Journal of Personalized Medicine

15 pages, 1081 KB

Open AccessArticle

Curative Brachytherapy for Inoperable Early-Stage Oesophageal Cancer: A Case Series and Narrative Review

by Elena Lluzar, Adriana Capdevila, Faegheh Noorian, Antonio Herreros, Cristina Castro, Àngels Gines, Glòria Fernández-Esparrach, Carmen Ares, Yao Qiang and Angeles Rovirosa

J. Pers. Med. 2026, 16(1), 13; https://doi.org/10.3390/jpm16010013 - 31 Dec 2025

Abstract

Background: A subset of patients with T1-T2 oesophageal cancer are not candidates for surgery or chemotherapy and have a poor prognosis due to limited treatment options. This study evaluated the combination of external beam radiotherapy (EBRT) and endo-oesophageal brachytherapy (EBT) as a [...] Read more.

Background: A subset of patients with T1-T2 oesophageal cancer are not candidates for surgery or chemotherapy and have a poor prognosis due to limited treatment options. This study evaluated the combination of external beam radiotherapy (EBRT) and endo-oesophageal brachytherapy (EBT) as a curative treatment in these patients, with cause-specific survival (CSS) and local recurrence-free survival (LRFS) as the primary endpoints. Methods: This was a single-centre retrospective analysis of 11 patients with T1-T2 oesophageal cancer treated between 2005 and 2024 with combined EBRT and EBT schedules. Clinical data, treatment schedules, outcomes, and complications were obtained from patient medical records and follow-up documentation. Descriptive statistics and Kaplan–Meier survival analysis were used. Results: The median follow-up was 22 months (2–61 months). CSS rates were 79.5% at 2 years, 66% at 3 years, and 30% at 5 years. LRFS rates were 74.1%, 59%, and 39%, respectively. One severe toxicity (grade ≥ 3) was observed. The most frequent mild toxicities were oesophageal mucositis (18.2%) and ulceration (18.2%). Conclusions: EBT in combination with EBRT seems to be a feasible and well-tolerated treatment with curative intent for inoperable T1-T2 oesophageal cancer patients, offering favourable survival outcomes in a population with limited therapeutic alternatives. Full article

(This article belongs to the Special Issue Personalized Radiation Therapy for Cancers: Current Status and Future Perspectives)

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20 pages, 593 KB

Open AccessReview

The Effect of Fibrin Sealants on Tubal Reanastomosis: A Comprehensive Review of the Literature

by Dimitrios Papageorgiou, Vasilios Pergialiotis, Ioakeim Sapantzoglou, Eleni Sivylla Bikouvaraki, Nikolaos Salakos, Stylianos Kykalos and Konstantinos Kontzoglou

J. Pers. Med. 2026, 16(1), 12; https://doi.org/10.3390/jpm16010012 - 31 Dec 2025

Abstract

Background/Objectives: Female tubal factor infertility is a major clinical challenge. While surgical repair of the fallopian tubes remains the traditional standard, biological fibrin sealants have been proposed to reduce tissue trauma and improve reproductive outcomes. Methods: We conducted database searches of [...] Read more.

