Journal of Personalized Medicine doi: 10.3390/jpm16080424

Authors: Cheedy Jaja Daniel M. Sop Andrew Campbell Wally R. Smith

Pain is a leading cause of morbidity and healthcare utilization in sickle cell disease (SCD), and opioids remain central to treating vaso-occlusive and chronic pain. Yet opioid response varies widely, raising the question of whether pharmacogenetic testing should inform opioid prescribing. Our review examined the PubMed literature on pharmacogenomics and opioid efficacy in SCD. We focus on CYP2D6 as the clearest current pharmacogenetic signal for codeine and tramadol, and assess SCD-specific implementation studies, preemptive testing, and African pharmacoequity. The current evidence supports targeted CYP2D6-informed prescribing in selected contexts rather than universal testing for all opioids, while highlighting the need to integrate genotype with pain phenotype, drug–drug interactions, liver function, and clinically grounded implementation studies, and better characterize African and African-ancestry pharmacogene variation.

Journal of Personalized Medicine doi: 10.3390/jpm16080423

Authors: Alifa Nasrin Muhammad Bin Asif Ramasamy Naidu Afzal Haq Asif Muhammad Shahzad Chohan Gausal Azam Khan Md Arifuzzaman Akm Azad Muhammad Ali Martuza

Background: Diabetes mellitus affects over 500 million people worldwide, yet many machine learning prediction models remain difficult to interpret, limiting their clinical applicability. This study proposes an explainable machine learning framework integrating the Marine Predators Algorithm (MPA) for hyperparameter optimization with SHAP-based explainability to diabetes prediction. Methods: Logistic Regression (LR), Random Forest (RF), and MPA-optimized XGBoost were evaluated using a publicly available Kaggle diabetes dataset of approximately 100,000 records. Statistical significance was assessed using Wilcoxon signed-rank tests with Bonferroni correction for fold-wise cross-validation results, while McNemar’s and DeLong’s tests were employed for paired comparison of independent test-set predictions and ROC-AUC values, respectively. Performance was assessed using accuracy, precision, recall, F1-score, specificity, ROC-AUC, and Brier score. SHAP was used to provide global and local model explanations. Results: The MPA-optimized XGBoost model achieved the highest performance, with 96.72% accuracy, 97.70% precision, 95.70% recall, 96.71% F1-score, and 99.56% ROC-AUC, significantly outperforming LR and RF (p < 0.001). The model demonstrated good calibration with a Brier score of 0.0262. SHAP analysis identified HbA1c level, blood glucose level, and age as the most influential predictors, while interaction analysis indicated a synergistic relationship between HbA1c and blood glucose. Conclusions: The proposed framework demonstrated strong predictive performance and interpretable model behavior on the publicly available diabetes dataset used in this study. These findings indicate the potential of MPA-based optimization combined with SHAP explainability for supporting transparent machine learning research in diabetes prediction. However, additional external validation using independent clinical datasets is required before considering the framework for clinical decision support or real-world deployment.

Journal of Personalized Medicine doi: 10.3390/jpm16080422

Authors: Alan Sinclair Ffion James Aswani Muraleedharan Ahmed Abdelhafiz

Introduction: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. Methods: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. Results: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. Conclusions: Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients.

Journal of Personalized Medicine doi: 10.3390/jpm16080421

Authors: Adil Sarvar Mohammed Sai Priyanka Mellacheruvu Zainab Gandhi Sai Prasanna Lekkala Suvidha Manne Umera Yasmeen Iramunisa Begum Rupak Desai Shrinivas Kambali Lakshmi Sai Meghana Kodali Shiny Teja Kolli Shaylika Chauhan Shweta Kambali

Background: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. Methods: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. Results: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (p < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. Conclusions: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine.

Journal of Personalized Medicine doi: 10.3390/jpm16080420

Authors: Ioannis Mykoniatis Athanasios Papatzelos Damianos Damon Dejan Nikolaou Nikolovski Asterios Symeonidis Christos Roidos Chrysovalantis Toutziaris Ioannis Vakalopoulos Petros Sountoulides

Background: Active surveillance (AS) represents a cornerstone of personalized medicine in uro-oncology, offering an individualized management strategy for low- and selected favourable intermediate-risk prostate cancer that aligns treatment intensity with patient-specific risk profiles; however, real-world adherence data from southern European academic centres remain scarce. This study aimed to evaluate AS discontinuation rates, reasons for transition to active treatment, and quality of life (QoL) in a single-centre Greek university hospital cohort. Methods: This is an observational retropective cohort study of patients enrolled in an AS protocol at the First Department of Urology, Aristotle University of Thessaloniki, between October 2016 and July 2022. Treatment-free survival (TFS) was estimated using Kaplan–Meier analysis. Associations between AS discontinuation and age at diagnosis, PSA level, and Charlson Comorbidity Index (CCI) were explored using univariable and multivariable Cox proportional hazards regression. QoL, erectile function, and anxiety were assessed cross-sectionally in patients remaining on AS using SF-12, IIEF-6, STAI-6, and MAX-PC. Results: Thirty-six patients were included (32 low-risk; 4 favourable intermediate-risk), with a median age of 69.5 years, median PSA of 6.92 ng/mL, and median CCI of 3. After a median follow-up of 24 months (IQR 21–45), 19 patients (52.8%) transitioned to active treatment; the median time to treatment was 21 months (IQR 17–34). Among the 10 patients with a known reason for discontinuation, 6 (31.6% of all discontinued) showed histopathological or clinical disease progression, 3 (15.8%) had a PSA increase alone, and 1 (5.3%) transitioned due to urinary symptoms; the reason was unknown in 9 cases (47.4%). In exploratory Cox regression, PSA ≥ 7.0 ng/mL was the only factor with complete documented output significantly associated with transition to active treatment (univariable HR 3.70, 95% CI 1.35–10.1, p = 0.011; multivariable HR 3.93, 95% CI 1.42–10.9, p = 0.008). Cross-sectional QoL assessment in 10 patients remaining on AS demonstrated median scores above established population norms for SF-12 and below clinical anxiety thresholds on STAI-6 and MAX-PC. Conclusions: In this single-centre cohort, AS discontinuation occurred early and at a rate higher than that of established international programmes, consistent with the institution’s initial AS experience. Higher PSA at diagnosis was the only factor with complete analytical documentation to be significantly associated with earlier transition.

Journal of Personalized Medicine doi: 10.3390/jpm16080419

Authors: Sergey Yu. Muraviev Zakhar A. Akulov Maria A. Sukhanova Miroslava O. Pilipenko Evgeniy A. Tarabrin Zelimkhan G. M. Berikkhanov Milena Yu. Ivanova Andrey M. Nikolaev Vadim S. Razumovsky Vladislav S. Rakintsev Aleksey G. Kotelnikov Sara Nourmahal Alexey L. Shestakov

Objectives: To assess whether muscle morphology and metabolism can inform personalised care in ventral hernias and to define which parts of a proposed postoperative remodelling model are supported by direct evidence. Methods: We conducted a structured narrative review of PubMed/MEDLINE, Scopus and Web of Science from 1 January 2010 through 30 April 2026. Two authors selected 38 publications. Evidence was classified as direct when generated in ventral or incisional hernia cohorts and indirect when drawn from inguinal hernia, transplantation, geriatric, oncological, animal or general muscle studies. No quantitative synthesis was undertaken. Results: Direct studies document lateral muscle displacement, impaired abdominal wall function, inconsistent associations between low muscle mass and clinical outcomes, and CT-derived increases in muscle cross-sectional areas after transversus abdominis release (TAR). The evidence for anterior abdominal wall myosteatosis, biomarker-guided care and the three proposed remodelling trajectories remains largely indirect. In a 37-patient TAR series, the median rectus abdominis cross-sectional area increased by 16.1% (IQR 11.4–27.0%); muscle function and metabolic recovery were not measured. Conclusions: Routine CT can yield muscle area, attenuation and intermuscular adipose tissue measures without further imaging. No anterior abdominal wall-specific thresholds or biomarker cut-offs have been validated, so these measures should not determine current treatment in isolation. Prospective studies should test whether combined imaging, functional and clinical phenotyping improves the selection of prehabilitation and follow-up.

Journal of Personalized Medicine doi: 10.3390/jpm16080418

Authors: Maria Efenesia Baffa Roberto Maglie Stefano Colabrese Carlo Pipitò Vincenzina Rubino Sasha Visinoni Lucrezia Cerchiai Marzia Caproni Emiliano Antiga

Vitiligo is an autoimmune depigmenting disorder characterized by marked heterogeneity in therapeutic response, both between patients and among lesions within the same individual. While current therapies primarily target interferon-γ (IFN-γ)-driven inflammation, clinical outcomes remain variable and frequently incomplete, suggesting that additional lesion-specific biological factors contribute to repigmentation potential. In this narrative review, we propose the concept of repigmentation competence to describe the capacity of an individual lesion to achieve clinically meaningful repigmentation under therapy. We hypothesize that this competence emerges from the interaction of four interconnected biological axes: (i) cytokine network and immune memory, (ii) local immune regulation, (iii) regenerative capacity, and (iv) microenvironmental permissiveness. A targeted search of PubMed/MEDLINE and ClinicalTrials.gov up to March 2026 was conducted to identify translational studies, mechanistic models, and clinical trials relevant to these pathways. Evidence was synthesized thematically with emphasis on cytokine-mediated mechanisms and their interaction with regenerative and tissue-context processes. The IFN-γ/CXCL9/CXCL10 axis and tissue-resident memory T cells (TRM) represent the most clinically validated drivers of disease persistence, as demonstrated by the therapeutic efficacy of JAK inhibitors, although immune suppression alone often fails to achieve complete or durable repigmentation. In contrast, regulatory pathways involving PD-1/PD-L1 signaling, regulatory T cells (Tregs), IL-10, TGF-β, and IL-2–based strategies remain biologically compelling but only partially translated into effective therapies. Regenerative capacity has also emerged as an important determinant of treatment response, with growing evidence supporting the role of melanocyte stem cell niches, follicular regeneration, and Wnt/β-catenin signaling. Accordingly, regenerative approaches such as non-cultured epidermal cell suspension (NCES) are increasingly being integrated into combination therapeutic strategies. The lesional microenvironment remains the least therapeutically developed axis despite growing experimental evidence supporting its importance in melanocyte survival and migration. Collectively, these observations suggest that the variable efficacy of current therapies may reflect different combinations of lesion-specific biological constraints. The emerging benefit of combination strategies may therefore derive not simply from additive effects, but from the simultaneous engagement of multiple axes involved in repigmentation competence. Our review supports a shift from a predominantly drug-centered model toward a lesion-oriented framework integrating immune, regenerative, regulatory, and microenvironmental determinants of response.

Journal of Personalized Medicine doi: 10.3390/jpm16080417

Authors: Aris Kaltsas Andreas Koumenis Evangelos N. Symeonidis Fotios Dimitriadis Nikolaos Sofikitis

Background/Objectives: Varicocele is usually clinically left-sided, but imaging and mechanistic studies suggest that contralateral venous reflux or bilateral testicular effects may be more common than physical examination indicates. This narrative review critically examines whether varicocele-associated infertility is better conceptualized as an asymmetric disorder with potential bilateral anatomical or functional involvement and considers the implications for diagnosis and treatment. Methods: PubMed/MEDLINE and Scopus were searched from inception to 21 June 2026 for studies on varicocele laterality, bilateral and subclinical disease, color Doppler ultrasonography, venography, and unilateral versus bilateral repair. Reference lists and contemporary clinical guidelines were also reviewed. Because the included studies differed substantially in patient selection, age, operator technique, diagnostic criteria, and reference standards, reported bilateral rates were not interpreted as head-to-head estimates of diagnostic sensitivity or as pooled prevalence estimates. Results: Physical examination identifies predominantly left-sided clinical disease. Bilateral involvement is reported more frequently when both sides are assessed using Doppler ultrasonography or venography, but estimates vary widely across referral-enriched and highly selected cohorts. Human and experimental evidence supports several mechanisms by which a clinically unilateral lesion may have bilateral functional effects, including shared scrotal hyperthermia, oxidative stress, endocrine disturbance, and venous cross-communication. Bilateral repair is consistent with standard treatment criteria when both varicoceles are clinically palpable. In men with a clinical left varicocele and non-palpable right-sided reflux, comparative evidence is mixed, and current guidelines do not support routine treatment of imaging-only disease. Conclusions: Varicocele is best viewed as an asymmetric disorder that may be anatomically or functionally bilateral in selected men, rather than as a universally bilateral disease. Deliberate bilateral clinical assessment and standardized bilateral ultrasonography when imaging is clinically indicated may improve phenotyping and operative planning. However, contralateral imaging abnormalities should not automatically be converted into a surgical indication.

Journal of Personalized Medicine doi: 10.3390/jpm16080416

Authors: Coco Ng Gurpreet K. Singhera Ea Chung Chang Amrit Samra Katherine A. Adolphs Evan H. Phillips Jamil Bashir Zachary Laksman Honglin Luo Gordon A. Francis Chi Lai Ying Wang

Background: Although cardiovascular disease (CVD) significantly impacts the quality of life of millions of patients worldwide, the high costs of developing new drugs and conducting clinical trials for CVD hinder therapeutic development in this field. Repurposing approved drugs, of which the safety has already been tested can significantly reduce the time and cost required for treating CVD. From the perspective of pharmacology, repurposed drugs are selected to specifically target CVD patients carrying the matching drug targets, enabling tailored, personalized intervention. In the context of drug repurposing, therapeutic target mapping is a process used to assess the enrichment of molecules that can be affected by a drug in order to produce a therapeutic effect. Methods: This narrative review summarizes the workflows and challenges of performing therapeutic target mapping to assess the potential of repurposing existing drugs for treating CVD. We also share our perspective of how retrospective studies of human specimens can contribute to therapeutic target mapping based on experience from the Bruce McManus Cardiovascular Biobank (BMCB), a large explanted heart biobank located in Vancouver, Canada. The literature we discuss was identified by non-systematic searches of PubMed, using search terms “human-derived specimens”, “drug repurposing”, and “cardiovascular disease”. We reviewed articles from 2012 to 2026 and prioritized studies conducted after 2019 to discuss recent advances in the field. Conclusions: Human specimens of high molecular quality are needed for evaluating the enrichment of drug targets in CVD. Therapeutic target mapping in diseased cardiovascular tissue requires integrated expertise from medical, translational, and applied sciences to identify suitable human specimens for molecular phenotyping, and to design hypothesis-driven approaches to validate the drugs suggested for repurposing.

Journal of Personalized Medicine doi: 10.3390/jpm16080415

Authors: Electra Chatzidimitriou Georgios Ntritsos Eleni Poptsi Emmanouil Tsardoulias Andreas L. Symeonidis Magda Tsolaki Panos Charalambous Chrissa Sioka Eleni Aretouli Ioannis Iakovou Katherine P. Rankin Panagiotis Ioannidis Despina Moraitou

Background and Objectives: Functional decline is a major determinant of disability, caregiver burden, and loss of independence in behavioral variant frontotemporal dementia (bvFTD). Although bvFTD is characterized by early and rapidly progressive deterioration in everyday functioning, the multimodal contributors associated with longitudinal functional change remain insufficiently understood. The present study aimed to identify the strongest cognitive, behavioral, personality, and neuroimaging correlates of longitudinal functional deterioration in bvFTD using an integrated multimodal framework over a 12-month follow-up period. Methods: Twenty-seven patients diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of the “AHEPA” University Hospital in Thessaloniki, Greece, and underwent comprehensive face-to-face neuropsychological assessment for the evaluation of a wide range of cognitive domains, alongside caregiver-based evaluations of behavioral disturbances, personality changes, and functional abilities, at baseline, 6 months, and 12 months. Brain perfusion single-photon emission computed tomography (SPECT) was acquired only at baseline, with regional cerebral blood flow (rCBF) quantified using a Brodmann area (BA)-based approach. Functional status was assessed using the Disability Assessment for Dementia (DAD) as the primary outcome, while the Frontotemporal Dementia Rating Scale (FRS) served as a secondary measure. Repeated-measures analysis of variance (ANOVA) was used to characterize longitudinal changes across cognitive, behavioral, personality, and functional domains, while linear mixed-effects (LME) models were applied to identify longitudinal correlates of functional decline and sources of inter-individual variability in functional outcomes. Results: Significant progressive decline in functional abilities was observed over the 1-year follow-up period, consistent with an aggressive and rapidly deteriorating clinical course in bvFTD. Reductions in functional performance were evident across both basic and instrumental activities of daily living, with deterioration being more pronounced in instrumental activities. Based on the final LME model, greater apathy-related (negative) behavioral symptoms, global cognitive impairment, attentional and processing speed deficits, and impaired inhibitory control were independently associated with poorer longitudinal functional outcomes (p < 0.001). At the neuroimaging level, reduced baseline perfusion in the right BA 24 within the anterior cingulate cortex was also significantly associated with greater loss of functional independence over time (p < 0.001). Conclusions: Longitudinal functional decline in bvFTD reflects the combined disruption of behavioral regulation, global cognition, executive control, and frontal–cingulate network integrity. The findings provide a preliminary foundation for future research investigating factors associated with accelerated functional decline. Further validation in larger, multicenter longitudinal cohorts is needed to determine the prognostic relevance of these factors and their potential applicability to patient stratification and individualized care planning.

Journal of Personalized Medicine doi: 10.3390/jpm16080414

Authors: Christian D’Elia Edda Russo Giada Santagata Riccardo Terenzi Francesca Li Gobbi Emanuele Antonio Maria Cassarà Elisa Cioffi Valentina Grossi Francesca Romano Barbara Lari Maria Infantino Mariangela Manfredi Serena Guiducci Maurizio Benucci

Background: Polymyalgia rheumatica (PMR) is a clinically heterogeneous inflammatory disorder in which conventional acute-phase reactants may inadequately reflect the complexity and biological variability of disease activity. Precision medicine approaches integrating multidimensional clinical and laboratory data may offer a more comprehensive characterization of inflammatory phenotypes. This study investigated whether the combined assessment of cytokine profiles, routine laboratory biomarkers, ultrasound findings, and clinical variables could improve disease activity stratification in PMR. Methods: A total of 103 consecutive patients with PMR were retrospectively analyzed. Disease activity was assessed using the PMR Activity Score (PMR-AS) and, for exploratory purposes, dichotomized according to the cohort median (≥11 vs. <11). Group differences were evaluated using non-parametric statistical methods. The multidimensional structure of the dataset was explored through Spearman correlation analysis, principal component analysis (PCA), and unsupervised clustering. Predictive models, including logistic regression, random forest, and gradient boosting, were developed to evaluate the potential contribution of integrated analytical approaches to patient stratification. Results: The study cohort included 103 patients (63.1% female), with a median age of 76 years (IQR 71–81); 57 patients (55.3%) presented PMR-AS ≥11. Patients with higher disease activity exhibited significantly increased levels of CRP, fibrinogen, platelet count, IL-6, serum amyloid A (SAA), and myeloid-related protein (MRP), together with a higher prevalence of joint effusion and Power Doppler positivity. Among the evaluated biomarkers, SAA demonstrated the strongest correlation with disease activity (Spearman ρ = 0.878; p < 0.001). Multivariate predictive modeling showed high discriminative performance, with random forest achieving the highest cross-validated AUC (0.934), whereas gradient boosting demonstrated the best overall accuracy (0.883). Unsupervised clustering analysis identified a subgroup characterized by a more pronounced inflammatory signature associated with higher PMR-AS values. Conclusions: These findings support the concept that disease activity in PMR may be more effectively represented through an integrated multidimensional inflammatory profile rather than isolated biomarkers. The combined evaluation of routine laboratory parameters, cytokines, and imaging features may contribute to more refined patient stratification within a precision medicine framework. Although exploratory, these results highlight the potential value of advanced data integration strategies for supporting biologically informed disease characterization in PMR, while underscoring the need for external validation before translation into clinical practice.

