Journal of Personalized Medicine

17 pages, 830 KB

Open AccessProtocol

Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents (PGx-GAP): Study Protocol for a Randomized Controlled Trial

by Meagan Shields, Laina McAusland, Madison Heintz, Katherine Rittenbach, Ross Tsuyuki, Adrian Box, Jon Emery, Jennifer Zwicker, Paul Arnold, Amanda Newton and Chad Bousman

J. Pers. Med. 2026, 16(2), 125; https://doi.org/10.3390/jpm16020125 - 22 Feb 2026

Viewed by 520

Abstract

Background: Treating depression and anxiety in adolescents can be challenging due to interindividual variability in medication response. With current trial-and-error prescribing practices, adolescents may undergo multiple medication changes over months or years before an effective and tolerated drug and dose are identified. [...] Read more.

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

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

12 pages, 1235 KB

Open AccessArticle

Spatiotemporal Gait Parameters in Fixed Versus Rotating Bearing Total Knee Arthroplasty: A Prospective 24-Month Longitudinal Study

by Andrei Machado Viegas da Trindade, Leonardo Pinheiro Rezende, Helder Rocha da Silva Araújo, Rodolfo Borges Parreira, Claudio Santili and Claudia Santos Oliveira

J. Pers. Med. 2026, 16(2), 126; https://doi.org/10.3390/jpm16020126 - 21 Feb 2026

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Abstract

Background/Objectives: The clinical superiority of rotating-bearing (RB) versus fixed-bearing (FB) total knee arthroplasty (TKA) remains controversial despite the proposed biomechanical advantages of mobile-bearing designs. Objective gait assessment with inertial measurement units (IMUs) provides a measurable view of functional recovery that may complement [...] Read more.

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

(This article belongs to the Special Issue Precision Orthopedics: Evolving Shoulder, Hip, and Knee Surgery Through Intelligent Technology and Personalized Clinical Care)

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12 pages, 3198 KB

Open AccessArticle

Implementation of an Intraoperative Augmented Reality Environment for Custom-Made Partial Pelvis Replacements—A Proof of Concept and Initial Results

by Yannik Hanusrichter, Carsten Gebert, Sven Frieler, Marcel Dudda, Arne Streitbuerger, Jendrick Hardes, Lee Jeys and Martin Wessling

J. Pers. Med. 2026, 16(2), 124; https://doi.org/10.3390/jpm16020124 - 21 Feb 2026

Viewed by 229

Abstract

Background: The use of augmented reality (AR) in orthopaedics is growing rapidly but is mainly limited to pre-operative planning and teaching. This study is one of the first to describe the intraoperative application within revision arthroplasty for the positioning of customised partial [...] Read more.

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

(This article belongs to the Special Issue Cutting-Edge Innovations in Hip and Knee Joint Replacement)

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10 pages, 763 KB

Open AccessArticle

The Diagnostic Gap Between Clinical and Pathological Extranodal Extension in Head and Neck Cancers: A 5-Year Nationwide Trend Analysis in Taiwan

by Hsuen-Fu Lin and Shih-Han Hung

J. Pers. Med. 2026, 16(2), 123; https://doi.org/10.3390/jpm16020123 - 20 Feb 2026

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Abstract

Background: Extranodal extension (ENE) is a critical prognostic factor in head and neck squamous cell carcinoma (HNSCC) and was incorporated into the AJCC eighth-edition staging system. However, the concordance between clinical (cENE) and pathological (pENE) ENE remains poorly understood in real-world practice. Methods: [...] Read more.

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

(This article belongs to the Special Issue Personalized Medicine for Otolaryngology (ENT))

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14 pages, 9996 KB

Open AccessCase Report

Implant Navigation During TMJ Reconstruction: A Proof-of-Concept Study

by Lauren C. M. Bulthuis, Jean-Pierre T. F. Ho, Petra C. M. Zuurbier, Michail Koutris, Ruud Schreurs and Jan de Lange

J. Pers. Med. 2026, 16(2), 122; https://doi.org/10.3390/jpm16020122 - 18 Feb 2026

Viewed by 209

Abstract

Background/Objectives: One key objective in temporomandibular joint replacement is to precisely position the implant according to the virtual surgical plan, utilizing drilling and osteotomy guides for accuracy. However, implementing this process can be challenging, as—even though the drilling and osteotomy guides should [...] Read more.

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

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

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5 pages, 178 KB

Open AccessEditorial

Personalized Medicine in Psychiatry: From Promise to Practice

by Gniewko Więckiewicz

J. Pers. Med. 2026, 16(2), 121; https://doi.org/10.3390/jpm16020121 - 18 Feb 2026

Viewed by 258

Abstract

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

(This article belongs to the Special Issue Personalized Medicine in Psychiatry: Challenges and Opportunities)

19 pages, 302 KB

Open AccessReview

Cytokine Profiling in Cutaneous Melanoma: The Emerging Role of Interleukins in Prognostic Stratification with an Up-to-Date Overview of Published Data

by Paola Negovetić, Klara Gaćina, Nika Franceschi and Marija Buljan

J. Pers. Med. 2026, 16(2), 120; https://doi.org/10.3390/jpm16020120 - 15 Feb 2026

Viewed by 326

Abstract

Background: Cutaneous melanoma is an aggressive malignancy driven by complex interactions between tumor cells and the host immune system. Tumor progression is shaped not only by intrinsic tumor characteristics but also by immune-mediated processes within the tumor microenvironment. Cytokines, particularly interleukins, are key [...] Read more.

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

(This article belongs to the Special Issue Translational Research and Novel Therapeutics in Cutaneous Melanoma)

38 pages, 2582 KB

Open AccessReview

Interleukin-23p19 Inhibitors in Inflammatory Bowel Disease: From Current Insights to Future Directions

by Ilse A. Pool, Antonius T. Otten, Jos G. W. Kosterink, Gerard Dijkstra, Paola Mian and Arno R. Bourgonje

J. Pers. Med. 2026, 16(2), 119; https://doi.org/10.3390/jpm16020119 - 14 Feb 2026

Viewed by 605

Abstract

Interleukin-23 (IL-23) is a pivotal cytokine driving intestinal inflammation in inflammatory bowel disease (IBD). The development of monoclonal antibodies selectively targeting the p19 subunit of IL-23, including risankizumab, mirikizumab and guselkumab, has significantly expanded the therapeutic landscape of IBD. Landmark phase 3 trials [...] Read more.

