medication implications.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recognizes asthma as a potential causal pathway for chronic obstructive pulmonary disease, referred to as the COPD-A etiotype. However, the clinical and inflammatory characteristics of this phenotype remain poorly defined. Objectives: This study aimed to characterize clinical traits and cytokine profiles in stable asthmatics exhibiting persistent airflow limitation compatible with COPD-A. Methods: In this cross-sectional study, 94 stable asthmatic patients (71.3% female; age = 54.0 ± 15.6 years) without relevant smoking or environmental exposures were evaluated. COPD-A was defined by a post-bronchodilator FEV₁/FVC ratio < 0.70. Asthma control (ACQ, ACT), quality of life (AQLQ), and lung function were assessed. Levels of IL-5, IL-8, IL-13, IL-17A, IL-17F, IL-25, IL-33, and TNF were quantified in nasal lavage, induced sputum, and blood samples. Results: Among the participants, 42 (44.7%) fulfilled COPD-A criteria. Compared with non-COPD-A subjects, those with COPD-A were older (60.5 vs. 48.7 years; p < 0.001) and had longer disease duration (39.8 vs. 30.1 years; p < 0.001), lower post-bronchodilator FEV₁% predicted (68.1 vs. 87.1%; p < 0.001), and poorer asthma control (ACQ = 1.00 vs. 0.64; p = 0.003). Cytokine levels were comparable between groups except for higher IL-8 concentrations in induced sputum of COPD-A subjects (7.66 vs. 2.51 pg/mL; p = 0.024). Sputum IL-8 ≥ 3.096 pg/mL independently predicted COPD-A (aOR = 12.82; p = 0.023). Conclusions: Over 40% of non-smoking asthmatics exhibited persistent airflow limitation consistent with COPD-A. Elevated sputum IL-8 levels may be a potential biomarker of this etiotype.

Background: Major Depressive Disorder (MDD) is a leading global health concern, yet its pharmacological management is hampered by a «trial-and-error» approach, with a significant proportion of patients failing to achieve remission with initial therapy. This challenge stems from the disorder's marked biological heterogeneity, which is poorly captured by current broad diagnostic categories. This literature review synthesizes the latest evidence across three complementary fields poised to revolutionize MDD treatment: pharmacogenetics testing (PGT), therapeutic drug monitoring (TDM), and artificial intelligence (AI). We hypothesize that integrating all three facilitates the transition from empirical prescribing to model-informed precision dosing (MIPD), enabling prediction of optimal antidepressant selection and dosage before the first dose is administered. The convergence of these technologies, supported by an interdisciplinary framework, has the potential to enhance current treatment strategies and contribute to more individualized psychiatric care. Conclusions: Antidepressant therapy for MDD may be further optimized through the combined use of TDM, PGT, and digital tools. However, the development of this field requires ongoing research and interdisciplinary work.

Background/Objectives: Some personalized alignment (PA) concepts have been described with symmetrical gaps in extension and flexion. However, laxity in native knees was significantly greater laterally than medially with respect to both extension and flexion. We hypothesized that a personalized alignment can restore the native knee alignment, keep a satisfying patellar tracking, and obtain physiological ligament balancing, that is, a symmetric gap in extension and an asymmetric gap in flexion. We aimed to assess: (1) the postoperative alignment of TKA and postoperative patellar tracking (primary outcome); (2) the ligament balancing at the end of the surgery; and (3) clinical outcomes and complication rates. Methods: In this single-center, retrospective case series, we evaluated 45 patients in a consecutive series who underwent robotic-assisted primary TKA using PA between January and September 2020 with a minimum follow-up of 5 years. Complication was defined as grade ≥3 according to the Clavien-Dindo classification. Data assessed were: TKA alignment and implant positioning on postoperative radiographs, patellar tracking on the merchant view, and ligament balancing in extension and flexion upon completion of surgery. Results: Mean follow-up was 62.1 ± 2.5 months. The postoperative mean HKA angle was 177.4° ± 2.2. The medial distal femoral angle was restored (91.1° ± 1.5 postoperatively versus 91.3° ± 2). A total of four TKAs had a patellar tilt superior to 5° (8.9%). No significant difference was found in the medial gap laxity-both in extension and in flexion-and the lateral gap laxity in extension. The lateral gap laxity in flexion was significantly higher than extension or medial gap laxity (+2.9 mm). One patient was readmitted for delayed wound healing. Average improvements in Knee Society knee and function scores were 55.86 and 51.84 points, respectively. Conclusions: This personalized alignment technique using anatomo-functional implant positioning allowed restoration of native knee alignment with a "safe zone" (3° varus/valgus) for the tibial implant, maintained satisfying patellar tracking, and restituted the asymmetrical gap laxity in flexion with a higher laxity in the lateral compartment. Being the longest system-specific study to date, the results are encouraging at 5 years with no major complications. However, longer follow-up will be required to confirm the use of this technique.