Journal of Personalized Medicine doi: 10.3390/jpm16080413

Authors: Luigi Angelo Vaira Hareem Qadeer Fabio Maglitto Giuseppe Consorti Giulio Cirignaco Giovanni Salzano Giacomo De Riu

Background/Objectives: Osteoradionecrosis of the jaws remains a severe late complication of head and neck radiotherapy. Current preventive strategies are still frequently based on population-level dose thresholds and broadly standardized dental-clearance protocols, despite substantial heterogeneity in individual risk. This comprehensive review aimed to integrate established preventive guidance with emerging tooth-level, spatial-dosimetric, prognostic, and causal approaches within an integrative conceptual framework for personalized osteoradionecrosis prevention. Methods: Structured searches of five databases were completed on 30 May 2026. Evidence sources were selected and mapped across six a priori thematic domains, with the selection process summarized in a simplified flow diagram and an evidence map. Priority was given to guidelines, systematic reviews, large cohorts, externally validated prediction models, and clinically actionable studies. Results: Osteoradionecrosis risk is determined by interactions among tumor site, surgical anatomy, mandibular dose distribution, dental and periodontal disease, smoking, diabetes, nutritional status, biological susceptibility, and expected survival. Tooth extraction is not uniformly protective, and its potential benefit depends on tooth prognosis, local radiation dose, oncological urgency, and patient-level vulnerability. Dose–volume parameters and site-specific mapping provide more clinically relevant information than prescribed dose alone. Contemporary normal tissue complication probability and machine-learning models increasingly support individualized risk estimation, although calibration, external validation, data quality, and workflow integration remain limiting. Competing-risk and causal-inference approaches may further distinguish baseline risk from the expected benefit of specific preventive interventions. Conclusions: The evidence reviewed can be organized within an integrative conceptual framework combining tooth-level prognosis, spatial dosimetry, systemic susceptibility, competing mortality, and intervention burden. This framework synthesizes and reorganizes existing evidence; it is not a validated clinical model and requires prospective validation and clinical-impact evaluation before routine implementation. Until then, available prediction models should support, rather than replace, multidisciplinary clinical judgement.

Journal of Personalized Medicine doi: 10.3390/jpm16080412

Authors: Cristina Stanescu Catalina Teodora Pintilie Roxana Elena Bogdan Goroftei Madalina Nicoleta Matei Iulia Chiscop Monica Boev Florina Popa Camelia Tamas

Background: Chronic wounds pose a persistent therapeutic challenge. Type I collagen and hyaluronic acid (HA) support tissue repair, but real-world evidence for describing their combined use in padformulations is limited. This study provides a real-world description of clinical outcomes observed within a tailored management, including Type I Collagen–Hyaluronic Acid pads (HCHA), on healing trajectories across diverse chronic wound etiologies. Methods: This retrospective observational analysis included 64 patients treated between 2017 and 2024 for chronic wounds, including burns (n = 32) and trophic ulcers of various etiologies (n = 32). Clinical data, including wound characteristics, daily healing rate (DHR), and procedural pain assessed using repeated VAS measurements, were extracted from medical records. Results: The daily healing rate (DHR) ranged from 3.22% in neglected burn wounds to 2.03% in non-burn chronic wounds. Percent area reduction (PAR) analysis at 7, 14, and 30 days showed greater wound area reduction in burn wounds (20%, 36%, and 62%) compared with non-burn wounds (13%, 25%, and 45%). Procedural pain decreased in both cohorts, with burn injuries presenting higher baseline VAS scores but following a similar downward trajectory over time (p < 0.001), converging to comparably low levels by day 30. Overall, the findings describe the outcomes observed within an individualized, multimodal wound care approach, which incorporates HCHA pads tailored to wound-specific characteristics. Conclusions: In this retrospective observational study, patients treated with HCHA pads as part of individualized multimodal wound care exhibited progressive granulation, favorable wound-healing trajectories, and lower procedural pain levels. Further controlled studies are warranted to validate these results and refine the patient selection criteria.

Journal of Personalized Medicine doi: 10.3390/jpm16080411

Authors: Alice B. Popejoy Deborah Cragun Megan C. Roberts Lisa M. Bendz Sarah Gonzales Susanne B. Haga R. Ryanne Wu Natasha J. Petry Laura B. Ramsey Ryley Uber Kaniz Momin Nina R. Sperber

Background: Pharmacogenetic (PGx) testing could identify actionable drug–gene interactions, reducing the risks of inappropriate prescribing of certain medications in some patients. An area of growing public health concern is rising global rates of depression and antidepressant use over the last two decades. Prior research has elucidated perspectives of healthcare providers who prescribe antidepressants regarding the clinical utility of genetic information, including PGx testing, but there is a gap in understanding how individual perspectives and systemic contextual factors may combine to influence PGx testing adoption. Objective: The objective of this study was to elucidate combinations of individual and contextual conditions associated with willingness to adopt PGx testing for Cytochrome P450 Subfamily IID, Polypeptide 6 (CYP2D6) and Subfamily IIC, Polypeptide 19 (CYP2C19) among antidepressant prescribers. Methods: We conducted a cross-sectional, mixed-methods study using structured questionnaires and semi-structured interviews with healthcare providers who prescribe antidepressants within their scope of practice across four healthcare systems in the United States. We collected data on implementation science concepts from the Theoretical Domains Framework, the Consolidated Framework for Implementation Research (CFIR), and the Implementation Outcomes Framework. Coincidence analysis (CNA), a case-based, Boolean logic-based method that identifies minimally sufficient combinations of conditions that lead to a particular outcome, was used to identify combinations of conditions for PGx test adoption among antidepressant prescribers. Interviews were also conducted with 10 patients who received pharmacogenetic testing within these healthcare systems to contextualize findings with patient perspectives. Results: Prescribers adopted PGx testing when they believed it would be beneficial to patients and were not deterred by cost-related concerns; the combination of these conditions led to PGx adoption in the most highly supported CNA model. Patient perspectives were also consistent with the selected model, with data suggesting they may have greater willingness to tolerate costs when they perceived or experienced benefits from testing. Conclusions: Insights from this study may be used by health system administrators and public health policymakers to inform future PGx implementation strategies that enhance uptake and awareness of existing evidence for clinical benefits of PGx testing and mitigate cost-related barriers to adoption.

Journal of Personalized Medicine doi: 10.3390/jpm16080410

Authors: Michele Salati Anna Chiara Nanto Mara Romito Alberto Roncon Michela Tiberi Gian Marco Guiducci Francesco Xiumè Francesca Barbisan Gaia Goteri Majed Refai

Background: Tumor Spread Through Air Spaces (STAS) is a histopathological pattern of invasion associated with aggressive behavior in lung adenocarcinoma. Its prognostic impact and implications for surgical strategy remain controversial. This study evaluated the impact of STAS on survival and recurrence outcomes in patients undergoing uniportal video-assisted thoracoscopic surgery (U-VATS) for lung adenocarcinoma. Methods: We retrospectively analyzed consecutive patients with histologically confirmed lung adenocarcinoma who underwent U-VATS resection between January 2020 and January 2023 at a single tertiary referral center. Propensity score matching (1:1) was performed to reduce selection bias between STAS-positive and STAS-negative patients. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier estimates and log-rank tests. Multivariable Cox proportional hazards regression models were used to identify independent predictors of survival. Subgroup analyses were performed according to the type of resection. Results: Among 365 included patients, 111 (30.4%) were STAS-positive. After propensity score matching, 222 patients were analyzed (111 STAS-positive and 111 STAS-negative). STAS-positive patients showed a higher overall recurrence rate compared with STAS-negative patients (36.9% vs. 27.9%, p = 0.15), with a significantly increased rate of local parenchymal recurrence (18.9% vs. 9.0%, p = 0.03). No significant differences in OS or RFS were observed between matched groups. Multivariable Cox regression analysis confirmed that STAS was not independently associated with OS (HR 0.88, 95% CI 0.50–1.53, p = 0.643). In STAS-positive patients, sublobar resection was associated with significantly worse survival outcomes compared with lobectomy and emerged as an independent predictor of mortality (HR 2.61, 95% CI 1.14–5.97, p = 0.02). Conclusions: STAS was associated with an increased risk of local recurrence but was not independently associated with overall survival after U-VATS resection for lung adenocarcinoma. However, in STAS-positive patients, sublobar resection was independently associated with worse survival outcomes, suggesting that surgical extent plays a critical role in this subgroup. These findings support consideration of a personalized surgical approach in patients with STAS-positive lung adenocarcinoma.

Journal of Personalized Medicine doi: 10.3390/jpm16080409

Authors: Gilberto Gremese Matteo Comuzzi Matteo Danielis Tommaso Piani Daniele Guerino Biasucci Giuseppe Cuttone Ciro Fittipaldi Francesca Lucchese Luigi Vetrugno Cristian Deana

Background: Critically ill patients undergo rapid and clinically significant skeletal muscle loss during the first week of ICU admission, driven by a complex interplay of systemic inflammation, neuroendocrine dysregulation, and accelerated protein catabolism. While CRP is an established marker of the inflammatory response, its temporal relationship with early muscle wasting—specifically whether the initial inflammatory peak or its subsequent persistence most strongly determines muscle loss—remains poorly characterised. This study investigated the serial dynamics of inflammatory biomarkers and their correlation with skeletal muscle changes during the first seven ICU days. Methods: This is a post hoc analysis of the NUTRITI prospective observational cohort, conducted at a single academic ICU in Udine, Italy (Ethics Committee approval: CEUR-2019-Os-17). Sixty-six adult critically ill patients with an anticipated ICU stay exceeding 72 h and requiring artificial nutritional support were included; patients on renal replacement therapy or with contraindications to bioelectrical impedance analysis (BIA) were excluded. Body composition—skeletal muscle mass (MM, kg) and phase angle (PA°)—was assessed by single-frequency BIA (50 kHz) on Day 1 and Day 7. The primary outcome was ΔMM%, the percentage change in muscle mass between admission and Day 7, calculated as ΔMM% = [(MMd − MMa)/MMa] × 100. Daily inflammatory biomarkers—CRP (mg/L), total WBC (×103/mm3), and lymphocyte count (×103/mm3)—were collected throughout. Spearman rank correlations between ΔMM% and serial biomarkers were computed for each day. Given the large number of tests (42 total), Bonferroni false discovery rate corrections were applied. Results: The cohort had a median age of 68.5 years (IQR 61–77.8), was predominantly male (71.2%), with median APACHE II 21.5 and SOFA 7. Median muscle mass declined significantly from 34.3 kg (IQR 29.9–39.5) at Day 1 to 30.6 kg (IQR 26.5–34.9) at Day 7 (p < 0.001), corresponding to a median MM% of −8.45% (IQR −14.2% to −1.52%). Phase angle also declined significantly (4.9° to 4.5°; p < 0.01). CRP showed no significant correlation with ΔMM% at Days 1 or 2, but a negative correlation emerged at Day 3 (ρ = −0.297; p = 0.020) and peaked at Day 4 (ρ = −0.355; p = 0.006), attenuating thereafter. CRP at Days 5 and 6 correlated with phase angle changes (p = 0.017 and p = 0.022, respectively). WBC showed no significant correlations at any time point. Day-7 lymphocyte count was nominally correlated with ΔMM% (ρ = −0.314; p = 0.040). Neither APACHE II nor SOFA at admission correlated with ΔMM%. No test survived correction for multiple comparisons. Conclusions: The kinetics of CRP—rather than its initial intensity—seem to be associated with early skeletal muscle catabolism in critically ill patients, with a temporally specific signal emerging at Days 3–4 of ICU admission. Although these findings are exploratory and did not survive multiple testing correction, their biological plausibility—grounded in the known kinetics of ubiquitin-proteasome activation and NF-κB signalling—and their alignment with the emerging concept of inflammation-guided nutritional timing both support their value as a hypothesis-generating observation. Serial CRP monitoring may represent a pragmatic candidate biomarker to identify the optimal window for nutritional escalation, pending prospective validation in adequately powered trials.

Journal of Personalized Medicine doi: 10.3390/jpm16080408

Authors: Pennipat Nabheerong Phuwadon Duangto Suttiwat Jeamtrakool Chairat Charoemratrote Pornpat Theerasopon

Background/Objectives: Dental age estimation is widely used in clinical and forensic practice. The Demirjian four-teeth methods were developed to simplify age assessment; however, their accuracy varies among populations and requires validation before use in specific ethnic groups. This study aimed to evaluate and compare the accuracy of Demirjian’s four-teeth methods I and II for dental age estimation in Southern Thai children and adolescents aged 7–15 years. Methods: This retrospective cross-sectional study included 360 digital panoramic radiographs (180 males and 180 females) from Southern Thai individuals aged 7–15 years. Dental age was estimated using Demirjian’s four-teeth method I (teeth 34, 35, 36, and 37) and method II (teeth 31, 34, 35, and 37). Estimated dental ages were compared with chronological ages using the Wilcoxon signed-rank test. Accuracy was assessed by mean error (ME), mean absolute error (MAE), and root mean square error (RMSE). Intra- and inter-observer reliability were evaluated using weighted kappa statistics. Results: Intra- and inter-observer agreement were excellent, ranging from 0.957 to 1.000 and 0.895 to 0.956, respectively. The mean chronological age was 11.53 ± 2.55 years. Both methods overestimated chronological age in males and females. ME ranged from 0.54 to 0.75 years, while MAE ranged from 0.97 to 1.01 years. Method II produced slightly lower estimation errors than method I. Significant differences between dental and chronological ages were found for both methods in both sexes (p < 0.05). Conclusions: Both methods overestimated chronological age by approximately one year in Southern Thai children and adolescents. Method II showed marginally lower errors; however, population-specific calibration may improve age estimation in Thai populations. These findings support the need for population-specific dental age estimation strategies, contributing to more personalized and accurate age estimation for Thai children in both clinical and forensic settings.

Journal of Personalized Medicine doi: 10.3390/jpm16080407

Authors: Nazym Sagandykova Madina Baurzhan Alexandr Gulyayev Sayagul Kairgeldina Shyngys Sergazy Gulnur Daniyarova Karlygash Absattarova Liudmila Kovalenko Akmaral Izbassarova

Background/Objectives: Chronic dust-induced lung diseases, including pneumoconiosis and asbestosis, require long-term monitoring and individualized management. Conventional rehabilitation and follow-up often depend on in-person visits and may not provide continuous assessment outside clinical settings. This scoping review mapped evidence on digital technologies used to monitor patients, assess respiratory symptoms and functional status, and support rehabilitation follow-up in chronic dust-induced lung diseases. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute methodology. PubMed, Scopus, and Web of Science were searched from inception to 29 June 2026 without language restrictions. Five eligible publications were included. Results: The evidence was grouped into three categories: wearable monitoring of activity and respiratory symptoms, analysis of data from a digital rehabilitation platform, and electronic medical record (EMR) analysis. Wearable sensors showed high performance in recognizing basic activity states and cough events under controlled conditions. Platform- and EMR-based approaches showed potential for using clinical and functional data to support patient stratification and monitoring. However, most studies were limited to early technical or algorithmic validation and did not assess long-term home use, patient adherence, integration into clinical workflows, or clinical and rehabilitation outcomes. Conclusions: Digital technologies may support objective monitoring and rehabilitation follow-up in chronic dust-induced lung diseases, but the evidence base remains small and clinically immature. Prospective studies in real-world settings should evaluate usability, external validity, workflow integration, and clinically meaningful outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16080406

Authors: Alessandro Girombelli Piergiuseppe Volpe Francesco Saglietti Dana Shiffer Giulia Sette Raymond M. Planinsic Francesco Vetrone

Introduction: Neuromonitoring during general anesthesia (GA) is recommended to reduce the incidence of postoperative delirium and intraoperative awareness, particularly during total intravenous anesthesia. Guidelines emphasize that anesthesiologists should not rely solely on processed depth-of-anesthesia indices such as the Bispectral Index or Patient State Index but should also interpret the raw electroencephalographic (EEG) waveform and the density spectral array (DSA). Although EEG patterns associated with individual anesthetic agents or combinations of hypnotics and opioids have been described, limited evidence exists regarding EEG activity during multimodal anesthetic regimens. This systematic review aimed to evaluate DSA patterns as pharmacodynamic markers of the cortical effects of GABAergic anesthetics, opioids, and ketamine. Methods: PubMed, Embase, and the Cochrane Library were searched without date restrictions up to September 2025. Eligible studies included adult patients undergoing general anesthesia and reporting raw EEG data or specific DSA patterns associated with the investigated drugs. Risk of bias was assessed using RoB 2 and ROBINS-I according to study design. Owing to the limited number of eligible studies, findings were synthesized narratively. Results: Out of 273 papers screened, 3 studies met the inclusion criteria, comprising 72 patients. The studies achieved an appropriate and stable effect-site concentration of propofol–remifentanil GA, demonstrated by a baseline DSA recorded before ketamine administration. Ketamine administration produced a shift from the baseline alpha–delta pattern to a beta–delta DSA pattern. Conclusions: Ketamine administration during stable propofol–remifentanil anesthesia produces a characteristic shift towards a beta–delta DSA pattern, which may increase processed EEG indices, leading to misinterpretation of anesthetic depth. Further studies are needed to characterize DSA signatures associated with multimodal anesthesia and to identify patterns indicative of adequate anesthetic depth when multiple agents are administered.

Journal of Personalized Medicine doi: 10.3390/jpm16080405

Authors: Takeshi Osonoi Shinichiro Shirabe Miyoko Saito Mitsuru Hosoya Norie Watahiki Nana Shiozawa Satako Douguchi Kensuke Ofuchi Makoto Katoh

Background: Patients with type 2 diabetes (T2D) frequently exhibit impaired erythrocyte deformability, which contributes to microvascular dysfunction. We previously reported that imeglimin, a mitochondrial-targeted antidiabetic agent, prolongs erythrocyte lifespan. This study investigated the effects of imeglimin on whole-blood fluidity and its clinical implications in patients with T2D. Methods: This post hoc analysis of the INFINITY study included 25 patients with T2D who completed 6 months of imeglimin treatment (2000 mg/day) followed by a 3-month follow-up. Whole-blood fluidity was assessed by measuring whole-blood passage time using a microchannel array flow analyzer (MC-FAN). Hematological parameters, glycemic markers, and vascular indices, including brachial-ankle pulse wave velocity (baPWV) and toe-brachial index (TBI), were also assessed. Results: Whole-blood fluidity, assessed by 3-month averages of whole-blood passage time, showed an improvement trend at Months 1–3 (p = 0.058) and a significant improvement at Months 4–6 (p = 0.016) compared with baseline; this effect was reversed after discontinuation. Erythrocyte lifespan significantly increased by 10–20% during treatment and remained prolonged after discontinuation. Conversely, red blood cell count, hemoglobin, and hematocrit decreased during treatment and returned toward baseline post-discontinuation. At Month 6, baPWV increased, and TBI decreased, both showing reversibility after treatment cessation. Conclusions: In this exploratory post hoc analysis, imeglimin treatment was associated with reduced whole-blood passage time measured using the MC-FAN system, suggesting improved whole-blood fluidity in patients with T2D. The clinical and mechanistic significance of this observation requires confirmation in future controlled prospective studies incorporating direct assessments of erythrocyte rheology and microvascular function.

Journal of Personalized Medicine doi: 10.3390/jpm16080404

Authors: Horia Tudor Stanca

The past decade has witnessed remarkable progress in the understanding and management of retinal diseases [...]

Journal of Personalized Medicine doi: 10.3390/jpm16080403

Authors: Sy Van Hoang Kha Minh Nguyen Hai Phuong Nguyen Tran Hung Phi Truong Tai Nhat Nguyen Sang Quang Ly

Background: Familial hypercholesterolaemia (FH) is a common monogenic cause of premature coronary artery disease (CAD), yet data from South-East Asia are sparse and the yield of family cascade screening has not previously been reported in Vietnam. Methods: In this prospective, single-centre cohort study (March 2023–September 2025), 500 consecutive patients with premature CAD (men < 55 years, women < 60 years) underwent targeted next-generation sequencing of LDLR, APOB and PCSK9, with Sanger confirmation of pathogenic or likely pathogenic (P/LP) variants. First-degree relatives of variant-positive index patients were offered structured counselling and cascade sequencing of the family-specific variant. Results: A P/LP variant was identified in 18 of 500 patients (3.6%; 95% CI 2.1–5.4%); 17 (94.4%) involved LDLR and one APOB. Nine distinct P/LP variants were observed, with several recurrent, consistent with possible founder effects. Two carriers were homozygous, including one with an APOB frameshift attributable to consanguinity. Variant carriers were younger (mean difference −5.6 years, 95% CI −9.2 to −2.0) with higher LDL-cholesterol (median 227.5 vs. 138 mg/dL) and more extensive coronary disease than non-carriers. Cascade screening was completed in 20 of 26 eligible families (77%); among 105 first-degree relatives tested, 46 (43.8%; 95% CI 34.7–53.4%) carried the family-specific variant, most of them young, asymptomatic offspring or siblings. Conclusions: Precise molecular diagnosis in a small number of index patients identified a much larger cohort of at-risk relatives who would otherwise have remained undiagnosed, providing the first Vietnamese evidence that hospital-anchored cascade screening is feasible and high-yielding in a resource-limited setting.

