Journal of Personalized Medicine

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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14 pages, 325 KB

Open AccessStudy Protocol

Empowering Healthy Lifestyle Behavior Through Personalized Intervention Portfolios Using a Healthy Lifestyle Recommender System to Prevent and Control Obesity in Young Adults: Pilot Study Protocol from the HealthyW8 Project

by Silvia García, Marina Ródenas-Munar, Torsten Bohn, Astrid Kemperman, Daniela Rodrigues, Suzan Evers, Elsa Lamy, María Pérez-Jiménez, Sarah Forberger, Maria Giovanna Onorati, Andrea Devecchi, Tiziana De Magistris, Jihan Halimi, Yoanna Ivanova, Boyko Doychinov, Cristina Bouzas and Josep A. Tur

J. Pers. Med. 2025, 15(12), 625; https://doi.org/10.3390/jpm15120625 - 13 Dec 2025

Abstract

Background: Rising obesity rates among young adults increase long-term health risks, especially cardiometabolic conditions such as type 2 diabetes mellitus. Digital interventions can offer scalable solutions to promote and support healthy behaviors by integrating personalized diet, physical activity promotion, and behavioral support. Objective: [...] Read more.

Background: Rising obesity rates among young adults increase long-term health risks, especially cardiometabolic conditions such as type 2 diabetes mellitus. Digital interventions can offer scalable solutions to promote and support healthy behaviors by integrating personalized diet, physical activity promotion, and behavioral support. Objective: To assess the feasibility, user friendliness, adherence, and satisfaction of the Healthy Lifestyle Recommender System (HLRS). Secondary outcomes will include measures of metabolic health and obesity. Methods: A 3-month, single-arm pilot study conducted across European countries, including Bulgaria, Germany, Italy, Netherlands, Portugal, and Spain, enrolling 351 young adults (18–25 years old, BMI 18.5–29.9 kg/m²). The intervention includes a mobile app for meal planning (Nutrida v.1), gamified physical activity encouragement (GameBus), and real-time monitoring via a wearable smartwatch device. Primary outcomes are adherence and engagement, measured through app usage and participant feedback; secondary outcomes include anthropometry, physical activity, dietary patterns, psychological well-being, and selected biomarkers of metabolic health. Expected Outcomes: Improved engagement is expected to enhance lifestyle behaviors, supporting weight management and overall well-being. Findings will guide future large-scale interventions. Conclusions: This study will contribute to minimizing the impact of obesity in Europe. Full article

(This article belongs to the Section Personalized Preventive Medicine)

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13 pages, 393 KB

Open AccessReview

A Critical Overview of the Validity of the Current Concept of Bipolar Disorder

by Diego J. Martino, Alejandro G. Szmulewicz and Boris Birmaher

J. Pers. Med. 2025, 15(12), 624; https://doi.org/10.3390/jpm15120624 - 12 Dec 2025

Abstract

Objectives: The main aim was to evaluate the origin and empirical support of the current diagnostic criteria for (hypo)manic and depressive episodes in BD focusing on their nosological (i.e., is it a real entity?) and diagnostic validity (i.e., how well do the [...] Read more.

Objectives: The main aim was to evaluate the origin and empirical support of the current diagnostic criteria for (hypo)manic and depressive episodes in BD focusing on their nosological (i.e., is it a real entity?) and diagnostic validity (i.e., how well do the criteria for the category portray the entity?). Methods: A narrative review of relevant textbooks/reports and articles published in peer-reviewed English-language journals (from the online databases PubMed and PsycInfo), covering the period 1900–2024 and using the terms “validity” OR “diagnosis” AND “manic-depressive”; “mania”; “hypomania”; “depression”; and “melancholia” was performed. Results: Mania appears to be a valid construct in nosological terms, although its validity in the diagnostic domain requires further research. There are scant and controversial empirical data on the nosological validity of separating hypomania from mania as different episodes. The current concept of bipolar depression combines different forms of episodes (melancholic and non-melancholic, with or without psychosis, recurrent or not) without conclusive evidence that all of them are necessarily part of the illness (i.e., limited nosological validity). Conclusions: The validity of the current definition of BD is limited and should be the focus of future research. A valid definition of BD would improve our ability to understand the pathophysiological basis of the illness and contribute to more tailored therapeutic approaches. Full article

(This article belongs to the Special Issue Advancements in Psychiatry: Exploring New Horizons in Mental Health)