Interleukin-23 (IL-23) is a pivotal cytokine driving intestinal inflammation in inflammatory bowel disease (IBD). The development of monoclonal antibodies selectively targeting the p19 subunit of IL-23, including risankizumab, mirikizumab and guselkumab, has significantly expanded the therapeutic landscape of IBD. Landmark phase 3 trials in Crohn’s disease (CD) and ulcerative colitis (UC) have demonstrated high efficacy and durable responses, followed by recent regulatory approvals across both indications. Notably, the SEQUENCE trial established the superiority of risankizumab over ustekinumab in achieving endoscopic and clinical endpoints in CD, underscoring the therapeutic value of IL-23p19 blockade and its differentiation from prior p40 inhibition. With additional agents in advanced development, IL-23p19 inhibitors are now emerging as a bona fide treatment class in IBD. Furthermore, IL-23p19 inhibitors display favorable safety profiles and convenient subcutaneous administration regimens, which broaden their applicability across diverse patient populations. However, key knowledge gaps remain regarding optimal treatment positioning, comparative effectiveness, and long-term disease outcomes. Precision medicine approaches will be crucial to fully exploit the potential of this drug class. For instance, early biomarkers can help monitor response, while future integration of serological and multi-omics biomarkers may enable the prediction of treatment success and guide personalized selection. This review summarizes the current knowledge base regarding IL-23p19 inhibitors in IBD, highlights their class effects and unique clinical value, and outlines a research agenda towards biomarker-driven and precision-guided use. Ultimately, IL-23p19-inhibition exemplifies how targeted immunotherapy and precision medicine can converge in order to reshape IBD management. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Diagnosis and Personalized Treatment)

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24 pages, 1216 KB

Open AccessReview

Contextual Regulation of the Kynurenine Pathway and Its Relevance for Personalized Psychiatry

by Stephen Murata, Gregory Oxenkrug and Angelos Halaris

J. Pers. Med. 2026, 16(2), 118; https://doi.org/10.3390/jpm16020118 - 14 Feb 2026

Viewed by 509

Abstract

The kynurenine pathway (KP) is the primary route of tryptophan metabolism and a key interface linking immune activation, metabolic state, and neurochemical signaling. Although KP biomarkers are widely studied in psychiatric disorders, their interpretation remains inconsistent, in part due to biological context and [...] Read more.

The kynurenine pathway (KP) is the primary route of tryptophan metabolism and a key interface linking immune activation, metabolic state, and neurochemical signaling. Although KP biomarkers are widely studied in psychiatric disorders, their interpretation remains inconsistent, in part due to biological context and compartmentalization. In this narrative review, we integrate evidence across peripheral and central systems to clarify how age, sex hormones, metabolic health, inflammation, and behavioral factors systematically bias KP flux and shape biomarker readouts. We re-examine the interpretation of the kynurenine/tryptophan ratio in light of differential IDO1 and TDO2 regulation, blood–brain barrier constraints, and cell-specific downstream metabolism that governs neuroprotective and neurotoxic outputs. We further synthesize clinical evidence linking KP alterations to symptom severity, cognitive dysfunction, treatment resistance, and suicidality, highlighting quinolinic acid as a mechanistic node connecting immune activation to glutamatergic dysregulation. Together, this framework reframes the kynurenine pathway not as a static biomarker of disease, but as a context-sensitive metabolic system with direct implications for study design, risk stratification, and personalized approaches in psychiatry. Full article

(This article belongs to the Special Issue Multiple Biomarkers for the Diagnosis and Precision Treatment of Depression)

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11 pages, 679 KB

Open AccessArticle

Sleep Fragmentation, Not Nocturnal Hypoxemia, Is the Primary Correlate of Attentional Slowing in Obstructive Sleep Apnea

by Márcio Luciano de Souza Bezerra, Sergio Luis Schmidt, Eelco van Duinkerken, Andreza Maia, Ana Luiza Caldas Coutinho and Kai-Uwe Lewandrowski

J. Pers. Med. 2026, 16(2), 117; https://doi.org/10.3390/jpm16020117 - 14 Feb 2026

Viewed by 364

Abstract

Background: Obstructive sleep apnea (OSA) is associated with slower response speed, yet conventional severity classification based on the apnea–hypopnea index (AHI) shows limited ability to predict cognitive outcomes. The AHI aggregates distinct pathophysiological processes, including intermittent hypoxemia and sleep fragmentation. Within emerging precision [...] Read more.

Background: Obstructive sleep apnea (OSA) is associated with slower response speed, yet conventional severity classification based on the apnea–hypopnea index (AHI) shows limited ability to predict cognitive outcomes. The AHI aggregates distinct pathophysiological processes, including intermittent hypoxemia and sleep fragmentation. Within emerging precision sleep medicine frameworks, disentangling these mechanisms is critical for improved phenotyping and personalized risk assessment. This study aimed to replicate prior findings using a Go/No-Go Continuous Visual Attention Test (CVAT) and to identify the most informative polysomnographic predictor of attentional performance in OSA. Methods: In this cross-sectional study, participants underwent full-night type I polysomnography and the CVAT. After exclusions, 84 patients with OSA and 22 polysomnographically normal controls were analyzed. The sample sizes for mean differences and correlational analyses were adequate. Attentional performance was indexed by standardized reaction time (RT), referenced to a normative database (n = 1244). Within the OSA group, linear regression with backward elimination evaluated hypoxemia and sleep fragmentation metrics. Results: Patients with OSA demonstrated significantly slower RTs than controls (p = 0.005). Within OSA, the AHI was not associated with attentional performance (p = 0.398). In the final regression model, sleep stage shifts—reflecting sleep–wake instability—emerged as the sole independent predictor of attentional slowing (β = 0.27, p = 0.013), whereas all hypoxemia indices were excluded. Conclusions: Sleep stage instability represents a cognitive vulnerability marker in OSA, independent of respiratory events. Integrating fragmentation metrics into precision sleep medicine models may enhance individualized phenotyping, identify patients at higher neurocognitive risk, and inform targeted interventions focused on stabilizing sleep architecture rather than relying solely on the AHI. Full article

(This article belongs to the Section Diagnostics in Personalized Medicine)

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17 pages, 571 KB

Open AccessSystematic Review

Population Heterogeneity of Diabetes in Indigenous Peoples of the Americas: A Systematic Scoping Review of the Existing Literature

by Alberto Barcelo, Roy Wong-McClure, Felicia Cañete, Ethel Santacruz, Noelia Cañete and Arise Garcia de Siqueira Galil

J. Pers. Med. 2026, 16(2), 116; https://doi.org/10.3390/jpm16020116 - 14 Feb 2026

Viewed by 475

Abstract

Background: In the Americas, the number of people living with diabetes is expected to rise from 92 million in 2024 to 120 million by 2050. Indigenous populations may experience distinct biological, environmental, and sociocultural risk factors; however, they are often treated as a [...] Read more.