Background/Objectives: Female tubal factor infertility is a major clinical challenge. While surgical repair of the fallopian tubes remains the traditional standard, biological fibrin sealants have been proposed to reduce tissue trauma and improve reproductive outcomes. Methods: We conducted database searches of PubMed/MEDLINE, EMBASE and Google Scholar until 31 August 2025, using the keywords “tubal anastomosis”, “tubal reanastomosis,” “tubal reanastomosis”, “uterine horn anastomosis”, “fibrin glue”, “fibrin sealant”, “biological sealant”, “tissue adhesive”, “rabbit”, “rat” and “sterilization reversal.” Reference lists of retrieved articles have been examined to find studies which tested end-to-end tubal (or small-animal uterine horn) anastomosis through biological adhesives with or without additional components to evaluate patency success, fertility results and adhesion formation. Results: Thirteen studies met the inclusion criteria (eleven animal; two human). Rat and rabbit models demonstrated that fibrin sealants with intraluminal splints and one-to-two anchoring sutures produced results comparable to microsutures for patency (tubal patency rates of 75–100%) and pregnancy success (pregnancy rates of 60–83%) while reducing surgical time and decreasing peritubal adhesions. The success rates of the procedures depended on the anastomosis locations. Isthmic–isthmic anastomosis produced better results than ampullary repairs which tended to fail or develop stenosis. Fibrin sealant-only repairs without splinting were associated with lower patency (almost 60%) despite acceptable histologic healing. Human data showed similar pregnancy rates (intrauterine pregnancy in about 40–50% of women) and tubal patency but no consistent decrease in adhesions. Ectopic pregnancy rates ranged from 9 to 11%. Conclusions: Fibrin sealants are useful adjuncts to microsurgical tubal repair, but they should not replace the basic repair procedures. The effectiveness of this procedure is dependent on three critical factors: precise segment alignment, proper use of splints and stents, and selection of segments with comparable caliber. In a personalized-medicine framework, fibrin-assisted reanastomosis may offer a tailored option for selected women who desire natural pregnancy. Modern standardized research is required to define indications and analyze how the adaptation of fibrin sealants in minimally invasive procedures affect reproductive outcomes, ectopic pregnancy rates, and adhesion development. Full article

(This article belongs to the Special Issue Novel Insights in Diagnostics and Personalized Therapeutics in Obstetrics and Gynecology)

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13 pages, 472 KB

Open AccessArticle

Semen Quality in Patients with Hematological Malignancies: A Retrospective Monocentric Study in the Perspective of Personalized Oncofertility Medicine

by Federica Cariati, Maria Grazia Orsi, Anna Capasso, Delia Pagano, Francesca Bagnulo, Gabriele Giuseppe Iorio, Maria Giuseppina Trinchillo, Roberta Ordichelli, Maurizio Guido, Andrea Estrusco, Carlo Alviggi and Alessandro Conforti

J. Pers. Med. 2026, 16(1), 11; https://doi.org/10.3390/jpm16010011 - 31 Dec 2025

Abstract

Background/Objectives: The hypothalamic-pituitary-testis axis is known to be dysregulated in patients with hematological malignancies. However, data on the association between the type of hematological malignancies and semen quality are discordant. In the era of personalized medicine, identifying disease-specific patterns of reproductive impairment is [...] Read more.

Background/Objectives: The hypothalamic-pituitary-testis axis is known to be dysregulated in patients with hematological malignancies. However, data on the association between the type of hematological malignancies and semen quality are discordant. In the era of personalized medicine, identifying disease-specific patterns of reproductive impairment is crucial to optimize fertility preservation strategies. While patients with leukemia often show a clear deterioration in semen quality, studies on Hodgkin and non-Hodgkin lymphomas have shown that spermatogenesis is not always compromised. Indeed, some patients may present normospermia before treatment. This study aimed to assess semen parameters in males affected by hematological malignancies compared with a non-cancer population and to explore implications for individualized fertility preservation counseling. Methods: We performed a retrospective monocentric study including all patients affected by hematological malignancies who underwent fertility preservation at the Maternal and Child Department, Gynecology and Obstetrics, Oncofertility Unit, Federico II of Naples, from January 2017 through December 2024. In total, 247 patients with hematological malignancies and 63 non-cancer males undergoing in vitro fertilization for female tubal factor, selected as a control group, were included in the analysis. Sperm parameters (semen volume, sperm concentration, motility, and morphology) were first compared between the hematological malignancy group and the control group, and then among hematological malignancies classified as Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and leukemia (L). Results: Overall, according to World Health Organization (WHO, 2021) criteria, semen parameters of patients with hematological malignancies were at the 25th percentile, except for motility, which was below the 5th percentile. Significant differences were observed in sperm concentration/mL, total sperm number, and percentage of total sperm motility between the hematological malignancy group and the control group (p = 0.0004; p = 0.0003; p < 0.0001). Based on disease classification, 158 patients had Hodgkin lymphoma, 54 had non-Hodgkin lymphoma, and 35 had leukemia. Significant differences in concentration/mL and total sperm number were found between the Hodgkin lymphoma group and the control group (p = 0.003; p = 0.001). The percentage of total sperm motility was significantly decreased in all subtypes of hematological malignancies compared with controls, especially in the leukemia group (HL p = 0.001; NHL p = 0.004; L p < 0.001). Conclusions: These findings highlight significant impairment of semen quality, particularly motility, reinforcing the role of personalized medicine in tailoring fertility preservation strategies according to malignancy subtype and baseline reproductive risk. Full article