Background: Nonattachment is an important component of Mindfulness-Based Interventions (MBIs), including its application within post-traumatic stress (PTS) contexts. However, within trauma contexts, there is limited understanding of the role and effectiveness of MBIs that integrate nonattachment. Objective: This study aimed to identify and evaluate evidence regarding the effectiveness of MBIs with nonattachment elements used with PTS populations. Methods: This review followed the PRISMA scoping guideline framework with searches conducted using Science Direct, PsycINFO, PubMed, and Google Scholar for peer-reviewed studies of MBIs with nonattachment principles or practices, and outcome measures related to PTS. The final search was conducted in January 2024, with no date restrictions for eligible studies. Results: Fourteen studies met the inclusion criteria including 7 randomized controlled trials, 4 cohort studies, and 1 quasi-experimental, 1 cross-sectional, and 1 qualitative study. Individual study samples ranged from 9 to 209 participants (n = 913). All studies showed promising results for interventions integrating nonattachment applied to PTS populations, with the MBI outperforming control conditions in 6 of 7 RCTs, and all cohort studies showing significant improvements. Improvements included reductions in PTSD assessment scores, stress and anxiety, negative self-concept, disturbances in relationships, expressive suppression and rumination, and experiential avoidance, as well as increased acceptance and compassion. Various quality issues were identified such as a lack of or poorly defined randomization, blinding procedures, controls for confounding variables, and small sample sizes. MBIs integrating nonattachment that target physiological stabilization, coupled with participant input into intervention decisions, appear most promising. Conclusions: MBIs that incorporate nonattachment elements may offer meaningful support for individuals experiencing PTS, particularly by fostering more flexible and less self-fixated ways of relating to thoughts and emotions.

Background: Pelvic floor dysfunctions, congenital anomalies, and acquired defects of the female genital, urethral, and anal tract represent complex conditions requiring multidisciplinary management. This review synthesizes current evidence and aims to evaluate reconstructive surgical techniques, prosthetic use, and cosmetic approaches with a focus on functional and aesthetic outcomes. Methods: A structured literature search of PubMed, Embase, and the Cochrane Library was performed for the period from January 2000 to May 2025 (last search: 31 May 2025). Eligible studies included randomized controlled trials, prospective or retrospective clinical studies, and case series in English or Italian, enrolling women aged ≥18 years with a minimum follow-up of 6 months. Primary outcomes were anatomical restoration, continence, sexual function, and quality of life; secondary outcomes included patient satisfaction, wound complications, donor-site morbidity, and recurrence. Recent high-quality studies published after 2018 were prioritized to ensure an updated and evidence-based synthesis. Results: Out of 532 records, 94 full texts were assessed and 41 studies met the eligibility criteria, comprising a total of 1862 women. Flap-based reconstruction (gluteus maximus, VRAM, gracilis, ALT) remained the cornerstone for large or irradiated defects, while prosthetic meshes improved anatomical outcomes but raised concerns of erosion and chronic pain, leading to a shift toward autologous tissue. Cosmetic gynecology procedures (labiaplasty, vaginoplasty, perineoplasty) showed high patient satisfaction, although the evidence was limited and heterogeneous. Across studies, improvements were observed in continence, sexual function, quality of life, and self-image when reconstructive and aesthetic principles were integrated. Conclusions: Reconstructive and cosmetic pelvic surgery significantly impacts functional recovery and psychological well-being. Standardized outcome reporting, prospective multicenter trials, and the integration of plastic surgery, physiotherapy, and psychological support are needed to optimize patient-centered care. The findings highlight the growing role of personalized surgical planning, with reconstructive decisions increasingly guided by patient-specific anatomy, functional goals, and validated patient-reported outcome measures.

