Journal of Personalized Medicine

18 pages, 2601 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in Cardiac Electrophysiology: A Comprehensive Review

by Pietro Cipollone, Nicola Pierucci, Andrea Matteucci, Marta Palombi, Domenico Laviola, Raffaele Bruti, Sara Vinciullo, Marco Bernardi, Luigi Spadafora, Angelica Cersosimo, Sara Trivigno, Tommaso Recchioni, Agostino Piro, Cristina Chimenti, Claudio Pandozi, Carmine Dario Vizza, Carlo Lavalle and Marco Valerio Mariani

J. Pers. Med. 2025, 15(11), 532; https://doi.org/10.3390/jpm15110532 - 3 Nov 2025

Cited by 9 | Viewed by 2738

Abstract

Background: Artificial Intelligence (AI) is a transformative innovation designed to enable machines to perform tasks typically requiring human intelligence. Among various medical fields, cardiology—and particularly electrophysiology—has seen rapid integration of AI technologies. The ability of AI to analyze large and complex datasets is [...] Read more.

Background: Artificial Intelligence (AI) is a transformative innovation designed to enable machines to perform tasks typically requiring human intelligence. Among various medical fields, cardiology—and particularly electrophysiology—has seen rapid integration of AI technologies. The ability of AI to analyze large and complex datasets is reshaping diagnostic and therapeutic approaches. Objectives: This review aims to provide a comprehensive overview of AI models and their applications in cardiac electrophysiology. The focus is on understanding how AI contributes to clinical practice through ECG interpretation, arrhythmia detection, atrial mapping, and catheter ablation, while also exploring its limitations and future potential. Methods: The review discusses various AI approaches, including Machine Learning (ML) and Deep Learning (DL), and highlights relevant literature illustrating their implementation in electrophysiological settings. Key clinical applications are examined thematically, with a narrative synthesis of current capabilities, technologies, and outcomes. Results: AI-based tools have demonstrated effectiveness in identifying supraventricular arrhythmias like atrial fibrillation (AF) and atrial flutter (AFL), as well as complex conditions such as ventricular tachycardias (VTs) and long QT syndrome (LQTS). In procedural contexts, AI enhances electro-anatomical mapping, reduces operative time, and supports tailored post-ablation management. Discussion: While AI offers clear advantages in diagnostic accuracy and procedural efficiency, challenges remain regarding data security, ethical transparency, and clinical adoption. Addressing these limitations will be crucial for integrating AI into routine electrophysiology and maximizing its potential in future cardiology practice. Full article

(This article belongs to the Special Issue Atrial Fibrillation: Toward Personalized Medicine)

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21 pages, 346 KB

Open AccessEditor’s ChoiceReview

Chrononutrition in Gestational Diabetes: Toward Precision Timing in Maternal Care

by Viktoria Xega and Jun-Li Liu

J. Pers. Med. 2025, 15(11), 534; https://doi.org/10.3390/jpm15110534 - 3 Nov 2025

Cited by 4 | Viewed by 2728

Abstract

Gestational diabetes mellitus (GDM) is a heterogeneous disorder that compromises maternal and offspring health. Conventional medical nutrition therapy focuses on nutrient composition and caloric targets but largely omits timing and individualized biology. This narrative review synthesizes mechanistic, epidemiologic and interventional evidence linking circadian [...] Read more.

Gestational diabetes mellitus (GDM) is a heterogeneous disorder that compromises maternal and offspring health. Conventional medical nutrition therapy focuses on nutrient composition and caloric targets but largely omits timing and individualized biology. This narrative review synthesizes mechanistic, epidemiologic and interventional evidence linking circadian biology and meal timing (chrononutrition) to maternal glycemic control. Observational cohorts associate late eating and breakfast skipping with worse glycemia, while pilot interventions and CGM-based studies indicate that front-loading carbohydrates, restricting evening carbohydrate, extending overnight fasting (≈10–12 h), and simple within-meal sequencing can reduce postprandial excursions and increase time-in-range. We propose a pragmatic, tiered clinical pathway in which routine second-trimester triage (50 g glucose challenge test and ultrasound abdominal subcutaneous fat thickness) identifies higher-risk women for short-term CGM phenotyping and prioritized chrononutrition counseling. Integrating phenotype-matched timing interventions with dietetic support and digital decision tools allows rapid, individualized adjustments informed by real-time glucose patterns and patient chronotype. In principle, this tiered strategy could improve daily glycemic profiles, reduce the need for pharmacotherapy, and translate into better neonatal outcomes if supported by larger randomized trials. Chrononutrition therefore offers a promising extension of standard care: simple, low-cost adjustments to “when” food is eaten, supported by digital tools, could allow nutrition therapy for GDM to become more precise, more responsive, and ultimately more effective for both mother and child. Key priorities include validating bedside and chrono-omic stratifiers, testing scalable delivery platforms, and ensuring equitable access to personalized chrononutrition in pregnancy. Full article

(This article belongs to the Special Issue Personalized Medicine of Obesity and Metabolic Disorders)

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20 pages, 6167 KB

Open AccessEditor’s ChoiceArticle

ICU Readmission and In-Hospital Mortality Rates for Patients Discharged from the ICU—Risk Factors and Validation of a New Predictive Model: The Worse Outcome Score (WOScore)

by Eleftherios Papadakis, Athanasia Proklou, Sofia Kokkini, Ioanna Papakitsou, Ioannis Konstantinou, Aggeliki Konstantinidi, Georgios Prinianakis, Stergios Intzes, Marianthi Symeonidou and Eumorfia Kondili

J. Pers. Med. 2025, 15(10), 479; https://doi.org/10.3390/jpm15100479 - 3 Oct 2025

Cited by 3 | Viewed by 3114

Abstract

Background: Intensive Care Unit (ICU) readmission and in-hospital mortality are critical indicators of patient outcomes following ICU discharge. Patients readmitted to the ICU often face worse prognosis, higher healthcare costs, and prolonged hospital stays. Identifying high-risk patients is essential for optimizing post-ICU [...] Read more.

Background: Intensive Care Unit (ICU) readmission and in-hospital mortality are critical indicators of patient outcomes following ICU discharge. Patients readmitted to the ICU often face worse prognosis, higher healthcare costs, and prolonged hospital stays. Identifying high-risk patients is essential for optimizing post-ICU care and resource allocation. Methods: This two-phase study included the following: (1) a retrospective analysis of ICU survivors in a mixed medical–surgical ICU to identify risk factors associated with ICU readmission and in-hospital mortality, and (2) a prospective validation of a newly developed predictive model: the Worse Outcome Score (WOScore). Data collected included demographics, ICU admission characteristics, severity scores (SAPS II, SAPS III, APACHE II, SOFA), interventions, complications and discharge parameters. Results: Among 1.190 ICU survivors, 126 (10.6%) were readmitted to the ICU, and 192 (16.1%) died in hospital after ICU discharge. Key risk factors for ICU readmission included Diabetes Mellitus, SAPS III on admission, and ICU-acquired infections (Ventilator-Associated Pneumonia (VAP) and Catheter-Related Bloodstream Infection, (CRBSI)). Predictors of in-hospital mortality were identified: medical admission, high SAPS III score, high lactate level on ICU admission, tracheostomy, reduced GCS at discharge, blood transfusion, CRBSI, and Acute Kidney Injury (AKI) during ICU stay. The WOScore, developed based on the results above, demonstrated strong predictive ability (AUC: 0.845 derivation, 0.886 validation). A cut-off of 20 distinguished high-risk patients (sensitivity: 88.1%, specificity: 73.0%). Conclusions: ICU readmission and in-hospital mortality are influenced by patient severity, underlying comorbidities, and ICU-related complications. The WOScore provides an effective, easy-to-use risk stratification tool that can guide clinicians in identifying high-risk patients at ICU discharge and guide post-ICU interventions, potentially improving patients’ outcomes and optimizing resource allocation. Further multi-center studies are necessary to validate the model in diverse healthcare settings. Full article

(This article belongs to the Section Personalized Medical Care)

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35 pages, 448 KB

Open AccessEditor’s ChoiceReview

Approaches for Predicting the Occurrence of Challenging Behaviors in Individuals with Autism Spectrum Disorder: A Narrative Review

by Jennifer Ferina, Emma Dando, Conor Anderson, Jenny Foster, Johanna Lantz, Theresa Hamlin and Juergen Hahn

J. Pers. Med. 2025, 15(10), 453; https://doi.org/10.3390/jpm15100453 - 29 Sep 2025

Cited by 3 | Viewed by 3862

Abstract

The presentation of autism spectrum disorder can be highly heterogeneous, and a significant percentage of individuals with autism exhibit challenging behaviors. However, the frequency and severity of challenging behaviors can vary significantly over time, even for the same person, and it is often [...] Read more.

The presentation of autism spectrum disorder can be highly heterogeneous, and a significant percentage of individuals with autism exhibit challenging behaviors. However, the frequency and severity of challenging behaviors can vary significantly over time, even for the same person, and it is often unclear what triggers a behavior. Being able to predict the occurrence of challenging behaviors has significant potential for improving the safety of individuals with ASD, as well as quality of life for them and their caregivers. Given the large heterogeneity found in the presentation of autism, most predictions need to be personalized to the individual or at least a subgroup of individuals. This work reviews the state of research in the field for predicting behaviors, ranging from short-term predictions just a few moments before a behavior occurs to predicting the probability of challenging behaviors a day in advance. Several reviewed approaches provide promising initial results, but few studies have been conducted on populations large and diverse enough to determine their generalizability. Full article

(This article belongs to the Section Personalized Medical Care)

15 pages, 2619 KB

Open AccessEditor’s ChoiceSystematic Review

Patient-Reported Outcomes of Digital Versus Conventional Impressions for Implant-Supported Fixed Dental Prostheses: A Systematic Review and Meta-Analysis

by Aspasia Pachiou, Evangelia Zervou, Nikitas Sykaras, Dimitrios Tortopidis, Alexis Ioannidis, Ronald E. Jung, Franz J. Strauss and Stefanos Kourtis

J. Pers. Med. 2025, 15(9), 427; https://doi.org/10.3390/jpm15090427 - 5 Sep 2025

Cited by 10 | Viewed by 3109

Abstract

Background/Objectives: To compare patient-reported outcome measures (PROMs) between digital and conventional impression techniques for implant-supported fixed dental prostheses (iFDPs). Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases up to June 2025, following PRISMA guidelines. Human [...] Read more.