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

(This article belongs to the Special Issue The Ethnoracial Diversity of Diabetes: Insights into Epidemiology, Genetics, Disease Management, and Personalized Therapies)

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14 pages, 1911 KB

Open AccessArticle

Protection Against Cellular Toxicity from Rotenone Treatment by the Neuroprotective, Novel Multifunctional Antiparkinsonian Drug D-512

by Pranay Ravipati, Liping Xu, Deepthi Yedlapudi and Aloke K. Dutta

J. Pers. Med. 2026, 16(2), 115; https://doi.org/10.3390/jpm16020115 - 14 Feb 2026

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Abstract

Objective: Exposure to rotenone, a naturally occurring pesticide, has been linked to an increased risk of developing Parkinson’s disease (PD). Rotenone strongly inhibits complex I of the mitochondrial respiratory chain, inducing oxidative stress both in vitro and in vivo, ultimately leading to [...] Read more.

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

(This article belongs to the Special Issue Advancing Personalized Medicine: Targeting Oxidative Stress in Neurodegenerative Diseases)

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1 pages, 139 KB

Open AccessCorrection

Correction: Khan et al. Challenges of E-Learning: Behavioral Intention of Academicians to Use E-Learning During COVID-19 Crisis. J. Pers. Med. 2023, 13, 555

by Mohammad Jamal Khan, Lingala Kalyan Viswanath Reddy, Javed Khan, Bayapa Reddy Narapureddy, Sunil Kumar Vaddamanu, Fahad Hussain Alhamoudi, Rajesh Vyas, Vishwanath Gurumurthy, Abdelrhman Ahmed Galaleldin Altijani and Saurabh Chaturvedi

J. Pers. Med. 2026, 16(2), 114; https://doi.org/10.3390/jpm16020114 - 14 Feb 2026

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Abstract

References [...] Full article

17 pages, 1981 KB

Open AccessSystematic Review

Cardiovascular and Thromboembolic Risk of Janus Kinase Inhibitors Compared to Other Disease-Modifying Drugs in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

by Diomidis C. Ioannidis, Efthymia Maria Kapasouri, Vassilios S. Vassiliou and Eleana Ntatsaki

J. Pers. Med. 2026, 16(2), 113; https://doi.org/10.3390/jpm16020113 - 13 Feb 2026

Viewed by 416

Abstract

Background/Objectives: Janus Kinase inhibitors (JAKi) are an effective treatment option for rheumatoid arthritis (RA); however, emerging concerns regarding cardiovascular and thromboembolic risk have prompted further investigation. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiovascular events [...] Read more.

Background/Objectives: Janus Kinase inhibitors (JAKi) are an effective treatment option for rheumatoid arthritis (RA); however, emerging concerns regarding cardiovascular and thromboembolic risk have prompted further investigation. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in patients receiving JAKi versus other disease-modifying anti-rheumatic drugs (DMARDs). Methods: Following PRISMA 2020 guidelines and a preregistered protocol, we systematically searched PubMed, Embase, and the Cochrane Library. Observational studies and randomized controlled trials (RCTs) reporting MACE or VTE among adults with RA treated with JAKi or comparator DMARDs were included. Hazard ratios (HRs) from observational studies and odds ratios (ORs) from RCTs were pooled using fixed- or random-effects models depending on heterogeneity. A sensitivity analysis was conducted for participants aged ≥ 65 years. Results: Twenty-five observational studies and eight RCTs were included. Across observational studies, the pooled HRs for MACE showed no significant difference between JAKi and other DMARDs, HR = 0.98, 95% CI = 0.85–1.13. This finding remained consistent in individuals aged ≥ 65 years. No increase in MACE risk was observed across RCTs, OR = 1.27, 95% CI = 0.89–1.81. In contrast, JAKi use was associated with a significantly higher risk of VTE in the observational studies (HR = 1.32, 95% CI = 1.08–1.61) but not in the RCTs (OR = 1.69, 95% CI = 0.94–3.02). Conclusions: JAKi use does not appear to increase the risk of MACE compared to DMARDs, including in older adults, but may be associated with a higher risk of VTE. These findings highlight the importance of a personalized approach when considering JAKi therapy, incorporating structured cardiovascular and thrombotic risk assessment, patient preferences, and mitigation of modifiable risk factors. Full article

(This article belongs to the Special Issue Personalized Medicine in Cardiovascular and Metabolic Diseases)

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13 pages, 1323 KB

Open AccessArticle

Personalized Strategies for Head and Neck Reconstruction Using Pedicled Flaps

by Giuseppe Riva, Andrea Canale, Gian Marco Motatto, Virginia Talamelli, Marco Briguglio, Alice Bordin, Teodros Veronesi and Giancarlo Pecorari

J. Pers. Med. 2026, 16(2), 112; https://doi.org/10.3390/jpm16020112 - 13 Feb 2026

Viewed by 298

Abstract

Background/Objectives: In recent decades, free flaps have emerged as the gold standard for head and neck reconstruction. However, their use is contraindicated in some cases due to advanced age and/or comorbidities. In such patients, a pedicled flap may be considered. The aim of [...] Read more.