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0 pages, 5059 KB

Open AccessArticle

The CanCURE Survey: Gender-Based Differences in HIV Cure Research Priorities

by Jessica Lu, Branka Vulesevic, Shari Margolese, Renee Masching, Wangari Tharao, Claudette Cardinal, Tanguy Hedrich, Chris Mallais, Karine Dubé, Eric Cohen, Nicolas Chomont and Cecilia T. Costiniuk

J. Pers. Med. 2025, 15(12), 623; https://doi.org/10.3390/jpm15120623 - 11 Dec 2025

Abstract

Background: The Canadian HIV Cure Enterprise (CanCURE) is a pan-Canadian research collaboratory, investigating approaches for achieving sustainable HIV remission. In preparation for the next research cycle, CanCURE researchers and the Community Advisory Board (CAB) co-designed a web-based survey to identify HIV research [...] Read more.

Background: The Canadian HIV Cure Enterprise (CanCURE) is a pan-Canadian research collaboratory, investigating approaches for achieving sustainable HIV remission. In preparation for the next research cycle, CanCURE researchers and the Community Advisory Board (CAB) co-designed a web-based survey to identify HIV research priorities from the perspective of people with HIV (PWH) in Canada. The current study examined gender-based differences in these priorities. Methods: From August to December 2024, we recruited PWH across Canada through community organizations and community members. We collected data using REDCap electronic data capture tools hosted at The Research Institute of the McGill University Health Centre. The survey included 36 demographic questions, 16 questions related to general knowledge about HIV and HIV cure-related concepts, and 21 questions ranking research priorities. Knowledge questions were multiple choice, while priorities could be ranked on a scale. We summarized participant characteristics via descriptive statistics, and the research priorities were further stratified according to gender. Results: Of 109 participants, 48.6% self-identified as men, 46.8% as women, and 4.6% as two-spirit, non-binary, agender, or other. The median age was 53 years old. Approximately one-third of participants had lived with HIV for ≤14 years, one-third for 15–24 years, and one-third for ≥25 years. Overall, the median knowledge score of respondents was 79%. Among the 78 participants with prior HIV research experience, three times as many men (61.1%) as women (19.0%) participated in interventional studies involving medication or medical procedures. Men ranked preventing HIV transmission to partners as a priority, studying where the virus hides as the second, and avoiding high comorbidity risks as the third. In contrast, women ranked not having to take pills daily as a priority and avoiding higher risks for comorbidities as the second priority. Both genders equally valued expanding community involvement in HIV cure research. However, men focused more on integrating social and behavioural research, while women emphasized the need for diverse ethnic representation in research. Conclusions: Although both men and women share some common priorities regarding HIV cure research, there are notable gender differences in their specific concerns. Furthermore, a significant gender gap in participation in interventional studies, essential for advancing HIV cure research, highlights the importance of aligning research priorities with concerns of both genders. Full article

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

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Open AccessReview

Biopsy-Driven Synovial Pathophenotyping in RA: A New Approach to Personalized Treatment

by Sheyda Ketabchi, Edda Russo, Maurizio Benucci, Maria Infantino, Mariangela Manfredi, Emanuele Antonio Maria Cassarà, Francesca Li Gobbi, Alessandro Mannoni and Riccardo Terenzi

J. Pers. Med. 2025, 15(12), 622; https://doi.org/10.3390/jpm15120622 - 11 Dec 2025

Abstract

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 [...] Read more.

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. Full article

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

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Open AccessArticle

Patient Awareness and Acceptance of Pharmacogenomics Services: A Survey of Attitudes Toward PGx Implementation and Pharmacist-Led Care

by Kendall Billman, Mayeesha Ahmed Feldman and Josiah D. Allen

J. Pers. Med. 2025, 15(12), 621; https://doi.org/10.3390/jpm15120621 - 11 Dec 2025

Abstract

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. [...] Read more.

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. Full article

(This article belongs to the Special Issue New Trends and Challenges in Pharmacogenomics Research)

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Open AccessArticle

Intravenous Lidocaine Modulates the Perioperative Hepatic Inflammatory Response: Implications for Personalized Medicine in Thoracic Surgery

by Ana Isabel Galve, Ignacio Garutti, Elena Vara, Guillermo González, Gabriel Cusati, Lisa Rancan, Luis Huerta, Javier Casanova and Carlos Simón

J. Pers. Med. 2025, 15(12), 620; https://doi.org/10.3390/jpm15120620 - 11 Dec 2025

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue New Insights into Personalized Medicine for Anesthesia and Pain)