Background/Objectives: To compare patient-reported outcome measures (PROMs) between digital and conventional impression techniques for implant-supported fixed dental prostheses (iFDPs). Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases up to June 2025, following PRISMA guidelines. Human clinical studies reporting PROMs between digital and conventional impression techniques for iFDPs were included. Studies using structured, but not necessarily validated, questionnaires were eligible. Two reviewers independently performed study selection, data extraction, and risk of bias assessment. Where possible, meta-analyses were conducted using a random-effects model to pool comparable outcomes across studies using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CIs). Results: Out of 1784 records screened, eighteen studies were included. Most studies showed that digital impressions were associated with higher patient satisfaction, compared to conventional impressions. Ten studies contributed data to at least one outcome; pooled analyses included the following: overall satisfaction (k = 5), comfort (k = 7), gagging/nausea (k = 5), esthetic satisfaction (k = 2), unpleasant taste (k = 5), anxiety (k = 5), discomfort (k = 2), pain (k = 5), and overall discomfort (k = 5). Digital impressions were significantly favored (p < 0.05) for anxiety (MD = 13.3, 95% CI: −22 to −4.5), nausea (MD = −26.4, 95% CI −46.8 to −6.0), bad taste (MD = −34.8, 95% CI −58.3 to −11.3), discomfort (SMD = −2.24, 95% CI −3.51 to −0.98), comfort (SMD = 1.77, 95% CI: 0.60 to 2.94), perceived procedure time (SMD = 0.96; 95% CI 0.29 to 1.62), and overall satisfaction (SMD = 0.55; 95% CI 0.01 to 1.09). No statistically significant differences were found for pain or esthetic evaluation. Substantial between-study heterogeneity was observed among the included studies. Conclusions: Current evidence indicates that digital impression workflows enhance the overall patient experience for implant-supported fixed restorations, especially in domains linked to comfort and procedural efficiency. These findings support PROM-informed personalization of impression workflows: screening for gagging, anxiety, or intolerance to impression materials could guide patient-tailored use of intraoral scanning while acknowledging no consistent advantage for pain or esthetic perception. Full article

(This article belongs to the Special Issue Advances in Oral Health: Innovative and Personalized Approaches)

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16 pages, 1822 KB

Open AccessEditor’s ChoiceSystematic Review

Female Sexual Function After Radical Treatment for MIBC: A Systematic Review

by Francesco Pio Bizzarri, Marco Campetella, Salvatore Marco Recupero, Fabrizio Bellavia, Lorenzo D’Amico, Francesco Rossi, Filippo Gavi, Giovanni Battista Filomena, Pierluigi Russo, Giuseppe Palermo, Nazario Foschi, Angelo Totaro, Mauro Ragonese, Maria Chiara Sighinolfi, Marco Racioppi, Emilio Sacco and Bernardo Rocco

J. Pers. Med. 2025, 15(9), 415; https://doi.org/10.3390/jpm15090415 - 2 Sep 2025

Cited by 6 | Viewed by 1320

Abstract

Background: Sexuality in women with muscle-invasive bladder cancer (MIBC) undergoing radical treatment represents a crucial aspect of their overall quality of life, which is increasingly recognized as a key component of patient-centered care and long-term well-being. This review aimed to analyze the available [...] Read more.

Background: Sexuality in women with muscle-invasive bladder cancer (MIBC) undergoing radical treatment represents a crucial aspect of their overall quality of life, which is increasingly recognized as a key component of patient-centered care and long-term well-being. This review aimed to analyze the available literature to provide a comprehensive overview of the effects of treatments on female sexual function. Methods: We included all qualitative and quantitative studies addressing sexual function in patients treated for MIBC. Excluded were narrative reviews, case reports, conference abstracts, systematic reviews, and meta-analyses. The included studies involved women undergoing either robot-assisted radical cystectomy (RARC) or open RC (ORC), often with nerve-sparing, vaginal-sparing, or pelvic organ-preserving techniques. Data on oncological and functional outcomes were collected. Results: A systematic review of 29 studies including 1755 women was conducted. RC was performed via robotic/laparoscopic approaches in 39% of cases and open techniques in 61%. Urinary diversions included orthotopic neobladders (48%), ileal conduits (42%), ureterocutaneostomies (3%), and Indiana pouches (7%). Radiotherapy, used in 6% of patients, was mainly applied in a curative, trimodal setting. Sexual function was evaluated using various pre- and/or postoperative questionnaires, most commonly the EORTC QLQ-C22, FACT-BL, Bladder Cancer Index (BCI), LENT SOMA, and Female Sexual Function Index (FSFI). Radiotherapy was associated with reduced sexual function, though outcomes were somewhat better than with surgery. Among surgical approaches, no differences in sexual outcomes were observed. Conclusions: Further qualitative research is essential to better understand the experience of FSD after treatment. Incorporating both patient and clinician perspectives will be key to developing tailored interventions. In addition, efforts should be made to standardize the questionnaires used to assess female sexual dysfunction, in order to improve comparability across studies and ensure consistent evaluation. Full article

(This article belongs to the Special Issue Urological Cancer: Clinical Advances in Personalized Therapy)

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17 pages, 308 KB

Open AccessEditor’s ChoiceReview

What Are the Game Changers in Total Knee Arthroplasty? A Narrative Review

by Andrea Baldini, Damiano Ardiri, Lorenzo Benvenuti, Mattia Chirico, Enrico Fiorilli, Alessandro Singlitico and Filippo Leggieri

J. Pers. Med. 2025, 15(8), 389; https://doi.org/10.3390/jpm15080389 - 20 Aug 2025

Cited by 5 | Viewed by 1973

Abstract

Background: Total knee arthroplasty (TKA) has evolved significantly, yet achieving consistently optimal outcomes remains challenging across diverse patient populations. This comprehensive narrative review identifies evidence-based “game changers” that genuinely transform TKA success while distinguishing them from interventions lacking clinical superiority. The analysis [...] Read more.

Background: Total knee arthroplasty (TKA) has evolved significantly, yet achieving consistently optimal outcomes remains challenging across diverse patient populations. This comprehensive narrative review identifies evidence-based “game changers” that genuinely transform TKA success while distinguishing them from interventions lacking clinical superiority. The analysis organizes findings across three perioperative phases: preoperative optimization, intraoperative techniques, and postoperative management. Preoperative game changers include end-stage bone-on-bone osteoarthritis, preoperative medical optimization of patients performed by dedicated practitioners, cryocompression therapy, and perioperative dexamethasone administration. Intraoperative interventions demonstrating substantial impact encompass reduced surgical time and optimized surgical instrumentation, personalized alignment, medial congruent bearings, cementless implants for high-demanding and high-BMI patients, and perioperative tranexamic acid. Postoperative game changers include early mobilization following surgery, venous thrombo-embolic prophylaxis avoiding high-bleeding-risk pharmaceuticals, and multimodal pain management. The review also identifies those initial promises without established clinical advantages, or “fake game changers”, that consume resources without meaningful benefits. This evidence synthesis demonstrates that TKA optimization requires systematic implementation of validated interventions rather than pursuing technological innovations indiscriminately. The future of TKA lies in evidence-based adoption of proven strategies that translate to genuine patient outcome improvements rather than merely increasing procedural complexity. Full article

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

15 pages, 563 KB

Open AccessEditor’s ChoiceReview

The Role of Oxidative Stress in the Relationship Between Periodontitis and Alzheimer’s Disease: A Review of the Literature

by Konstantinos Antonios Papadakis, Aikaterini-El Doufexi, Mary S. Kalamaki, Evangelos Bourazanas and Evgenia Lymperaki

J. Pers. Med. 2025, 15(8), 384; https://doi.org/10.3390/jpm15080384 - 18 Aug 2025

Cited by 14 | Viewed by 2627

Abstract

Periodontitis, a chronic inflammatory disease affecting the supporting tissues of the teeth, has been linked to the onset of neurological diseases, including Alzheimer’s disease (AD). A primary mechanism connecting these two issues is oxidative stress caused by an imbalance between antioxidant defenses and [...] Read more.

Periodontitis, a chronic inflammatory disease affecting the supporting tissues of the teeth, has been linked to the onset of neurological diseases, including Alzheimer’s disease (AD). A primary mechanism connecting these two issues is oxidative stress caused by an imbalance between antioxidant defenses and reactive oxygen species (ROS) synthesis. This review compiles results from both animal and human studies that explore how oxidative stress resulting from periodontitis leads to neuroinflammation, mitochondrial dysfunction, and cognitive decline in AD. Studies in animals indicate that periodontal infections worsen brain oxidative damage, as evidenced by elevated lipid peroxidation markers, such as malondialdehyde (MDA), and indicators of oxidative DNA damage, including 8-hydroxy-2′-deoxyguanosine (8-OHdG). Additionally, significant reductions in crucial antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase, along with neuroinflammation and cognitive deficits, are observed in mouse models of induced periodontitis. Supporting evidence from human studies reveals lower total antioxidant capacity (TAC) in individuals with both Alzheimer’s disease (AD) and periodontitis, as well as increased systemic oxidative stress markers, such as advanced oxidation protein products (AOPRs). These findings suggest a mechanistic relationship through oxidative stress pathways between periodontal inflammation and neurodegeneration. Given the extensive impact of periodontitis, enhancing periodontal health could be a viable strategy to reduce oxidative damage and lower the risk of cognitive decline. Further research is needed to clarify causality and to investigate antioxidant treatments aimed at preventing or slowing the progression of AD in patients with periodontal disease. Full article

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

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12 pages, 7710 KB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of Personalized Percutaneous Single-Probe Cryoablation Using Liquid Nitrogen in the Treatment of Abdominal Wall Endometriosis

by Ghizlane Touimi Benjelloun, Malek Mokbli, Tarek Kammoun, Sinda Ghabri, Skander Sammoud, Wissem Nabi, Vincent Letouzey, Jean-Paul Beregi and Julien Frandon

J. Pers. Med. 2025, 15(8), 373; https://doi.org/10.3390/jpm15080373 - 13 Aug 2025

Cited by 1 | Viewed by 2099

Abstract

Background: Abdominal wall endometriosis (AWE) is a rare but debilitating condition, often occurring in surgical scars after Caesarean sections. It is characterized by cyclic pain and a palpable mass, significantly impacting patients’ quality of life. Traditional treatments, including hormonal therapy and surgery, [...] Read more.

Background: Abdominal wall endometriosis (AWE) is a rare but debilitating condition, often occurring in surgical scars after Caesarean sections. It is characterized by cyclic pain and a palpable mass, significantly impacting patients’ quality of life. Traditional treatments, including hormonal therapy and surgery, have limitations, prompting interest in minimally invasive techniques such as cryoablation. This study evaluates the efficacy and safety of percutaneous image-guided single-probe cryoablation using liquid nitrogen for symptomatic AWE. Purpose: To evaluate the effectiveness and safety of percutaneous image-guided single-probe cryoablation using liquid nitrogen in treating symptomatic AWE lesions, with a primary objective to assess pain relief using the Visual Analog Scale (VAS). Materials and Methods: This retrospective, single-center study included 14 patients (23 lesions) treated with percutaneous cryoablation between September 2022 and April 2025. Clinical, imaging (MRI and ultrasound), and procedural data were analyzed. Pain scores (VAS scale) were assessed before treatment and at 3-month follow-up. Hydro- and/or carbo-dissection were used to protect adjacent structures. Response to treatment was evaluated with MRI and clinical follow-up. Statistical analysis was performed using median, range, and percentage calculations, with comparisons made using the Mann–Whitney test. Results: A total of 23 AWE lesions were treated in 14 patients (mean age: 39.6 years). The median lesion volume was 3546 mm³, with a range from 331 mm³ (8 × 4.6 × 9 mm) to 45,448 mm³ (46 × 26 × 38 mm). Most of the lesions were located in the muscle (69.6%, n = 16), while 17.4% (n = 4) involved both muscle and subcutaneous tissue, and 13.0% (n = 3) were purely subcutaneous. Among the 23 treated lesions, 8.7% (n = 2) appeared as purely hemorrhagic, 13.0% (n = 3) as fibrotic, and 78.3% (n = 18) were classified as mixed, based on imaging characteristics. Procedures were performed under general anesthesia in 65% of cases and under sedation in 35%. Hydrodissection was used in 48% of lesions, carbo-dissection in 4%, and combined hydro–carbo-dissection in 26%. A single 13G cryoprobe was used in 83% of cases, and a 10G probe in 17%. The median ablation time was 15 min (range: 6–28 min), and the median total procedure time was 93 min (range: 22–240 min). Pain scores significantly decreased from a median of 8/10 (range: 6–10) before treatment to 0/10 (range: 0–2) at follow-up (p < 0.0001). MRI follow-up confirmed complete coverage of the ablation zone and disappearance of hemorrhagic inclusions in all cases. Two patients (14%) required re-treatment, both with satisfactory outcomes. No peri- or post-procedural complications were observed, and no visible scars were noted. Conclusions: Percutaneous cryoablation using a single probe with liquid nitrogen is a safe and effective treatment for AWE, offering significant pain relief, minimal morbidity, and excellent cosmetic outcomes. It should be considered as part of multidisciplinary care. Further prospective studies with longer follow-up are warranted to confirm these findings. Full article

(This article belongs to the Special Issue Interventional Radiology: Towards Personalized Medicine)

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24 pages, 2270 KB

Open AccessEditor’s ChoiceReview

Established and Emerging Asthma Biomarkers with a Focus on Biologic Trials: A Narrative Review

by Philip F. Lavere, Kaitlin M. Phillips, Nicola A. Hanania and Muhammad Adrish

J. Pers. Med. 2025, 15(8), 370; https://doi.org/10.3390/jpm15080370 - 13 Aug 2025

Cited by 6 | Viewed by 7271

Abstract

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic [...] Read more.

