Journal of Personalized Medicine最新文献

Background/Objectives: Bioresorbable polylactic acid (PLA) matrices have shown promise in supporting wound healing through their biocompatibility, tissue integration, and potential involvement in immune regulatory mechanisms. This study aimed to analyze the clinical performance of a PLA-based matrix in the treatment of chronic wounds under real-world conditions in a single-center setting. Methods: This retrospective study included patients with chronic wounds treated with the polylactic acid matrix at Evangelisches Waldkrankenhaus Spandau between February 2023 and February 2025. Wounds were surgically debrided in the operating room prior to matrix application. The matrix remained in place until resorption or detachment, with reapplications occurring at a mean interval of approximately 14 days. Data was anonymized and analyzed descriptively. Results: A total of 14 patients with 16 chronic wounds were treated in this study. The mean patient age was 76.1 years. The most common underlying causes were ischemia and trauma, with an average wound size of 23.6 cm². Complete wound closure was achieved in 15 out of 16 cases (93.8%), with a mean time to complete wound closure of 72.9 days. The average duration of hospitalization was 24.8 days. Conclusions: The polylactic acid matrix demonstrated a high rate of short-term wound closure in a heterogeneous cohort of chronic wounds, with a mean time to closure of 73 days and no requirement for skin grafting. Further prospective studies with standardized long-term follow-up are warranted.

Background: Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with epidermal growth factor receptor (EGFR) inhibitors improving outcomes in patients with metastatic CRC (mCRC) harboring KRAS wild-type tumors. Inflammation has emerged as a potential determinant of treatment efficacy, and the neutrophil-to-lymphocyte ratio (NLR) represents an accessible biomarker reflecting the balance between protumoral neutrophils and antitumor lymphocytes. Methods: We conducted a retrospective study of 44 patients with left-sided, KRAS wild-type mCRC treated at the Institute of Oncology "Prof. Dr. Ion Chiricuta" between 2015 and 2024 with first-line FOLFOX/FOLFIRI plus panitumumab. Baseline NLR (bNLR) and NLR after four treatment cycles were assessed, with progression-free survival (PFS) as the primary endpoint. Results: Receiver operating characteristic analysis identified an optimal bNLR cutoff of 3.06 (AUC = 0.78, p = 0.004). Patients with low bNLR (≤3.06) had significantly longer PFS than those with high bNLR (>3.06) (14 vs. 7 months, HR = 2.7, p = 0.002). Notably, patients with a positive ΔNLR (increase during therapy) also demonstrated superior PFS compared to those with a negative ΔNLR (18 vs. 11 months, HR = 0.47, p = 0.022). In multivariate analysis, only bNLR remained independently associated with PFS. Conclusions: These results suggest that both baseline and dynamic NLR may serve as low-cost prognostic biomarkers in mCRC patients treated with anti-EGFR therapy.

The pathophysiology of ST-elevated myocardial infarction (STEMI) extends beyond coronary artery occlusion to include microvascular and endothelial dysfunction, both of which critically influence outcomes. Endocan, a soluble dermatan sulfate proteoglycan secreted by endothelial cells, has emerged as a novel biomarker of endothelial activation and dysfunction. Recent studies suggest that elevated endocan levels may carry prognostic significance in patients with STEMI, particularly those undergoing percutaneous coronary intervention (PCI). A comprehensive search of PubMed, Cochrane Library, and Google Scholar was conducted to identify studies evaluating endocan as a prognostic biomarker in STEMI. Review articles, case reports, case series, and experimental studies were excluded. Seven clinical studies, comprising sample sizes ranging from 80 to 320 patients, met the inclusion criteria. Across these studies, endocan levels were analyzed in relation to established prognostic markers and clinical outcomes. Key findings demonstrated that higher endocan levels correlated with stress hyperglycemia (r = 0.21, p < 0.05), higher SYNTAX scores, and worse in-hospital outcomes. A cutoff value of 1.7 ng/mL predicted STEMI with 76.1% sensitivity and 73.6% specificity. Elevated endocan levels also showed positive correlations with the TIMI risk score, major adverse cardiovascular events (MACE), and were identified as independent predictors of incomplete ST-segment resolution (STR) (p = 0.044) and no-reflow phenomenon (NRP) (p < 0.001, OR = 2.39, 95% CI = 1.37-4.15). Collectively, the evidence indicates that endocan is strongly associated with endothelial dysfunction, MACE, NRP post-PCI, and impaired reperfusion. Moreover, traditional prognostic indices such as TIMI and SYNTAX scores appear to correlate with circulating endocan levels. However, variability in reported cutoff values across studies highlights the need for larger, multicenter trials with standardized endpoints to establish endocan's diagnostic and prognostic utility in STEMI.