Journal of Personalized Medicine doi: 10.3390/jpm16080402

Authors: Teresa Sinicropi Carmelo Mazzeo Mariausilia Franchina Maria Iannello Francesco Fleres

Introduction: Desmoid fibromatosis (DF) is a rare, locally invasive, and typically non-metastatic neoplasm. Its pathophysiology is poorly understood, and the subtle clinical presentation makes diagnosis challenging. A multidisciplinary approach is necessary to achieve a definitive diagnosis and identify the most effective therapeutic strategy. Because of its heterogeneous presentation and unpredictable behavior, DF cannot be managed through a standardized protocol, and diagnostic and therapeutic decisions must instead be tailored to the individual patient, consistent with a personalized-medicine approach. We present an unusual case in which we aim to evaluate the diagnostic procedures and treatments used and determine whether they align with the recent literature. Materials and Methods: A case report. A 27-year-old man presented with fever and worsening abdominal pain, without clinical signs of intestinal obstruction. He had undergone a sleeve gastrectomy five years earlier. A computed tomography (CT) scan revealed an intra-abdominal mass in the mesohypogastric region, likely originating from the mesentery of the small intestine. The patient underwent a right hemicolectomy extended to the terminal ileum. Histopathological examination and immunohistochemistry confirmed the diagnosis of DF. The patient was discharged on the 5th postoperative day (POD) in good general clinical condition. To date, there are no signs of recurrence. Conclusions: The multidisciplinary approach is essential for managing DF and R0 surgical resection remains the gold standard. The diagnostic and therapeutic pathway followed in our patient appears consistent with the recent literature. This case illustrates how individualized clinical reasoning can be applied even to a rare, heterogeneous neoplasm for which no standardized protocol exists. Furthermore, an established post-surgical management protocol for DF has not yet been developed. Additionally, we observed a possible, hypothesis-generating association between bariatric surgery and the subsequent onset of an intra-abdominal desmoid tumor; given the rarity of desmoid fibromatosis relative to the high volume of bariatric procedures performed worldwide, this observation should not be interpreted as a confirmed correlation, and we conducted a literature review to explore it as a hypothesis. Numerous studies are needed on this matter, but we hope that this case can provide a small starting point for subsequent studies.

Journal of Personalized Medicine doi: 10.3390/jpm16080401

Authors: Marco Chiappetta Alessandra Cancellieri Carolina Sassorossi Filippo Lococo Teresa Ferrazzo Chiara Scognamiglio Alessia Senatore Adriana Nocera Qianqian Zhang Andrea Guarneri Silvia Taralli Maria Lucia Calcagni Flaminia Vocaturo Luca Boldrini Huong Elena Tran Isabella Sperduti Stefano Margaritora

Background: Spread through air spaces (STAS) is a prognostic factor for survival in non-small cell lung cancer (NSCLC), but the chance to identify it before surgery remains challenging. In this study, we consider clinical, pathological and metabolic factors, with the aim to identify possible STAS predictors in NSCLC. Methods: Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1 January 2018 to 31 December 2023 were retrospectively reviewed and analyzed. Patients with GGO, AIS, or MIA tumors, metastases, or undergoing neoadjuvant therapy were excluded. The parameters assessed by 18F-FDG PET/CT were: SUVmax, SUVmean, SUVpeak, TLG and MTV. The primary endpoint was the association between clinical, metabolic, and pathologic characteristics with the presence of STAS. A univariate and multivariate logistic regression model was developed to identify independent predictors of STAS. Results: The final analysis was conducted on 224 patients. Non-lepidic-acinar adenocarcinomas showed a statistically significant higher risk of STAS than the lepidic-acinar histotype: 20.8% vs. 4.3%, p = 0.003, OR 5.87, 95%CI 1.83–18.78. Furthermore, tumor grade was significantly associated with STAS: 4.6% in G1–G2 tumors vs. 23.5% in G3 tumors (p = 0.001, OR 5.79, 95%CI 2.12–15.78); as well as lymph vascular invasion (p = 0.034) and tumor size >2 cm (p = 0.017). Multivariate analysis confirmed high tumor grade as an independent risk factor (OR 4.73, 95%CI 1.16–19.23, p = 0.030). Conclusions: In our study, risk of STAS is not correlated with metabolic parameters, while adenocarcinoma subtypes and tumors grading seem to stratify the risk of STAS occurrence. These results may be consolidated in an external validation analysis to possibly better plan the extent of lung resection.

Journal of Personalized Medicine doi: 10.3390/jpm16080400

Authors: Stamatios Katsimperis Lazaros Tzelves Patrick Juliebø-Jones Andreas Skolarikos

Testicular germ cell tumors (TGCTs) are highly curable malignancies, yet their clinical management still relies heavily on conventional serum tumor markers, including alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase, which have limited sensitivity and specificity in several clinically relevant settings. Circulating microRNAs, particularly miR-371a-3p, have emerged as promising liquid biopsy biomarkers with potential applications across the TGCT disease continuum. This narrative review summarizes the current evidence on the biological basis, diagnostic performance, clinical utility, and limitations of circulating microRNAs in TGCTs. MiR-371a-3p demonstrates high diagnostic accuracy for viable non-teratomatous TGCTs and consistently outperforms classical serum tumor markers in primary diagnosis. Its rapid decline after effective treatment and its association with tumor burden support potential roles in chemotherapy monitoring, early relapse detection during surveillance, and the assessment of selected post-chemotherapy residual masses. However, its inability to detect teratoma remains a major biological limitation, particularly in non-seminomatous residual disease and surveillance settings. Additional barriers to implementation include assay heterogeneity, the lack of universally accepted cutoffs, the variable use of serum versus plasma, and the absence of broad regulatory approval. Emerging translational data suggest that miR-371a-3p may also contribute to tumor–microenvironment communication and cisplatin resistance, although these findings remain preclinical. Overall, miR-371a-3p represents one of the most promising biomarkers in TGCT management, but its routine clinical integration will require standardized analytical protocols and prospective validation in marker-guided decision pathways.

Journal of Personalized Medicine doi: 10.3390/jpm16080399

Authors: Athanasios Syllaios Dimitrios Schizas

Gastrointestinal (GI) diseases comprise a heterogeneous group of disorders that collectively account for a substantial proportion of global morbidity, mortality, and healthcare expenditure [...]

Journal of Personalized Medicine doi: 10.3390/jpm16080398

Authors: Emanuele Rocco Villani Rosa Liperoti Laura Franza Francesca Maria Secciani Antonella Di Paola Graziano Onder Angelo Carfì

Background/objective: Down syndrome (DS) is characterized by premature aging, with comorbidities observed in the older population without DS, a high prevalence of multimorbidity and cognitive decline. The use of multiple medications further increases clinical complexity. The objective of this paper is to evaluate anticholinergic use and the anticholinergic burden (ACB) in a sample of persons with DS. Methods: cross-sectional retrospective study involving community-dwelling persons with DS, afferent to the DS clinics of the Fondazione Policlinico Universitario “A. Gemelli” (Rome, Italy). Individuals were assessed through a standardized clinical protocol. ACB was evaluated according to the anticholinergic cognitive burden scale, with a score ≥ 3 indicating high risk of anticholinergic side effects. Results: 337 individuals were taking ≥ 1 chronic medication, mean age was 37.7 (±14.6), 158 (43.8%) were females. 143 (39.6%) individuals took ≥ 1 medication with known anticholinergic burden, 51 (14.1%) individuals showed high risk ACB score. High risk ACB score prevalence increased with age (<18 years n = 0, 0%; 18–39 years n = 14, 8.2%; 40+ years n = 37, 22.3% p < 0.001). Polypharmacy was more prevalent among individuals with high ACB score (n = 20, 39.2% vs. n = 23, 7.4%, p < 0.001). The most prevalent drugs in individuals with high risk ACB score were antipsychotics (n = 34, 66.6% vs. n = 17, 33.3%, p < 0.001). The most prevalent comorbid condition was psychosis (n = 34, 66.6% vs. n = 16, 33.3%, p < 0.001). Discussion: individuals with DS show a high prevalence of anticholinergic drug use, increasing with age and associated with polypharmacy and psychiatric conditions. These medications are directly addressing the underlying psychiatric or neurological conditions in DS, rather than causing them. Nevertheless, these medications are often essential for managing psychiatric disorders, simultaneously increasing ACB, posing a risk of exacerbating pre-existing vulnerabilities (e.g., cognitive decline), which warrants the need for a more personalized strategy. Conclusions: A thorough assessment of drug history is mandatory in the DS population, to apply deprescribing, pharmacological switches, non-pharmacological approaches, to lower or even prevent high ACB, promoting overall a personalized and tailored approach to this population.

Journal of Personalized Medicine doi: 10.3390/jpm16080397

Authors: Pasquale Niscola Valentina Gianfelici Roberta Laureana Marco Giovannini Carla Mazzone Fabio Efficace Maria Ilaria Del Principe

Acute Myeloid Leukemia (AML) is a heterogeneous group of aggressive blood-related cancers that arise from the hematopoietic system, requiring specific treatments due to their genetic diversity and complexity. Artificial intelligence (AI) has emerged as a transformative technology in healthcare, with considerable potential to help manage AML. The application of AI approaches, such as Machine Learning (ML) models and Deep Learning (DL) algorithms, has been shown to aid risk stratification, diagnosis, treatment planning, and surveillance. This review highlights recent developments in AI applications for the personalized management of AML. We focus specifically on three major axes of personalization in AML: (1) the use of predictive models combining different data sources to improve prognostic assessment and guide risk-adaptive treatments; (2) prediction of treatment responses to various therapies based on data analysis; and (3) the use of AI for monitoring and adaptive trials in AML patients.

Journal of Personalized Medicine doi: 10.3390/jpm16080396

Authors: Tianyi Shen Nicholas Kai Yi Tan Wen Xuan Chew Matthias Yi Quan Liau Vor Luvira Vinay K. Kapoor Orestis Ioannidis Vishal G. Shelat

Gallbladder cancer (GBC) is the most common biliary tract malignancy and is among the most lethal gastrointestinal cancers. Since its inclusion in cancer staging manuals, the GBC Tumour–Node–Metastasis (TNM) classification has undergone repeated revisions intended to improve anatomical precision and prognostic discrimination. This narrative review traces the evolution of GBC staging across AJCC editions and the 2025 UICC TNM update and critically examines whether these refinements have translated into clinically meaningful risk stratification. In the 2025 UICC TNM 9 grouping, Stage IA corresponds to T1aN0M0 and Stage IB to T1bN0M0, while T2aN0M0 and T2bN0M0 remain Stage IIA and IIB, respectively. Structured literature searches were performed to identify historical staging documents, population-based analyses, validation studies, and prognostic reports relevant to stage migration, survival discrimination, and emerging staging modifiers. Successive changes, including T-category refinement and the transition from nodal location to nodal burden, have improved anatomical resolution. However, available validation studies suggest that gains in overall prognostic performance remain modest, with reported concordance indices often remaining near 0.66. Contemporary evidence increasingly shows that tumour location, adequacy of lymphadenectomy, number of positive lymph nodes, lymph node ratio, log odds of positive lymph nodes, obstructive jaundice, residual disease status, and selected molecular alterations may capture inter-patient heterogeneity beyond anatomy alone. Future staging refinement should therefore preserve TNM as a common anatomical language while developing validated parallel modifiers that support more individualized prognostication and treatment selection.

Journal of Personalized Medicine doi: 10.3390/jpm16080395

Authors: Costanza Martorelli Alessandra Monzio Compagnoni Matteo Massa Gianluigi Pasta Federico Alberto Grassi Michela Saracco Eugenio Jannelli

Background: Obesity is increasingly prevalent among patients undergoing total hip arthroplasty (THA). While outcomes are well reported, fewer studies assess postoperative BMI trends, digital templating accuracy, and biomechanical restoration. Purpose: To evaluate BMI evolution, templating accuracy, restoration of limb length and femoral offset, and clinical outcomes after primary THA in obese patients, compared with normal-weight controls. Methods: Retrospective comparative cohort including 75 obese patients (BMI ≥ 30 kg/m2) undergoing primary THA between July 2021 and December 2024. BMI was recorded preoperatively and at last follow-up. OrthoView™ 7.1 digital templating guided preoperative planning; accuracy was defined as implanted versus planned component sizes. Radiographic assessment of limb length and femoral offset was performed in 60 obese patients and 60 normal-weight controls. Clinical outcomes included Harris Hip Score (HHS), Oxford Hip Score (OHS), and EQ-5D-5L. Postoperative complications were recorded in the obese cohort. Results: BMI remained stable postoperatively (33.68 ± 2.57 vs. 34.06 ± 2.78 kg/m2; p = 0.138). Templating accuracy within ±1 size was high (femoral stem 80.2%; acetabular cup 94.7%). Limb-length discrepancy was low and comparable between obese and normal-weight patients (3.55 vs. 3.78 mm; p = 0.687). Femoral offset restoration was similarly comparable. Patient-reported outcomes improved significantly in both groups, with no significant differences in postoperative scores. Conclusions: In obese patients, THA provides reliable digital planning accuracy, satisfactory biomechanical reconstruction, and substantial functional improvement comparable to normal-weight patients. BMI remains essentially unchanged after surgery, indicating THA does not substantially influence postoperative weight trajectory in this population.

Journal of Personalized Medicine doi: 10.3390/jpm16070394

Authors: Clayton Peixoto Melanie Navarro Carolina Gomes Carrilho Antonio José Grande Antonio Egidio Nardi Adriana Cardoso André Barciela Veras

Background: Sexual function in postmenopausal women is influenced by both hormonal and psychological factors. This study investigates the associations between sex hormones, sexual function, and sexual beliefs in this population. Objective: This research seeks to assess the relationship between sex hormones, sexual function, and dysfunctional sexual beliefs in postmenopausal women. Methods: A cross-sectional study was conducted with 42 postmenopausal women aged 45–65 years. Instruments included the FSFI and SDBQ. Hormones assessed were testosterone, estradiol, progesterone, prolactin, DHEA, SHBG, and LH. Blood samples were collected in the morning and analyzed using chemiluminescence or radioimmunoassay. Pearson correlation tests were used, with Bonferroni adjustment applied to control for multiple comparisons. Results: Free testosterone was positively correlated with sexual desire and negatively associated with dysfunctional beliefs regarding sexual desire. Estradiol also showed a positive correlation with desire, while prolactin was negatively associated. No other FSFI domains showed significant hormonal associations. Conclusions: Findings suggest that testosterone may influence both sexual desire and the internalization of dysfunctional sexual beliefs in postmenopausal women, highlighting the interplay between biological and psychological dimensions of sexuality, which may be relevant for a more comprehensive clinical assessment of sexual function in this population.

Journal of Personalized Medicine doi: 10.3390/jpm16070393

Authors: Stefano Pagano Sebastian Dendorfer Tobias Renkawitz

Background/Objectives: Commercial wearables are increasingly used after total hip and knee arthroplasty (THA/TKA) to record activity and gait outside the clinic and may help tailor recovery pathways. We reviewed the evidence on commercial devices, digital phenotyping, and data-informed rehabilitation after arthroplasty. Methods: We performed a structured narrative search of PubMed and Google Scholar. Of 916 records, 63 duplicates were removed, 853 were screened, 245 full texts were assessed, and 76 publications were included. Findings were synthesized thematically; no formal risk-of-bias assessment or evidence grading was undertaken. Results: Recovery differed by outcome and procedure. PROMs commonly improved within 1–3 months, while gait-quality measures recovered over about 7–13 weeks after THA and 13–24 weeks after TKA. Frequency-domain gait features, sample entropy, and machine-learning models provided information beyond step counts. Tracker-based interventions most consistently increased postoperative steps when introduced early and combined with behavior-change support, while digital rehabilitation was generally non-inferior to conventional rehabilitation. Wrist-worn consumer devices remained inaccurate with gait aids, compliance definitions varied, and higher step counts did not consistently correspond to better PROMs. Conclusions: Commercial wearables already support phenotyping and remote follow-up of individual recovery trajectories, but evidence for fully adaptive rehabilitation remains limited.

Journal of Personalized Medicine doi: 10.3390/jpm16070392

Authors: Theodora Palyvou Ioannis Stefanou Sotirios Kympouris Theodora Imant Dionysia Thermou Stavriella Seferli Vasiliki Kanellopoulou Despoina Chatzopoulou Katrin Spyropoulou Nikolaos Kardaras Milena Iotova Asimina Ntotsika Maria-Christina Kapoutsi Iasonas Priftis Mara Bouga Christina Bolanou Georgios Sygkounas Spyridon Volteas

Introduction: Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy arising from the smooth muscle tissue of the uterine wall. It typically presents with abnormal vaginal bleeding, pelvic pain, or a pelvic mass. In rare instances, symptoms may result from local invasion or metastasis. We report a case of uLMS initially diagnosed following colonic perforation due to direct tumor invasion, accompanied by a comprehensive narrative review of the literature on the incidental identification of uterine sarcomas during emergency general surgery to further emphasize the diagnostic challenges, treatment approaches, and need for individualized care in these complex cases. Case Presentation: A 45-year-old woman presented to the Emergency Department with acute abdominal pain of several hours’ duration, in the absence of other associated symptoms. An emergency exploratory laparotomy was performed, revealing feculent peritonitis secondary to sigmoid colon rupture, resulting from local invasion by a large uterine mass. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was undertaken, followed by en bloc resection of the sigmoid colon, appendectomy and construction of a terminal colostomy. Her postoperative course was uneventful, and she was discharged on postoperative day eight. Histopathological examination of the specimen revealed a high-grade uterine leiomyosarcoma. Following evaluation by a multidisciplinary oncology board, the patient received adjuvant chemotherapy. Methods and Results: A narrative review of the literature was performed to identify cases of uterine sarcomas incidentally diagnosed during emergency surgery performed by general surgeons. Including the present case, six cases were identified. Most patients presented with acute abdomen mimicking gastrointestinal pathology, with diagnosis established intraoperatively or postoperatively. Definitive surgical management was achieved during the initial emergency procedure in all cases. Conclusion: Although exceptionally rare, uterine sarcoma should be considered in the differential diagnosis of acute abdomen in female patients undergoing emergency surgery. Awareness of this atypical presentation, the appropriate diagnostic approach, real-time intraoperative adaptability, and individualized multidisciplinary management are essential for ensuring appropriate surgical management and optimizing patient care.

Journal of Personalized Medicine doi: 10.3390/jpm16070391

Authors: Rebecca L. Beres Kenneth D. R. Setchell Marialena Mouzaki Xueheng Zhao

Pruritus is a debilitating symptom frequently affecting patients with cholestatic liver disease, often resistant to conventional antipruritic therapies. The pathogenesis of cholestatic pruritus (CP) is multifactorial, implicating not only bile acids but also a complex array of other potential pruritogenic mediators and neural signaling pathways. Identification of the exact pruritogen has been elusive, and gaps remain in understanding the pathogenesis of pruritus, so developing targeted treatments is critical. The stratum corneum (SC), the outermost lipid-rich layer of the skin, may act as a reservoir for circulating pruritogens, offering a novel window to explore the pathogenesis of CP. Recent advancements in lipidomics and non-invasive tape stripping have enabled detailed profiling of SC lipid alterations in disease states. In this review, we synthesize the current understanding of CP and its candidate pruritogens and describe state-of-the-art approaches for SC lipid analysis, combining tape stripping to sample the skin surface with mass spectrometry-based lipidomics. Finally, we summarize cutaneous molecular findings and discuss how these techniques are facilitating biomarker discovery and informing therapeutic development. This review discusses the paradigm shift from a single-molecule perspective to a more integrated view of CP as a product of complex mediator interactions and highlights the potential of SC profiling to uncover novel targets for intervention strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16070390

Authors: Yee Ming Lee Elizabeth Kearney David F. Kisor Christopher L. Farrell

Background/Objectives: Germline pharmacogenomics (PGx) testing performed by clinical laboratories and companies can reveal secondary findings (SF) related to gene-disease risk that clinicians must appropriately manage. This study evaluated PGx panel content for potential SF using the Clinical Pharmacogenomics (ClinPGx) resource, the Clinical Genome Resource (ClinGen), and the American College of Medical Genetics and Genomics (ACMG). Methods: A cross-sectional review of PGx panels offered by laboratories and companies was assessed for ClinPGx PGx annotation, ClinGen’s gene-disease validity and clinical actionability classifications, Clinical Pharmacogenetics Implementation Consortium (CPIC) incidental finding (IF) comments, and ACMG SF v3.3 inclusion. Results/Discussion: Forty-four testing sites provided panel content, yielding 125 genes, alleles, and variants. Of these, 26.4% (33/125) had PGx annotations while 73.6% (92/125) did not. A small subset of genes—CACNA1S, CFTR, G6PD, LDLR, MT-RNR1, and RYR1—had actionable recommendations based on CPIC and ACMG. Additional genes such as ATM, F5, ITGB3, and SCN1A may require consultation with genetics professionals. These findings underscore the need for a centralized resource for identifying gene-specific SF from germline PGx testing and guidance on their clinical management. Conclusions: PGx panels often include genes with and without established PGx annotations, some of which have potential SF implications. ClinGen’s PGx Working Group, which aims to integrate PGx into the broader context of genomic medicine, may be well-positioned to facilitate the development of a standardized framework for managing potential SF from panel-based PGx testing as the field evolves.