Background/Objectives: In recent decades, free flaps have emerged as the gold standard for head and neck reconstruction. However, their use is contraindicated in some cases due to advanced age and/or comorbidities. In such patients, a pedicled flap may be considered. The aim of this observational study was to evaluate strategies for head and neck reconstruction using pedicled flaps in the era of free flaps. Furthermore, the complication rate was analyzed. Methods: Patients who underwent head and neck reconstruction with pedicled flaps were included. The following flaps were considered: the pectoralis major (PMF), deltopectoral, platysma, frontal, temporal, nasolabial, supraclavicular artery island (SCAIF), infrahyoid, sternocleidomastoid, buccal fat pad, and facial artery myomucosal flap (FAMM). Patients’ characteristics, flap type, recipient sites, and flap-related complications were systematically recorded. Results: A total of 112 pedicled flaps were analyzed. A PMF was most commonly used for tongue and hypopharyngeal reconstruction. Partial and complete flap necrosis occurred in 11.6% and 1.8% of cases, respectively. Wound dehiscence was reported in 12.5% of cases, while pharyngo-/oro-cutaneous fistulas developed in 6.3% of patients. Hemorrhage from the donor site or flap occurred in 3.6% of cases, and pharyngeal stenosis in 0.9%. Conclusions: Each reconstructive strategy depends on the site and extent of tissue loss. Given the low complication rates, pedicled flaps remain a valid option for head and neck reconstruction in selected patients. Full article

(This article belongs to the Special Issue Personalized Medicine in Otolaryngology—Head and Neck Surgery: Updates and Challenges)

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18 pages, 297 KB

Open AccessCommentary

Enhancing Extended Reality Technology for Neuromusculoskeletal Rehabilitation: Recommendations for the Development of Clinically Relevant Serious Games

by Adrien Moevus, An Kateri Vu, Karla Rodrigues Soares Menezes, Mindy F. Levin and Dahlia Kairy

J. Pers. Med. 2026, 16(2), 111; https://doi.org/10.3390/jpm16020111 - 12 Feb 2026

Viewed by 358

Abstract

Background: Although traditional rehabilitation methods are effective in promoting recovery for patients with disabilities, some approaches can involve repetitive tasks, making it challenging to maintain high patient engagement and adherence. This can impact the amount of therapy patients receive, which can sometimes [...] Read more.

Background: Although traditional rehabilitation methods are effective in promoting recovery for patients with disabilities, some approaches can involve repetitive tasks, making it challenging to maintain high patient engagement and adherence. This can impact the amount of therapy patients receive, which can sometimes limit their overall recovery potential, particularly given constraints in healthcare resources. Extended reality (XR) technologies, which include virtual reality (VR) and augmented reality (AR), offer promising benefits to personalize care and enhance rehabilitation and engagement by increasing motivation and engagement through interactive and immersive environments. Despite these promising advantages, their successful integration in clinical practice has remained limited, partly due to lack of early involvement of clinicians and end-users in the development process. Objective: We aim to provide recommendations for XR rehabilitation technology development, including researchers and industry professionals, to foster more personalized, adoptable and effective tools for patients with neuromusculoskeletal disorders in a clinical setting. Methods: Principles from motor control and game theory are used to describe key features and recommendations for XR rehabilitation technology development to optimize rehabilitation applications in a clinical setting. These recommendations stem from established motor learning and game design principles, a state-of-the-art narrative review of emerging XR rehabilitation literature (2015–2025) and insights from the Ensemble! Program, a living lab where clinicians, researchers, and patients collaborate to explore emerging technologies, including but not limited to serious games using XR technologies. Results: Key design recommendations include strategies for supporting patient motivation, adjusting game difficulty, providing feedback and handling data collection. Conclusions: Integrating motor control and game theory principles into XR rehabilitation technology can help optimize its therapeutic effectiveness and clinical applicability for patients with neuromusculoskeletal conditions. By addressing clinician and patient needs early in the development process, these technologies can be better tailored to meet therapeutic goals and facilitate broader adoption in clinical practice. Full article

(This article belongs to the Special Issue Ehealth, Telemedicine, and AI in the Precision Medicine Era)

16 pages, 10304 KB

Open AccessArticle

The Forgotten Healer: The Role of Adipose Tissue in Spontaneous Healing After Free Flap Finger Reconstruction

by Macarena Vizcay, Giorgio E. Pajardi, Alessandro Mastroiacovo and Luigi Troisi

J. Pers. Med. 2026, 16(2), 110; https://doi.org/10.3390/jpm16020110 - 12 Feb 2026

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Abstract

Background: Digital pulp reconstruction with toe-based flaps reliably restores sensibility and contour, yet the healing behavior of viable subcutaneous fat remains underexplored. Because adipose tissue exhibits patient-specific regenerative and volumetric responses, its preservation represents a key element of personalized fingertip reconstruction. This study [...] Read more.

Background: Digital pulp reconstruction with toe-based flaps reliably restores sensibility and contour, yet the healing behavior of viable subcutaneous fat remains underexplored. Because adipose tissue exhibits patient-specific regenerative and volumetric responses, its preservation represents a key element of personalized fingertip reconstruction. This study evaluates the outcomes of toe pulp flaps with targeted fat preservation to assess how individual tissue biology influences contour and functional recovery. Methods: We retrospectively reviewed consecutive digital reconstructions performed with free toe flaps and several variations (pulp toe flap, chimeric pulp toe flap, trimmed great toe flap and chimeric pulp+ trimmed great toe). Particular attention was given to healthy subcutaneous fat that was deliberately maintained or exposed to help shape the final contour. All patients were followed clinically and photographically until complete healing occurred. Results: A total of 126 patients underwent a finger reconstruction with free toe flaps and several variations. The preserved fat layer was intentionally left exposed to promote healthy granulation and spontaneous epithelialization, contributing favorably to the final contour of the distal pulp as the nail advanced. All wounds healed without the need for skin grafts. All patients achieved good to excellent functional and esthetic outcomes with minimal donor-site morbidity. Conclusions: This large retrospective series confirms the reliability of a healthy flap to help shape the digital reconstruction, highlighting the regenerative potential of viable digital fat. Incorporating this concept into the flap design may reduce the need for grafting, minimize donor-site morbidity, and enhance reconstructive outcomes in hand surgery. Full article

(This article belongs to the Special Issue Personalized Technologies in Plastic, Reconstructive and Aesthetic Surgery: From Imaging to Regeneration)

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13 pages, 2149 KB

Open AccessReview

Patient-Controlled Analgesia in ICU: A Scoping Review

by Angela Califano, Riccardo Caldonazzo, Miriam Gotti, Giovanni Sabbatini, Andrea Galimberti, Pezzi Angelo and Paolo Formenti

J. Pers. Med. 2026, 16(2), 109; https://doi.org/10.3390/jpm16020109 - 12 Feb 2026

Viewed by 349

Abstract

Background/Objectives: Patient-Controlled Analgesia (PCA) is a well-established strategy for managing postoperative pain, but its use in the Intensive Care Unit (ICU) remains poorly defined, poorly standardized, and fragmented. The aim of this scoping review is to map the extent, nature, and characteristics [...] Read more.