Background/Objectives: Internalizing problems commonly increase during adolescence, yet the precise nature of their reciprocal relationship with stress remains unclear. The present study aimed to clarify the directionality of this association by disentangling stable dispositional influences from dynamic, within-person processes. Specifically, we examined whether stress and internalizing symptoms exhibit bidirectional effects over time or are primarily shaped by enduring individual differences. Methods: A large, representative sample of 1618 secondary school students (671 males, 947 females; M = 16.3 years) completed measures of subjective stress, emotional problems, and peer problems across three time points spaced six months apart. Data were analyzed using the Random Intercept Cross-Lagged Panel Model (RI-CLPM), which separates stable between-person variance from within-person fluctuations. Model fit was assessed using established criteria (CFI, TLI, RMSEA). Results: Subjective stress and emotional problems were strongly associated, whereas the relationship between stress and peer problems was weaker. In both domains, associations were largely explained by stable, trait-like individual differences. All cross-lagged effects at the within-person level were non-significant, indicating no dynamic, time-ordered influence between constructs. These findings provide no empirical support for the stress sensitization or stress generation hypotheses but are consistent with diathesis-stress models emphasizing enduring dispositional vulnerability. Conclusions: The results suggest that the link between stress and internalizing symptoms during adolescence primarily reflects stable personality-based factors, such as neuroticism or emotional instability, rather than reciprocal causal processes. Preventive interventions should target emotional regulation and resilience to mitigate the impact of dispositional vulnerabilities on adolescent mental health.

Background: Dysregulation of the hypothalamic-pituitary-adrenal axis is implicated in both gestational diabetes mellitus (GDM) and mood disorders, suggesting a shared pathophysiology. However, the impact of GDM on maternal depressive symptoms, particularly among women with "low and late" fertility, remains poorly characterized. Methods: We compared the risk of postpartum depressive symptoms, assessed on the second postpartum day using the Edinburgh Postnatal Depression Scale (EPDS), with a cut-off score ≥ 12, and the Anhedonia, Anxiety, and Depression subscales, between Northeast Italian women with GDM and control participants with normal oral glucose tolerance tests (OGTT), classified as having "low and late fertility". Results: Among the 2560 women included in the analysis, 231 (9.02%) had GDM. Compared with controls with normal OGTT, women with GDM were older (36.0 vs. 33.0 years, p < 0.001) and had higher pre-pregnancy BMI (23.4 vs. 21.6 kg/m², p < 0.001), but lower gestational weight gain (GWG) (11.0 vs. 13.0 kg, p < 0.001), with no difference in parity [2.00 vs. 1.00, p = 0.5. In addition, GDM was not associated with increased postpartum depressive symptoms (15% EPDS scores ≥12 in both groups, p > 0.9) or with Anhedonia, Anxiety, or Depression subscale scores (p = 0.7). Conclusions: Advanced maternal age and reduced parity, hallmarks of women postponing childbearing, do not appear to confer an increased risk of early postpartum mood comorbidities in the context of GDM. Promoting healthy physical and mental well-being among women in this demographic category requires integrated strategies encompassing nutrition, healthcare, and education.