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 (T2) asthma endotype. Emerging biomarkers, or older biomarkers with emerging utility, include sputum inflammatory cells (eosinophils, neutrophils, interleukins), thymus and activation-regulated chemokine (TARC), plasma eotaxin-3, eosinophil peroxidase (EPX), Clara/club cell secretory protein (CC16), and quantitative computerized tomography (QCT) imaging biomarkers (evaluating mucus plugging, air trapping, airway wall thickness, small airway remolding) and are increasingly used in clinical trials as secondary endpoints in evaluating efficacy, as well as in the clinical setting at specialized centers. The rapid advances in asthma research, due in part to biomarkers and biologic therapies, may soon standardize an end goal: symptom-free asthma remission without exacerbations. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches to Asthma in Clinical Medicine)

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21 pages, 360 KB

Open AccessEditor’s ChoiceReview

Prognostic Models in Heart Failure: Hope or Hype?

by Spyridon Skoularigkis, Christos Kourek, Andrew Xanthopoulos, Alexandros Briasoulis, Vasiliki Androutsopoulou, Dimitrios Magouliotis, Thanos Athanasiou and John Skoularigis

J. Pers. Med. 2025, 15(8), 345; https://doi.org/10.3390/jpm15080345 - 1 Aug 2025

Cited by 6 | Viewed by 3134

Abstract

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more [...] Read more.

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more complex models incorporating biomarkers (e.g., NT-proBNP, sST2), imaging, and artificial intelligence techniques. In acute HF, models like EHMRG and STRATIFY aid early triage, while in chronic HF, tools like SHFM and BCN Bio-HF support long-term management decisions. Despite their utility, most models are limited by poor generalizability, reliance on static inputs, lack of integration into electronic health records, and underuse in clinical practice. Novel approaches involving machine learning, multi-omics profiling, and remote monitoring hold promise for dynamic and individualized risk assessment. However, these innovations face challenges regarding interpretability, validation, and ethical implementation. For prognostic models to transition from theoretical promise to practical impact, they must be continuously updated, externally validated, and seamlessly embedded into clinical workflows. This review emphasizes the potential of prognostic models to transform HF care but cautions against uncritical adoption without robust evidence and practical integration. In the evolving landscape of HF management, prognostic models represent a hopeful avenue, provided their limitations are acknowledged and addressed through interdisciplinary collaboration and patient-centered innovation. Full article

(This article belongs to the Special Issue Personalized Treatment for Heart Failure)

46 pages, 1152 KB

Open AccessEditor’s ChoiceSystematic Review

Key Determinants Influencing Treatment Decision-Making for and Adherence to Active Surveillance for Prostate Cancer: A Systematic Review

by Pani Nasseri, Jorien Veldwijk, Christa Niehot, Esmee F. H. Mulder, Esther W. de Bekker-Grob, Monique J. Roobol and Lionne D. F. Venderbos

J. Pers. Med. 2025, 15(7), 315; https://doi.org/10.3390/jpm15070315 - 15 Jul 2025

Cited by 4 | Viewed by 3690

Abstract

Background/Objectives: Men choosing active surveillance (AS) for low- and intermediate risk prostate cancer (PCa) must weigh its harms and benefits against those of active treatment (AT). To understand factors influencing treatment decision-making (TDM) for and adherence to AS, we performed a systematic [...] Read more.

Background/Objectives: Men choosing active surveillance (AS) for low- and intermediate risk prostate cancer (PCa) must weigh its harms and benefits against those of active treatment (AT). To understand factors influencing treatment decision-making (TDM) for and adherence to AS, we performed a systematic review. Methods: This systematic review followed the PRISMA guidelines and was registered with PROSPERO (ID CRD42024490427). A comprehensive search strategy from 1990 to 2024 was executed across multiple databases, including Medline and Embase. Studies were included if they examined factors influencing TDM for AS or active monitoring (AM) and adherence to AS/AM. Results: Of the 8316 articles identified, 223 articles were eligible for inclusion. The decision for AS was influenced by different factors, including comprehensive information about treatment options, social support, and wanting to avoid side-effects. Key reasons to choose AT over AS included a lack of information from healthcare professionals about AS and fear of disease progression. Reasons for adhering to the AS protocol included better quality of life and social support. While non-adherence to the AS protocol is prompted by, e.g., biopsy burden and uncertainty, AS discontinuation is generally a results of medical reasons (namely disease upgrading) or from anxiety and family pressure. Conclusions: Numerous factors influence men’s treatment pathway choices. Involving family members in shared decision-making and ensuring that patients have detailed information about AS as a treatment option could help to improve AS uptake. Addressing psychosocial challenges through education and family involvement could improve AS adherence. These insights can help healthcare providers by addressing men’s needs during TDM and AS. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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13 pages, 771 KB

Open AccessEditor’s ChoiceArticle

The Anesthesiologic Impact of Single-Port Robot-Assisted Partial Nephrectomy: A Tertiary Referral Comparative Analysis Between Full-Flank Transperitoneal, Retroperitoneal, and Supine Lower Anterior Access (LAA)

by Luca Lambertini, Matteo Pacini, Paolo Polverino, Nikki R. Wilkinson, Ruben Sauer Calvo, Donato Cannoletta, Antony Angelo Pellegrino, Greta Pettenuzzo, Fabrizio Di Maida, Andrea Mari, Gabriele Bignante, Francesco Lasorsa, Alessandro Zucchi, Sergio Serni, Andrea Minervini, David B. Glick and Simone Crivellaro

J. Pers. Med. 2025, 15(7), 306; https://doi.org/10.3390/jpm15070306 - 11 Jul 2025

Cited by 7 | Viewed by 1839

Abstract

Objective: To explore the impact of supine retroperitoneal single-port robot-assisted partial nephrectomy with lower anterior access on perioperative ventilatory, cardiovascular, and pain-related outcomes compared to a cohort of patients treated with single-port robot-assisted retroperitoneal or transperitoneal partial nephrectomy with standard flank patient positioning. [...] Read more.

Objective: To explore the impact of supine retroperitoneal single-port robot-assisted partial nephrectomy with lower anterior access on perioperative ventilatory, cardiovascular, and pain-related outcomes compared to a cohort of patients treated with single-port robot-assisted retroperitoneal or transperitoneal partial nephrectomy with standard flank patient positioning. Materials and Methods: Clinical and surgical data of all consecutive patients treated with single-port robot-assisted partial nephrectomy between March 2019 and January 2024 were prospectively collected and retrospectively analyzed. Specific same-day-discharge guidelines were applied to all cases. Failed same-day discharge was defined as the presence of early (<90 days) perioperative complications or the absence of opioid-free postoperative recovery. Results: Overall, 105 consecutive patients treated with single-port robot-assisted partial nephrectomy were analyzed. No differences emerged in baseline features. Peak inspiratory pressure and plateau pressure changes were significantly lower in the supine retroperitoneal lower anterior access group from the time of CO₂ insufflation throughout every 30-min operative setpoint assessment (p = 0.02, p = 0.03, and p = 0.02, respectively). The transperitoneal group showed significantly higher values of mean, systolic, and diastolic blood pressure compared to retroperitoneal approaches. The supine lower anterior access group also showed significantly lower non-surgical operative room time, perioperative opioid administration, and postoperative median VAS pain score. Conclusions: The adoption of supine lower anterior access improved perioperative ventilatory, cardiovascular, and pain-related outcomes, also optimizing operating room efficiency. Further multicenter series with longer follow-ups are still needed to validate our preliminary results. Full article

(This article belongs to the Special Issue Targeted Surgery and Artificial Intelligence in Personalized Medicine and Robotic Surgery: Current Challenges and Future Prospects)

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12 pages, 519 KB

Open AccessEditor’s ChoiceArticle

Cardiac Autonomic Measures Predict Clinician-Rated Anxiety and Behavioral Response to Propranolol in Autistic Children and Young Adults

by Carrina Appling, Nanan Nuraini, Ryan Holem, Samantha Hunter, Kathy Hirst, Nicole Takahashi, Micah O. Mazurek, Stephen M. Kanne, Bradley Ferguson and David Q. Beversdorf

J. Pers. Med. 2025, 15(7), 286; https://doi.org/10.3390/jpm15070286 - 3 Jul 2025

Cited by 5 | Viewed by 3141

Abstract

Propranolol, a nonselective beta-adrenergic antagonist, has shown potential for improving anxiety in autistic individuals. Heart rate variability (HRV), a noninvasive cardiac marker of autonomic nervous system functioning, may help identify individuals most likely to benefit from propranolol. Objectives: Determine if baseline resting [...] Read more.

Propranolol, a nonselective beta-adrenergic antagonist, has shown potential for improving anxiety in autistic individuals. Heart rate variability (HRV), a noninvasive cardiac marker of autonomic nervous system functioning, may help identify individuals most likely to benefit from propranolol. Objectives: Determine if baseline resting HRV and other cardiac measures predict the response to propranolol for anxiety and core autism symptomology in autistic children and young adults. Methods: Sixty-two autistic individuals (ages 7–24) participated in a two-phase (i.e., a 12-week randomized controlled trial and a 12-week open-label extension) trial of propranolol. Baseline (i.e., resting state, prior to treatment) HRV and other cardiac measures were obtained from an electrocardiogram. Clinical global impression for anxiety symptoms and overall behavioral treatment impact were assessed after the 12-week trial period. Group-level (i.e., all participants) and responder groups (i.e., strong, minimal, and non-responders to propranolol) were analyzed for treatment effects. Results: HRV variables predicted group-level anxiety response to propranolol, particularly for strong responders. Also, lower baseline values of parasympathetic HRV indices were significantly correlated with greater behavioral improvement after treatment with propranolol. Last, several baseline cardiac variables were associated with improvement in multiple behavioral domains after treatment with propranolol. Conclusions: HRV may be a potential biomarker for predicting reduced anxiety and behavioral symptoms in response to propranolol in autistic children and young adults. Identifying autonomic profiles associated with positive treatment outcomes could guide future personalized interventions in autism. The results presented herein should be regarded as preliminary until the findings are replicated in future clinical trials. Full article

(This article belongs to the Special Issue Personalized Medicine for Autism Spectrum Disorder)

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36 pages, 4138 KB

Open AccessEditor’s ChoiceArticle

Shoulder and Scapular Function Before and After a Scapular Therapeutic Exercise Program for Chronic Shoulder Pain and Scapular Dyskinesis: A Pre–Post Single-Group Study

by Ana S. C. Melo, Ana L. Soares, Catarina Castro, Ricardo Matias, Eduardo B. Cruz, J. Paulo Vilas-Boas and Andreia S. P. Sousa

J. Pers. Med. 2025, 15(7), 285; https://doi.org/10.3390/jpm15070285 - 2 Jul 2025

Cited by 1 | Viewed by 8847

Abstract

Background/Objectives: Scapular adaptations have been associated with shoulder pain. However, conflicting findings have been reported after scapular-focused interventions. The present study aims to evaluate scapula-related outcomes before and after a scapular therapeutic exercise program. Methods: Eighteen adult volunteers with chronic shoulder [...] Read more.