Background/Objectives: Patient-Controlled Analgesia (PCA) is a well-established strategy for managing postoperative pain, but its use in the Intensive Care Unit (ICU) remains poorly defined, poorly standardized, and fragmented. The aim of this scoping review is to map the extent, nature, and characteristics of the available evidence on the use of PCA in ICU patients, identifying key areas of uncertainty and knowledge gaps that require further study. Methods: Scoping review reported according to the PRISMA-ScR guidelines. Results: 12 relevant studies were identified. Available evidence suggests that PCA can provide pain control comparable to traditional techniques in post-cardiac surgery patients in the ICU, while data on its use in non-surgical patients are limited. The studies reported good feasibility and a generally favorable safety profile, with a low incidence of significant respiratory events thanks to intensive monitoring. Methodological variability prevents direct comparisons between studies. Conclusions: PCA supports personalized pain management based on patient-specific clinical conditions and response. However, more standardized studies are needed to define its role. Full article

(This article belongs to the Special Issue Advancing Anesthesia and Pain Control Through Precision Medicine)

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11 pages, 859 KB

Open AccessArticle

Dupilumab in Severe Asthma–COPD Overlap: Real-Life Experience on a Case Series

by Bruno Sposato, Gianna Camiciottoli, Leonardo Gianluca Lacerenza, Elena Bargagli, Paolo Cameli, Giovanna Elisiana Carpagnano, Manuela Latorre, Elisa Petrucci, Valentina Fabbrini, Laura Giannini, Alberto Ricci, Andrea Serafini and Marco Scalese

J. Pers. Med. 2026, 16(2), 108; https://doi.org/10.3390/jpm16020108 - 10 Feb 2026

Viewed by 469

Abstract

Background/Objective: Little is known about the efficacy of biologics and in particular Dupilumab in patients with severe asthma associated with COPD (SA-COPD) features. The objective of this study was to determine whether Dupilumab has similar clinical/functional efficacy in individuals with SA-COPD and [...] Read more.

Background/Objective: Little is known about the efficacy of biologics and in particular Dupilumab in patients with severe asthma associated with COPD (SA-COPD) features. The objective of this study was to determine whether Dupilumab has similar clinical/functional efficacy in individuals with SA-COPD and in those with pure severe asthma (SA). Methods: We retrospectively selected 11 consecutive patients with SA with COPD features (smoking history of at least 15 pack/years; emphysema on chest CT scan; FEV₁ < 80%; RV and TLC > 130%; DLCO < 70; salbutamol reversibility test < 12%) treated with Dupilumab for at least 1 year. These subjects were compared with 33 consecutive patients with SA alone who were also treated with the same biologic for at least 12 months. Results: FEV₁ and FEF_25–75 changes after treatment were 10 ± 18.3% and 18.6 ± 26.5% in the SA group, whereas they were 4.8 ± 7.6% and 7.2 ± 6.8% in individuals with SA-COPD (p = 0.909 and p = 0.102 respectively). Similarly, ACT (5.3 ± 3.1 vs. 5.6 ± 3.7; p = 0.783) and exacerbation changes (−2.97 ± 1.3 vs. −4 ± 4.3; p = 0.960) after Dupilumab were similar in the two groups. No differences were also found in FeNO and BEC changes (−18 ± 22 vs. −21.3 ± 21.1 ppb and −63.6 ± 415 vs. −142 ± 299 cells/µL respectively; p = 0.984 and p = 0.481). The percentages of subjects that reduced and stopped OC therapy and those that stepped down the level of ICS dose after treatment were also similar in the two populations. After adjustment for multiple confounding factors, changes in all evaluated outcomes also remained comparable between patients with SA-COPD and those with SA. Conclusions: In our experience, Dupilumab is effective both in patients with SA alone and in those with asthma–COPD overlap. We must always consider T2 inflammation in the management of such patients in order to provide the most appropriate treatment. Full article

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

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12 pages, 247 KB

Open AccessArticle

The Impact of PRAC EMA/AIFA Recommendations on the Prescriptions of JAKi and b-DMARDs: Preliminary Results of the Survey from 21 Rheumatological Italian Centers Affiliated with CReI

by Emanuele Antonio Maria Cassarà, Daniela Marotto, Crescenzio Bentivenga, Luis-Severino Martin Martin, Gianpiero Baldi, Norma Carrozzo, Raffaele Zicolella, Riccardo Terenzi, Andrea Delle Sedie and Maurizio Benucci

J. Pers. Med. 2026, 16(2), 107; https://doi.org/10.3390/jpm16020107 - 10 Feb 2026

Viewed by 344

Abstract

Objective: To evaluate the impact of recommendations issued by the Pharmacovigilance Risk Assessment Committee (PRAC) and endorsed by the European Medicines Agency (EMA) and the Italian Medicines Agency (AIFA) on rheumatologists’ prescribing patterns of Janus kinase inhibitors (JAK inhibitors) and biologic disease-modifying antirheumatic [...] Read more.

Objective: To evaluate the impact of recommendations issued by the Pharmacovigilance Risk Assessment Committee (PRAC) and endorsed by the European Medicines Agency (EMA) and the Italian Medicines Agency (AIFA) on rheumatologists’ prescribing patterns of Janus kinase inhibitors (JAK inhibitors) and biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA), within a personalized, risk-adapted care framework. Methods: A brief survey was conducted across 21 Italian rheumatology centers. This retrospective multicenter study included 4421 RA patients assessed before PRAC recommendations (1 January 2022–1 January 2023) and 4376 patients evaluated afterward (2 January 2023–1 January 2024). Prescribing behaviors, cardiovascular risk management, and clinical outcomes were compared between cohorts. Results: Following PRAC recommendations, a more individualized cardiovascular risk management strategy was observed, with increased use of targeted treatments for hypercholesterolemia, hypertension, and diabetes. The post-PRAC cohort showed a significant reduction in myocardial infarction incidence (0.90% vs. 0.47%; p = 0.02) and increased statin use (8.25% vs. 11.1%; p = 0.05). No increase in cardiovascular risk was observed among JAK inhibitor users. Notably, upadacitinib utilization remained stable despite regulatory restrictions. Conclusions: PRAC recommendations promoted safer prescribing practices and improved cardiovascular risk stratification in RA. These findings support a shift toward precision medicine, integrating real-world evidence with advanced diagnostic and decision-support tools, including future artificial intelligence-based approaches, to optimize personalized therapeutic strategies in autoimmune diseases. Full article

(This article belongs to the Special Issue Advancing Tailored Diagnostics and Therapeutics in Autoimmune and Rheumatic Diseases via Integration of Traditional Approaches and AI Technologies)

14 pages, 588 KB

Open AccessReview

Personalized Treatments for Functional Disorders of the Sphincter of Oddi: A Short Muscle with a Long History of Discussion and Controversies

by Zoltán Berger and Ákos Pap

J. Pers. Med. 2026, 16(2), 106; https://doi.org/10.3390/jpm16020106 - 10 Feb 2026

Viewed by 406

Abstract

The sphincter of Oddi (OS) is a small group of smooth muscles that plays a crucial role in the regulation of the flow of biliopancreatic secretions into the duodenal lumen. Its motility, including phasic contractions and relaxation, is under complex neurohumoral control. Organic [...] Read more.