(This article belongs to the Section Personalized Preventive Medicine)

12 pages, 830 KB

Open AccessArticle

Bioresorbable Polylactic Acid Matrix for Chronic Non-Healing Wounds: First Clinical Experience in Europe

by Ioannis-Fivos Megas, Paul Christian Fuchs, Florian Pinterits, Akshay Mrigendra Jain, Panagiotis Fikatas, Götz Habild, Sarina Delavari and David Breidung

J. Pers. Med. 2026, 16(1), 10; https://doi.org/10.3390/jpm16010010 - 31 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Plastic Surgery: New Perspectives and Innovative Techniques)

10 pages, 606 KB

Open AccessArticle

Baseline and Dynamic Neutrophil-to-Lymphocyte Ratio as Prognostic Biomarkers in Metastatic Colorectal Cancer Patients Treated with Panitumumab

by Teodor Marian Vancea, Andrada Olivia Tapirdea, Mihai Gabriel Zait, Daniel Sur, Calin Cainap and Claudia Burz

J. Pers. Med. 2026, 16(1), 9; https://doi.org/10.3390/jpm16010009 - 31 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Precision Medicine for Digestive Diseases)

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17 pages, 1247 KB

Open AccessArticle

Development of a Machine Learning-Based Prognostic Model Using Systemic Inflammation Markers in Patients Receiving Nivolumab Immunotherapy: A Real-World Cohort Study

by Ugur Ozkerim, Deniz Isik, Oguzcan Kinikoglu, Sila Oksuz, Yunus Emre Altintas, Goncagul Akdag, Sedat Yildirim, Tugba Basoglu, Heves Surmeli, Hatice Odabas and Nedim Turan

J. Pers. Med. 2026, 16(1), 8; https://doi.org/10.3390/jpm16010008 - 31 Dec 2025

Abstract

Background: Systemic inflammation is an essential factor in the formation of the tumor microenvironment and has an impact on patient response to immune checkpoint inhibitors. Although there is a growing interest in biomarkers of inflammation, there is a gap in understanding their predictive [...] Read more.

Background: Systemic inflammation is an essential factor in the formation of the tumor microenvironment and has an impact on patient response to immune checkpoint inhibitors. Although there is a growing interest in biomarkers of inflammation, there is a gap in understanding their predictive value for response to nivolumab in clinical practice. The objective of this research was to design and assess a multi-algorithmic machine learning (ML) model based on regular systemic inflammation measurements to forecast the response of treatment to nivolumab. Methods: An analysis of a retrospective real-world cohort of 177 nivolumab-treated patients was performed. Baseline inflammatory biomarkers, such as neutrophils, lymphocytes, platelets, CRP, LDH, albumin, and derived indices (NLR, PLR, SII), were derived. After preprocessing, 5 ML models (Logistic Regression, Random Forest, Gradient Boosting, Support Vector Machine, and Neural Network) were trained and tested on a 70/30 stratified split. Accuracy, AUC, precision, recall, F1-score, and Brier score were used to evaluate predictive performance. The interpretability of the model was analyzed based on feature-importance ranking and SHAP. Results: Gradient Boosting performed best in terms of discriminative (AUC = 0.816), whereas Support Vector Machine performed best on overall predictive profile (accuracy = 0.833; F1 = 0.909; recall = 1.00; and Brier Score = 0.134) performance. CRP and LDH became the most common predictors of all models, and then neutrophils and platelets. SHAP analysis has verified that high CRP and LDH were strong predictors that forced the prediction to non-response, whereas higher lymphocyte levels were weak predictors that increased the response probability prediction. Conclusions: Machine learning models based on common inflammatory systemic markers give useful predictive information about nivolumab response. Their discriminative ability is moderate, but the high performance of SVM and Gradient Boosting pays attention to the opportunities of inflammation-based ML tools in making personalized decisions regarding immunotherapy. A combination of clinical, radiomic, and molecular biomarkers in the future can increase predictive capabilities and clinical use. Full article