Background/Objectives: Scapular adaptations have been associated with shoulder pain. However, conflicting findings have been reported after scapular-focused interventions. The present study aims to evaluate scapula-related outcomes before and after a scapular therapeutic exercise program. Methods: Eighteen adult volunteers with chronic shoulder pain participated in an 8-week scapular therapeutic exercise program that was personalized according to their pain condition and the presence of scapular dyskinesis. This program included preparation and warm-up, scapular neuromotor control, and strengthening and stretching exercises. Both self-reported (shoulder pain and function, psychosocial factors, and self-impression of change) and performance-based outcomes (scapular muscular stiffness and activity level, tridimensional motion, rhythm, and movement quality, measured while participants drank a bottle of water) were used for analysis. Results: After the intervention, participants presented reduced shoulder pain (p < 0.0001) and pain catastrophizing (p = 0.004) and increased shoulder function (p < 0.0001). Additionally, the participants presented changes in scapular winging (p < 0.0001 to p = 0.043), increased scapular downward rotation (p < 0.0001) and depression (p = 0.038), and decreased global movement smoothness (p = 0.003). These were associated with changes in serratus anterior activity (p = 0.016 to p = 0.035), decreased middle (p < 0.0001 to p = 0.002) and lower trapezius (p < 0.0001) and levator scapulae (p = 0.048) activity levels, and decreased middle trapezius muscle stiffness (p = 0.014). Patients’ self-perception of change was rated favorably. Conclusions: After a scapular therapeutic exercise program, changes were observed in both self-reported and performance-based outcomes. These results need to be confirmed by a randomized controlled trial. Full article

(This article belongs to the Special Issue Personalized Medicine in Physical Medicine and Rehabilitation: Pediatrics, Adolescents and the Elderly)

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30 pages, 4082 KB

Open AccessEditor’s ChoiceSystematic Review

Prostate MRI Using Deep Learning Reconstruction in Response to Cancer Screening Demands—A Systematic Review and Meta-Analysis

by Stephan Ursprung, Georgios Agrotis, Petra J. van Houdt, Leon C. ter Beek, Thierry N. Boellaard, Regina G. H. Beets-Tan, Derya Yakar, Anwar R. Padhani and Ivo G. Schoots

J. Pers. Med. 2025, 15(7), 284; https://doi.org/10.3390/jpm15070284 - 2 Jul 2025

Cited by 6 | Viewed by 2770

Abstract

Background/Objectives: There is a growing need for efficient prostate MRI protocols due to their increasing use in managing prostate cancer (PCa) and potential inclusion in screening. Deep learning reconstruction (DLR) may enhance MR acquisitions and improve image quality compared to conventional acceleration [...] Read more.

Background/Objectives: There is a growing need for efficient prostate MRI protocols due to their increasing use in managing prostate cancer (PCa) and potential inclusion in screening. Deep learning reconstruction (DLR) may enhance MR acquisitions and improve image quality compared to conventional acceleration techniques. This systematic review examines DLR approaches to prostate MRI. Methods: A search of PubMed, Web of Science, and Google Scholar identified eligible studies comparing DLR to conventional reconstruction for prostate imaging. A narrative synthesis was performed to summarize the impact of DLR on acquisition time, image quality, and diagnostic performance. Results: Thirty-three studies showed that DLR can reduce acquisition times for T₂w and DWI imaging while maintaining or improving image quality. It did not significantly affect clinical tasks, such as biopsy decisions, and performed comparably to human readers in PI-RADS scoring and the detection of extraprostatic extension. However, AI models trained on conventional data might be less accurate with DLR images. The heterogeneity in image quality metrics among the studies prevented quantitative synthesis. Discussion: DLR has the potential to achieve substantial time savings in prostate MRI while maintaining image quality, which is especially relevant because of increased MRI demands. Future research should address the effect of DLR on clinically relevant downstream tasks, including AI algorithms’ performances and biopsy decisions, and explore task-specific accelerated protocols for screening, image-guided biopsy, and treatment. Full article

(This article belongs to the Special Issue Diagnosis of Prostate Cancer: Population-Based Early Detection, Risk Stratification and Imaging)

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18 pages, 1117 KB

Open AccessEditor’s ChoiceReview

Surgical Management of Mediastinal Ectopic Parathyroids

by Giacomo Rabazzi, Gianmarco Elia, Vittorio Aprile, Stylianos Korasidis, Maria Giovanna Mastromarino, Diana Bacchin, Alessandra Lenzini, Marcello Carlo Ambrogi, Greta Alì, Filomena Cetani, Gabriele Materazzi and Marco Lucchi

J. Pers. Med. 2025, 15(7), 276; https://doi.org/10.3390/jpm15070276 - 30 Jun 2025

Cited by 6 | Viewed by 2118

Abstract

Primary hyperparathyroidism is commonly caused by parathyroid adenomas, hyperplasia, or, rarely, carcinoma. In up to 20% of cases, parathyroid tissue may be ectopic, often located in the mediastinum due to aberrant embryologic migration. Ectopic parathyroid glands pose a diagnostic and therapeutic challenge, and [...] Read more.

Primary hyperparathyroidism is commonly caused by parathyroid adenomas, hyperplasia, or, rarely, carcinoma. In up to 20% of cases, parathyroid tissue may be ectopic, often located in the mediastinum due to aberrant embryologic migration. Ectopic parathyroid glands pose a diagnostic and therapeutic challenge, and an accurate preoperative localization is essential for an effective and safe resection. Imaging modalities such as CT scan, TC-sestamibi scintigraphy, PET/CT, ultrasonography and MRI are routinely employed, whereas combined techniques offer improved diagnostic accuracy. Emerging approaches, however, including PET/CT with choline tracers, have shown promise in enhancing sensitivity in complex or recurrent cases. When ectopic glands are in the mediastinum, thoracic surgical intervention is required. Traditional open approaches, such as sternotomy or thoracotomy, are associated with significant morbidity. The development and evolution of minimally invasive surgery (MIS) has become the preferred approach in selected cases. When MIS is performed, intraoperative assessment and parathyroid identification are crucial to ensure complete gland removal. Intraoperative parathyroid hormone (ioPTH) monitoring provides real-time confirmation of surgical success. The integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques significantly improves surgical outcomes while minimizing complications and accelerating patient recovery. Ultimately, the effective treatment of ectopic parathyroid glands relies on a personalized approach, adapting both diagnostic and surgical strategies to the unique anatomical and clinical context of each patient. Integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques, combined with a multidisciplinary team involving endocrinologists, radiologists, and thoracic surgeons, is key to optimizing outcomes and reducing patient morbidity. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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17 pages, 627 KB

Open AccessEditor’s ChoiceReview

Major Allele Frequencies in CYP2C9 and CYP2C19 in Asian and European Populations: A Case Study to Disaggregate Data Among Large Racial Categories

by Horng-Ee Vincent Nieh and Youssef Malak Roman

J. Pers. Med. 2025, 15(7), 274; https://doi.org/10.3390/jpm15070274 - 27 Jun 2025

Cited by 7 | Viewed by 6451

Abstract

CYP2C9 and CYP2C19 are major CYP450 enzymes that heavily influence the hepatic metabolism and bioactivation of many medications, including over-the-counter and narrow therapeutic index drugs. Compared to the wild-type alleles, genetic variants in either gene could potentially alter the pharmacokinetics of widely used [...] Read more.

CYP2C9 and CYP2C19 are major CYP450 enzymes that heavily influence the hepatic metabolism and bioactivation of many medications, including over-the-counter and narrow therapeutic index drugs. Compared to the wild-type alleles, genetic variants in either gene could potentially alter the pharmacokinetics of widely used medications, affect the desired therapeutic outcomes of a drug therapy, or increase the risk of undesired adverse events. The frequency of genetic polymorphisms associated with CYP450 enzymes can widely differ across and between racial and ethnic groups. This narrative review highlights the differences in CYP2C9 and CYP2C19 allele frequencies among European and Asian population subgroups, using published literature. Identifying the substantial differences across European and Asian populations, as well as within Asian subgroups, indicates the need to further scrutinize general population data. Clinical scientists and healthcare providers should advocate for more inclusive clinical pharmacogenomic data and racially and ethnically diverse pharmacogenomic databases. Clinical trials of limited racial and geographical diversity may not necessarily have strong external generalizability for all populations. Furthermore, clinical trials that designate an all-inclusive Asian population consisting of multiple ethnicities may not be adequate due to the perceived genetic differences among Asian subgroups. Gravitating towards a more comprehensive approach to utilizing pharmacogenomic data necessitates granular population-level genetic information which can be leveraged to improve how drug therapies are prescribed, achieve health equity, and advance the future of precision medicine. Full article

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

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26 pages, 2477 KB

Open AccessEditor’s ChoiceReview

Deciphering Breast Tumor Heterogeneity Through Patient-Derived Organoids and Circulating Tumor Cells

by Benedetta Policastro, Nikoline Nissen and Carla L. Alves

J. Pers. Med. 2025, 15(7), 271; https://doi.org/10.3390/jpm15070271 - 25 Jun 2025

Cited by 6 | Viewed by 2970

Abstract

Breast cancer is a highly heterogeneous disease, with tumors capable of adapting to shifting conditions, making the development of effective personalized therapies particularly challenging. Patient-derived models, such as patient-derived organoids (PDOs) and circulating tumor cell (CTC) cultures, have emerged as powerful tools for [...] Read more.

Breast cancer is a highly heterogeneous disease, with tumors capable of adapting to shifting conditions, making the development of effective personalized therapies particularly challenging. Patient-derived models, such as patient-derived organoids (PDOs) and circulating tumor cell (CTC) cultures, have emerged as powerful tools for investigating intra- and inter-tumor heterogeneity. These models largely retain the genetic, phenotypic, and microenvironmental features of the original tumors, providing valuable insights into disease progression, drug response, and resistance mechanisms. Furthermore, by enabling tumors’ spatiotemporal molecular profiling, PDOs and CTCs offer a dynamic approach to assess treatment efficacy over time. However, to fully capture the complexity of breast cancer heterogeneity, it is required to develop models from multiple tumor and blood samples collected throughout the course of treatment. This review explores the potential of integrating PDOs and CTC models to better understand intra-tumor heterogeneity while addressing key challenges in developing patient-derived models that accurately recapitulate patients’ tumors to advance personalized care. The integration of PDOs and CTCs could represent a paradigm shift in the personalized management of metastatic breast cancer. Full article

(This article belongs to the Section Disease Biomarkers)

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21 pages, 661 KB

Open AccessEditor’s ChoiceArticle

Clinical Pharmacogenetics: Results After Implementation of Preemptive Tests in Daily Routine

by Xando Díaz-Villamarín, María Martínez-Pérez, María Teresa Nieto-Sánchez, Emilio Fernández-Varón, Alicia Torres-García, Isabel Blancas, José Cabeza-Barrera and Rocío Morón

J. Pers. Med. 2025, 15(6), 245; https://doi.org/10.3390/jpm15060245 - 10 Jun 2025

Cited by 4 | Viewed by 2763

Abstract

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug–gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., [...] Read more.