Background/Objectives: Individuals carrying pathogenic/likely pathogenic (P/LP) variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch Syndrome (LS)- have increased risk for various types of cancer. The study compared health behaviors, i.e., smoking, alcohol consumption, level of physical activity, and body mass index (BMI) among affected and unaffected (never diagnosed) individuals with P/LP variants associated with HBOC or LS. Methods: We used baseline and 18-month follow-up data from individuals with HBOC- or LS-associated P/LP variants from the Swiss CASCADE study, an open-ended, prospective, family-based cohort. Generalized linear models with random effects were applied. Results: A total of 856 records from 518 participants (HBOC: 410; LS: 108) were analyzed. More than half (58%) of participants had at least one cancer diagnosis. After controlling for potential confounders, the proportion of current smokers was not significantly different between the two groups (ß = 3.5, p = 0.24). Alcohol intake was not associated with cancer diagnosis (adjusted: ß = -0.2, p = 0.57), although it was positively associated with time since genetic testing (ß = 0.11, p < 0.01). Levels of physical activity were lower among affected individuals compared to unaffected (adjusted: ß = -0.5, p = 0.03). There was no difference in BMI between the two groups. Conclusions: No significant differences in health behaviors, i.e., smoking, alcohol consumption, or BMI, were detected in individuals with P/LP variants associated with HBOC or LS unaffected by cancer and those with cancer diagnosis. Lower levels of physical activity in those with a cancer diagnosis could potentially be attributed to cancer treatment. Future studies should examine whether adjustments in health behavior are associated with the genetic diagnosis.

Background: Pharmacogenetic markers associated with the need to switch patients from methotrexate (MTX) to biologic agents in moderate-to-severe psoriasis remain insufficiently studied. The pharmacokinetics of MTX depend on the individual characteristics of the patient, as well as on the function of specific transporters and enzymes involved in its absorption, distribution, metabolism, and elimination; therefore, polymorphisms in genes encoding these proteins may be considered pharmacogenetic predictors of MTX intolerance or insufficient efficacy. This study aimed to investigate genetic variants associated with MTX intolerance or insufficient efficacy leading to therapy switch. Methods: A total of 80 patients with moderate-to-severe psoriasis were included: 43 who required switching from MTX to biologics and 37 who continued MTX therapy. Twelve polymorphisms in transporter and metabolism-related genes (ABCB1 (rs1045642), MTHFR (rs1801133), ABCB1 (rs1128503), ABCC2 (rs3740066), ABCC2 (rs717620), ABCG2 (rs2231137), GSTP1 (rs1695), SLC19A1 (rs1051266), COL18A1 (rs9977268), SLCO1B1 (rs2306283), SLCO1B1 (rs4149056), and ABCB1 (rs2229109)) were analyzed using next-generation sequencing. Results: Significant differences in genotype frequencies were observed for SLC19A1 rs1051266 (p = 0.03) and COL18A1 rs9977268 (p = 0.02). Carriers of the T allele in both genes were more frequent among patients requiring biologic therapy, suggesting a possible association with MTX intolerance or reduced efficacy. Conclusions: The study revealed an association between polymorphisms in the SLC19A1 rs1051266 and COL18A1 rs9977268 genes and the need to switch from MTX to biologic therapy in patients with moderate-to-severe psoriasis. These findings suggest that carriers of the C allele in these genes may have an increased risk of methotrexate intolerance.