(This article belongs to the Section Disease Biomarkers)

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18 pages, 1248 KB

Open AccessReview

Endocan as a Novel Biomarker for Endothelial Dysfunction and Cardiovascular Prognosis in ST-Elevation Myocardial Infarction: A Contemporary Literature Review

by Sourabh Khatri, Pooja Suchday, Ananth Guddeti, Supritha Nanna, Shashank Gupta, Haritha Darapaneni, Adil Sarvar Mohammed, Rupak Desai and Hassaan Imtiaz

J. Pers. Med. 2026, 16(1), 7; https://doi.org/10.3390/jpm16010007 - 29 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue New Perspectives and Current Challenges in Myocardial Infarction)

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15 pages, 486 KB

Open AccessArticle

Health Behaviors and Cancer Diagnosis Among Individuals with Pathogenic Variants Associated with Hereditary Breast and Ovarian Cancer or Lynch Syndrome

by Mahesh Sarki, Günther Fink, Souria Aissaoui, Fulvia Brugnoletti, Nicole Bürki, Rossella Graffeo, Christian Monnerat, Manuela Rabaglio, Ursina Zürrer-Härdi, Pierre O. Chappuis, Karl Heinimann and Maria C. Katapodi

J. Pers. Med. 2026, 16(1), 6; https://doi.org/10.3390/jpm16010006 - 26 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Precision Oncology)

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13 pages, 261 KB

Open AccessArticle

Genetic Markers of Methotrexate Treatment Failure in Psoriasis

by Maria N. Vikhreva, Lavrenty G. Danilov, Andrey A. Martynov, Olga A. Levashova, Svetlana N. Tuchkova, Sherzod P. Abdullaev, Karin B. Mirzaev, Andrey S. Glotov, Oleg S. Glotov and Dmitry A. Sychev

J. Pers. Med. 2026, 16(1), 5; https://doi.org/10.3390/jpm16010005 - 25 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue New Approaches in Pharmacogenomics)

17 pages, 609 KB

Open AccessSystematic Review

Natural Protein-Restricted Diets and Their Impact on Linear Growth in Patients with Propionic and Methylmalonic Acidemia: A Systematic Review

by Jessica Ramirez, María Jesús Leal-Witt, Juan Francisco Cabello and Verónica Cornejo

J. Pers. Med. 2026, 16(1), 4; https://doi.org/10.3390/jpm16010004 - 22 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Inborn Errors of Metabolism: From Pathomechanisms to Treatment)

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13 pages, 1162 KB

Open AccessArticle

Somatic Mutational Landscape in Follicular Thyroid Cancer: Insights from AACR GENIE Data

by Beau Hsia, Julia Kuzniar, Joey Luzarraga, Asritha Sure, Vinay Veluvolu, Eli Oved, Peter T. Silberstein, Joseph Thirumalareddy, Abubakar Tauseef, Vijay Patel and Aliasgher Khaku

J. Pers. Med. 2026, 16(1), 3; https://doi.org/10.3390/jpm16010003 - 21 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Otolaryngology in Clinical Practice: The Necessity of Personalized Medicine)

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12 pages, 429 KB

Open AccessArticle

Genomic Profiling of Laryngeal Squamous Cell Carcinoma Reveals Novel Biomarkers for Precision Medicine

by Beau Hsia, Gabriel A. Bitar, Nathan S. Tran, Katelin Keenehan, Pedro S. Bonilla, Saif Alshaka, Eli Oved, Peter T. Silberstein, Abubakar Tauseef, Vijay A. Patel and Aliasgher Khaku

J. Pers. Med. 2026, 16(1), 2; https://doi.org/10.3390/jpm16010002 - 20 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Otolaryngology in Clinical Practice: The Necessity of Personalized Medicine)