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug–gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., single-gene vs. multi-gene panels), or how to translate genotypes into actionable therapeutic recommendations. Methods: We describe the implementation of PGx in real daily clinical routine at a single institution to guide other centers. We analyze the drug–gene interactions and genetic variants included in our program based on allelic, genotypic, and phenotypic frequencies, resulting therapeutic recommendations. Linkage disequilibrium and haplotype analyses are also performed. Results and Conclusions: PGx testing was primarily requested by the oncology department. Not all variants included in typical panels had clinical utility in our setting. We do not recommend testing CYP2C19*17 prior to clopidogrel prescription, as it does not translate into a dosing recommendation. TPMT*3B may be considered just to confirm TPMT*3A due to its linkage with TPMT*3C. Similarly, we do not recommend the routine testing of CYP2C9*2 prior to siponimod prescription, as it does not inform therapeutic decisions according to the current drug label. Full article

(This article belongs to the Section Pharmacogenetics)

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26 pages, 9374 KB

Open AccessEditor’s ChoiceReview

Right Ventricular Strain by Echocardiography: Current Clinical Applications and Future Directions for Mechanics Assessment of the Forgotten Ventricle

by Mahmoud Abdelnabi, Ramzi Ibrahim, Hoang Nhat Pham, Bobbi Jo Heon, George Bcharah, Girish Pathangey, Milagros Pereyra Pietri, Juan M. Farina, Ian C. Chang, Reza Arsanjani and Chadi Ayoub

J. Pers. Med. 2025, 15(6), 224; https://doi.org/10.3390/jpm15060224 - 30 May 2025

Cited by 2 | Viewed by 8653

Abstract

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV [...] Read more.

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV longitudinal strain (RVLS) in clinical practice. RVLS provides a more sensitive indicator of subtle myocardial dysfunction than conventional parameters for RV function assessment (i.e., tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction), with utility for the risk stratification and surveillance of conditions affecting the right heart. However, accurate interpretation of RVLS requires a comprehensive understanding of RV mechanics, pathology, and loading conditions across various cardiovascular conditions, as well as the effects of image quality and technical aspects of image acquisition and tracking in RV strain measurements. This review provides an updated overview of current practical guidelines for RV strain analysis, current clinical applications, and future directions for its potential use in clinical practice. Full article

(This article belongs to the Special Issue New Advances in Techniques and Personalized Medicine in Cardiology)

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19 pages, 649 KB

Open AccessEditor’s ChoiceReview

Interstitial Lung Diseases and Lung Cancer: A Review on Similarities, Common Pathogenesis and Therapeutic Approach

by Gioele Castelli, Elisabetta Cocconcelli, Giuliana Grimaudo, Irene Di Leo, Serena Bellani, Giordano Fiorentù, Giacomo Giulianelli, Nicol Bernardinello, Elisabetta Balestro and Paolo Spagnolo

J. Pers. Med. 2025, 15(5), 213; https://doi.org/10.3390/jpm15050213 - 21 May 2025

Cited by 4 | Viewed by 5105

Abstract

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that [...] Read more.

Interstitial lung disease (ILD) prevalence and survival are increasing due to improvement in scientific research together with clinical complications typical of advanced disease. Lung cancer (LC) is described as a possible event occurring in lung parenchyma in the context of fibrotic abnormalities that worsen patients’ prognosis. This growth of malignant cells on a fibrotic background has also been called scar-cinoma. For this reason, not only an early diagnosis but also personalized decisions on the best treatment approach should be considered for each patient in a multidisciplinary discussion, since in some cases chemotherapy or surgery could be detrimental for patients with pulmonary fibrosis. LC and lung fibrosis may share common pathogenetic mechanisms like an altered healing process in response to repeated tissue damage from environmental exposure in genetically susceptible individuals. Smoking history and air pollution together with mutations in telomere and surfactant protein genes lead to the production of cytokines and nitro derivatives in the microenvironment that facilitate the carcinomatous transformation during fibrogenesis. The evolution of LC therapy and the implementation of immunotherapy acting on targetable immune checkpoints have raised interest in evaluating ILD-LC actionable mutations. The main pathogenetic mechanisms, clinical presentations and treatment implications are presented in this review. Full article

(This article belongs to the Special Issue Pathology and Molecular Diagnostics in the Personalized Treatment of Lung Diseases)

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17 pages, 2456 KB

Open AccessEditor’s ChoiceArticle

The Accuracy of ChatGPT-4o in Interpreting Chest and Abdominal X-Ray Images

by Pietro G. Lacaita, Malik Galijasevic, Michael Swoboda, Leonhard Gruber, Yannick Scharll, Fabian Barbieri, Gerlig Widmann and Gudrun M. Feuchtner

J. Pers. Med. 2025, 15(5), 194; https://doi.org/10.3390/jpm15050194 - 10 May 2025

Cited by 11 | Viewed by 7000

Abstract

Background/Objectives: Large language models (LLMs), such as ChatGPT, have emerged as potential clinical support tools to enhance precision in personalized patient care, but their reliability in radiological image interpretation remains uncertain. The primary aim of our study was to evaluate the diagnostic accuracy [...] Read more.

Background/Objectives: Large language models (LLMs), such as ChatGPT, have emerged as potential clinical support tools to enhance precision in personalized patient care, but their reliability in radiological image interpretation remains uncertain. The primary aim of our study was to evaluate the diagnostic accuracy of ChatGPT-4o in interpreting chest X-rays (CXRs) and abdominal X-rays (AXRs) by comparing its performance to expert radiology findings, whilst secondary aims were diagnostic confidence and patient safety. Methods: A total of 500 X-rays, including 257 CXR (51.4%) and 243 AXR (48.5%), were analyzed. Diagnoses made by ChatGPT-4o were compared to expert interpretations. Confidence scores (1–4) were assigned and responses were evaluated for patient safety. Results: ChatGPT-4o correctly identified 345 of 500 (69%) pathologies (95% CI: 64.81–72.9). For AXRs 175 of 243 (72.02%) pathologies were correctly diagnosed (95% CI: 66.06–77.28), while for CXRs 170 of 257 (66.15%) were accurate (95% CI: 60.16–71.66). The highest detection rates among CXRs were observed for pulmonary edema, tumor, pneumonia, pleural effusion, cardiomegaly, and emphysema, and lower rates were observed for pneumothorax, rib fractures, and enlarged mediastinum. AXR performance was highest for intestinal obstruction and foreign bodies, and weaker for pneumoperitoneum, renal calculi, and diverticulitis. Confidence scores were higher for AXRs (mean 3.45 ± 1.1) than CXRs (mean 2.48 ± 1.45). All responses (100%) were considered to be safe for the patient. Interobserver agreement was high (kappa = 0.920), and reliability (second prompt) was moderate (kappa = 0.750). Conclusions: ChatGPT-4o demonstrated moderate accuracy for the interpretation of X-rays, being higher for AXRs compared to CXRs. Improvements are required for its use as efficient clinical support tool. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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13 pages, 1104 KB

Open AccessEditor’s ChoiceReview

Temporary Mechanical Support in Cardiogenic Shock Secondary to Heart Failure: An Evolving Paradigm

by Nandini Nair, Dongping Du and Balakrishnan Mahesh

J. Pers. Med. 2025, 15(5), 184; https://doi.org/10.3390/jpm15050184 - 2 May 2025

Cited by 3 | Viewed by 2540

Abstract

Cardiogenic shock can be defined as a state of circulatory collapse resulting in hypoperfusion and end-organ dysfunction. It carries a large burden of mortality, but management strategies are driven by expert consensus rather than adequately powered randomized clinical trials. The goal of this [...] Read more.

Cardiogenic shock can be defined as a state of circulatory collapse resulting in hypoperfusion and end-organ dysfunction. It carries a large burden of mortality, but management strategies are driven by expert consensus rather than adequately powered randomized clinical trials. The goal of this review is to highlight the differences in presentation and outcomes in cardiogenic shock depending on the etiology, such as acute myocardial infarction (AMI) versus acute-on-chronic heart failure (HF), gender-based differences in treatment strategies and outcomes and the need for more precise risk stratification and modeling to improve the efficiency of treatment delivery in a personalized fashion. PubMed and Google Scholar were used to search the literature for this qualitative review. The differences in gender and etiology of cardiogenic shock are not consistent in all studies in the exiting literature. There is a need for identification of novel risk factors that define the different phenotypes that present with similar hemodynamic and biomarker profiles. There is an urgent need to devise a methodology to understand and differentiate the different cardiogenic shock phenotypes and their trajectories. Better risk prediction models should be generated to help deliver well-tailored treatment, paving the way to the efficient delivery of personalized medicine. Full article

(This article belongs to the Special Issue New Perspectives of Critical Care Medicine)

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13 pages, 601 KB

Open AccessEditor’s ChoiceArticle

The Association of Assisted Reproductive Technology with Placental and Umbilical Abnormalities

by Antonios Siargkas, Ioannis Tsakiridis, Sonia Giouleka, Petya Chaveeva, Maria Mar Gil, Walter Plasencia, Catalina De Paco Matallana, Efstratios M. Kolibianakis and Themistoklis Dagklis

J. Pers. Med. 2025, 15(5), 176; https://doi.org/10.3390/jpm15050176 - 27 Apr 2025

Cited by 4 | Viewed by 2735

Abstract

Objective: Global utilization of assisted reproductive technology (ART) is increasing; however, it is associated with adverse perinatal outcomes. Placental and umbilical cord abnormalities contribute significantly to these negative outcomes. However, it remains unclear whether ART independently increases the risk of such abnormalities. This [...] Read more.