Journal of Personalized Medicine doi: 10.3390/jpm16070389

Authors: Athanasios Saplaouras Panagiotis Mililis Stavroula Koskina Athanasios Makris Sokratis Oikonomou Vasileios Cheilas Theodoros Efremidis Athena Batsouli Ourania Kariki George Bazoukis Sotirios Xydonas Theodoros Karamitsos Christodoulos Papadopoulos Nikolaos Fragakis Michael Efremidis Konstantinos P. Letsas

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12–0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88–1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection.

Journal of Personalized Medicine doi: 10.3390/jpm16070388

Authors: Akira Sezai Masanori Abe Takashi Maruyama Makoto Taoka Hisakuni Sekino Masashi Tanaka

Background/Objectives: Esaxerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) with potent cardiorenal protective effects. However, the clinical effects of switching from eplerenone to esaxerenone in patients with chronic heart failure complicated by hypertension remain unclear. This study investigated the effects of switching from eplerenone to esaxerenone on blood pressure, heart failure biomarkers, renal function, and the renin–angiotensin–aldosterone system (RAAS). Methods: A total of 156 patients with chronic heart failure and hypertension who had been receiving eplerenone for more than one year were prospectively enrolled. Eplerenone was switched to esaxerenone, and the patients were followed for 6 months. Blood pressure, heart rate, brain natriuretic peptide (BNP), renal function, urinary albumin-to-creatinine ratio (UACR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary osmolality (U-OSM) were evaluated. Results: Following the switch to esaxerenone, systolic and diastolic blood pressure significantly decreased (both p < 0.001), whereas heart rate remained unchanged. BNP levels significantly decreased at 3 and 6 months (p = 0.008 and p = 0.002, respectively). Serum creatinine decreased (p = 0.017), estimated glomerular filtration rate increased (p = 0.028), and UACR significantly decreased at both time points (both p < 0.001). PRA and PAC significantly increased after switching (both p < 0.05), whereas angiotensin II levels remained unchanged. U-OSM significantly decreased (p = 0.01 and p = 0.002 at 3 and 6 months, respectively). No major cardiovascular events or severe adverse events were observed. Conclusions: In patients with chronic heart failure and hypertension, switching from eplerenone to esaxerenone was associated with reductions in blood pressure, BNP, UACR, and urinary osmolality, together with improvements in renal function. These findings suggest favorable physiological changes following the switch from a steroidal to a non-steroidal mineralocorticoid receptor antagonist, although confirmation in randomized controlled studies with clinical outcome measures is warranted.

Journal of Personalized Medicine doi: 10.3390/jpm16070387

Authors: Thomas Repantis Ioanna Lianou Ioannis Papaioannou Maria Papathanasiou Lexi de Jager Andreas Filippopoulos Andreas Baikousis

Background/Objectives: Minimally invasive (percutaneous) pedicle screw fixation (PPSF) was initially introduced for the treatment of degenerative spinal deformities. Since then, its indications have progressively expanded to a broad spectrum of spinal pathologies. This method has gained increasing acceptance in spinal surgery due to lower morbidity when compared with conventional open procedures. This study presents a comprehensive review of the recent literature on hybrid minimally invasive spinal instrumentation techniques, focusing on the combined use of PPSF with open or mini-open approaches and their roles in personalized surgical management. Methods: A literature search was conducted in PubMed and Web of Science to identify studies reporting expanded indications of percutaneous pedicle screw fixation (combined with other approaches), novel surgical techniques, and their clinical outcomes. Results: Thirty-five studies met the inclusion criteria and were categorized according to pathology. Most included studies were retrospective observational investigations corresponding to Oxford CEBM Levels III–IV evidence, with a smaller number of prospective studies and systematic reviews. Conclusions: The findings from this review highlight the expanding role of hybrid methods in the management of complex spinal disorders. These approaches provide adequate stability and enable decompression or deformity correction, while minimizing tissue trauma, blood loss, and perioperative morbidity, thereby facilitating improved recovery and functional outcomes. The included literature predominantly represents moderate levels of evidence, supporting a patient-specific, pathology-driven surgical strategy that optimizes individualized outcomes in spinal surgery.

Journal of Personalized Medicine doi: 10.3390/jpm16070386

Authors: Dimitris Koukoulias Eustathios Kenanidis Michael Potoupnis Panagiotis V. Tsaklis Eleftherios Tsiridis

Background/objectives: Evidence on gait and postural recovery after robotically assisted total knee arthroplasty (raTKA), particularly with the ROSA system, remains limited. This study compared early gait, postural, functional, and patient-reported outcomes (PROMs) between ROSA raTKA and manual TKA (mTKA), with PROMs also assessed at final follow-up. Methods: This comparative cohort study included primary TKA patients treated by a single senior surgeon using the same implant and alignment strategy. Patients underwent either ROSA raTKA or mTKA. At three months, a senior physiotherapist assessed quadricep and tibialis anterior maximum voluntary isometric strength (MVIS), centre-of-mass (CoM) kinematics, lower-limb weight distribution, timed-up-and-go (TUG), range of motion (ROM), KOOS Pain, activities of daily living (ADL), and quality of life (QoL). The same KOOS domains were compared at final follow-up. Results: Seventy primary TKAs were included: 46 raTKAs and 24 mTKAs. No intraoperative complications occurred. Groups were comparable for age, BMI, sex, grip strength, and preoperative KOOS. At three months, no significant differences were found in quadricep MVIS (p = 0.257), tibialis anterior MVIS (p = 0.327), CoM kinematics (p = 0.066), weight distribution (p = 0.189), TUG (p = 0.599), ROM (p = 0.165), or KOOS domains. At final follow-up, KOOS-ADL (p = 0.041) and QoL (p = 0.032) were better in the raTKA group, but after Holm–Bonferroni correction, they were no longer significant (QoL, p = 0.384; ADL, p = 0.451). Conclusions: ROSA raTKA showed comparable early gait and postural recovery to mTKA. The marginal differences in KOOS domains are exploratory, as they were no longer significant after multiple-comparisons correction.

Journal of Personalized Medicine doi: 10.3390/jpm16070385

Authors: Carmine Iacovazzo Andrea Uriel de Siena Katarzyna Kotfis Pasquale Buonanno Serena Nappi Raffaele Merola Maria Vargas Giuseppe Servillo Pratik P. Pandharipande Annachiara Marra

Background: Non-invasive ventilation (NIV) is a well-established approach for preventing endotracheal intubation (ETI) in critically ill patients with acute respiratory failure (ARF). Sedation is frequently used to improve comfort. This study aimed to analyze the impact of sedation during NIV on ETI rates and NIV success in critically ill patients. Methods: We systematically searched in PubMed, EMBASE, MEDLINE, Web of Science, and CENTRAL up to September 2023, including prospective observational studies, retrospective cohort studies (nRCTs), and randomized controlled trials (RCTs). Primary outcomes were NIV success and ETI rates; secondary outcomes were hypotension, bradycardia, 28-day mortality, delirium, and oversedation. Proportions were used for observational studies, odds ratios (OR) for retrospective studies, and risk ratios (RR) for RCTs. Retrospective studies compared intermittent and continuous analgosedation, while RCTs evaluated dexmedetomidine versus other sedatives, including direct comparisons. Results: Four observational studies, 2 retrospective studies, and 7 RCTs (738 patients) were selected. Dexmedetomidine showed increased NIV success (RR = 1.167, 95%C.I. 1.014–1.343, p = 0.032) and reduced ETI rate (RR = 0.553, 95%C.I. 0.405–0.755, p < 0.001), but higher rate of bradycardia (RR = 2.172, 95%C.I. 1.819–4.042, p < 0.001) and hypotension (RR = 2.441, 95%C.I. 1.608–3.706, p < 0.001). nRCTs revealed higher NIV success (Proportion = 0.694, 95%C.I. 0.528–0.912, p = 0.009), moderate ETI rates (Proportion = 0.379, 95%C.I. 0.282–0.511, p < 0.001), and low bradycardia and hypotension rates. Conclusions: Our findings suggest that sedation, particularly dexmedetomidine-based strategies, may enhance NIV success and lower ETI rates. However, dexmedetomidine was also associated with higher rates of bradycardia and hypotension, especially compared with midazolam. To establish the correct sedation strategy, it is important to tailor the drug to the patient, considering its hemodynamic instability, delirium risk, and mortality risk.

Journal of Personalized Medicine doi: 10.3390/jpm16070384

Authors: Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Diana Chavez-Muñoz Rebeca Garazi Elguezabal Rodelo Octavio Gonzalez-Chon Luigi La Via

Background/Objectives: Intraoperative hypotension (IOHs) affects up to 87% of patients under general anesthesia and is consistently associated with acute kidney injury, myocardial damage, stroke, and mortality. The intermittent unavailability of ephedrine across healthcare systems underscores the need for evidence-based alternatives. This review critically evaluates pharmacological options for IOH when ephedrine is unavailable, focusing on receptor pharmacodynamics, population-specific evidence, and clinical consequences of inadequately managed hypotension. Methods: A narrative, evidence-based review was conducted examining mechanisms of action, dosing strategies, adverse effect profiles, and clinical applicability of key vasoactive agents: ephedrine, phenylephrine, norepinephrine, and epinephrine. Population-specific evidence across obstetric, pediatric, and elderly cohorts was synthesized from randomized controlled trials, meta-analyses, and observational studies. The clinical impact of IOH on neurological, cardiovascular, and renal outcomes was reviewed. Results: Each vasopressor exhibits a distinct receptor-selectivity profile that determines its hemodynamic effect and optimal clinical context. Norepinephrine’s favorable α1/β1 balance tends to preserve cardiac output better than pure α1-agonists and has emerged as a promising alternative in obstetric and elderly populations, although the optimal agent ultimately depends on the underlying mechanism of hypotension and individual patient characteristics. Epinephrine provides combined vasopressor and inotropic support for hypotension with myocardial depression. IOH is associated with a greater than twofold increase in postoperative AKI and significantly elevated risks of myocardial infarction and stroke, with outcomes driven by cumulative hypotensive exposure rather than isolated pressure nadirs. Conclusions: Effective management of IOH requires individualized vasopressor selection guided by underlying pathophysiology, cardiovascular profile, and surgical context. A physiology-based strategy—rather than protocol-driven drug substitution—enables anesthesiologists to achieve precise hemodynamic control and preserve end-organ perfusion even when ephedrine is unavailable.

Journal of Personalized Medicine doi: 10.3390/jpm16070383

Authors: Petra Valković Zujić Nina Bartolović Manuela Avirović Emina Babarović Lucija Požgaj Maja Prutki Emina Grgurević Dujmić Ana Car Peterko

Background: Accurate delineation of ductal carcinoma in situ (DCIS) remains a key challenge in surgical planning. Although contrast-enhanced mammography (CEM) improves lesion detection, its clinical role in informing individualized surgical strategies remains unclear. This study evaluated the impact of CEM on preoperative assessment and surgical planning, with particular emphasis on whether its effect varies across patient subgroups. Methods: This multicentre pilot observational cohort study included 102 patients: 51 prospective patients undergoing preoperative CEM and mammography (MMG) and 51 retrospective controls assessed with MMG alone. Imaging-derived lesion size and planned resection volume were compared with pathological size using correlation analysis, intraclass correlation coefficient (ICC), and Bland–Altman methods. Surgical outcomes were assessed, and subgroup analyses explored differences according to CEM enhancement status. Results: CEM showed improved correlation with pathological DCIS size compared with MMG (ρ = 0.54 vs. 0.37), with the strongest agreement in CEM-positive lesions (ρ = 0.67; ICC 0.745). However, its clinical impact was not uniform. At the population level, CEM did not significantly change planned resection volume or surgical thresholds. In contrast, in CEM-positive patients, CEM was associated with larger planned resections, proportional to pathological tumor burden. Reoperation rates were lower in the CEM cohort (5.9% vs. 17.6%), without statistical significance, and margin status was comparable. Conclusions: The impact of CEM on surgical planning in DCIS is heterogeneous and largely confined to patients with enhancing lesions. These findings suggest that the value of CEM may lie in its selective use, where it can refine assessment of disease extent in specific subgroups rather than in routine application. Further studies incorporating predictive approaches are needed to support risk-adapted imaging strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16070382

Authors: Xue-Qing Li Roslyn Stella Thelingwani Leif Bertilsson Ulf Diczfalusy Tommy B. Andersson Collen Masimirembwa

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Journal of Personalized Medicine doi: 10.3390/jpm16070381

Authors: Shilpa Bhandi Ahmed Al Kahtani Mohammed Mashyakhy Loai Alsofi Prabhadevi C. Maganur Satish Vishwanathaiah Luca Testarelli Andrea Del Giudice Deepak Mehta Nishant Vyas Vikrant R. Patil A. Thirumal Raj Shankargouda Patil

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Journal of Personalized Medicine doi: 10.3390/jpm16070380

Authors: Tímea Szigethi Dorottya Olajos Levente Molnár István Ferenc Édes György Bárczi Dávid Becker László Gellér Béla Merkely Zoltán Ruzsa

Background: Transradial access has become a preferred strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) because of lower access site complication rates and increasing feasibility for complex CTO techniques using large-bore slender or sheathless systems. However, long-term outcomes after successful transradial CTO recanalization and their predictors remain incompletely defined. We aimed to identify long-term clinical and procedural predictors of major adverse cerebrovascular and cardiac events (MACCEs) after successful transradial CTO PCI. Methods: We performed a prospective dual-center cohort study including 227 consecutive patients who underwent successful transradial CTO PCI at two high-volume catheterization laboratories with dedicated CTO programs. A total of 405 CTO PCI procedures were screened; all femoral access cases were excluded and only transradial cases were eligible. Baseline clinical characteristics, left ventricular ejection fraction (LVEF), lesion complexity including J-CTO score, coronary disease extent, and procedural variables were prospectively collected and/or verified from institutional databases. The primary endpoint was MACCEs, defined as a composite of all-cause death, non-fatal myocardial infarction, target vessel revascularization, and stroke/transient ischemic attack. Event rates were estimated using Kaplan–Meier methods. Predictors were explored using Cox proportional hazards regression with clinically relevant covariates and procedural characteristics entered into multivariable models. Results: Among 227 patients with successful transradial CTO recanalization and complete 5-year follow-up among survivors, cumulative MACCEs and all-cause mortality were 44.0% and 21.5%, respectively. In multivariable Cox analysis, prior myocardial infarction, right coronary artery target vessel, and a higher number of implanted stents were independently associated with increased MACCE risk, whereas previous PCI and preserved LVEF (≥40%) were associated with lower MACCE risk. For all-cause mortality, preserved LVEF was independently protective, while right coronary artery target vessel intervention was associated with increased mortality risk; severe chronic kidney disease showed a significant univariable association and remained a strong signal after multivariable adjustment. Conclusions: After successful transradial CTO PCI, long-term MACCEs appear to be driven primarily by baseline comorbidity and coronary disease burden. No deaths were related to access site bleeding, and vascular access was not associated with fatal complications. These findings contribute to personalized cardiovascular medicine by identifying readily available clinical, anatomical, and procedural factors that enable individualized long-term risk stratification following successful transradial CTO recanalization. Integrating these predictors into post-procedural assessment may support tailored secondary prevention, follow-up strategies, and patient management according to individual risk profiles.

Journal of Personalized Medicine doi: 10.3390/jpm16070379

Authors: Paul Whiteley Kevin Carr Paul Shattock Malcolm Hooper Carol Stott Karl Hardy Ben Marlow Chandoshi Rhea Mukherjee Athena Whiteley

Plural autisms offer one important way of organising the massive heterogeneity that is currently included under the singular diagnostic label of autism spectrum disorder (ASD). Characterised exclusively by behavioural criteria related to social communication skills and restricted or repetitive patterns of symptoms, the observable diversity in presentations and developmental trajectories partially explains the lack of universally applicable biomarkers and answers about underlying biology. One particularly important area potentially pertinent to several manifestations of the plural autisms is a connection to the immune system, whether noted across differing patterns of immune functions or following immune challenge in the context of inflammatory processes exerting an effect on developmental processes and behaviour. Utilising a narrative review, we highlight various research analysing a role for immune functions in the context of the heterogeneous autisms stretching across under-, over- and autoimmune processes. Current evidence for immune system involvement in various autisms carries considerable limitations, and studies are often based on small sample sizes, focusing on selective clinical subgroups, and using case-based observations. Notwithstanding the available evidence, substantial and more detailed further studies are required in relation to immune-related screening, building also on the currently limited evidence on the potential usefulness of personalised immune-affecting interventions following appropriate screening and identification of pertinent immune-related issues.

Journal of Personalized Medicine doi: 10.3390/jpm16070378

Authors: Rocío Martín-Valero Antonia M. Ruiz-Moreno Pablo J. Gallardo-García María Dolores Martínez Colmena Catalina Muñoz Pagan Pedro González-Rojas Paloma Ortega Quiñonero

Background/Objectives: Genitourinary Syndrome of Menopause (GSM) negatively affects quality of life in postmenopausal women, causing sexual dysfunction, vaginal atrophy, and pelvic discomfort. Personalized medicine highlights the need for individualized, non-hormonal therapeutic options for women with contraindications to or preferences against hormonal treatment. Non-hormonal therapies, such as laser treatments, have emerged as potential alternatives, but evidence comparing intravaginal and extravaginal K-Laser therapy remains limited. This study aimed to evaluate the efficacy of intravaginal and extravaginal K-Laser therapy on the symptoms of Genitourinary Syndrome of Menopause (GSM) in postmenopausal women. Methods: In this single-center, randomized, single-blind, placebo-controlled trial, 57 postmenopausal women were randomly assigned to receive either intravaginal and extravaginal K-Laser Cube Plus 30 therapy (n = 36) or a simulated control treatment (n = 21). The primary outcome was sexual function, measured by the Female Sexual Function Index (FSFI). Secondary outcomes included vaginal pH and pelvic floor muscle function assessed via the PERFECT protocol. Outcomes were assessed at baseline and after 6 weeks. Results: Sixty-seven women were enrolled, and ten were lost to follow-up. The treatment group showed significant improvements over the control group in FSFI (mean difference = 6.38; p < 0.001), PERFECT protocol scores (mean difference = 0.78; p = 0.004), CPPQ-Mohedo (mean difference = 5.44; p < 0.001), and Menopause Rating Scale (mean difference = 6.50; p = 0.017). Significant reductions were also observed in vaginal dryness, vulvar dystrophy, and atrophy (p < 0.001). Conclusions: Intravaginal and extravaginal K-Laser therapy appears to be a safe and effective non-hormonal treatment for GSM and may support personalized management strategies. However, further well-designed randomized clinical trials with larger samples, longer follow-up of both laser-treated and control groups, and objective outcome measures are needed to provide higher-quality evidence regarding efficacy and identify the patients most likely to benefit.

Journal of Personalized Medicine doi: 10.3390/jpm16070377

Authors: Ayokunle Osonuga Madhavi Dave Ikponmwosa Jude Ogieuhi David B. Olawade Stergios Boussios

Cardiovascular disease remains the leading global health challenge, claiming approximately 19.8 million lives annually. The convergence of wearable technology and artificial intelligence represents a transformative shift in cardiovascular healthcare, enabling continuous real-time monitoring beyond conventional clinical settings. This narrative review synthesises current evidence on integrating consumer-grade and medical-grade wearable devices with AI algorithms for continuous cardiovascular monitoring applications, with particular attention to real-world translational applicability and global health equity. This review examined the technological landscape of wearable cardiovascular monitoring devices, including smartwatches with photoplethysmography and electrocardiogram capabilities, continuous cardiac monitoring patches, and emerging biosensor technologies. Also, the review explored AI methodologies, particularly machine learning and deep learning architectures, employed in processing complex physiological data streams from these devices. Clinical applications demonstrate impressive capabilities: arrhythmia detection with sensitivity rates exceeding 98%, continuous blood pressure monitoring through cuffless technologies, heart failure decompensation prediction, and cardiovascular risk stratification. However, substantial challenges persist, including data quality assurance, algorithm interpretability, regulatory compliance, and seamless clinical workflow integration. Privacy concerns, health disparities in algorithm performance, and the need for robust validation across diverse populations remain critical considerations. AI-enhanced wearable systems hold considerable potential for shifting cardiovascular care from reactive treatment paradigms towards predictive, preventive, and precision medicine approaches. Future directions include edge computing architectures, federated learning approaches, personalised AI models, enhanced interoperability with electronic health records, and expansion to resource-limited settings, ultimately improving patient outcomes whilst reducing healthcare costs.