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37 pages, 3930 KB

Open AccessReview

Targeted Hepatic Delivery of Bioactive Molecules via Nanovesicles: Recent Developments and Emerging Directions

by Alessia Rita Canestrale, Sharad Kholia, Veronica Dimuccio and Maria Beatriz Herrera Sanchez

J. Pers. Med. 2026, 16(1), 1; https://doi.org/10.3390/jpm16010001 - 19 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Omics/Informatics)

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25 pages, 2418 KB

Open AccessArticle

Effect of Rehabilitation Program for Muscle Strength, Balance, and Gait Retraining with Visual Feedback in Older Women with and Without Knee Osteoarthritis: Clinical Trial

by Tatiane Silva de Souza, Daniel Borges Pereira, Rodrigo Jugue Hagihara, Carolina Tayama Fuzinato and Ana Paula Ribeiro

J. Pers. Med. 2025, 15(12), 631; https://doi.org/10.3390/jpm15120631 - 18 Dec 2025

Abstract

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: [...] Read more.

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). Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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3 pages, 150 KB

Open AccessEditorial

How to Undertake Personalized Assessments and Administer Cures for Pain

by Barbara Rocca

J. Pers. Med. 2025, 15(12), 630; https://doi.org/10.3390/jpm15120630 - 18 Dec 2025

Abstract

Pain is a multidimensional and highly individualized experience shaped by biological, psychological, and social determinants [...] Full article

(This article belongs to the Special Issue How to Undertake Personalized Assessments and Cures for Pain)

23 pages, 907 KB

Open AccessArticle

by Claudia Lommatzsch, Antoine Capucci, Swaantje Grisanti, Carsten Heinz and Kai Rothaus

J. Pers. Med. 2025, 15(12), 629; https://doi.org/10.3390/jpm15120629 - 17 Dec 2025

Abstract

Purpose: Current pediatric ophthalmology practice relies on adult reference values for optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) interpretation due to limited age-appropriate normative data, potentially leading to diagnostic misclassification. Methods: We conducted a prospective, cross-sectional study comparing [...] Read more.

Purpose: Current pediatric ophthalmology practice relies on adult reference values for optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) interpretation due to limited age-appropriate normative data, potentially leading to diagnostic misclassification. Methods: We conducted a prospective, cross-sectional study comparing OCT and OCT-A parameters between 37 healthy Caucasian children (1–17 years) and 28 adults (19–65 years) using identical Zeiss CIRRUS protocols. Parameters included peripapillary retinal nerve fiber layer (RNFL), macular thickness, ganglion cell-inner plexiform layer (GCIPL), optic nerve head (ONH) perfusion, and macular vascular density. Results: Children exhibited significantly thinner parafoveal macular thickness compared to adults (251.67 ± 21.32 vs. 270.36 ± 17.02 μm; p < 0.001) while RNFL thickness remained comparable. OCT-A demonstrated higher ONH perfusion in children across multiple sectors (p < 0.001). Within the pediatric cohort, younger children (1–9 years) showed higher macular vessel and perfusion density than older children (10–17 years). All pediatric scans achieved excellent image quality with no exclusions. Conclusions: Clinically significant age-related differences in retinal structure and vasculature necessitate pediatric-specific reference ranges. The demonstrated technical feasibility supports routine OCT/OCT-A implementation in pediatric practice with age-appropriate interpretation guidelines. Full article

(This article belongs to the Special Issue Personalized Medicine in Retinal Diseases)

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3 pages, 330 KB

Open AccessCorrection

Correction: Hansen et al. Two-Year Results of 0.01% Atropine Eye Drops and 0.1% Loading Dose for Myopia Progression Reduction in Danish Children: A Placebo-Controlled, Randomized Clinical Trial. J. Pers. Med. 2024, 14, 175

by Niklas Cyril Hansen, Anders Hvid-Hansen, Flemming Møller, Toke Bek, Dorte Ancher Larsen, Nina Jacobsen and Line Kessel