Objective: Global utilization of assisted reproductive technology (ART) is increasing; however, it is associated with adverse perinatal outcomes. Placental and umbilical cord abnormalities contribute significantly to these negative outcomes. However, it remains unclear whether ART independently increases the risk of such abnormalities. This study aimed to investigate the association between ART and key umbilico-placental abnormalities, after adjustment for confounders. Methods: In this retrospective cohort study, singleton pregnancies receiving routine antenatal care (January 2015 to June 2024) at the 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece, were analyzed. Pregnancies conceived via ART were compared to those conceived spontaneously. To investigate placental and cord anomalies, this study employed multiple logistic regression. This approach adjusted for various confounders, including maternal age, BMI, parity, smoking status, history of previous cesarean section, diabetes mellitus, and thyroid disease. Results: This study included a total of 13,854 singleton pregnancies, of which 647 were conceived via ART. ART was significantly associated with an increased risk of placenta previa (aOR 1.99, 95% CI 1.10–3.61), low-lying placenta (aOR 1.71, 95% CI 1.38–2.11), bilobate placenta (aOR 2.81, 95% CI 1.92–4.11), single umbilical artery (aOR 2.62, 95% CI 1.022–6.715), marginal (aOR 1.63, 95% CI 1.32–2.01) and velamentous cord insertion (aOR 3.13, 95% CI 1.98–4.95), and vasa previa (aOR 5.51, 95% CI 1.28–23.76). Conclusions: ART-conceived pregnancies appear to carry a higher risk for certain placental and umbilical cord abnormalities, potentially contributing to adverse perinatal outcomes. Further studies are required to investigate the pathophysiology underlying these associations. Full article

(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Maternal Fetal Medicine)

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20 pages, 679 KB

Open AccessEditor’s ChoiceReview

Beyond Biomarkers: Machine Learning-Driven Multiomics for Personalized Medicine in Gastric Cancer

by Dongheng Ma, Canfeng Fan, Tomoya Sano, Kyoka Kawabata, Hinano Nishikubo, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Tasuku Matsuoka and Masakazu Yashiro

J. Pers. Med. 2025, 15(5), 166; https://doi.org/10.3390/jpm15050166 - 24 Apr 2025

Cited by 18 | Viewed by 4754

Abstract

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with most cases diagnosed at advanced stages. Traditional biomarkers provide only partial insights into GC’s heterogeneity. Recent advances in machine learning (ML)-driven multiomics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, [...] Read more.

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with most cases diagnosed at advanced stages. Traditional biomarkers provide only partial insights into GC’s heterogeneity. Recent advances in machine learning (ML)-driven multiomics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, pathomics, and radiomics, have facilitated a deeper understanding of GC by integrating molecular and imaging data. In this review, we summarize the current landscape of ML-based multiomics integration for GC, highlighting its role in precision diagnosis, prognosis prediction, and biomarker discovery for achieving personalized medicine. Full article

(This article belongs to the Special Issue The Intersection of Multi-Omics Data and Machine Learning in Medicine)

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13 pages, 1544 KB

Open AccessEditor’s ChoiceArticle

Multimodal Performance of GPT-4 in Complex Ophthalmology Cases

by David Mikhail, Daniel Milad, Fares Antaki, Jason Milad, Andrew Farah, Thomas Khairy, Jonathan El-Khoury, Kenan Bachour, Andrei-Alexandru Szigiato, Taylor Nayman, Guillaume A. Mullie and Renaud Duval

J. Pers. Med. 2025, 15(4), 160; https://doi.org/10.3390/jpm15040160 - 21 Apr 2025

Cited by 11 | Viewed by 1992

Abstract

Objectives: The integration of multimodal capabilities into GPT-4 represents a transformative leap for artificial intelligence in ophthalmology, yet its utility in scenarios requiring advanced reasoning remains underexplored. This study evaluates GPT-4’s multimodal performance on open-ended diagnostic and next-step reasoning tasks in complex ophthalmology [...] Read more.

Objectives: The integration of multimodal capabilities into GPT-4 represents a transformative leap for artificial intelligence in ophthalmology, yet its utility in scenarios requiring advanced reasoning remains underexplored. This study evaluates GPT-4’s multimodal performance on open-ended diagnostic and next-step reasoning tasks in complex ophthalmology cases, comparing it against human expertise. Methods: GPT-4 was assessed across three study arms: (1) text-based case details with figure descriptions, (2) cases with text and accompanying ophthalmic figures, and (3) cases with figures only (no figure descriptions). We compared GPT-4’s diagnostic and next-step accuracy across arms and benchmarked its performance against three board-certified ophthalmologists. Results: GPT-4 achieved 38.4% (95% CI [33.9%, 43.1%]) diagnostic accuracy and 57.8% (95% CI [52.8%, 62.2%]) next-step accuracy when prompted with figures without descriptions. Diagnostic accuracy declined significantly compared to text-only prompts (p = 0.007), though the next-step performance was similar (p = 0.140). Adding figure descriptions restored diagnostic accuracy (49.3%) to near parity with text-only prompts (p = 0.684). Using figures without descriptions, GPT-4’s diagnostic accuracy was comparable to two ophthalmologists (p = 0.30, p = 0.41) but fell short of the highest-performing ophthalmologist (p = 0.0004). For next-step accuracy, GPT-4 was similar to one ophthalmologist (p = 0.22) but underperformed relative to the other two (p = 0.0015, p = 0.0017). Conclusions: GPT-4’s diagnostic performance diminishes when relying solely on ophthalmic images without textual context, highlighting limitations in its current multimodal capabilities. Despite this, GPT-4 demonstrated comparable performance to at least one ophthalmologist on both diagnostic and next-step reasoning tasks, emphasizing its potential as an assistive tool. Future research should refine multimodal prompts and explore iterative or sequential prompting strategies to optimize AI-driven interpretation of complex ophthalmic datasets. Full article

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

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17 pages, 889 KB

Open AccessEditor’s ChoiceArticle

Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience)

by Marco Di Nicola, Maria Pepe, Giacomo d’Andrea, Ilaria Marcelli, Mauro Pettorruso, Ileana Andriola, Stefano Barlati, Matteo Carminati, Carlo Ignazio Cattaneo, Massimo Clerici, Domenico De Berardis, Sergio De Filippis, Bernardo Dell’Osso, Giorgio Di Lorenzo, Giuseppe Maina, Mirko Manchia, Matteo Marcatili, Vassilis Martiadis, Cinzia Niolu, Antonino Petralia, Gianluca Rosso, Gianluca Serafini, Maria Salvina Signorelli, Tommaso Vannucchi, Matteo Vismara, Raffaella Zanardi, Antonio Vita, Gabriele Sani, Giovanni Martinotti and REAL-ESKperience Study Group Show full author list Hide full author list

J. Pers. Med. 2025, 15(4), 161; https://doi.org/10.3390/jpm15040161 - 21 Apr 2025

Cited by 16 | Viewed by 4806

Abstract

Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients’ perspective on this treatment are limited. This multicentric [...] Read more.

Background. Treatment-resistant depression (TRD) is a prevalent, high-burden disorder. Esketamine nasal spray (ESK-NS) has been approved for, T.R.D.; and efficacy has been observed in both clinical trials and real-world studies. However, observations integrating patients’ perspective on this treatment are limited. This multicentric Italian study explored experiences with ESK-NS in TRD patients, focusing on perceived therapeutic effects and overall satisfaction. Methods. A self-report survey was administered to 236 outpatients with TRD (55.1% females, 54.1 ± 14.1 years) treated with ESK-NS for at least three consecutive months within standard clinical care. Based on satisfaction levels, participants were classified as “unsatisfied” (10.2%), “partially satisfied” (19.1%), “satisfied” (44.4%), or “very satisfied” (26.3%), and compared for sociodemographic, clinical characteristics, and feedback on perceived benefits. Artificial intelligence (OpenAI) served to categorize responses to an open-ended question. Results. Enhanced quality of life was reported by 88.4% of participants. Significant differences emerged in earliest self-perceived benefits, most relevant effects, and impact on global functioning across groups. Specifically, “very satisfied” patients described the following: early improvements in depressed mood, suicidal thoughts, and restlessness; decreased suicidal thoughts among the most significant effects; and functional gains across all domains. OpenAI identified experiences of personal growth and rediscovery and a desire for tailored settings and approaches as recurring topics. Conclusions. Most patients reported a positive perception of ESK-NS treatment. The most satisfied participants highlighted significant benefits to depressed mood, suicidal thoughts, and overall functioning. Patient-reported experiences offer insights into different psychopathological dimensions, including functional outcomes and quality of life. Integrating these perspectives into clinical practice might assist treatment personalization, improving patients’ adherence and satisfaction. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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12 pages, 519 KB

Open AccessEditor’s ChoiceArticle

Effect of Flecainide in Idiopathic Premature Ventricular Contractions and the Induced Cardiomyopathy—UNIFLECA: A Single Arm, Non-Randomized Trial: Review of the Literature and Initial Results

by Sotirios Kotoulas, Dimitrios Tsiachris, Michail Botis, Athanasios Kordalis, Dimitrios Varvarousis, Georgios Leventopoulos, Eleftherios Kallergis, Ioannis Doundoulakis, Leonidas E. Poulimenos and Konstantinos Tsioufis

J. Pers. Med. 2025, 15(4), 132; https://doi.org/10.3390/jpm15040132 - 29 Mar 2025

Cited by 5 | Viewed by 7452

Abstract

Background/Objectives: Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend flecainide for PVCs originating from the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study, aiming to assess the [...] Read more.

Background/Objectives: Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend flecainide for PVCs originating from the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study, aiming to assess the efficacy and safety of flecainide in PVC burden reduction in adults, irrespective of PVC origin, focusing secondarily on symptom relief and improvement of left ventricular ejection fraction (LVEF) in patients suffering from PVC-induced cardiomyopathy. Methods: Participants were adults with frequent PVCs, defined as PVC burden > 5%, confirmed by two 24 h Holter recordings taken at least one month apart, who denied catheter ablation treatment. Patients who were deemed ineligible for catheter ablation were also included. A total of 50 patients were screened and 35 were administered Flecainide, with dosage adjustment based on follow-up Holter results and QRS increases. Changes in PVC burden, LVEF, symptomatic status, along with treatment adherence, were evaluated. Results: In adults with frequent PVCs, flecainide led to a significant reduction in PVC burden, with a mean decrease of 76.2% in the first month, and 63.1% of patients achieving a PVC burden reduction greater than 80%. Conclusions: UNIFLECA contributes to the understanding of how personalized, non-interventional therapeutic modalities can be employed to manage PVCs, especially for patients unwilling to have or ineligible for ablation procedures. Full article

(This article belongs to the Special Issue The Challenges and Therapeutic Prospects in Cardiovascular Disease)

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17 pages, 3545 KB

Open AccessEditor’s ChoiceArticle

Artificial Intelligence Detection of Occlusive Myocardial Infarction from Electrocardiograms Interpreted as “Normal” by Conventional Algorithms

by Shifa R. Karim, Hans C. Helseth, Peter O. Baker, Gabriel A. Keller, H. Pendell Meyers, Robert Herman and Stephen W. Smith

J. Pers. Med. 2025, 15(4), 130; https://doi.org/10.3390/jpm15040130 - 28 Mar 2025

Cited by 9 | Viewed by 4964

Abstract

Background: Some authors advocate that ECGs with conventional computer algorithm (CCA) interpretations of “normal” need not be immediately reviewed. However, such ECGs may actually manifest findings of acute coronary occlusion myocardial infarction (OMI). We sought to determine if such cases can be [...] Read more.