Journal of Personalized Medicine doi: 10.3390/jpm16070376

Authors: Nick Weidner Christian von Löffelholz Robert Patejdl Jan Seyfferth Heinrich Volker Groesdonk

Gastrointestinal dysfunction is common in critically ill patients and frequently compromises the delivery and tolerance of enteral nutrition. Traditional bedside markers such as gastric residual volume or nonspecific abdominal symptoms provide only limited diagnostic accuracy and often fail to capture dynamic alterations in gastrointestinal function. Gastrointestinal ultrasound (GIUS) has emerged as a noninvasive, bedside-applicable method that enables structural and functional assessment of the gastrointestinal tract and may support more individualized nutritional management in intensive care. This narrative review summarizes the physiology and pathophysiology of gastric emptying and intestinal transit in critically ill patients, reviews established GIUS protocols, including Gastrointestinal and Urinary Tract Sonography (GUTS), Acute Gastrointestinal Injury Ultrasound Scoring (AGIUS), the Lai protocol, and the Ultrasound Meal Accommodation Test (UMAT), and proposes pragmatic GIUS-based algorithms for enteral feeding decisions. Three clinical use cases are addressed: 8 h monitoring during ongoing enteral nutrition, preprandial assessment of feeding readiness, and once-daily screening of gastrointestinal function. Current evidence supports the clinical relevance of key sonographic parameters such as gastric antral cross-sectional area and small-bowel diameter, whereas other measures, including mucosal thickness, colonic wall thickness, and Doppler-derived resistive indices, require further validation. UMAT adds a dynamic component to static sonographic assessment and may improve the evaluation of gastric accommodation and emptying in selected patients. Structured GIUS protocols offer a promising, evidence-informed extension of bedside assessment for enteral nutrition management in the intensive care unit. However, the available literature remains heterogeneous and is largely based on physiological studies, observational cohorts, and expert consensus. Prospective multicenter studies are needed to validate cutoff values, training standards, and outcome effects before GIUS-based algorithms can be adopted as stand-alone decision tools.

Journal of Personalized Medicine doi: 10.3390/jpm16070375

Authors: Dhirendra K. Singh Yukihiro Yamaguchi Lei Huang Chieko Saito Olivia G. Cassidy Keita Nishiyama

DNA methylation plays a fundamental role in maintaining intestinal homeostasis, immune tolerance, and inflammatory balance. Active DNA demethylation, mediated by the ten-eleven translocation family of dioxygenases (TET1, TET2, and TET3), has emerged as an important epigenetic mechanism linking environmental and metabolic cues to gene regulatory programs in the gut. In the intestinal epithelium, TET-dependent DNA hydroxymethylation contributes to intestinal stem cell maintenance, epithelial differentiation, regeneration, and barrier integrity. Perturbations in TET activity are associated with epithelial dysfunction, chronic inflammation, and increased susceptibility to colorectal tumorigenesis. Within the immune compartment, TET-mediated demethylation is required for the epigenetic stabilization of gut-associated immune cells. Altered TET function has been implicated in immune imbalance in inflammatory bowel disease, Hirschsprung’s disease, and colitis-associated colorectal cancer. Emerging evidence further indicates that intestinal microbiota-derived metabolites, including short-chain fatty acids and aryl hydrocarbon receptor ligands, modulate TET activity, positioning TET enzymes as epigenetic sensors of microbial and metabolic signals. In turn, TET-dependent programs shape immune responses to commensal microbes and pathogens, establishing a bidirectional microbiota–epigenetic axis that influences both intestinal and systemic immunity. In this review, we summarize and critically evaluate current evidence on the roles of TET enzymes in intestinal epithelial biology, immune cell regulation, and host–microbiota interactions in colorectal inflammation and disease.

Journal of Personalized Medicine doi: 10.3390/jpm16070374

Authors: Gustavo Fabregat-Cid Natalia Escrivá-Matoses José De Andrés

Pain biomarkers have been proposed as potential tools to improve patient stratification, treatment selection, and individualized therapeutic strategies in chronic pain. However, despite an increasing volume of research across neuroimaging, electrophysiological, and molecular domains, their translation into clinical practice remains limited. A central challenge lies in the conceptual and methodological misalignment between biomarker discovery and clinical applicability. Many studies labelled as “predictive” rely on measurements obtained during or after intervention, small sample sizes, or lack of external validation, limiting their ability to inform real-world decision-making. In addition, the distinction between predictive, monitoring, and mechanistic biomarkers is often blurred, further complicating interpretation and implementation. This Perspective examines why many candidate pain biomarkers, although biologically informative, have not yet become clinically actionable tools for treatment selection. We distinguish between associative, mechanistic, monitoring, preventive, and truly predictive biomarkers using clinically relevant examples from pain research, and we outline the methodological requirements needed to translate biomarker discovery into precision pain medicine. We argue that the field requires a more rigorous framework for defining and validating predictive biomarkers, encompassing appropriate timing of measurement, robust study design, external validation, and patient-relevant endpoints. Without this framework, pain biomarker research risks continuing to generate biologically informative but clinically non-actionable findings that do not advance individualized therapeutic decision-making.

Journal of Personalized Medicine doi: 10.3390/jpm16070372

Authors: Ángela Solleiro-Vidal Diego Santos-García Alfredo Puy Núñez Teresa de Deus Fonticoba Pablo Mir Gracia Pons Pons Juan García Caldentey Nuria Caballol Jorge Hernández Vara Lydia López Manzanares Bárbara Vives Pastor Maria A. Ávila Rivera Isabel González Aramburu Rocío García-Ramos Carmen Borrué Julio Dotor García-Soto María Álvarez Sauco Iria Cabo Guillermo González Ortega COPPADIS Study Group COPPADIS Study Group

Background and Objective: Depression is frequent in Parkinson’s disease (PD), but it is unclear how mood changes and impacts patient’s quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients’ QoL. Patients and Methods: PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. Results: The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (p < 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [p = 0.896]). The prevalence of depression remained around 50–54% in the PwP group and 21–25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients’ QoL was associated with the depressive state throughout the entire follow-up period (p < 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N = 348). Conclusions: Mood change over time in PwP is associated with QoL.

Journal of Personalized Medicine doi: 10.3390/jpm16070373

Authors: Virginia Cinelli Federico Moretti Chiara Comisi Antonio Mascio Gloria Assegbede Vincenzo La Vergata Giulio Maccauro Carlo Perisano Tommaso Greco

Background: Fibular nonunion is an uncommon but clinically relevant complication following fractures or surgical procedures, often resulting in persistent pain and functional impairment. Due to its rarity, current evidence remains limited and no standardized treatment guidelines are available. Purpose: To systematically review the literature on fibular nonunion, focusing on clinical presentation, diagnostic approaches, and treatment outcomes. Methods: A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE, Scopus, and Web of Science were searched up to July 2025. Studies including adult patients (≥18 years) with fibular nonunion treated either conservatively or surgically were included. Data regarding demographics, clinical presentation, and treatment outcomes were extracted and analyzed descriptively. Results: Nineteen studies comprising 183 patients were included. The mean patient age was 45.7 years, with a predominance of males (58.4%). The distal third of the fibula was the most frequently involved site (75.9%). The mean time to diagnosis was 28.6 weeks. Surgical treatment was performed in 65.6% of cases, most commonly using open reduction and internal fixation. Among studies reporting union outcomes, favorable radiographic healing rates were observed following surgical treatment. Conservative treatment was primarily reserved for asymptomatic or minimally symptomatic patients. The overall complication rate was low (3.8%), mainly consisting of minor infections and hardware-related issues. Conclusions: Fibular nonunion is an uncommon but clinically significant condition. Available evidence suggests that surgical management may represent the most consistently successful treatment strategy in symptomatic and mechanically unstable cases, while nonoperative treatment may remain appropriate in carefully selected asymptomatic or minimally symptomatic patients. However, the available literature is limited by retrospective study designs, heterogeneous populations, inconsistent outcome reporting, and variable definitions of nonunion, highlighting the need for prospective multicenter studies and standardized treatment protocols.

Journal of Personalized Medicine doi: 10.3390/jpm16070371

Authors: Seung-Bo Lee

Background: Intraoperative hypotension (IOH) is the leading modifiable contributor to postoperative acute kidney injury (AKI), yet most evidence is associational and the heterogeneity of its effect is unknown. We estimated the causal effect of IOH burden on AKI and tested whether the most susceptible patients can be identified preoperatively. Methods: In a retrospective cohort of 2726 general-anesthesia cases from VitalDB, the exposure was the time-integrated mean arterial pressure (MAP) <65 mmHg burden (≥30, ≥60 and ≥120 mmHg·min) and the outcome was KDIGO-defined AKI within 7 days. The primary estimator was pre-treatment-adjusted augmented inverse-probability weighting (AIPW; doubly robust) with bootstrap 95% confidence intervals (CIs). Sensitivity analyses comprised a controlled-direct-effect model, negative control outcomes, E-values and vasopressor-stratified estimates. Effect heterogeneity was estimated with a causal forest; preoperative gradient-boosted models and decision-curve analysis assessed personalization and clinical utility. Results: AKI occurred in 205 (7.52%) cases. At 60 mmHg·min the AIPW risk difference was +3.00 percentage points (pp; 95% CI +0.84 to +5.26), with a monotonic dose–response (+2.78 to +7.62 pp across thresholds) and E-values rising from 2.08 to 3.44. The effect was concentrated in patients with elevated preoperative creatinine (conditional effect +9.86 pp, more than twice the cohort average). This susceptibility was recoverable from routine preoperative variables alone, with intraoperative waveform features conferring no measurable improvement (ΔAUROC −0.001). For predicting AKI itself, a parsimonious 4-feature preoperative score matched a 27-feature model (AUROC 0.775 vs. 0.768) and provided positive net benefit. Conclusions: Intraoperative hypotension burden shows a dose-dependent association with postoperative AKI that is consistent with a causal effect, concentrated in patients with reduced baseline renal reserve who are identifiable from routine preoperative data without intraoperative waveform infrastructure.

Journal of Personalized Medicine doi: 10.3390/jpm16070370

Authors: Theresa Mally Nina Rubicz Paul Martin Zwittag

Background: Migrated foreign bodies in the prevertebral region represent a rare but potentially serious condition. This case underscores the importance of thorough visual and digital intraoperative exploration for successful foreign body retrieval and highlights the potential diagnostic and surgical challenges associated with migrated foreign bodies in the cervical region. Case report: A 77-year-old female patient presented with dysphagia following the intake of an Angiotensin-Converting Enzyme (ACE) inhibitor. Due to hemodynamic instability and laboratory findings that indicated multiple organ failure, a computed tomography (CT) scan was performed, which revealed a left-sided prevertebral abscess with gas collections. Because of persistently elevated and fluctuating inflammatory markers, multiple CT scans were performed, which showed an obliquely oriented, wire-like tubular structure approximately 30 mm in length, 5 mm in width and 1 mm in diameter in the prevertebral region of the previous abscess cavity. Eventually, after three surgical interventions—one transoral and two transcervical approaches—the foreign body could be identified and removed. Afterwards, the patient’s inflammatory markers decreased and her dysphagia resolved. Conclusions: This case demonstrates that early diagnosis and timely removal of foreign bodies in the cervical space are essential to prevent complications such as retropharyngeal abscess formation or mediastinitis. A combination of careful clinical examination, endoscopic evaluation, and cross-sectional imaging—particularly CT scan—is crucial for accurate localization. Finally, this report highlights the importance of maintaining a high index of suspicion for migrated foreign bodies in patients presenting with persistent symptoms or unexplained cervical infections following suspected foreign body ingestion.

Journal of Personalized Medicine doi: 10.3390/jpm16070369

Authors: Kathleen D. McDaniel Neda Ghousifam Rodney A. Bowling Catherine Z. Chen Wei Zheng Zeenat A. Shyr

Background: Mucopolysaccharidosis type IIIB (MPSIIIB, Sanfilippo syndrome type B) is a rare lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU) enzyme, leading to progressive accumulation of heparan sulfate and severe neurological decline. MPSIIIB’s significant genetic heterogeneity presents a major barrier to developing broadly effective treatments and suggests a need for personalized therapeutic strategies. Methods: We established a personalized drug repurposing platform using high-content imaging with lysotracker dye as an indirect functional readout of lysosomal dysfunction to screen compounds that correct lysosomal defects in patient-derived fibroblasts. We screened 2807 compounds on cells from an MPSIIIB patient with a homozygous NAGLU p.Arg297Ter mutation. Hits that reduced lysosomal accumulation by at least 25% with minimal cytotoxicity were validated and subsequently tested for efficacy in fibroblasts from a second patient with a different, compound heterozygous NAGLU genotype. Results: The primary screen yielded 72 hits (2.6% hit rate), with 10 confirmed in dose–response assays. Notably, four clinically approved drugs—baclofen, dextrose, epalrestat and moxifloxacin—reduced lysosomal accumulation in the index patient’s cells. However, none of these four drugs were effective in the second patient’s cells, demonstrating a profound patient-specific effect. Only one non-clinical compound, 6-chlorothymol, showed a trend toward activity in both cell lines. Conclusions: Our study demonstrates a feasible framework for conducting rapid, N-of-1 drug repurposing screens for rare diseases. While we identified four promising candidates for the index patient, the lack of efficacy in a second patient cell line underscores that genetic heterogeneity may preclude a “one-size-fits-all” approach for MPSIIIB. These findings support the integration of individualized drug screening as a potential precision-medicine strategy, offering a potential path toward patient-specific therapies for rare diseases rather than traditional drug development.

Journal of Personalized Medicine doi: 10.3390/jpm16070368

Authors: Archana Ramgopal Tsuyoshi Fujita Breana K. Goscicki Shiva Sridar Daniel Klein Li Wang Ramasubramanian Kalpatthi Jignesh Dalal

Background/Objectives: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a serious complication of hematopoietic stem cell transplantation (HSCT), particularly in high and very high-risk pediatric patients. Despite known risk factors, U.S. data remain limited. The benefit of prophylactic defibrotide is uncertain, with prior trials yielding inconclusive results. This study evaluates its use and association with SOS incidence, healthcare burden, and outcomes. Methods: We performed a retrospective cohort study of 10,250 pediatric HSCT encounters using the Pediatric Health Information System. Patients were stratified as high-risk (n = 9584) or very high-risk (n = 666) per HARMONY criteria. Prophylactic defibrotide was used in 344 encounters; 9906 received none (therapeutic use allowed after SOS diagnosis). Outcomes included SOS incidence, length of stay (LOS), ICU admission, mortality, acute GVHD, and costs. Mixed-effects logistic regression models with patients as a random intercept were used (p < 0.05). Results: SOS incidence differences between the defibrotide prophylaxis and non-prophylaxis groups were not statistically significant in either risk category (high-risk: 26% [n = 79/302] vs. 7.1% [n = 663/9282] p = 0.495, OR 1.457, 95% CI 0.494–4.296; very high-risk: 31.0% [n = 13/42] vs. 21.6% [n = 135/624], p = 0.970, OR 1.081, 95% CI 0.019–60.769). The extremely wide confidence intervals indicate that the data are consistent with both benefit and harm of prophylaxis. Median LOS was longer in the prophylactic group (40 vs. 33 days, p < 0.001; 56 vs. 49 days, p = 0.296, respectively). ICU admissions (50.7% vs. 32.8%; 69.0% vs. 50.8%), mortality (7.9% vs. 3.5%; 23.8% vs. 10.9%), and costs ($443,537 vs. $205,325; p < 0.001) were also higher in the prophylaxis group. Acute GVHD incidence differences were not statistically significant, with contradictory directions between risk subgroups. Conclusions: Prophylactic defibrotide was not associated with reduced SOS incidence and was associated with higher ICU use, longer LOS, increased mortality, and greater costs. These findings represent associations, not causation, and likely reflect residual confounding by indication—as defibrotide prophylaxis was preferentially administered to patients perceived to be at highest clinical risk. Prospective studies with appropriate confounding adjustment are needed to clarify the role of defibrotide in SOS prevention.

Journal of Personalized Medicine doi: 10.3390/jpm16070367

Authors: Daniele Salvatore Paternò Luigi La Via Marco Lo Presti Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Emilia Concetta Lo Giudice Giordana Russo Mattia Pratini Paolo Tummino Giuseppe Scibilia Marco Barbanti Massimiliano Sorbello

Cardiac arrhythmias complicate 20–50% of surgical procedures and contribute substantially to perioperative morbidity, mortality, and healthcare costs, with postoperative atrial fibrillation (POAF) being the most frequent form. Their genesis reflects the convergence of surgical stress, anaesthetic agents, autonomic imbalance, systemic inflammation, and electrolyte disturbances, explaining the limited efficacy of single-mechanism interventions. This narrative review synthesises contemporary evidence on pathophysiology, risk stratification, prevention, acute management, and emerging technologies, emphasising individualised, patient-tailored approaches. MEDLINE, Embase, and Cochrane CENTRAL were searched (January 2010–January 2026), prioritising randomised trials, meta-analyses, and guidelines. Contemporary risk stratification integrates clinical scores, biomarkers, and electrocardiographic parameters; machine-learning models show moderate discrimination (pooled AUC 0.84) and may enable more personalised prediction pending external validation. Evidence-based prophylaxis—beta-blockade, magnesium, selective amiodarone, and emerging anti-inflammatory strategies such as colchicine—reduces POAF in high-risk populations, while acute management is guided by haemodynamic status and individual risk. Anticoagulation follows CHA2DS2-VASc stratification, although optimal timing and duration remain undefined. Wearable monitoring, AI-based detection, and atrial-selective agents show clinical promise. Systematic, personalised integration of risk assessment, prophylaxis, monitoring, and management offers the clearest path to reducing arrhythmia-associated morbidity.

Journal of Personalized Medicine doi: 10.3390/jpm16070366

Authors: Berkan Aliev Boyko Atanasov

Enhanced Recovery After Surgery (ERAS) pathways have improved perioperative outcomes by standardizing evidence-based interventions across the surgical continuum. However, substantial variability in postoperative recovery persists, even within well-implemented ERAS programs. This heterogeneity reflects differences in clinical risk, functional reserve, biological response to surgical stress, treatment responsiveness, and contextual factors that are not fully captured by uniform protocols. Precision medicine provides a potential framework for refining ERAS by integrating patient-specific data into perioperative risk assessment, intervention selection, patient monitoring, and recovery planning. Nevertheless, most precision medicine tools remain insufficiently validated for routine ERAS implementation, and their clinical utility is limited by heterogeneous evidence, data integration challenges, costs, workflow complexity, and equity concerns. Future progress will require prospective validation, pragmatic implementation studies, interoperable data systems, and evaluation of patient-centered outcomes. This narrative review examines the emerging role of precision medicine tools in perioperative practice and proposes an idealized conceptual model of “precision ERAS” in which standardized evidence-based care is preserved as the foundation, while selected interventions are adapted according to individual risk, biological phenotype, and recovery trajectory.

Journal of Personalized Medicine doi: 10.3390/jpm16070365

Authors: Bradley C. Nelson Mark J. Lambrechts

Technological advances in spine surgery have allowed for significantly improved precision. Perhaps no technology has allowed for more personalized and precise surgery than endoscopic spine surgery. Although this technology has been around for decades, advancements in camera resolution have led to enhanced magnification and visualization of nerve root compression. Given our improved understanding of the interplay between spinal stability, spine pain, and muscle health, minimizing muscle disruption and bone resection has now become a key principle in spinal care. This narrative review will talk about common lumbar spine pathologies and how spinal endoscopy can be implemented to potentially improve patient care and outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16070364

Authors: Isolina Riaño-Galan Corsino Rey María Bogaerts Marquez Laura Muñoz Rebeca García César Bazó Julián Rodríguez

Background: Telemedicine complements traditional healthcare delivery and may improve access, continuity of care, and patient engagement, particularly in chronic conditions requiring regular follow-up. Video consultation is a widely adopted telemedicine modality and is increasingly integrated into hybrid care models. Methods: This real-world implementation project describes scheduled video consultations embedded in a hybrid care model for children and adolescents with type 1 diabetes using continuous glucose monitoring (CGM) and integrated insulin delivery technologies as part of routine clinical care. A total of 38 families were offered video consultations as part of routine care; 18 adopted the hybrid model. Video consultations were used for routine follow-up, shared review of device data, treatment adjustment, and diabetes education. Family experience was assessed using a voluntary 5-point Likert-scale satisfaction questionnaire. Complete longitudinal CGM data were available for 13 participants, all of whom were established users of the same automated insulin delivery (AID) platform (MiniMed™ 780G (Medtronic MiniMed, Inc. Minneapolis, MN, USA) integrated with Guardian™ 4 (Medtronic MiniMed, Inc. Minneapolis, MN, USA) continuous glucose monitoring). Results: Between 2022 and 2024, 162 video consultations were conducted. Acceptability was high, with 95% (17/18) of respondents reporting high satisfaction (score ≥ 4 on the 5-point Likert scale). 89% (16/18) of families perceived the quality of care as comparable to face-to-face visits for routine follow-up. Families highlighted convenience, reduced travel burden, and flexibility, as well as the value of shared review of CGM and AID system data. Group-level CGM-derived metrics appeared descriptively similar across sequential face-to-face visits and video consultations. Individual patient trajectories showed expected variability but no consistent pattern of deterioration during periods of remote follow-up. Conclusions: Video consultation is a feasible and well-accepted complementary modality within hybrid care models for pediatric type 1 diabetes. When integrated with CGM and automated insulin delivery systems, it supports personalized, data-driven clinical decision-making and continuity of care. Structured implementation and systematic evaluation are essential for sustainable integration into routine practice.