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0 pages, 1052 KB

Open AccessReview

Gene Therapy for Inherited Retinal Disease: Current Strategies, Personalized Medicine, and Future Implications—A Comprehensive Review

by Fahad R. Butt, Thanansayan Dhivagaran, Boaz Li, Mark Ashamalla, Brendan K. Tao, Michael Balas, Austin Pereira, Peng Yan and Parnian Arjmand

J. Pers. Med. 2025, 15(12), 619; https://doi.org/10.3390/jpm15120619 - 11 Dec 2025

Abstract

Gene therapy represents a transformative frontier in ophthalmology, offering the potential to address inherited and acquired retinal diseases at their genetic origin rather than through symptomatic management. By introducing exogenous genetic material to restore or modulate gene expression, gene therapy aims to preserve [...] Read more.

Gene therapy represents a transformative frontier in ophthalmology, offering the potential to address inherited and acquired retinal diseases at their genetic origin rather than through symptomatic management. By introducing exogenous genetic material to restore or modulate gene expression, gene therapy aims to preserve or even restore vision in patients with mutations that disrupt normal retinal function. The eye’s small, compartmentalized structure, relative immune privilege, and direct accessibility through subretinal or intravitreal routes make it an ideal target for localized delivery with minimal systemic exposure. The approval of voretigene neparvovec-rzyl for RPE65-mediated retinal dystrophy marked a pivotal milestone, establishing proof of concept for durable and safe gene replacement therapy. Looking ahead, continued refinements in vector design, CRISPR-based editing strategies, and delivery platforms are expected to expand the therapeutic reach of gene therapy beyond monogenic disorders. With multiple early-phase clinical trials underway for inherited and acquired retinal diseases, the coming decade is poised to bring broader applicability, improved durability, and more accessible gene-based treatments across the spectrum of retinal pathology. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Ophthalmology—2nd Edition)

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Open AccessArticle

Readmissions to a Surgical Intensive Care Unit: Incidence and Risk Stratification for Personalized Patient Care

by Silvia Ramos, Rafael Ramos Fernández, Raul Sevilla, Eneko Cabezuelo, Alberto Calvo, Raquel Vela, Claudia Menendez, Sergio Garcia Ramos, Javier Hortal Iglesias, Ignacio Garutti and Patricia Piñeiro

J. Pers. Med. 2025, 15(12), 618; https://doi.org/10.3390/jpm15120618 - 11 Dec 2025

Abstract

Background/Objectives: Unplanned readmission to the surgical intensive care unit (UR-SICU) is a serious adverse event linked to higher morbidity, prolonged stay, and increased mortality. Most evidence derives from mixed ICUs, limiting applicability to surgical cohorts. We aimed to identify risk factors for [...] Read more.

Background/Objectives: Unplanned readmission to the surgical intensive care unit (UR-SICU) is a serious adverse event linked to higher morbidity, prolonged stay, and increased mortality. Most evidence derives from mixed ICUs, limiting applicability to surgical cohorts. We aimed to identify risk factors for UR-SICU and assess their impact on outcomes. Methods: We performed a retrospective cohort study of adults admitted to a 20-bed SICU in a tertiary hospital between June 2021 and December 2022 after non-cardiac surgery (elective, urgent, trauma, or liver transplantation). Patients dying during the first SICU stay or transferred to another ICU were excluded. Demographics, comorbidities, severity scores, treatments, and complications were recorded. Logistic regression identified predictors. Kaplan–Meier curves analyzed survival. Results: Among 1361 patients, 82 (6.4%) required UR-SICU. Half were surgical (mainly hemorrhage and sepsis), while respiratory and infectious complications predominated among medical readmissions. Independent predictors for UR-SICU were age (OR 1.03/year; p = 0.002), active malignancy (OR 1.79; p = 0.012), and delirium during the first SICU stay (OR 1.86; p = 0.030). UR-SICU patients had longer hospital stays [46 vs. 13 days; p < 0.001] and higher hospital mortality (27.1% vs. 1.48%; OR 24.68; p < 0.001). Mortality remained higher at 6 months (33.3% vs. 7.1%) and 1 year (42.3% vs. 11.1%). Conclusions: UR-SICU occurred in 6.4% of patients and was independently associated with age, malignancy, and delirium. Readmission was strongly linked to prolonged hospitalization and increased short- and long-term mortality. Early recognition of high-risk patients and targeted, personalized preventive strategies may help reduce avoidable readmissions. Full article

(This article belongs to the Special Issue Personalized Medicine in Anesthesia and Intensive Care)

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