Background/Objectives: Propionic acidemia (PA) and methylmalonic acidemia (MMA) affect methionine, threonine, valine (Val), and isoleucine (Ile) (MTVI) metabolism, leading to the production of highly neurotoxic organic acids. Treatment involves a diet restricted in natural proteins and supplemented with a protein substitute (PS) with traces of MTVI. The aim was to analyze natural protein and PS intake in relation to linear growth impairment in individuals with PA and MMA. Methods: We followed the PRISMA protocol. We considered articles published between 1970 and 2025. We determined the eligibility criteria for selecting articles and evaluated the quality. Results: Thirteen studies were selected: two case reports, eight longitudinal, three cohorts, and one cross-sectional. Articles demonstrated that natural protein intake decreases with age, consistent with previous reports, underscoring the need for PS supplementation to meet protein requirements. Subjects with PA and non-responsive MMA had greater restriction of natural proteins, and the majority required PS; a higher PS intake was negatively correlated with a higher height-for-age (H/A) z-score. When analyzing the ratio of protein to energy (P:E), a negative correlation was found between the intake of natural proteins and energy, and a positive correlation with H/A z-score (p-value < 0.05). Supplementation with PS increased leucine levels, causing an imbalance with MTVI amino acids. This imbalance led to the paradoxical need to supplement L-Val and L-Ile, both propiogenic amino acids. As a result, a decrease in the H/A z-score was observed, particularly in PA and non-responsive MMA. Responsive MMA tolerated more natural proteins, received a lower intake of PS, and had a better H/A z-score. Conclusions: Restriction of natural proteins and PS is associated with a lower H/A z-score, primarily in subjects with PA and non-responsive MMA.

Objective(s): To delineate the somatic mutational landscape of follicular thyroid carcinoma (FTC) from a large, real-world cohort to identify molecular subtypes and actionable targets for personalized therapeutic interventions. Methods: Genomic and clinical data for 168 FTC samples were retrieved from the AACR Project GENIE^® registry via cBioPortal. This study assessed mutation frequencies, copy number alterations, and subgroup differences (primary vs. metastatic; adult vs. pediatric) using statistical tests. Results: NRAS was the most common mutation (33.9%), followed by TERT (22.6%), DICER1 (15.5%), HRAS (11.9%), and PTEN (10.7%). DICER1 mutations were significantly enriched in pediatric cases (44.4% vs. 4.6% in adults, p < 0.001), while TERT mutations were exclusive to adults (42%). NRAS mutations were more frequent in metastatic tumors (42.4%) than primary tumors (29.2%). Conclusions: FTC tumorigenesis is driven by distinct molecular pathways, with significant heterogeneity between pediatric and adult patients as well as primary and metastatic disease. These findings underscore the necessity of molecular profiling for patient stratification and provide a strong rationale for developing personalized treatment strategies to improve clinical outcomes.

Objective(s): To characterize the somatic mutational landscape of laryngeal squamous cell carcinoma (LSCC) using AACR Project GENIE data to identify potential biomarkers for tumor progression and guide precision therapy. Methods: Clinical and genomic data from 135 LSCC samples (primary and metastatic) were analyzed from the AACR Project GENIE database. Mutations were compared by tumor site and gender using chi-squared and Mann-Whitney U tests; co-occurrence and mutual-exclusivity analyses were performed. Results:TP53 mutations were most common (89.6%), followed by KMT2D (27.4%), FAT1 (20.7%), and NOTCH1 (20.7%). CDK8 mutations were enriched in females (p = 0.011) and ATP8B1 in males (p = 0.013). DMD mutations characterized primary tumors (p = 0.049), whereas ATP8B1 and SAMD9L were linked to metastases (p < 0.001). The cohort was 85.9% male and 71.5% White; 59.2% of samples were primary and 39.2% recurrent/metastatic. Co-occurrence analysis identified distinct molecular subtypes. The identification of distinct molecular subtypes and gender-specific mutations, such as CDK8 in females and ATP8B1 in males, suggests potential avenues for tailored therapeutic interventions. Conclusions: LSCC exhibits marked genetic heterogeneity dominated by TP53 alterations. ATP8B1 and SAMD9L mutations may mark metastatic disease, and gender-specific mutations suggest avenues for personalized therapy. These insights support development of targeted strategies, including immunotherapies such as pembrolizumab in TP53-altered tumors. These insights into the genomic heterogeneity of LSCC lay the groundwork for developing targeted therapeutic strategies and patient stratification, ultimately advancing a personalized medicine approach to this disease.