Journal of Personalized Medicine doi: 10.3390/jpm16070363

Authors: Joana O. Pinto Bruno Peixoto Artemisa R. Dores Fernando Barbosa

The main purpose of this work is to critically review the literature on neurocognitive disorders (ND) diagnosis. A critical review was conducted in PubMed, Scopus, and EBSCO. Systematic reviews and meta-analyses focusing on ND diagnosis were included. The selected studies were critically analyzed and conceptually integrated to identify relevant dimensions for the diagnosis of ND. The review included 88 studies. Most studies focused on Alzheimer’s disease and mild cognitive impairment. The literature remained predominantly centred on isolated diagnostic domains, and important limitations were consistently identified, including methodological heterogeneity, lack of standardized thresholds, and reduced clinical applicability. Based on the identified conceptual and methodological limitations, a Multidimensional Model of Neurocognitive Disorders (MOND model) for ND diagnosis was proposed. The MOND model was developed as a multidimensional, multilevel, transdiagnostic model integrating biological, neurocognitive, neuropsychiatric, motor, functional, frailty, reserve-related, and socio-environmental dimensions. The model may contribute to research, symptom classification, severity characterization, prognosis, and personalized intervention planning across different ND trajectories. Future studies using the MOND model should focus on refining algorithms to estimate the risk of ND.

Journal of Personalized Medicine doi: 10.3390/jpm16070362

Authors: Ourania S. Kotsiou Georgios I. Barkas Konstantinos I. Gourgoulianis Zoe Daniil

Background: Biologic therapies have transformed severe asthma management, but real-world evidence comparing phenotypes, lung function trajectories, and persistence across biologic classes remains limited. Objective: To characterize a real-world cohort of biologic-treated severe asthma patients, focusing on baseline phenotypes, longitudinal post-bronchodilator spirometry (including a spirometric surrogate suggestive of small airways involvement), and discontinuation/switching patterns. Methods: In this retrospective observational study at a tertiary referral center, adults with severe asthma treated with benralizumab, mepolizumab, omalizumab, or tezepelumab were included. Demographic, clinical, biomarker, and functional data were collected at baseline and follow-up. Post-bronchodilator FEV1 and FEF25–75 (% predicted) were assessed at baseline, 6 months, 12 months, and 24–36 months when available. Longitudinal outcomes were analyzed using multivariable linear mixed-effects models; discontinuation and switching were recorded. Results: Eighty-seven patients were included (benralizumab n = 13, omalizumab n = 10, mepolizumab n = 30, tezepelumab n = 34), representing 10.9% of the clinic’s population. Most had long-standing disease, elevated body mass index, and a T2-high profile. Baseline characteristics were generally similar across groups, with expected differences in total IgE (p = 0.007) and blood eosinophils (p < 0.001). The primary endpoint (FEV1 % predicted change from baseline to 12 months) showed adjusted mean changes of +12.46 (95% CI +1.63 to +19.29; p = 0.020) with benralizumab, +15.82 (+8.35 to +23.64; p < 0.001) with mepolizumab, +16.65 (+1.58 to +31.71; p < 0.001) with omalizumab, and +15.69 (+6.52 to +24.87; p = 0.030) with tezepelumab; trajectories differed by biologic class (time × biologic p = 0.019). Although the interaction term indicated heterogeneous temporal patterns, these adjusted findings should be interpreted as associative in the context of biomarker-driven treatment selection and not as evidence of comparative superiority of any biologic class. Discontinuation occurred in 15/87 (17.2%), with switching most commonly due to inadequate control. Conclusions: Real-world severe asthma patients demonstrate heterogeneous phenotypes and spirometric trajectories on biologics. Integrating biomarkers with longitudinal lung function monitoring, including small-airway spirometric surrogates, supports individualized management.

Journal of Personalized Medicine doi: 10.3390/jpm16070361

Authors: Behrouz Ebrahimi Albert K. Dadzie Mansour Abtahi Masrur A. Sadhin Daniel Kim Srishti Kolla Baoxin Li R. V. Paul Chan Michael J. Heiferman Xincheng Yao

Objective: To predict pixel-wise retinal thickness maps from near-infrared (NIR) fundus images using deep learning (DL), and to identify image features in NIR fundus photographs serving as surrogate markers of retinal thickness, with implications for decentralized diabetic macular edema (DME) screening, progression monitoring, and treatment assessment. Methods: A DL model based on a U-Net architecture was trained on paired NIR fundus and OCT images from 531 eyes across three groups: healthy controls, diabetic retinopathy (DR) without DME, and DME. Model performance was evaluated using mean absolute error (MAE), root mean squared error (RMSE), structural similarity index (SSIM), and center-involved DME (ci-DME) classification at a central subfield thickness threshold of 300 µm. Controlled image manipulation experiments, including spatial disruption of vascular patterns, relocation of hard exudates, and contrast enhancement, were performed to identify image-level features serving as surrogate markers of retinal thickness. Results: The model achieved an MAE of 30.41 ± 18.68 µm, RMSE of 36.14 ± 21.05 µm, and SSIM of 0.87 ± 0.04 across the macula, with consistent performance across ETDRS subfields. For ci-DME classification, it achieved an accuracy of 84.1%, sensitivity of 69.1%, and specificity of 88.7%. Interpretability analyses were performed as qualitative assessments to visualize image regions contributing to model predictions. These analyses highlighted retinal vascular structures, hard exudates, and local contrast variations as visual features observed in relation to model outputs. Conclusions: NIR fundus images contain sufficient structural information to support pixel-wise retinal thickness estimation, with vascular architecture, hard exudates, and local contrast variations identified as image features potentially associated with model predictions. These findings suggest that NIR-based deep learning approaches may have potential applications in the assessment of diabetic macular edema and warrant further prospective and external validation to determine their role in screening, triage support, longitudinal monitoring, and treatment-related assessment, particularly in decentralized and re-source-limited care environments.

Journal of Personalized Medicine doi: 10.3390/jpm16070360

Authors: Joanna Zygadło Leszek Blicharz Joanna Czuwara Joanna Nowaczyk Karolina Makowska Małgorzata Olszewska Lidia Rudnicka

Background/Objectives: Facial discoid dermatosis is a rare inflammatory dermatosis presenting with round, superficial erythematous lesions located on the face. Diagnosis may be challenging and often requires careful clinicopathological correlation due to overlapping clinical and histopathological features. Skin lesions are typically resistant to a wide range of topical and systemic treatments. From the perspective of personalized medicine, improved phenotyping of rare inflammatory dermatoses may support more precise diagnosis, individualized therapeutic decisions, and non-invasive disease monitoring. This study aimed to characterize facial discoid dermatosis using line-field confocal optical coherence tomography and reflectance confocal microscopy and to discuss its differential diagnosis and therapeutic implications. Methods: We report a case of facial discoid dermatosis in a 35-year-old patient examined with line-field confocal optical coherence tomography and reflectance confocal microscopy. The imaging findings were interpreted in correlation with clinical and histopathological features. A literature review was performed to summarize differential diagnoses, therapeutic perspectives, and the proposed relationship between facial discoid dermatosis and pityriasis rubra pilaris. Results: Non-invasive imaging revealed morphological features consistent with a psoriasiform inflammatory dermatosis and provided additional in vivo information supporting the diagnosis. The literature review showed limited evidence for a direct association between facial discoid dermatosis and pityriasis rubra pilaris, with only isolated reports suggesting possible overlap or progression. Conclusions: Facial discoid dermatosis appears to represent a distinct psoriasiform dermatosis. Line-field confocal optical coherence tomography and reflectance confocal microscopy may contribute to a personalized diagnostic approach by supporting differential diagnosis and potentially guiding individualized monitoring in rare inflammatory facial dermatoses.

Journal of Personalized Medicine doi: 10.3390/jpm16070359

Authors: Panagis Lykoudis Maria Papadoliopoulou Alexios Kozonis Georgios Kirkilesis Marios-Konstantinos Tasoulis Mahrokh Nohadani Mihir A. Gudi

Background/Objectives: Immunohistochemistry is an integral component of the diagnostic approach in breast cancer and remains essential for tumor characterization and therapeutic decision-making. p63 gene expression may have potential diagnostic and prognostic roles in breast cancer patients. Methods: In this study, 127 specimens of invasive breast carcinoma and 50 control cases were evaluated for p63 gene expression and compared to other pathology factors. Results: None of the 50 control cases was assessed as positive for p63 expression. Progesterone and estrogen receptor status were the only factors that demonstrated a statistically significant negative correlation with p63 expression (p = 0.005 and p = 0.017, respectively). Tumor size demonstrated a marginally non-significant correlation with p63 expression (p = 0.051). None of the remaining factors was significantly correlated with p63 expression. Conclusions: In conclusion, p63 expression is inversely correlated with estrogen and progesterone receptor status, and type, size and grade of the tumors are not correlated with the gene’s expression, nor is HER2 status. This conclusion might impact genotype-based stratification pertinent to diagnosis and tailored treatment.

Journal of Personalized Medicine doi: 10.3390/jpm16070358

Authors: Mariangela Pati Immacolata Blasi Giovanna Botticelli Andrea Musarò Flavio Vanacore Giulia Galeati Lorenzo Aguzzoli Maria Paola Bonasoni

Background: Trisomy 21 (T21) is strongly associated with congenital heart disease, particularly atrioventricular septal defect (AVSD), ventricular septal defect (VSD), atrial septal defect (ASD) and selected conotruncal and arch anomalies. First- and second-trimester ultrasound, Doppler and fetal cardiac MRI enable increasingly early and detailed characterization of these lesions, while advances in molecular cardiogenesis have linked specific phenotypes to dosage-sensitive genes on chromosome 21. Methods: This narrative review synthesizes contemporary evidence on structural and functional cardiovascular anomalies in T21 fetuses in the first and second trimester, integrating fetal echocardiography, Doppler assessment and fetal cardiac MRI with embryologic and molecular insights, and summarizing trimester-specific detectability and pathophysiologic links to candidate genes in the Down syndrome-critical region. Approximately one quarter to one third of T21 fetuses have major congenital heart disease on high-quality prenatal echocardiography, with AVSD representing about half of all lesions and VSD, tetralogy of Fallot (TOF), arch anomalies, venous return abnormalities and functional markers (increased nuchal translucency, tricuspid regurgitation, ductus venosus abnormalities) comprising the remainder. Results: First-trimester detection relies on functional markers and early four-chamber and outflow-tract views, whereas second-trimester studies refine anatomic definition and hemodynamics, with MRI reserved for complex cases. Overexpression of genes such as DSCAM, COL6A1/COL6A2, DYRK1A and RCAN1 perturbs endocardial cushion, conotruncal and vascular development. Conclusions: Early, protocol-driven cardiac imaging in T21 supports timely diagnosis, risk stratification and multidisciplinary counselling, and links fetal imaging phenotypes with chromosome 21 gene dosage to advance personalized management and future genotype–phenotype research.

Journal of Personalized Medicine doi: 10.3390/jpm16070357

Authors: Luis Chauca Bajaña Tatiana Cruz Moreno Diego Quiguango Farias Sandra Vélez Cevallos Eliana Pazmiño Troncoso Alisson Juiña Jaime Mauricio Rosales Pavón Byron Velásquez Ron

Background: Temporomandibular disorders (TMD) are multifactorial musculoskeletal conditions frequently associated with chronic pain, inflammation, and functional impairment. Increasing evidence suggests that oxidative stress may contribute to the pathophysiology of TMD, and salivary biomarkers have emerged as a promising non-invasive approach for evaluating these biological alterations. Objective: This systematic review and meta-analysis aimed to systematically evaluate and quantitatively synthesize the available evidence regarding salivary oxidative stress biomarkers in patients with temporomandibular disorders compared with healthy controls. Materials and Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. Electronic searches were performed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases. Observational studies and clinical trials evaluating salivary oxidative stress biomarkers in patients with TMD were included. The primary biomarkers assessed were malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). Data extraction and risk of bias assessment were independently performed by two reviewers using the Newcastle–Ottawa Scale and RoB 2 tool when applicable. Random-effects meta-analyses were conducted using weighted or standardized mean differences with 95% confidence intervals. Included studies demonstrated substantial methodological variability regarding TMD diagnostic criteria, saliva collection protocols, biomarker assays, and sampling conditions. Results: Pooled analyses showed significantly elevated salivary malondialdehyde levels in patients with TMD compared with healthy controls, suggesting increased lipid peroxidation and oxidative stress activity. In contrast, total antioxidant capacity and catalase activity demonstrated inconsistent and non-significant findings across studies. Considerable heterogeneity was identified among studies, limiting the comparability and interpretability of pooled estimates. Salivary oxidative stress biomarkers, particularly malondialdehyde, appear to be associated with temporomandibular disorders and may reflect underlying oxidative and inflammatory mechanisms. Conclusions: However, substantial methodological heterogeneity and lack of standardized protocols currently limit their clinical applicability. Future well-designed longitudinal studies using harmonized diagnostic and analytical methodologies are required to clarify their translational value in TMD assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16070356

Authors: Federica Zito Marino Carminia Maria Della Corte Vincenza Ciaramella Stefania Erra Andrea Ronchi Alfonso Fiorelli Giovanni Vicidomini Mario Santini Giosuè Scognamiglio Floriana Morgillo Fortunato Ciardiello Renato Franco Marina Accardo

The journal retracts the article titled “AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma” [...]

Journal of Personalized Medicine doi: 10.3390/jpm16070355

Authors: Isabel Dirven Marre W. Kamminga Lise M. Verhoef Rogier M. Thurlings Ruben L. Smeets Arjan van Caam Madelon C. Vonk

Background: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by inflammation, vasculopathy, and fibrosis. It is associated with the highest mortality among rheumatic diseases. Very early SSc may represent a critical phase with risk of developing progressive disease. Although timely treatment may be effective in patients with progressive disease, it carries risks of adverse events, underscoring the need for early identification of individuals at risk. Biomarkers for progression in the early stage offer opportunities for timely intervention and improved long-term outcomes. Therefore, validating biomarkers that predict progression is an important research priority. In this narrative literature review, we summarize and evaluate blood circulating biomarkers associated with different progression endpoints in (very) early SSc. Methods: The literature search was conducted using PubMed. Eligible studies assessed biomarkers in very early SSc or early SSc cohorts with longitudinal follow-up and progression-related outcomes. Results: The identified studies investigated biomarkers associated with interstitial lung disease (ILD), skin progression, overall disease progression, and mortality. Anti-topoisomerase I was associated with ILD development. A high interferon score was linked to reduced lung function and mortality. KL-6 was associated with progression in early SSc-ILD. PRO-C3 and PRO-C6 showed the strongest associations with skin involvement. Finally, IgG anti-centromere antibody was associated with organ involvement and progression to definite SSc. CXCL10 and TNFRII were linked to progression and significant survival differences in the discovery and replication cohorts. However, effect sizes were often modest, and findings were inconsistent across cohorts. Substantial heterogeneity in study design, populations, endpoints, and biomarker assessment methods limited comparability. Moreover, most biomarkers demonstrated associations at the group level but lacked sufficient discriminatory power for individual risk prediction. Only a minority of studies included validation cohorts, and replication of findings was limited. Conclusions: Multiple biomarkers show promising associations with progression in very early and early SSc, but a single biomarker is unlikely to reliably predict disease progression.

Journal of Personalized Medicine doi: 10.3390/jpm16070354

Authors: Christos Tsilivigkos Eleftherios Ferekidis Marios Stavrakas

Introduction: Cochlear implantation is a well-established treatment for adults with bilateral postlingual deafness. In recent years, increasing research attention has focused on its use in patients with single-sided deafness (SSD) with or without tinnitus. Restoration of binaural auditory input through cochlear implantation may partially reestablish binaural processing. Methods: We conducted a narrative review of the literature focusing on studies examining the basic mechanisms associated with hearing impairment in SSD, as well as cochlear implantation outcomes in this population, including hearing performance, tinnitus suppression, and quality of life (QoL). We also reviewed comparative studies between cochlear implants (CIs) and alternative hearing devices, along with current candidacy criteria and the challenges associated with cochlear implantation in this patient group. Results: Current evidence suggests that CIs can provide significant benefits in this population, including tinnitus reduction or suppression, improved speech perception in both quiet and noise, enhanced sound localization, and better disease-specific and overall QoL. Furthermore, numerous studies—despite some variability in outcomes—indicate that CIs may offer superior performance compared with alternative options, such as contralateral routing of signals hearing aids (CROS-HAs) and bone-conduction devices, particularly in terms of speech perception, localization, tinnitus control, and aspects of QoL. Nevertheless, appropriate candidacy criteria and key challenges—most notably device non-use—should be carefully considered when evaluating cochlear implantation in this patient population. Conclusions: Further research is required to address these challenges and to advance a more personalized approach to cochlear implantation in individuals with SSD, with the aim of optimizing outcomes and reducing cochlear implant non-use.

Journal of Personalized Medicine doi: 10.3390/jpm16070353

Authors: Daniela Valle Almeida Figueredo Silvia de Lourdes Loreto Faquini Edward Araujo Júnior Tammy Caram Sabatine Gustavo Yano Callado Antonio Braga Roberta Granese Alex Sandro Rolland Souza

Objective: To review the literature on palliative care protocols and models of care for pregnant women and their fetuses with life-limiting conditions. Methods: A narrative literature review was conducted in the PubMed/MEDLINE and Virtual Health Library (VHL)—BIREME/SciELO/LILACS, using the descriptors “palliative care” and “prenatal care”. Studies of all designs published between February 2015 and May 2025 were considered for inclusion. Articles in languages other than Portuguese, English, and Spanish, duplicates, and those that did not discuss care protocols or experiences in perinatal palliative care for life-limiting fetal conditions starting from prenatal care were excluded. Articles were selected through title, abstract, and full-text screening. Results: Twenty-one studies focused on prenatal care were selected, presenting protocols and experiences of care in palliative fetal medicine. Most addressed the diagnosis of life-limiting fetal malformations, prenatal care, birth and delivery plan, perinatal grief and the puerperium. Across the included studies, a recurring emphasis on individualized, patient and family-centered approaches was identified, reflecting core principles of personalized medicine. Tailoring communication, care planning, and bereavement support to the specific clinical, genetic, cultural, and psychosocial profile of each dyad emerged as a structural characteristic of effective perinatal palliative care models. Conclusions: There is a scarcity of specific palliative care protocols for pregnancy, indicating a need to expand studies. The reviewed literature can contribute to the creation and adaptation of palliative care protocols and models for pregnant women and their fetuses with life-limiting conditions, may support more consistent care planning, improved communication, and better alignment with parental values.

Journal of Personalized Medicine doi: 10.3390/jpm16070352

Authors: Johannes Moritz Mittendorfer Zehra Duezguen Lukas Horak Andreas Gahleitner Elisabeth Marlene Mandler Lena Hirtler

Background/Objectives: Accurate identification of the functional femoral attachment of the anterior (ACL) and posterior cruciate ligament (PCL) is essential for anatomic reconstruction and for patient-specific femoral tunnel planning, yet correct intraoperative localization remains inconsistent. This anatomical study investigated whether subcortical bone features provide evidence of functional cruciate ligament attachment and whether surrounding osseous ridges are reliable landmarks. Methods: Computed tomography (CT) scans of 20 paired, fresh-frozen distal femora (10 body donors) were processed using 3D volume rendering to visualize the intercondylar fossa walls and to assess the presence of four characteristic ridges: lateral intercondylar ridge (LIR), lateral bifurcate ridge (LBR), medial intercondylar ridge (MIR) and medial bifurcate ridge (MBR). In addition, thin-ground section histology of the femoral insertion sites was performed to characterize insertion morphology. Results: Histology demonstrated distinct direct and indirect insertions for both ligaments; the direct insertion exhibited a characteristic four-layer transition (ligament, non-calcified fibrocartilage, calcified fibrocartilage, bone), whereas the indirect insertion showed collagen fibers attaching directly to bone. The LIR and MIR were present in 85% and 80% of specimens, respectively, while the LBR and MBR were less frequent (LBR 25%, MBR 10%). No significant associations were found between ridge presence and age, sex or laterality. Conclusions: These findings support the direct insertion as the functional cruciate attachment and suggest that the LIR and MIR—due to their consistent occurrence and location at the rim of the direct insertion—are the most useful bony landmarks for individualized femoral tunnel orientation, whereas bifurcate ridges should be considered adjunctive when present. The observed variability provides a rationale to stratify cases requiring adjunct imaging or navigation.