The sphincter of Oddi (OS) is a small group of smooth muscles that plays a crucial role in the regulation of the flow of biliopancreatic secretions into the duodenal lumen. Its motility, including phasic contractions and relaxation, is under complex neurohumoral control. Organic or functional obstruction of the OS is an important factor in severe diseases, such as cholangitis and pancreatitis, as well as in functional disorders and recurrent abdominal pain. In this review, we summarize the function of the OS, its disorders, and their diagnostic methods and potential therapeutics. While organic diseases of the papilla often require invasive, mainly endoscopic, treatment, functional disorders should be managed with conservative, individualized treatment, and involve the patient and their family in decision-making. Full article

(This article belongs to the Special Issue Laparoscopy, Perioperative Care and Complications in Surgery for Gastrointestinal Diseases)

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18 pages, 517 KB

Open AccessReview

Advances in Non-CPAP Management of Obstructive Sleep Apnea: Spotlight on Pharmacological Therapies

by Matteo Siciliano, Martina de Scisciolo, Antonio Fratini, Costanza Sottani, Federico Giordani and Valerio Brunetti

J. Pers. Med. 2026, 16(2), 105; https://doi.org/10.3390/jpm16020105 - 10 Feb 2026

Viewed by 537

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder associated with significant cardiometabolic morbidity, impaired neurocognitive functioning, daytime sleepiness, and reduced quality of life. Although continuous positive airway pressure (CPAP) therapy remains the cornerstone of treatment for moderate-to-severe OSA, long-term adherence [...] Read more.

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder associated with significant cardiometabolic morbidity, impaired neurocognitive functioning, daytime sleepiness, and reduced quality of life. Although continuous positive airway pressure (CPAP) therapy remains the cornerstone of treatment for moderate-to-severe OSA, long-term adherence is frequently suboptimal, and a substantial proportion of patients experience residual symptoms despite adequate therapy. These limitations have driven increasing interest in non-CPAP treatment strategies and, more recently, in pharmacological approaches tailored to specific OSA pathophysiological mechanisms. This narrative review provides an updated overview of non-CPAP therapies for OSA, including oral appliances, surgical interventions, positional therapy, hypoglossal nerve stimulation, and behavioral strategies, with a particular focus on emerging and established pharmacological treatment and their role in endotype/phenotype-guided management of OSA. Overall, the expanding pharmacological landscape of OSA reflects a paradigm shift toward personalized, multimodal management. Integrating non-CPAP and pharmacological therapies with patient-specific pathophysiology may improve symptom control, adherence, and long-term outcomes in OSA. Full article

(This article belongs to the Special Issue Treatment and Management of Sleep Apnea)

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13 pages, 793 KB

Open AccessArticle

Comparative Effectiveness of Pessary Placement, Cervical Cerclage, or Expectant Management in Preventing Preterm Delivery in Twin Pregnancies

by Christina Pagkaki, Nektaria Kritsotaki, Anastasia Bothou, Vasiliki Kourti, Georgios Tsatsaris, Barbara Niesigk, Efthymios Oikonomou, Nikolaos Machairiotis, Nikolaos Tsikouras, Spyridon Michalopoulos, Anastasia Grapsa, Angeliki Gerede, Nikoletta Koutlaki, Alexander Tobias Teichmann and Panagiotis Tsikouras

J. Pers. Med. 2026, 16(2), 104; https://doi.org/10.3390/jpm16020104 - 10 Feb 2026

Viewed by 259

Abstract

Objective: The objective of this study was to evaluate the association between cervical management strategies, specifically pessary placement, cervical cerclage, or expectant management, and gestational age at delivery in twin pregnancies and to assess the prognostic value of cervical characteristics for early preterm [...] Read more.

Objective: The objective of this study was to evaluate the association between cervical management strategies, specifically pessary placement, cervical cerclage, or expectant management, and gestational age at delivery in twin pregnancies and to assess the prognostic value of cervical characteristics for early preterm birth (<33 weeks). Methods: We conducted a retrospective cohort study including 120 twin pregnancies managed at a tertiary referral center between 2019 and 2024. Pregnancies with positive vaginal or cervical microbiological cultures or abnormal cervical cytology were excluded. The management strategy was selected based on cervical characteristics and clinical judgment. Gestational age at delivery was compared across intervention groups using descriptive statistics, kernel density plots, boxplots, and Kaplan–Meier survival analysis. Multivariable Cox proportional hazards regression was performed to estimate adjusted hazard ratios (HRs) for early delivery, including intervention type and cervical parameters (length, diameter, and funneling). Results: Overall, 26 of 120 pregnancies (21.6%) resulted in delivery before 33 weeks. Pessary placement was associated with longer gestational duration compared with cerclage or expectant management. Kaplan–Meier analysis demonstrated a clear separation of survival curves by intervention group, with the pessary group maintaining pregnancy to later gestational ages (log-rank p < 0.001). In multivariable Cox regression analysis, pessary use was associated with a significantly lower hazard of early delivery compared with cerclage (HR = 0.088, 95% CI: 0.035–0.220; p < 0.001). Expectant management showed a trend toward an increased risk of early delivery (HR = 2.44; p = 0.067). Cervical length and diameter were not independently associated with early delivery after adjustment for intervention type. Funneling was associated with a lower hazard of early delivery, a finding that warrants cautious interpretation. Conclusions: In this retrospective cohort of twin pregnancies without microbiological evidence of infection, pessary placement was associated with prolonged gestation and a lower hazard of early preterm delivery compared with cerclage or expectant management. These findings support a personalized, risk-adapted approach to cervical intervention selection in twin pregnancies. Prospective, randomized studies incorporating etiologic stratification are needed to confirm these associations and guide clinical practice. Full article

(This article belongs to the Special Issue Multiple Pregnancies: Optimal Follow-Up, Early Detection and Management of Complications, and Appropriate Mode and Time of Delivery)

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14 pages, 1446 KB

Open AccessReview

Infective Endocarditis and Complications; Surgical Indications and Management: An Integrative Review

by Daniel Bishev, Michael V. DiCaro, Shudipan Chakraborty, Gregory-Thomas Stanger, Camille Ho and Tahir Tak

J. Pers. Med. 2026, 16(2), 103; https://doi.org/10.3390/jpm16020103 - 9 Feb 2026

Viewed by 784

Abstract

Infective endocarditis (IE) is an infection of the endocardial surface of the heart involving native or prosthetic valves, endocardial structures, or intracardiac devices/leads. Unfortunately, incidence has risen in many settings over recent years. Historically, the incidence has been about 3–10 cases for every [...] Read more.