J. Pers. Med. 2025, 15(12), 628; https://doi.org/10.3390/jpm15120628 - 17 Dec 2025

Abstract

In the original publication [...] Full article

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5 pages, 255 KB

Open AccessCorrection

Correction: Degni et al. Safety of Primary Tracheoesophageal Puncture in Patients Submitted to Enlarged Total Laryngectomy with Pectoralis Major Reconstruction. J. Pers. Med. 2025, 15, 435

by Emilia Degni, Sebastiana Lai, Carlo Camillo Ciccarelli, Gamze Yesilli Puzella, Claudia Crescio, Paolo Tropiano, Valeria Fois, Claudio Parrilla, Jacopo Galli and Francesco Bussu

J. Pers. Med. 2025, 15(12), 627; https://doi.org/10.3390/jpm15120627 - 15 Dec 2025

Abstract

In the original publication [...] Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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12 pages, 401 KB

Open AccessArticle

Association of oXiris^® Therapy with Lower Vasopressor Requirements and Modulation of Hemodynamic, Inflammatory, and Perfusion Markers in Septic Shock: A Retrospective Cohort Study

by Nazrin Bakhshaliyeva, Fernando Ramasco Rueda, Ana Estiragués Barreiro and Miguel Ángel Olmos Alonso

J. Pers. Med. 2025, 15(12), 626; https://doi.org/10.3390/jpm15120626 - 14 Dec 2025

Abstract

Background: Septic shock remains a critical challenge with high mortality, particularly in refractory cases requiring high doses of vasopressors. Hemoadsorption with the oXiris^® membrane, capable of simultaneously removing endotoxins, cytokines, and damage-associated molecular patterns (DAMPs), represents a personalized therapeutic strategy targeting [...] Read more.

Background: Septic shock remains a critical challenge with high mortality, particularly in refractory cases requiring high doses of vasopressors. Hemoadsorption with the oXiris^® membrane, capable of simultaneously removing endotoxins, cytokines, and damage-associated molecular patterns (DAMPs), represents a personalized therapeutic strategy targeting the underlying pathophysiology. However, clinical evidence on its impact remains limited and lacks consensus. This study aims to analyze the effects of oXiris^® therapy on hemodynamic, inflammatory, and perfusion parameters in a real-world cohort of patients with septic shock. Methods: We conducted a retrospective cohort study in a surgical Intensive Care Unit (ICU) at a tertiary hospital, including 45 adult patients with septic shock treated with continuous renal replacement therapy using the oXiris^® membrane for at least 48 h. The institutional protocol involved filter changes at least every 24 h during the first 48 h of therapy. Hemodynamic variables, vasopressor doses, and biochemical markers were collected at baseline (T0), 24 h (T1), and 48 h (T2). The primary objective was to describe the evolution of these parameters. Secondary objectives included analysis of 30-day mortality and identification of prognostic factors. Results: The cohort consisted of 45 patients (80.0% male, median age 71 years), with a predominance of abdominal infectious focus (71.1%). A significant reduction in median norepinephrine requirements was observed from T0 to T2 (p < 0.00001), along with a significant increase in mean arterial pressure (MAP) (p < 0.00001). Key markers of perfusion and inflammation also improved, with a significant decrease in arterial lactate (p < 0.00001) and procalcitonin (p = 0.00082) at 48 h. No significant changes were observed in the Sequential Organ Failure Assessment (SOFA) score. The observed mortality rate in the ICU was 31.1%, lower than the median predicted mortality by Simplified Acute Physiology Score II (SAPS II) (37%). Baseline Charlson Comorbidity Index (CCI), creatinine, arterial lactate, and SOFA score were independent predictors of mortality. Conclusions: In this cohort of septic shock patients, therapy with oXiris^®, applied with a frequent filter exchange protocol, was associated with a significant reduction in vasopressor requirements and an improvement in key hemodynamic, perfusion, and inflammatory markers. The observed ICU mortality was lower than predicted by severity scores. These findings support the role of oXiris^® as a personalized adjuvant therapy in specific septic shock phenotypes and underscore the need for prospective randomized trials to confirm these benefits. Full article

(This article belongs to the Special Issue Emergency and Critical Care in the Context of Personalized Medicine)

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