Journal of Personalized Medicine doi: 10.3390/jpm16070351

Authors: Dmitry Oskin Stanislav Kotlyarov

Background/Objective: Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) are among the most prevalent respiratory disorders worldwide and frequently coexist in the same patient. However, the contribution of active TB and post-tuberculosis lung disease to COPD exacerbations and long-term prognosis remains incompletely defined. This paper aim to evaluate the prevalence, clinical correlates, and prognostic significance of tuberculosis and its sequelae in patients with COPD. Materials and methods: We conducted a population-based retrospective cohort study using de-identified data from the regional healthcare information system. The cohort included all adults aged 18 years or older with a recorded diagnosis of COPD (ICD-10 code J44). Tuberculosis was identified by codes A15–A19 and B90. The primary outcomes were COPD exacerbations and all-cause mortality. Group comparisons, cluster analysis, Kaplan–Meier survival analysis, Cox proportional hazards modeling, and multivariable logistic regression were performed. Results: Tuberculosis and/or its sequelae were identified in 267 of 16,714 patients (1.60%): post-TB sequelae (B90) in 197 (73.8%), active TB (A15–A19) in 22 (8.2%), and both in 48 (18.0%). Compared with patients without TB, those with COPD-TB were younger (63.5 ± 14.2 vs. 65.7 ± 14.7 years; p = 0.018), more often male (75.3% vs. 52.0%; p < 0.001), and had higher mortality (16.5% vs. 10.6%; p = 0.003). COPD-TB was associated with bronchiectasis (OR = 6.07; 95% CI, 3.03–12.16), pulmonary fibrosis (OR = 5.67; 95% CI, 3.40–9.45), and pneumonia (OR = 2.01; 95% CI, 1.50–2.71), but with lower prevalences of obesity, diabetes mellitus, and hypertension. Patients with TB experienced more COPD exacerbations, including recurrent exacerbations. In multivariable models, tuberculosis was associated with COPD exacerbations after adjustment for age and sex (adjusted OR = 1.43; 95% CI, 1.05–1.96); this association was attenuated and lost significance after further adjustment for post-tuberculosis structural lung disease, indicating that it is largely mediated by post-TB sequelae. Tuberculosis remained associated with mortality after adjustment for available covariates, both in logistic regression (adjusted OR = 1.61; 95% CI, 1.14–2.28) and in Cox analysis (hazard ratio = 1.37; 95% CI, 1.01–1.85). Conclusions: Tuberculosis and post-tuberculosis lung disease are clinically accessible risk markers associated with COPD exacerbations and mortality. These findings support recognizing patients with COPD and a history of TB as a high-risk subgroup requiring intensified follow-up, proactive exacerbation prevention, and prioritized vaccination counseling. In the context of personalized medicine, a documented history of tuberculosis and post-tuberculosis lung changes represents a clinically accessible marker that can be used to stratify individual risk and to tailor monitoring and prevention in patients with COPD.

Journal of Personalized Medicine doi: 10.3390/jpm16070350

Authors: Thomas Karagkounis Angeliki Alifragki Ioannis Zoupas Sofia Sarantou Nikolaos Schizas Konstantinos S. Mylonas Dimitrios C. Iliopoulos

Background/Objectives: Minimally invasive (MIS) mitral valve surgery has been proven to be a safe and effective alternative to median sternotomy (ST), with advantages in postoperative recovery and morbidity. However, its role in the setting of infective endocarditis (IE) remains uncertain. This meta-analysis aims to evaluate the outcomes of MIS in mitral valve surgery for infective endocarditis. Methods: A PRISMA-compliant search for studies including patients undergoing MIS for mitral valve IE was performed through 14 January 2026, in PubMed, Scopus and Cochrane. Time-to-event data were reconstructed from published Kaplan–Meier curves. A secondary comparative analysis focusing on MIS versus ST techniques was conducted. Results: Fourteen retrospective studies comprising 949 patients were analyzed. In the MIS cohort, early mortality was 4.2% (95%CI: 1.8%, 7.4%). Overall survival was 86.7% at 1 year, 75.2% at 5 years and 56.2% at 10 years. Freedom from IE-related reoperation remained high at 97.5%, 95.9%, and 90.7% at 1, 5, and 10 years, respectively. Mitral valve repair was performed in 52.5% of patients. In secondary comparative analyses, overall survival at 4-year follow-up was not different between MIS and ST [HR: 0.82 (95%CI: 0.43, 1.57), p = 0.55]. MIS was associated with a significantly shorter intensive care unit (ICU) stay [MD: −1.52 days (95%CI: −2.08, −0.97), p < 0.01]. Conclusions: MIS for mitral valve IE is associated with favorable early and long-term outcomes, comparable survival with sternotomy, and reduced ICU stay. These findings suggest that MIS may be considered as a feasible and potentially effective alternative for the management of mitral valve IE in carefully selected patients. Further prospective comparative studies are warranted.

Journal of Personalized Medicine doi: 10.3390/jpm16070349

Authors: Ahmad I. Kamaludin Ashwin Kumaria Keyoumars Ashkan

Background: Neuromodulation is a rapidly developing field with growing interest in its application in neuro-oncology, particularly since the publication of the EF-14 trial which demonstrated a survival benefit conferred by tumour treating fields (TTF) in patients with glioblastoma. In addition, the emerging field of cancer neuroscience has postulated the role of neural–tumour communication in tumour aetiology, which is theoretically targetable by neuromodulation strategies. This scoping review therefore aims to comprehensively evaluate current or future applications of neuromodulation in managing patients with brain tumours, encompassing preclinical and clinical studies. Methods: The MEDLINE database was queried for all relevant articles from inception to 1 December 2024. A synthesis of findings was performed, broadly categorised to preclinical and clinical research. Findings: The database search returned 3296 results, from which 187 full-text articles were further assessed. A total of 79 studies met the inclusion and exclusion criteria and were included. The results from preclinical studies (n = 18) were stratified according to modality which included electrical therapy, electroporation, electromagnetic field (EMF) and deep brain stimulation (DBS). Similarly, clinical studies (n = 61) were classified to preoperative modalities such as transcranial magnetic stimulation (TMS) and transcranial direct stimulation (tDCS), and postoperative modalities such as TMS, TTF, EMF and spinal cord stimulation (SCS). Interpretation: The application of neuromodulation as adjunctive therapy in the context of neuro-oncology is an emerging field, with encouraging results in various modalities across a wide range of applications from surgical planning and functional rehabilitation, to its therapeutic potential. Further research is urgently needed to harness the potential of neuromodulation in improving patient outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16070348

Authors: Gorazd Kovac Ernst Josef Müller Martin Liebhauser Jochen Jung Haro Stettner Martin Halbherr

Background: Dislocations and fracture-dislocations of the lower cervical spine represent complex injuries with a high risk of neurological damage. Especially in the presence of a confirmed traumatic disc lesion, an anterior surgical approach is described as favoured in the literature. However, studies show that with sufficient reduction technique, even in the presence of a confirmed disc protrusion, posterior stabilization can be considered a safe therapeutic option. The aim of this study is to analyze anterior and posterior treatment of dislocations and fracture-dislocations of the subaxial cervical spine with regard to neurological and radiological outcomes. Methods: In our monocentric cohort study, we investigated the immediate postoperative radiological and neurological outcome depending on the chosen surgical approach and the presence of a disc protrusion. Patients treated at our centre between January 2005 and June 2025 were included. Patients with preoperative complete spinal cord injury were excluded. Neurological status was assessed using the ASIA score preoperatively at admission and postoperatively at discharge or prior to staged surgery. Results: A total of 92 patients were included in the study. Most patients showed an ASIA score C (33.7%). A total of 49 patients (53.3%) were operated anteriorly and 42 patients (45.6%) posteriorly. One patient was primarily stabilized bilaterally. Nine patients initially treated anteriorly had to be secondarily stabilized additionally from posterior. In both groups, neurological deterioration occurred in one case. All other patients remained stable on the ASIA score or improved by at least one point on the scale. Conclusions: The findings provide evidence in favour of a personalized, pathology-oriented approach to lower cervical spine fracture-dislocations rather than selecting the surgical approach based solely on the presence of traumatic disc protrusion. Further prospective studies are needed to validate these observations.

Journal of Personalized Medicine doi: 10.3390/jpm16070347

Authors: Adham M. Khalafallah Manav Daftari Tanuj Prajapati Sebastian Vargas-George Anurag Aka Christian K. Ramsoomair Malek Bashti Seth S. Tigchelaar Timur Urakov

Objectives: Tandem spinal stenosis (TSS) is often underdiagnosed and traditionally managed with multi-stage surgery (MSS). Single-stage surgery (SSS) is an alternative, but prior studies largely emphasize younger, healthier patients. This study evaluated perioperative and functional outcomes after SSS for TSS in a surgically diverse cohort. Methods: A retrospective chart review included 20 patients who underwent SSS for TSS at a single academic institution. Mean age was 63.75 years, and median modified frailty index was 2. Etiologies included degenerative, traumatic, and neoplastic disease across cervical, thoracic, and lumbar regions. Outcomes included operative characteristics, complications, readmissions, and functional recovery measured by Visual Analog Scale (VAS) pain and modified Japanese Orthopaedic Association (mJOA) scores. Results: The mean number of operated levels was 5.2, mean operative time was 232.4 min, total OR time was 355.1 min, and length of stay was 6.9 days. Surgical complications occurred in 15% of patients, medical complications in 25%, and 90-day readmission in 15%, with no 30-day mortality. Mean mJOA improved from 12.86 at baseline to 16.08 at first follow-up and 16.46 at 3 months; REML mixed-effects modeling showed a significant timepoint effect (F (4, 34.55) = 9.15, p < 0.001), with significant Sidak-adjusted improvement at both timepoints. VAS pain showed no significant longitudinal effect. Conclusions: SSS for TSS appears feasible in a real-world, surgically diverse cohort including older and moderately frail patients. These findings support individualized SSS candidacy assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16070346

Authors: Giuseppe Mazza Giuseppe Neri Helenia Mastrangelo Alessandro Russo Isabella Aquila Matteo Antonio Sacco Jessica Ielapi Corrado Pelaia Mario Cannataro Chiara Lupia Francesca Serapide Federico Longhini Vincenzo Bosco Zaninni Caroleo Andrea Bruni Eugenio Garofalo the SEPSIS-UMG Collaborative Group the SEPSIS-UMG Collaborative Group

Background/Objectives: Artificial intelligence (AI), machine-learning (ML), and deep-learning (DL) models are increasingly used for prognostic prediction in intensive care unit (ICU) sepsis, but their clinical readiness remains uncertain. This systematic review aimed to evaluate AI-, ML-, and DL-based models for mortality and clinically relevant outcome prediction in adult ICU patients with sepsis or septic shock. Methods: PubMed/MEDLINE, Scopus, and the Cochrane Library were searched up to April 2026. Eligible studies included adult ICU sepsis or septic shock cohorts evaluating AI/ML/DL-based prognostic models. Screening, full-text assessment, and data extraction were performed independently by two reviewers. Outcomes, model families, validation strategies, discrimination, calibration, clinical utility, explainability, comparative performance versus conventional severity scores, risk of bias, and reporting completeness were synthesized. Risk of bias was assessed using PROBAST domains supplemented by PROBAST + AI considerations, and reporting completeness was evaluated according to TRIPOD/TRIPOD + AI domains. Results: Seventy-five studies were included, comprising 50 PubMed-derived and 25 additional Scopus-derived studies. AUROC or C-statistic was extractable in 64 studies, external validation was reported in 27, prospective evaluation in three, calibration in 38, decision-curve analysis or clinical utility assessment in 37, and explainability in 64. Across 17 directly extractable within-study comparisons from nine studies, AI/ML models usually, but not uniformly, achieved higher discrimination than conventional severity scores, with a median paired ΔAUROC of +0.108 (IQR, +0.082 to +0.148; range, −0.013 to +0.203). Externally validated fixed-horizon models showed clinically relevant but heterogeneous discrimination across sepsis phenotypes, with stronger evidence in selected sepsis-induced coagulopathy cohorts and more variable transportability in respiratory and liver-injury subgroups. However, 45 studies were judged at high risk of bias, mainly because of limitations in the analysis domain. Conclusions: AI/ML models for adult ICU sepsis show a recurrent signal of prognostic discrimination and often perform comparably to or better than conventional severity scores in directly extractable within-study comparisons; however, this signal should be interpreted cautiously given clinical and methodological heterogeneity, limited prospective validation, incomplete calibration, and frequent high risk of bias. The strongest evidence comes from externally validated, phenotype-specific models, although routine clinical implementation remains limited by heterogeneous endpoints, incomplete calibration, insufficient prospective validation, and scarce workflow-level evaluation. Future studies should shift from retrospective AUROC optimization toward calibrated, externally validated, clinically actionable, and workflow-integrated decision-support tools tested in prospective ICU settings.

Journal of Personalized Medicine doi: 10.3390/jpm16070345

Authors: Fernando Diaz Dilernia Mutaz Tageldein Emad Anam Aaron Campbell Gavin Wood

Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without patellar resurfacing. Methods: We retrospectively reviewed a consecutive cohort of 39 patients (48 knees) who underwent PFJ replacement for isolated patellofemoral osteoarthritis between 2011 and 2021. Median age at surgery was 59 years, and median body mass index (BMI) was 31 kg/m2. Median follow-up for clinical and revision surveillance was 9 years (IQR 8–10). Functional outcomes were assessed using the Oxford Knee Score (OKS) and SF-12 Physical and Mental Component Scores (PCS and MCS). Implant survivorship was analyzed using Kaplan–Meier methodology, with conversion to total knee arthroplasty (TKA) as the endpoint. Statistical analyses were primarily descriptive and exploratory because only five TKA revisions occurred. Results: Median OKS improved from 19 (IQR 16–24) preoperatively to 36 (IQR 24–42) at the latest follow-up, with a median paired improvement of 17 points. SF-12 PCS improved from 25 to 47, and SF-12 MCS from 36 to 55. Eight knees (16.7%) underwent non-revision reoperation, and five knees (10.4%) underwent conversion to TKA. All TKA revisions were performed for the progression of tibiofemoral osteoarthritis. Kaplan–Meier survivorship free from TKA revision was 89.6% at 9 years (95% CI 76.8–95.5). No clear difference in TKA-free survivorship was detected between resurfaced and non-resurfaced knees. Conclusions: PFJ replacement demonstrated substantial functional improvement and mid- to long-term survivorship comparable to published registry ranges in a selected cohort with isolated patellofemoral osteoarthritis. TKA revision was uncommon and was attributable to the progression of tibiofemoral osteoarthritis. Because of the retrospective design, small cohort size, bilateral cases, and limited number of revision events, subgroup and risk-factor analyses should be interpreted as exploratory.

Journal of Personalized Medicine doi: 10.3390/jpm16070344

Authors: Nurlybek Mombekov Nigara Yerkhojayeva Aliya Ualiyeva Nazira Zharkinbekova Cigdem Ozkara Gulnaz Nuskabayeva Karlygash Sadykova Assylbek Mombek Bakhytkul Yernazarova Tangsholpan Zholdassova Rissalat Abdullayeva Aziz Nabiyev Nursultan Nurdinov

Background/Objectives: Adult epilepsy is clinically heterogeneous, and individual clinical predictors may not fully capture the multidimensional burden associated with drug-resistant epilepsy (DRE). This study aimed to identify latent clinical phenotypes in adults with epilepsy and examine their cross-sectional associations with DRE and broader disease burden. Methods: This regional observational cohort study used a source database of 1100 patients with epilepsy. After excluding two patients aged <18 years, the adult analytic cohort included 1098 patients. Complete-case latent class analysis (LCA) was performed in 1054 patients using age at onset, disease duration, seizure type, seizure frequency, serial seizures/status, postictal confusion, neurological status, neuroimaging category, and number of antiseizure medications. Model selection was based on statistical fit, class size, and clinical interpretability. Internal clinical validation outcomes included DRE, quality of life, cognitive screening, and stigma scores. Post hoc characterization described the classes by epilepsy etiology, derived epilepsy type, and seizure categories aligned with current terminology. Results: A three-class solution was selected, with class sizes of 314, 465, and 275. DRE prevalence increased stepwise across classes: 5.7%, 14.2%, and 33.1%, respectively (p < 0.001). In adjusted analysis, Class 2 had higher odds of DRE than Class 1 (odds ratio 2.70, 95% confidence interval 1.56–4.67), while Class 3 showed the strongest association (odds ratio 8.19, 95% confidence interval 4.15–16.16; both p < 0.001). Higher-burden classes showed lower quality-of-life and cognitive scores and higher stigma scores. Conclusions: LCA identified three clinically interpretable, burden-enriched phenotypic profiles associated with a stepwise gradient in DRE and broader multidimensional disease burden. These cross-sectional profiles may provide a useful framework for describing clinical heterogeneity in adult epilepsy and generating hypotheses for future validation studies.

Journal of Personalized Medicine doi: 10.3390/jpm16070343

Authors: Maysa Al-Hussaini Anas Al Okaily Osama Alsmadi

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has fundamentally transformed the treatment landscape for relapsed and refractory B-cell malignancies, yet antigen escape remains a persistent therapeutic challenge that limits long-term remission durability. While antigen loss is typically considered a somatic event acquired during tumor evolution under therapeutic selective pressure, germline CD19 polymorphisms could theoretically influence CAR-binding kinetics, alter epitope presentation, and modulate therapeutic outcomes in ways that remain largely not characterized. Unfortunately, Middle Eastern populations are underrepresented in pharmacogenomic databases and CAR-T clinical trials, creating a knowledge gap that may perpetuate global health disparities in access to precision immunotherapy. We analyzed publicly available whole-exome sequencing data from 1196 individuals of Arab origin to comprehensively characterize CD19 variants with potential relevance to CAR T-cell immunotherapy. The L174V (rs2904880) variant stood out, and showed the Valine/Valine (V/V) genotype frequency was 65.3%, corresponding to a V174 allelic frequency of 76.6%, while the minor allele, L174, has a frequency of 23.4%. The missense mutation (c.520C > G) responsible for this variant results in a leucine-to-valine (L174V) substitution at position 174 of the CD19 protein, relative to the reference genome. The cohort genotypes (CC, CG, and GG) exhibited a significant deviation from Hardy–Weinberg equilibrium (p < 0.00001). While this deviation is consistent with the high consanguinity rates (25–60%) amongst Arab populations, it remains not fully explained, and may be attributed to population structure, relatedness, or technical factors. We further emphasize that our computational analysis cannot establish any direct clinical or functional impact due to this variant, and therefore we refrain from suggesting any specific actions at the current time. In light of these findings, we hypothesize that the distinctive genetic architecture of consanguineous populations should not be viewed as a confounding variable. Instead, it presents a unique opportunity to investigate the clinical relevance of germline variation in the context of precision oncology, particularly at therapy-relevant loci, pending functional validation.

Journal of Personalized Medicine doi: 10.3390/jpm16070342

Authors: Filip Gajewski Grzegorz Kurec Aleksandra Litkowska Joanna Pec Jakub Kleinrok Weronika Pająk Oliwia Burdan Paweł Krawczyk Agnieszka Korolczuk

Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial–mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation.

Journal of Personalized Medicine doi: 10.3390/jpm16070341

Authors: Rui-Bin Huang Jia-Pang Jhang Bo-Da Huang Mansour Abtahi Albert K. Dadzie Behrouz Ebrahimi Xincheng Yao Yi-Ting Hsieh

Objective: This study aimed to evaluate the predictability of baseline optical coherence tomography angiography (OCTA) metrics utilizing a specialized capillary–large vessel segmentation analysis framework in patients with diabetic macular edema (DME) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Forty-two treatment-naïve eyes with DME receiving three monthly loading anti-VEGF injections were included. Superficial capillary plexus (SCP) images from 3 × 3 mm OCTA scans were processed to isolate the capillary network from the large vessels via image processing. Vessel density and skeleton density were extracted for the total, large-vessel, and capillary components. Multiple linear and logistic regression models were used to identify independent predictors of post-treatment best-corrected visual acuity (BCVA) and “good visual outcome” (≥3-line improvement or final BCVA of 20/40 or better). Results: Following three monthly anti-VEGF injections, the mean BCVA significantly improved from 0.57 ± 0.36 to 0.37 ± 0.30 LogMAR (p < 0.0001), and the mean central retinal thickness decreased from 424.3 ± 117.7 μm to 316.9 ± 84.7 μm (p < 0.0001). The proportion of patients who achieved a good visual outcome was 73.8%. Baseline central retinal thickness was associated with baseline BCVA (p = 0.049) but not predictive of post-treatment BCVA (p = 0.38) or good visual outcomes (p = 0.79). Baseline capillary vessel density was identified as a significant independent predictor of post-treatment BCVA (p = 0.024), whereas total and large-vessel metrics were not. Capillary vessel density was also the only significant predictor of good visual outcomes (p = 0.044). Conclusions: Baseline capillary vessel density is a robust predictor of visual prognosis after anti-VEGF therapy in patients with DME, underscoring the importance of capillary network integrity in functional recovery.