Infective endocarditis (IE) is an infection of the endocardial surface of the heart involving native or prosthetic valves, endocardial structures, or intracardiac devices/leads. Unfortunately, incidence has risen in many settings over recent years. Historically, the incidence has been about 3–10 cases for every 100,000 person-years and was elevated to about 13.8 cases per 100,000 person-years in 2019. Despite advancements in both detection and treatment, mortality remains high, seen with inpatient mortality rates of 18%, along with a 6-month mortality rate of 30%. IE can be a fatal condition if left untreated, in part due to the multiple serious complications that can arise. By anticipating certain complications, clinicians can be better prepared to treat patients with this condition. This article provides an integrative review of the potential complications of IE. These complications vary depending on whether the patient has native or prosthetic valves. There are cardiac, embolic, and immune-complex mediated complications that can occur. Ultimately, IE can lead to multiorgan dysfunction and result in septic shock and disseminated intravascular coagulopathy (DIC). While the mainstay of treatment for IE remains medical, certain cases require surgical intervention. Due to their close relationship, a review of the indications for surgery in the treatment of IE is also presented in this article. By having a general scope of the complications of IE and when to get a surgical consult, clinicians can be better equipped to care for patients with a potentially fatal condition that is becoming increasingly more frequent. Full article

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

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13 pages, 1633 KB

Open AccessArticle

Association Between ADA (Age–D-dimer–Albumin) Score and Chest CT Severity Score in COVID-19 Pneumonia

by Enrico Maggio, Giacomo Bonito, Alessandra Oliva, Claudio Maria Mastroianni, Riccardo Vezza, Francesco Pugliese, Francesco Violi, Paolo Ricci, Lorenzo Loffredo and Pasquale Pignatelli

J. Pers. Med. 2026, 16(2), 102; https://doi.org/10.3390/jpm16020102 - 9 Feb 2026

Viewed by 481

Abstract

Background/Objectives: This study aims to assess the relation between the ADA score with the severity of pneumonia, as evaluated by chest tomography using a severity score. Methods: In this observational study we enrolled 350 consecutive adult patients (≥18 years) [...] Read more.

Background/Objectives: This study aims to assess the relation between the ADA score with the severity of pneumonia, as evaluated by chest tomography using a severity score. Methods: In this observational study we enrolled 350 consecutive adult patients (≥18 years) with COVID-19-related severe acute pneumonia requiring hospitalization, consecutively admitted to non-intensive care unit (ICU) medical wards from April 2020 to March 2022. A standard high-resolution chest computed tomography (HRCT) was performed in all cases with a multidetector CT scanner without intravenous contrast injection, except in case of suspicion of pulmonary embolism. The ADA score and semi-quantitative 25-point CT Severity Score (CTSS) were calculated for all patients. Results: A total of 350 COVID-19 patients (154 males (44%) and 196 females (56%)) were recruited. A logistic regression analysis showed that CTSS is statistically associated with the ADA score (Exp(B): 1.116; 95% CI: 1.027–1.212; p = 0.009) and the need for ICU (Exp(B): 8.719; 95% CI: 2.994–25.390; p < 0.001), while the linear regression analysis showed a relation between the CTSS and ADA score, GFR and CRP (p = 0.003) (predictors: ADA score [β coeff 0.276; 95% CI: 0.041–−0.402; p = 0.017], GFR [β coeff −0.219; 95% CI: −0.095–−0.001; p = 0.045], CRP [β coeff −0.226; IC 95% −0.077–−0.001; p = 0.044]). Furthermore, a ROC curve analysis determined the optimal ADA score cut-off values for predicting severe CT findings at 44.5 (sensibility: 0.971; 1-specificity: 0.670; AUC: 0.750; SE 0.039; p < 0.001; 95% CI: 0.674–0.826; Youden’s J index= 0.301). Conclusions: This study highlights the potential clinical utility of integrating laboratory- and imaging-based scores for a comprehensive assessment of patients hospitalized with SARS-CoV-2 infection. The combined use of these scores may enable a more accurate identification of patients with extensive pulmonary involvement and an increased prothrombotic burden at hospital admission, facilitating the early recognition of high-risk patients. Full article

(This article belongs to the Section Diagnostics in Personalized Medicine)

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1 pages, 138 KB

Open AccessCorrection

Correction: Tian et al. Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells. J. Pers. Med. 2022, 12, 1318

by Shiliu Tian, Rui Su, Ke Wu, Xuhan Zhou, Jaydutt V. Vadgama and Yong Wu

J. Pers. Med. 2026, 16(2), 101; https://doi.org/10.3390/jpm16020101 - 9 Feb 2026

Viewed by 177

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)

11 pages, 666 KB

Open AccessBrief Report

Can Physical Activity, Sleep Parameters, and Sleep–Wake Patterns Predict Outcome of Combined Chronotherapy in Mood Disorder During Routine Clinical Practice? An Exploratory Study

by Stella J. M. Druiven, Olga Minaeva, Benno C. M. Haarman, Ybe Meesters, Robert A. Schoevers, Jeanine Kamphuis and Harriëtte Riese

J. Pers. Med. 2026, 16(2), 100; https://doi.org/10.3390/jpm16020100 - 7 Feb 2026

Viewed by 323

Abstract

Background/Objectives: Combined chronotherapy (CCT), which combines repeated sleep deprivation and light therapy, is used in the clinical treatment of severe depression. Despite its potential to rapidly reduce depressive symptoms, CCT is infrequently used in clinical practice. We explored whether actigraphy-derived within-patient changes [...] Read more.