Liver diseases, including fibrosis, viral hepatitis, hepatocellular carcinoma, and monogenic genetic disorders, represent a major global health burden with limited therapeutic options and frequent systemic toxicity from conventional treatments. Nanovesicle-based drug and gene delivery systems offer targeted approaches that may improve therapeutic precision and reduce off-target effects. This review aims to evaluate the promise and comparative potential of three key nanovesicle platforms-lipid nanoparticles (LNPs), extracellular vesicles (EVs) and liposomes-for drug and gene delivery in liver disease therapy. A systematic search of peer-reviewed studies published in electronic databases was performed, focusing on preclinical and clinical research investigating the use of LNPs, EVs and liposomes for hepatic drug or gene delivery. Studies were analyzed for vesicle composition, targeting efficiency, payload capacity, therapeutic outcomes, and reported limitations. The analysis indicates that LNPs demonstrate strong efficiency in nucleic acid encapsulation and delivery, supported by growing clinical translation. EVs show promising biocompatibility and innate targeting to hepatic cells but face challenges in large-scale production and standardization. Liposomes remain versatile and well-characterized platforms capable of carrying diverse therapeutic molecules, though rapid clearance can limit their efficacy. Together, these nanovesicle systems hold considerable potential for advancing targeted drug and gene therapies in liver disease. Future work should focus on improving stability, manufacturing scalability, and cell-specific targeting to support clinical translation.

Background: Therapeutic exercises have gained great prominence due to the benefits shown in the treatment of knee osteoarthritis (OA). However, to date, there is no evidence on the effects of an exercise program combined with balance and gait training with visual feedback. Objective: To evaluate the therapeutic effect of an intervention program combining lower-limb muscle strengthening, balance training, and gait exercises with visual feedback on the chronic pain, functional, and biomechanical aspects of older women with and without OA knee. Methods: Clinical trials study with stratified allocation based on disease status (two-arm, triple-blind-assessor, interventionist, and data manager, parallel-group). In total, 40 older women were recruited: 20 in the OA knee group (OAG, n = 20) and 20 in the control group (CG, n = 20). The intervention included a muscular resistance training program in the lower limbs, and reactive and proactive balance and gait training associated with visual feedback. Both groups received the same intervention. The primary outcomes were pain measured by the Visual Analogue Scale and the questionnaires Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne Algofunctional Index. The secondary outcomes were the six-minute walk test, the Falls Risk Awareness Questionnaire, the Timed Up and Go Test, plantar load distribution during gait, and patients' acceptability. Results: The intervention was effective in improving pain and increasing functionality in older women with OA knee, as measured pre- and post-intervention, compared to the control, with a moderate to high effect size. Body balance increased in older women with OA, as indicated by perceptions of fall risk and walk-test pre- and post-intervention. During gait, a reduction in plantar load (midfoot and rearfoot areas) was observed pre- and post-intervention in OAG compared to the CG. Both groups showed excellent acceptability, suitability, and feasibility of the intervention program. Conclusions: The intervention protocol was effective over 2 consecutive months in reducing pain and increasing knee functionality, balance, walking distance, and perception of falls in older women with OA of the knee compared with women without the condition. During gait, when visual feedback was combined with the intervention protocol, it promoted a better distribution of plantar load over the midfoot and the medial and lateral rearfoot regions in older women with knee OA. Clinical Trial: ReBEC (RBR-5w67pz4). Ethics Committee approval (number: 4.091.004).