Journal of Personalized Medicine doi: 10.3390/jpm16070340

Authors: Andrea Giovanni Parato Vincenzo Mirco La Fazia Marco Marino Marcello Marchetta Laura Colarocchio Giovanni Albano Francesco Pocelli Emanuele Chiarazzo Alessandro Di Francesco Lorenzo Gerardi Weili Marco Xu Valerio Marongiu Giuseppe Stifano Andrea Natale

Background: Venous closure devices (VCDs) are being increasingly used after femoral venous access to facilitate recovery, but their comparative efficacy and safety versus manual compression or figure-of-eight suture remain uncertain. Because femoral venous access management is influenced by patient-related and procedural factors, VCDs may contribute to a more personalized postprocedural recovery strategy. Objective: Evaluation of the impact of VCDs on procedural recovery and vascular complications in patients undergoing cardiac procedures via femoral venous access. Methods: We systematically searched PubMed, Embase, and CENTRAL through to April 2025 for randomized controlled trials (RCTs) comparing VCDs with manual compression and/or figure-of-eight suture. Primary efficacy outcomes were time to hemostasis (TTH), time to ambulation (TTA), time to discharge (TTD), and time to discharge eligibility (TTDe). Safety outcomes were major and minor vascular complications. Risk of bias was assessed with RoB 2, and certainty of evidence assessed with GRADE. Random-effects models were used to pool standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: Seven RCTs (n = 948) were included. VCDs use significantly reduced TTH (SMD: −1.00; 95% CI: −1.57 to −0.42) and TTA (SMD: −1.50; 95% CI: −2.42 to −0.58). TTD showed a non-significant trend favoring VCDs (SMD: −0.99; 95% CI: −2.13 to 0.15), while TTDe was consistently shorter with VCDs across three trials. Major vascular complications were rare and similar between groups (RR: 0.41; 95% CI: 0.09–1.89). Minor vascular complications were significantly reduced with VCDs (RR: 0.42; 95% CI: 0.22–0.79). Conclusions: In patients requiring femoral venous access for interventional cardiology procedures, VCDs improve time to hemostasis and ambulation and reduce minor vascular complications without increasing major events. These findings support VCDs as an effective and safe strategy for venous closure.

Journal of Personalized Medicine doi: 10.3390/jpm16070339

Authors: Cicerone Clelia Fabrizio Fanizzi Arianna Dal Buono Ilaria Faggiani Ferdinando D’Amico Alessandra Zilli Tommaso Lorenzo Parigi Virginia Solitano Federica Furfaro Sara Massironi Alessandro Armuzzi Silvio Danese Mariangela Allocca

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterized by marked heterogeneity, challenging disease monitoring and individualized treatment. Despite advances in treat-to-target strategies, unmet needs persist, particularly in assessing transmural healing and optimizing therapeutic decisions. This narrative review evaluates the role of intestinal ultrasound (IUS) as a key tool for precision medicine in IBD. IUS is a non-invasive, repeatable, and cost-effective imaging modality with diagnostic accuracy comparable to endoscopy and magnetic resonance enterography, with reported sensitivities and specificities frequently exceeding 80–90% for detecting active disease. It enables real-time assessment of transmural inflammation and complications, while parameters such as bowel wall thickness and Doppler vascularity support prognostic stratification. Early reductions in bowel wall thickness (≥25–30%) have been associated with improved treatment response, allowing identification of responders within weeks of therapy initiation. IUS informs therapeutic decision-making, including initiation, optimization, and de-escalation of advanced therapies, and may reduce reliance on invasive procedures. Integration into routine care has been associated with improved disease control and cost-effectiveness. Standardization of protocols, operator training, and prospective validation are required to establish IUS as a cornerstone of precision medicine in IBD.

Journal of Personalized Medicine doi: 10.3390/jpm16070338

Authors: Carlos Fonseca Pedro Ribeiro Karla de Carvalho Rodrigo Andraus Renata de Moura Andrei da Trindade Arislander Dumont Tiago Fernandes Daniel Marconi Hugo Pasin Neto Danilo Armbrust Claudia Oliveira

Background/Objectives: Chronic non-specific low back pain (CNLBP) is a leading cause of disability worldwide. Although several randomized trials have evaluated treatment effectiveness, less attention has been given to the responsiveness of outcome measures used to assess clinical change. This study aimed to evaluate the internal and external responsiveness of commonly used outcome measures in individuals with CNLBP. Methods: This study is a secondary analysis of a randomized controlled trial. Participants were analyzed as active and placebo groups and assessed at baseline, post-intervention, and follow-up. Internal responsiveness was evaluated using standardized mean differences (SMD) and standardized response means (SRM). External responsiveness was assessed using anchor-based approaches, including correlations with the Global Rating of Change Scale (GRCS) and receiver operating characteristic (ROC) curve analysis. Results: Outcome measures demonstrated moderate to high internal responsiveness, with large effect sizes observed for pain intensity (NRS) and quality of life (EQ-5D-3L). However, external responsiveness was limited, with all instruments presenting area under the curve (AUC) values below 0.70. The Bournemouth Questionnaire showed the highest discriminative performance among the instruments. Conclusions: The evaluated instruments were sensitive to detecting change at the group level but showed limited ability to discriminate clinically meaningful improvement at the individual level. These findings support the use of combined outcome measures to improve clinical interpretation and decision-making in CNLBP.

Journal of Personalized Medicine doi: 10.3390/jpm16070337

Authors: Christos Doukas Petros Galanis Athanasios Douzenis Panagiota Bali Marie Louise Psarra Ioannis Michopoulos Nikolaos Smyrnis Konstantinos Tasios

Precision psychiatry promises a more objective and effective approach to psychiatric care, yet its implementation raises growing ethical challenges as technology advances. This narrative review offers a qualitative synthesis of the ethical issues reported in 62 studies, with emphasis on the practical tensions that arise when core principles conflict. Rather than organising concerns around traditional ethical principles, the review maps them across the main modalities of precision psychiatry, namely genomics, neuroimaging, digital phenotyping, and AI-driven interventions. Four explicit positions are advanced. First, equity must be engineered from the outset rather than assumed. Second, interpretability should outweigh marginal gains in accuracy in a field built on subjective report. Third, stigma is bidirectional and contingent on framing and the availability of meaningful intervention. Fourth, individualised care must demonstrate clinical and economic superiority over standardised approaches. Precision psychiatry is likely to reshape psychiatric practice and the therapeutic relationship itself. Interdisciplinary collaboration, clear guidelines, and continuous ethical vigilance will be essential for responsible adoption and sustained public trust.

Journal of Personalized Medicine doi: 10.3390/jpm16060335

Authors: Victor A. Shahen Cheng-Hon Yap

Sublobar pulmonary resection has become an increasingly adopted approach for early-stage non-small cell lung cancer, driven by evidence that anatomical segmentectomy can achieve oncological outcomes comparable to lobectomy in selected patients. Safe execution of sublobar resection depends on accurate preoperative identification of segmental bronchovascular anatomy, which demonstrates substantial variability. Conventional two-dimensional (2D) computed tomography (CT) imposes significant limitations on anatomical interpretation, particularly at the segmental and subsegmental level. Three-dimensional (3D) bronchovascular modelling provides patient-specific representations of segmental anatomy and relationships that address these limitations. This narrative review examines the current and emerging roles of 3D modelling in personalised thoracic surgery. It discusses the anatomical basis for its application, the limitations of conventional imaging, and the contribution of 3D modelling to preoperative planning and intraoperative decision making. It also considers broader applications, current limitations, and future directions, with emphasis on how patient-specific 3D modelling can support more tailored operative strategies and more individualised surgical care.

Journal of Personalized Medicine doi: 10.3390/jpm16060336

Authors: Rauno Joks Tamar Smith-Norowitz Shawn Mathew Mansi R. Kothari Sairaman Nagarajan

Objective: Low serum albumin has been linked to morbidity and mortality in critically ill patients, including those with COVID-19. Whether serum globulin levels and albumin/globulin ratios (AGRs) can serve as biomarkers in COVID-19 is less well-characterized. This study assessed serum total protein, albumin, globulin levels, and AGR in relation to clinical outcomes in adults hospitalized with COVID-19 pneumonia. Methods: A retrospective EMR analysis was conducted among 569 hospitalized patients with COVID-19 pneumonia identified during the study period, of whom 60 met inclusion criteria of the required clinical immunologic and laboratory data and comprised the final analytic cohort. Variables included demographics and laboratory markers (total protein, albumin, globulin, immunoglobulins, CRP, and IL-6). The study evaluated: (1) Charlson Comorbidity Index (CCI), (2) Charlson 10-Year Estimated Survival (C10YES), (3) clinical severity using the NEWS-2 score, (4) length of hospital stay (LOS), and (5) mortality. Spearman correlations, chi-square tests, and regression analyses were conducted. Results: Albumin was independently associated with CCI, C10YES, and LOS in adjusted models (p = 0.01, p = 0.004, and p < 0.001, respectively), as was AGR (p = 0.012, p = 0.006, and p = 0.024, respectively). Decreasing total protein levels were independently associated with higher NEWS-2 scores, lower C10YES, and longer LOS (p = 0.009, p = 0.042, and p < 0.001, respectively). Increasing age was associated with longer LOS after adjustment for sex and the other plasma proteins. Globulin levels were not associated with clinical outcomes. Conclusions: Lower serum total protein was associated with higher COVID-19 severity, and lower albumin and AGR were associated with greater morbidity, lower predicted survival, and longer LOS. Increasing age was associated with longer LOS. In patients hospitalized with COVID-19 pneumonia, albumin and AGR may serve as potential biomarkers facilitating personalized risk stratification of hospital course and recovery.

Journal of Personalized Medicine doi: 10.3390/jpm16060334

Authors: Roopa S. Rao Divya Biligere Shivanna Surendra Lakshminarayana Kirti Shankar Mahadevpur Yaser Ali Alhazmi Mohammed Mousa H. Bakri Hazar S. Alharbi Khalid J. Alzahrani Khalaf F. Alsharif Hamsa Jameel Banjer Mrim M. Alnfiai Rodolfo Reda Shankargouda Patil Luca Testarelli

The Author Contributions is incomplete in the original publication [...]

Journal of Personalized Medicine doi: 10.3390/jpm16060333

Authors: Livio Vitiello

Over the past two decades, ophthalmology has been reshaped by the convergence of high-resolution multimodal imaging, pharmacological innovation and the broader paradigm of personalized medicine [...]

Journal of Personalized Medicine doi: 10.3390/jpm16060332

Authors: Heayyean Lee Khadijah Sajid Dayeon Lee

Pharmacogenomics AI offers significant potential for individualized drug therapy; however, its clinical benefits remain unevenly distributed. Models trained predominantly on European-ancestry data consistently underperform in non-European populations, with polygenic risk scores (PRS) showing an estimated 39–73% reduction in predictive accuracy in African-ancestry cohorts across complex traits. These disparities have driven increased interest in moving beyond single-layer genomic approaches. Multi-omics frameworks integrating genomic, transcriptomic, proteomic, and metabolomic data have emerged as a promising strategy to improve prediction across heterogeneous clinical populations, as each molecular layer provides distinct and complementary biological information. Among these layers, metabolomics may represent a particularly transferable component across populations. Metabolite profiles capture the downstream functional output of biological systems influenced by genetic, environmental, dietary, and microbiome-related factors, and may therefore be less reliant on ancestry-stratified allele frequency structures that underlie performance disparities in genomic models. This review synthesizes evidence regarding the mechanistic basis of genomic bias in pharmacogenomics AI, the emerging role of multi-omics integration, especially metabolomics, in improving predictive performance, and the current landscape of computational strategies for bias mitigation, including federated learning, transfer learning, domain adaptation, and synthetic data generation. Collectively, current evidence supports metabolomics-inclusive multi-omics frameworks as a biologically plausible, hypothesis-generating strategy to reduce reliance on ancestry-linked genomic features. However, direct evidence that such frameworks reduce ancestry-related bias in clinical AI outputs remains limited, underscoring the need for globally diverse datasets and prospective multi-population validation.

Journal of Personalized Medicine doi: 10.3390/jpm16060331

Authors: Joel Costoya Joaquin J. Jimenez

Growth hormone-releasing hormone (GHRH) antagonists have displayed anti-neoplastic activity against a multitude of cancers in vitro, as well as in vivo, via xenografted tumors in nude mice. Following a successful demonstration of GHRH antagonists treating non-Hodgkin’s lymphoma and the discovery of GHRH mRNA and peptide products in immune cells, GHRH antagonism was explored in acute myeloid leukemia (AML), a disease characterized by a malignant expansion of immature myeloid progenitors, and poor 5-year survival. Targeted therapies have yielded breakthroughs in treatment response and overall survival, such as all-trans retinoic acid/arsenic trioxide (ATRA/ATO) for acute promyelocytic leukemia (APL), or FLT3 inhibitors, IDH inhibitors, and menin inhibitors for AML harboring actionable genetic lesions. However, therapeutic resistance remains a major barrier to durable remission. GHRH receptor (GHRH-R) has been reported in several experimental models of AML, including drug-resistant sublines. Significant time- and dose-dependent reduction in leukemic growth was observed in vitro and in vivo following MIA-602 treatment. FLT3 inhibitor resistance has been associated with activation of PI3K/AKT, ERK/MAPK, inflammatory, stromal, and apoptotic escape pathways. The documented effects of GHRH-R antagonism raise the possibility that it could influence signaling networks relevant to therapeutic resistance in AML. This hypothesis remains speculative; to date no studies have stratified AML by FLT3 status in the context of GHRH-R expression or GHRH antagonism, and there is currently no evidence that MIA-602 directly alters FLT3 receptor signaling or inhibitor sensitivity.

Journal of Personalized Medicine doi: 10.3390/jpm16060330

Authors: Joshua E. Chan Lisa C. Zaba

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation.

Journal of Personalized Medicine doi: 10.3390/jpm16060329

Authors: Shakta Mani Satyam Sainath Prabhakar Tanya Densil Husham Taha Mohammed Rashmi Kumari Mohamed El-Tanani Abdul Rehman Ahmad Kharoufeh Mohammed Dalbah Mohamed Talat Zaky Mahmoud Eltrabishi

Pediatric drug therapy remains fundamentally challenged by profound interindividual variability driven by dynamic development, genetic, and environmental factors. Although dosing strategies based on age, body weight, or body surface area remain important starting points in pediatric pharmacotherapy, they may not fully capture ontogeny-dependent variability in drug disposition and response. Consequently, clinically relevant differences in efficacy and toxicity may still occur among children receiving similar weight-adjusted doses. Pharmacogenomics offers a promising framework for individualized therapy; however, its clinical translation in pediatrics is limited by developmental variability in gene expression and enzyme activity. Emerging evidence highlights the pivotal role of epigenetic regulation, including DNA methylation, histone modifications, and microRNAs, in modulating pharmacogenetic expression across developmental stages, thereby reshaping drug response trajectories. Concurrently, advances in artificial intelligence and next-generation sequencing enable integration of multidimensional datasets, facilitating predictive modeling of drug efficacy and toxicity. This narrative review provides a comprehensive synthesis of developmental pharmacology, pharmacogenomics, and epigenetic mechanisms, while critically evaluating current translational gaps and implementation challenges. Importantly, it proposes an integrative precision framework that incorporates genetic, epigenetic, and computational insights to optimize pediatric pharmacotherapy. By bridging mechanistic biology with emerging digital health technologies, this work advances a paradigm shift from empirical prescribing toward predictive, adaptive, and individualized therapeutic strategies. The proposed approach holds significant potential to enhance clinical outcomes, minimize adverse effects, and accelerate the realization of precision medicine in pediatric populations.

Journal of Personalized Medicine doi: 10.3390/jpm16060328

Authors: Aikaterini-Eleftheria Karanikola Agapi Ploussi Dimitrios Tsiachris Efstathios P. Efstathopoulos

Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a promising yet underexplored approach to address these challenges by enabling precise molecular imaging and site-specific therapeutic interventions. This review summarizes current and emerging nanotechnology-based approaches for the diagnosis and treatment of cardiovascular inflammation, highlighting their potential in clinical practice and remaining challenges. In addition, recent advances, including the development of biomimetic nanoplatforms, are discussed, along with future perspectives and the potential integration of artificial intelligence to further enhance precision in cardiovascular medicine.

Journal of Personalized Medicine doi: 10.3390/jpm16060327

Authors: Bohye Gil Sohyun Shim Yoon Jang Joong Sik Shin Nara Lee Mi Kyoung Kim Yong Wook Jung Seok Ju Seong Mi-La Kim

Objective: This study aimed to evaluate clinical characteristics and outcomes of complete uterine rupture during pregnancy and identify factors associated with adverse neonatal outcomes. Methods: This retrospective cohort study analyzed data from a single center between January 2008 and July 2024. Complete uterine rupture was defined as full-thickness myometrial and serosal rupture confirmed during surgery. Results: Among 50,185 deliveries, 22 cases of complete uterine rupture were identified (incidence: 0.044%). Most patients (86.4%) had a scarred uterus, exclusively due to previous myomectomy (n = 19). While abdominal pain was the primary symptom (72.7%), 22.7% of patients were asymptomatic. There were no cases of maternal mortality or peripartum hysterectomy. Of the 25 neonates, 12 (48%) experienced adverse outcomes, defined as NICU admission or perinatal death. Adverse neonatal outcomes were significantly associated with preterm delivery (p = 0.030), fetal heart rate abnormalities (p = 0.040), and a prolonged symptom-to-delivery interval (p = 0.032). Univariate analysis identified preterm delivery and abdominal pain as significant predictors of poor neonatal prognosis. Conclusions: Complete uterine rupture is a rare but critical obstetric emergency. Although maternal outcomes were favorable in this study, nearly half of the neonates experienced adverse outcomes. Preterm labor and abdominal pain serve as significant prognostic indicators. These findings emphasize that early clinical suspicion and minimizing the time from symptom detection to delivery are vital for optimizing neonatal survival and health.

Journal of Personalized Medicine doi: 10.3390/jpm16060326

Authors: Marco Agostini Pietro Traldi Mahmoud Hamdan

Medulloblastoma is one of the most prevalent pediatric brain tumors. Currently, existing therapies for this devastating type of cancer can only prolong survival time with severe side-effects and relapse. These therapies are not curative for almost a third of treated patients, while most survivors are condemned to a poor quality of life. The addition of immune checkpoint inhibitors (ICIs) to immune therapy has given some hope to those suffering from this type of cancer. Although ICIs provide a valuable contribution to immunotherapy, the exploitation of immune checkpoint inhibition within existing therapeutic strategies to cure Medulloblastoma remains understudied. However, the identification of the main molecular subgroups of medulloblastoma is considered one of the success stories of oncology. This advancement in molecular profiling of MB paved the way to subgroup-directed clinical trials, which may lead to efficacious immune-targeted therapy. However, this relatively new development is still hampered by a substantial biological heterogeneity of the disease and the absence of a full understanding of the various mechanisms behind its resistance to existing therapeutic modalities. The inclusion of chimeric antigen receptor (CAR) T and CAR NK cell therapy within various therapeutic strategies and ongoing clinical trials has given fresh hope those suffering from this fatal disease. However, ongoing clinical trials suggest that this highly promising therapy can be impaired by a number of serious limitations, including cytokine release syndrome, Graft-versus-host disease, the scarcity of target antigens, and severe adverse events. Some of the ongoing clinical trials also suggest that CAR NK is less prone to some of these limitations. This review also highlights the contribution of mass spectrometry-based proteomics, and the increasing role of liquid biopsy rather than tissue biopsy.

Journal of Personalized Medicine doi: 10.3390/jpm16060325

Authors: Evelina Maines Roberto Franceschi

In 1922, Leonard Thompson, a 14-year-old patient with severe Type 1 Diabetes (T1D), became the first patient to receive an insulin injection [...]