Background/Objectives: Combined chronotherapy (CCT), which combines repeated sleep deprivation and light therapy, is used in the clinical treatment of severe depression. Despite its potential to rapidly reduce depressive symptoms, CCT is infrequently used in clinical practice. We explored whether actigraphy-derived within-patient changes in physical activity, sleep parameters, and sleep–wake patterns prior to CCT can help identify those most likely to benefit from this treatment, supporting personalized mental health care. Methods: Actigraphy data from nine severely depressed patients were collected before, during, and after CCT. Data were assessed with a questionnaire on depressive symptoms (Inventory of Depressive Symptomatology—Self Report, IDS-SR) and actigraphy measures for sleep–wake patterns and physical activity: daily mean activity level, rhythm (intradaily variability (IV), interdaily stability (IS)), Midpoint of Sleep (MSF), time in bed, sleep efficiency (SE), and the fragmentation index (FI). Variables were compared before and after CCT by systematic visual inspection due to the small sample size. A prior set Minimal Clinically Important Difference (MCID) of a 30% change in IDS scores from before and the week after CCT was used to categorize patients as responders (n = 3) or nonresponders (n = 6) to CCT. Results: After CCT, for both responders and nonresponders, there was a notable decrease in IDS, IV and FI. Prior to CCT, responders, compared to nonresponders, were characterized with higher IDS, more time in bed and higher FI, while having lower SE. Conclusions: We concluded that actigraphy assessments during regular CCT are feasible and found preliminary evidence that patients with the most disrupted sleep–wake patterns prior to treatment may benefit most from CCT. Full article

(This article belongs to the Section Diagnostics in Personalized Medicine)

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36 pages, 1595 KB

Open AccessReview

Probiotics as Microbiome Modulators in Male Infertility: Rethinking Dysbiosis Across the Gut–Testis Axis

by Aris Kaltsas, Spyros Pournaras, Ilias Giannakodimos, Eleftheria Markou, Marios Stavropoulos, Stamatis Papaharitou, Fotios Dimitriadis, Athanasios Zachariou, Nikolaos Sofikitis and Michael Chrisofos

J. Pers. Med. 2026, 16(2), 99; https://doi.org/10.3390/jpm16020099 - 6 Feb 2026

Viewed by 416

Abstract

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured [...] Read more.

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut–testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood–testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence. Full article

(This article belongs to the Special Issue Urological Diseases: Updates and Challenges on Personalized Diagnosis, Treatment, and Management)

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20 pages, 339 KB

Open AccessReview

One Score Fits All? A Narrative Review on Early Warning Scores for Older Adults in the Emergency Department in the Era of Personalized Medicine

by Valeria Maccauro, Piergiacomo Maria Cacciamani Fanelli, Davide Antonio Della Polla, Nicola Bonadia, Giuseppe De Matteis, Andrea Piccioni, Antonio Gasbarrini, Claudio Sandroni, Francesco Franceschi and Marcello Covino

J. Pers. Med. 2026, 16(2), 98; https://doi.org/10.3390/jpm16020098 - 6 Feb 2026

Viewed by 453

Abstract

Background: The growing use of Emergency Departments (EDs) by older adults highlights the need for early and accurate identification of clinical deterioration. Early Warning Scores (EWSs) are widely implemented tools based on standardized vital sign thresholds; however, their performance in elderly patients is [...] Read more.

Background: The growing use of Emergency Departments (EDs) by older adults highlights the need for early and accurate identification of clinical deterioration. Early Warning Scores (EWSs) are widely implemented tools based on standardized vital sign thresholds; however, their performance in elderly patients is inconsistent, likely reflecting the biological heterogeneity, multimorbidity, and reduced physiological reserve typical of this population. Objectives: This narrative review aims to summarize current evidence on the use of EWSs in adults aged ≥ 65 years presenting to the ED, with a specific focus on mortality and intensive care unit (ICU) admission, and to discuss their role within the evolving framework of personalized medicine. Sources: A narrative review of 36 clinical studies published between 2014 and 2025 was conducted. Content: Traditional scores such as National Early Warning Score (NEWS), National Early Warning Score 2 (NEWS2), Modified Early Warning Score (MEWS), VitalPAC Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS) show variable and often reduced prognostic accuracy in older and frail patients. Evidence consistently suggests that applying uniform cut-off values fails to capture individual vulnerability in elderly patients. The integration of age, frailty, comorbidities, and baseline physiological status improves risk stratification. Second-generation tools—including Copeptin-NEWS, NEWS-L, suPAR-NEWS, OPERA, and RISE UP—as well as artificial intelligence-based models, represent emerging personalized approaches to clinical deterioration prediction. Implications: No single score currently provides reliable early risk prediction for all elderly ED patients. Moving beyond “one-size-fits-all” EWSs toward adaptive, person-centered models may better reflect the complexity of geriatric emergency care and improve prognostic accuracy. Full article

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

24 pages, 1931 KB

Open AccessReview

Glucagon-like Peptide Receptor Agonists and Kidney Outcomes in the Era of Personalized Medicine: Focus on Albuminuria

by Ana Checa-Ros, Owahabanun Joshua Okojie, Jacob Gabriel Wassouf, Aida Yedean, Wei-Chung Hsueh, Patryk Hebda, Esther Rodriguez Llobell, Greta Bianca Muhmenthaler, Martin Duc-Duy Tran and Luis D’Marco

J. Pers. Med. 2026, 16(2), 97; https://doi.org/10.3390/jpm16020097 - 6 Feb 2026

Viewed by 548

Abstract

The aim of this narrative review is to critically assess the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in managing albuminuria among patients with type 2 diabetes mellitus within the framework of personalized medicine. By integrating current evidence from clinical trials and [...] Read more.

The aim of this narrative review is to critically assess the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in managing albuminuria among patients with type 2 diabetes mellitus within the framework of personalized medicine. By integrating current evidence from clinical trials and meta-analyses, the review highlights how GLP-1RAs not only enhance glycemic control but also reduce blood pressure, induce weight loss, and mitigate inflammatory responses. While these given factors may vary according to individual patient profiles, they also collectively contribute to slowing the progression of diabetic kidney disease (DKD). Additionally, the discussion emphasizes the dual cardiovascular and renal benefits from these agents, underscoring their role in reducing albuminuria and preserving renal function. The review also identifies gaps in knowledge, suggesting future research directions for optimizing patient selection and treatment regimens to maximize therapeutic benefits. Full article

(This article belongs to the Special Issue Precision Medicine in Chronic Kidney Disease: Diagnostics, Treatment, and Outcomes)

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