Background: Some authors advocate that ECGs with conventional computer algorithm (CCA) interpretations of “normal” need not be immediately reviewed. However, such ECGs may actually manifest findings of acute coronary occlusion myocardial infarction (OMI). We sought to determine if such cases can be detected by artificial intelligence (AI). Methods: We studied a retrospective series (2014–2024) of cases with ≥1 pre-angiography ECGs with a proven OMI outcome with a CCA ECG interpretation of “normal”. The OMI outcome was defined as (1) the diagnosis of acute type I MI, (2) an angiographic culprit with intervention, and (3) one of the following, (a) TIMI-0-2 flow, or (b) TIMI-3 or unknown flow, with high peak troponin or new wall abnormality. Each ECG as retrospectively interpreted by the PMcardio OMI AI ECG model. The primary analysis was the performance of AI in diagnosing "OMI" among these CCA “normal” ECGs. Results: Forty-two patients with OMI met the inclusion criteria. The first ECG was interpreted as “normal” by the CCA in 88% of cases; AI interpreted 81% as OMI and 86% as abnormal. Of the 78 total ECGs interpreted by the CCA, 73% were diagnosed as “normal”. Of this 73%, AI identified 81% as abnormal and 72% as OMI. Conclusion: The Conventional Computer Algorithm may interpret an ECG manifesting OMI as “normal”. AI not only recognized these as abnormal, but in 81% of patients, correctly recognized OMI on the first ECG and recognized 72% of all the CCA “normal” ECGs as OMI. It was rare for AI to diagnose a normal ECG for any OMI patient. Full article

(This article belongs to the Section Personalized Medical Care)

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15 pages, 247 KB

Open AccessEditor’s ChoiceReview

The Role of Dual-Energy CT in Differentiating Adrenal Adenomas from Metastases: A Comprehensive Narrative Review

by Francesco Tiralongo, Cristina Mosconi, Pietro Valerio Foti, Aldo Eugenio Calogero, Sandro La Vignera, Corrado Ini’, Davide Giuseppe Castiglione, Emanuele David, Stefania Tamburrini, Sebastiano Barbarino, Stefano Palmucci and Antonio Basile

J. Pers. Med. 2025, 15(4), 131; https://doi.org/10.3390/jpm15040131 - 28 Mar 2025

Cited by 4 | Viewed by 2183

Abstract

Dual-energy CT (DECT) has emerged as a novel imaging modality that offers a multiparametric approach for noninvasive adrenal lesion characterization. This narrative review examines recent advances in DECT—including virtual non-contrast imaging, iodine density quantification, spectral curve analysis, and material density mapping—for differentiating benign [...] Read more.

Dual-energy CT (DECT) has emerged as a novel imaging modality that offers a multiparametric approach for noninvasive adrenal lesion characterization. This narrative review examines recent advances in DECT—including virtual non-contrast imaging, iodine density quantification, spectral curve analysis, and material density mapping—for differentiating benign adrenal adenomas from metastases. Conventional CT techniques rely primarily on unenhanced attenuation measurements and contrast washout kinetics; however, these methods may be limited in evaluating lipid-poor adenomas, and in cases where imaging features overlap with metastatic lesions. Although virtual non-contrast imaging with DECT tends to overestimate attenuation relative to true non-contrast scans, the recalibration of diagnostic thresholds and integration with complementary parameters, such as the iodine density-to-virtual non-contrast attenuation ratio, can significantly enhance sensitivity and specificity. Additional parameters, including fat fraction analysis and the evaluation of attenuation changes across energy spectra, further refine tissue characterization by quantifying intracellular lipid content and vascularity. Material density analysis has demonstrated near-perfect diagnostic accuracy in select studies. By tailoring imaging evaluation to the unique spectral and compositional features of each adrenal lesion, DECT contributes to a more personalized diagnostic approach. This individualization allows for better differentiation between benign and malignant findings, potentially avoiding unnecessary interventions and enabling more targeted clinical management. Despite these promising developments, challenges remain regarding the standardization of acquisition protocols, optimization of diagnostic thresholds, and minimization of interobserver variability. Emerging radiomics and machine learning applications may further automate lesion classification and improve diagnostic accuracy. Thus, DECT holds considerable potential to improve diagnostic confidence, reduce radiation exposure, and streamline the management of patients with adrenal incidentalomas, although further multicenter validation is warranted. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

31 pages, 1617 KB

Open AccessEditor’s ChoiceReview

The Role of the Gut–Biliary–Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications

by Mario Romeo, Marcello Dallio, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Giuseppina Martinelli, Pierluigi Federico, Simone Olivieri, Patrizia Iodice and Alessandro Federico

J. Pers. Med. 2025, 15(4), 124; https://doi.org/10.3390/jpm15040124 - 24 Mar 2025

Cited by 8 | Viewed by 2102

Abstract

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut–liver [...] Read more.

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut–liver axis and gut–biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools. Full article

(This article belongs to the Section Mechanisms of Diseases)

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13 pages, 1097 KB

Open AccessEditor’s ChoiceReview

Advances in Basivertebral Nerve Ablation for Chronic Low Back Pain: A Narrative Review

by Sujeivan Mahendram and Paul J. Christo

J. Pers. Med. 2025, 15(3), 119; https://doi.org/10.3390/jpm15030119 - 19 Mar 2025

Viewed by 6763

Abstract

Chronic low back pain has traditionally been thought to stem from intervertebral disc degeneration. However, emerging evidence over the last few decades has revealed other contributing sources. One such etiology of chronic non-radiating axial low back pain has been attributed to vertebral end [...] Read more.

Chronic low back pain has traditionally been thought to stem from intervertebral disc degeneration. However, emerging evidence over the last few decades has revealed other contributing sources. One such etiology of chronic non-radiating axial low back pain has been attributed to vertebral end plate disruption and degeneration, leading to basivertebral nerve-mediated nociception. These degenerative events, described as Modic changes on MRI, provide a means of diagnosis and offer personalized treatment options, like minimally invasive radiofrequency ablation, to help address this source of low back pain. This review focuses on recent advancements, rationale, efficacy, and safety profile intraosseous basivertebral nerve ablation in the treatment of vertebrogenic back pain, and discusses current knowledge gaps that may help guide future research in the field. Full article

(This article belongs to the Special Issue Towards Precision Anesthesia and Pain Management)

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10 pages, 932 KB

Open AccessEditor’s ChoiceArticle

Impact of Surgical Timing, Fasciotomy, and External Fixation on Infection Risk in Tibial Plateau Fractures

by Salvatore Risitano, Antonio Rea, Giorgia Garofalo, Francesco Onorato, Ahmed Elzeiny, Stefano Artiaco, Marcello Capella, Pier Francesco Indelli and Alessandro Massè

J. Pers. Med. 2025, 15(3), 108; https://doi.org/10.3390/jpm15030108 - 11 Mar 2025

Cited by 8 | Viewed by 2929

Abstract

Background/Objectives: Tibial plateau fractures (TPFs) are commonly associated with complex patterns requiring advanced surgical strategies. High-energy trauma often results in severe soft tissue damage, complicating surgical outcomes. Despite advancements in soft tissue management, postoperative complications such as surgical site infections (SSIs) remain [...] Read more.

Background/Objectives: Tibial plateau fractures (TPFs) are commonly associated with complex patterns requiring advanced surgical strategies. High-energy trauma often results in severe soft tissue damage, complicating surgical outcomes. Despite advancements in soft tissue management, postoperative complications such as surgical site infections (SSIs) remain prevalent, with rates ranging from 9.9% to 30%. This study aims to analyze risk factors and surgical approaches influencing acute SSIs following TPF fixation. Methods: A retrospective analysis was conducted on 365 patients treated for TPFs with open or arthroscopy-assisted reduction and internal fixation (ORIF/ARIF) at a single center between January 2018 and December 2023. Inclusion criteria encompassed fractures classified by the Schatzker system and definitive management through ORIF/ARIF. Exclusion criteria included non-tibial plateau fractures, polytrauma, multiligament injuries and associated femoral fractures. Patient demographics, fracture patterns, surgical interventions, and postoperative complications were reviewed. Statistical analysis was performed using chi-square and ANOVA tests, with significance set at p < 0.05. Results: The final cohort included 364 patients (mean age: 45.4 ± 17.4 years; 59.2% male). High-energy fractures (Schatzker IV–VI) accounted for 47.7%, with 6.86% being open fractures. The mean interval to surgery was 14.9 ± 20.6 days. Superficial infections occurred in 21 cases (5.8%), predominantly at external fixator pin sites, while 15 cases (4.1%) involved deep infections. A statistically significant correlation was observed between SSIs and preoperative fasciotomy (p < 0.0001), damage control orthopedic protocols (p < 0.0001), and delays in definitive treatment of 10–30 days (p < 0.0001). No significant associations were found between infection rates and fracture type, dual surgical approaches, or the use of arthroscopy. Conclusions: External fixation, preoperative fasciotomy, and delayed definitive treatment are independent risk factors for SSIs following TPF fixation. High-energy injuries and soft tissue damage exacerbate infection risk. A personalized surgical approach, based on minimally invasive techniques and optimized surgical timing may mitigate these complications and significantly improve clinical outcomes in TPFs. Full article

(This article belongs to the Special Issue Computer-Assisted Diagnosis and Personalized Treatment of Fracture)

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10 pages, 5487 KB

Open AccessEditor’s ChoiceArticle

Testing the Reliability of ChatGPT Assistance for Surgical Choices in Challenging Glaucoma Cases

by Matteo Mario Carlà, Gloria Gambini, Federico Giannuzzi, Francesco Boselli, Laura De Luca and Stanislao Rizzo

J. Pers. Med. 2025, 15(3), 97; https://doi.org/10.3390/jpm15030097 - 28 Feb 2025

Cited by 7 | Viewed by 1430

Abstract

Background: This study’s aim is to assess ChatGPT’s capability to analyze detailed case descriptions in glaucomatous patients and suggest the best possible surgical treatment. Methods: We conducted a retrospective analysis of 60 medical records of surgical glaucoma cases, divided into “ordinary” cases ( [...] Read more.

Background: This study’s aim is to assess ChatGPT’s capability to analyze detailed case descriptions in glaucomatous patients and suggest the best possible surgical treatment. Methods: We conducted a retrospective analysis of 60 medical records of surgical glaucoma cases, divided into “ordinary” cases (n = 40) and “challenging” cases (n = 20). We entered every case description into ChatGPT-3.5’s interface and inquired “What kind of surgery would you perform?”. The frequency of accurate surgical choices made by ChatGPT, compared to those reported in patients’ files, was reported. Furthermore, we assessed the level of agreement with three senior glaucoma surgeons, asked to analyze the same 60 cases and outline their surgical choices. Results: Overall, ChatGPT surgical choices were consistent with those reported in patients’ files in 47/60 cases (78%). When comparing ChatGPT choices with the three glaucoma specialists, levels of agreement were 75%, 70%, and 83%, respectively. In ordinary cases, we did not report any significant differences when comparing ChatGPT answers with those of the three glaucoma specialists, when both of them were matched with patients’ files (p > 0.05 for all). ChatGPT’s performances were lower in “challenging” cases: when compared to patients’ files, the accuracy was 13/20 (65%); when compared to glaucoma specialists, the level of agreement was 50%, 40%, and 70%, respectively. Conclusion: In ordinary conditions, ChatGPT was able to propose coherent personalized treatment plans, and its performance was comparable to that of skilled glaucoma specialists but showed its limitations in the evaluation of more complex cases. Full article

(This article belongs to the Special Issue Advances in Personalized Diagnosis and Treatment of Ophthalmic Diseases)

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13 pages, 2416 KB

Open AccessEditor’s ChoiceReview

Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome

by Dimitra Mougiou, Georgia Gioula, Lemonia Skoura, Cleo Anastassopoulou and Melania Kachrimanidou

J. Pers. Med. 2025, 15(3), 94; https://doi.org/10.3390/jpm15030094 - 28 Feb 2025

Cited by 10 | Viewed by 5420

Abstract

Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and [...] Read more.

Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection’s symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI. Full article

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

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23 pages, 1360 KB

Open AccessEditor’s ChoiceSystematic Review

Executive Functions Training Improves Language Abilities in Aphasia Rehabilitation: A Systematic Review

by Laura Culicetto, Desirèe Latella, Viviana Lo Buono, Fabio Orecchio, Anna Maria Murdaca, Angelo Quartarone and Silvia Marino

J. Pers. Med. 2025, 15(3), 92; https://doi.org/10.3390/jpm15030092 - 27 Feb 2025

Cited by 2 | Viewed by 7038

Abstract

Background/Objectives: In recent years, the popularity of non-verbal cognitive training for aphasia has increased. Building on evidence that language abilities engage brain areas involved in executive functions (EFs) processing, this review aims to analyze the utility of EFs training alone or combined [...] Read more.

Background/Objectives: In recent years, the popularity of non-verbal cognitive training for aphasia has increased. Building on evidence that language abilities engage brain areas involved in executive functions (EFs) processing, this review aims to analyze the utility of EFs training alone or combined with traditional rehabilitation approaches to improve language abilities in aphasia. Methods: Systematic searches were performed in four databases evaluating studies focusing on the effects of EFs training in language rehabilitation, yielding 185 studies. After reading the full text of the selected studies and applying predefined inclusion criteria, nine studies were included based on pertinence and relevance to the topic. This systematic review has been registered in the Prospective Register of Systematic Reviews (PROSPERO 2024) with the number CRD42024519087. Results: The results of the analyzed studies indicate that various EFs training methods, such as computer-assisted executive control training, Cognitive Flexibility in Aphasia Therapy (CFAT), and the Dr. Neuronowski^® program, as well as the combination of transcranial direct current stimulation (tDCS) with EFs training, can lead to improvements in language abilities in people with aphasia. Additionally, EFs training often results in specific effects on treated functions like working memory (near transfer effects) and untreated ones such as spoken sentence comprehension (far transfer effects). Conclusions: Despite the heterogeneity of the treatments and the small simple size of the studies analyzed, preliminary results are promising. Future research should further explore the effectiveness and specific contribution of EFs training to improving language functions in aphasia. Full article

(This article belongs to the Special Issue The Applications of Non-Invasive Brain Stimulation in Neuropsychiatric Research and Treatment)

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13 pages, 2007 KB

Open AccessEditor’s ChoiceArticle

Comparison of Outcomes Between Functionally and Mechanically Aligned Total Knee Arthroplasty: Analysis of Parallelism to the Ground and Weight-Bearing Position of the Knee Using Hip-to-Calcaneus Radiographs

by Hongyeol Yang, Chanjin Park, Jaehyeok Cheon, Jaeyeon Hwang and Jongkeun Seon

J. Pers. Med. 2025, 15(3), 91; https://doi.org/10.3390/jpm15030091 - 27 Feb 2025

Cited by 5 | Viewed by 2136

Abstract

Background: The objective of this study was to compare the outcomes between patients undergoing mechanically aligned conventional total knee arthroplasty (MA-CTKA) and functionally aligned robotic-arm-assisted TKA (FA-RTKA). Methods: We reviewed a prospectively collected database of consecutive patients who underwent primary total knee arthroplasty [...] Read more.

Background: The objective of this study was to compare the outcomes between patients undergoing mechanically aligned conventional total knee arthroplasty (MA-CTKA) and functionally aligned robotic-arm-assisted TKA (FA-RTKA). Methods: We reviewed a prospectively collected database of consecutive patients who underwent primary total knee arthroplasty (TKA) for knee osteoarthritis between June 2022 and May 2023. Patients were divided into two groups—MA-CTKA (n = 50) and FA-RTKA (n = 50)—based on the introduction of a robotic-arm-assisted system during the study period. The hip–knee–ankle (HKA) angle, joint line orientation angle (JLOA) relative to the floor, and weight-bearing line (WBL) ratio were evaluated using full-length standing hip-to-calcaneus radiographs to compare the conventional mechanical axis (MA) and the ground mechanical axis (GA) passing through the knee joint between the groups. Clinical outcomes were also compared between the two groups. Results: There were no significant differences in the postoperative HKA angle between the groups, due to discrepancies in the targeted alignment strategies (FA-RTKA: 2.0° vs. MA-CTKA: 0.5°; p = 0.001). The postoperative JLOA in the FA-RTKA group was more parallel to the floor, whereas the MA-CTKA group showed a downward angulation toward the lateral side (0.6° vs. −2.7°; p < 0.001). In the FA-RTKA group, the GA passed through a neutral position when accounting for the calcaneus, while the MA-CTKA group showed a more lateral GA position (48.8% vs. 53.8%; p = 0.001). No significant differences in clinical outcomes were shown between the FA-RTKA and MA-CTKA groups, with the FA-RTKA group demonstrating higher Forgotten Joint Scores and a greater range of motion (all p < 0.05). Conclusions: Functionally aligned TKA demonstrated improved joint line parallelism to the floor and more neutral weight-bearing alignment in the GA compared to mechanically aligned TKA. These findings indicate a more balanced load distribution across the knee, which may contribute to the superior clinical outcomes observed in the functionally aligned group. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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18 pages, 441 KB

Open AccessEditor’s ChoiceReview

A Personalized, Risk-Based Approach to Active Surveillance for Prostate Cancer with Takeaways from Broader Oncology Practices: A Mixed Methods Review

by Jeroen J. Lodder, Sebastiaan Remmers, Roderick C. N. van den Bergh, Arnoud W. Postema, Pim J. van Leeuwen and Monique J. Roobol

J. Pers. Med. 2025, 15(3), 84; https://doi.org/10.3390/jpm15030084 - 25 Feb 2025

Cited by 4 | Viewed by 3870

Abstract

Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a [...] Read more.

Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a systematic review and a narrative review. The systematic review was conducted according to the Preferred Reporting Items for Systematic rviews and Meta-Analyses (PRISMA) guidelines, with searches performed in the Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Only studies evaluating personalized, risk-based AS programs for PCa were included. The narrative review focused on AS approaches in other solid tumors (thyroid, breast, kidney, and bladder cancer) to contextualize the findings and highlight lessons learned. Results: After screening 3137 articles, 9 were suitable for inclusion, describing the following four unique risk-based AS tools: PRIAS, Johns Hopkins, Canary PASS, and STRATCANS. These models were developed using data from men with low-risk (Grade Group 1) disease, with little to no magnetic resonance imaging (MRI) data. They used patient information such as (repeated) prostate-specific antigen (PSA) measurements and biopsy results to predict the risk of upgrading at the next biopsy or at radical prostatectomy, or to assign a patient to a pre-defined risk category with a corresponding pre-defined follow-up (FU) regimen. Performance was moderate across models, with the area under the curve/concordance index values ranging from 0.58 to 0.85 and calibration was generally good. The PRIAS, Canary PASS, and STRATCANS models demonstrated the benefits of less burdensome biopsies, clinic visits, and MRIs during FU when used, compared to current one-size-fits-all practices. Although little is known about risk-based AS in thyroid, breast, kidney, and bladder cancer, learning from their current practices could further refine patient selection, streamline monitoring protocols, and address adoption barriers, improving AS’s overall effectiveness in PCa management. Conclusions: Personalized, risk-based AS models allow for a reduction in the FU burden for men at low risk of progression while maintaining sensitive FU visits for those at higher risk. The comparatively limited evidence and practice of risk-based AS in other cancer types highlight the advanced state of AS in PCa. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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17 pages, 4178 KB

Open AccessEditor’s ChoiceArticle

Towards Trustworthy AI in Healthcare: Epistemic Uncertainty Estimation for Clinical Decision Support

by Adrian Lindenmeyer, Malte Blattmann, Stefan Franke, Thomas Neumuth and Daniel Schneider

J. Pers. Med. 2025, 15(2), 58; https://doi.org/10.3390/jpm15020058 - 31 Jan 2025

Cited by 9 | Viewed by 3814

Abstract

Introduction: Widespread adoption of AI for medical decision-making is still hindered due to ethical and safety-related concerns. For AI-based decision support systems in healthcare settings, it is paramount to be reliable and trustworthy. Common deep learning approaches, however, have the tendency towards overconfidence [...] Read more.

Introduction: Widespread adoption of AI for medical decision-making is still hindered due to ethical and safety-related concerns. For AI-based decision support systems in healthcare settings, it is paramount to be reliable and trustworthy. Common deep learning approaches, however, have the tendency towards overconfidence when faced with unfamiliar or changing conditions. Inappropriate extrapolation beyond well-supported scenarios may have dire consequences highlighting the importance of the reliable estimation of local knowledge uncertainty and its communication to the end user. Materials and Methods: While neural network ensembles (ENNs) have been heralded as a potential solution to these issues for many years, deep learning methods, specifically modeling the amount of knowledge, promise more principled and reliable behavior. This study compares their reliability in clinical applications. We centered our analysis on experiments with low-dimensional toy datasets and the exemplary case study of mortality prediction for intensive care unit hospitalizations using Electronic Health Records (EHRs) from the MIMIC3 study. For predictions on the EHR time series, Encoder-Only Transformer models were employed. Knowledge uncertainty estimation is achieved with both ensemble and Spectral Normalized Neural Gaussian Process (SNGP) variants of the common Transformer model. We designed two datasets to test their reliability in detecting token level and more subtle discrepancies both for toy datasets and an EHR dataset. Results: While both SNGP and ENN model variants achieve similar prediction performance (AUROC:

\approx 0.85

, AUPRC:

\approx 0.52

for in-hospital mortality prediction from a selected MIMIC3 benchmark), the former demonstrates improved capabilities to quantify knowledge uncertainty for individual samples/patients. Discussion/Conclusions: Methods including a knowledge model, such as SNGP, offer superior uncertainty estimation compared to traditional stochastic deep learning, leading to more trustworthy and safe clinical decision support. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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23 pages, 1309 KB

Open AccessEditor’s ChoiceSystematic Review

Mineralocorticoid Receptor Antagonists and Cognitive Outcomes in Cardiovascular Disease and Beyond: A Systematic Review

by Paola Pastena, Gabriele Campagnoli, Ali Reza Rahmani and Andreas P. Kalogeropoulos

J. Pers. Med. 2025, 15(2), 57; https://doi.org/10.3390/jpm15020057 - 30 Jan 2025

Cited by 5 | Viewed by 5229

Abstract

Background/Objectives: Cognitive impairment is a debilitating comorbidity affecting diverse patient populations, yet the cognitive effects of therapies like mineralocorticoid receptor antagonists (MRAs) remain underexplored. Preclinical evidence suggests that MRAs, particularly spironolactone, may reduce cognitive decline by modulating aldosterone-dependent pathways and targeting hippocampal receptors. [...] Read more.

Background/Objectives: Cognitive impairment is a debilitating comorbidity affecting diverse patient populations, yet the cognitive effects of therapies like mineralocorticoid receptor antagonists (MRAs) remain underexplored. Preclinical evidence suggests that MRAs, particularly spironolactone, may reduce cognitive decline by modulating aldosterone-dependent pathways and targeting hippocampal receptors. However, evidence in humans is fragmented, and no systematic review has consolidated these findings. This review evaluates the cognitive effects of MRAs, synthesizes current data, and identifies research gaps. Methods: A literature search using terms related to MRAs and cognitive outcomes was performed in PubMed and Web of Science from 1979 to 2023. A total of 143 articles were identified and 85 were screened after removing duplicates. Ultimately, 44 studies were included and were classified based on study design and population focus (preclinical, healthy controls, patients with psychiatric disorders, and cardiovascular patients). Results: Spironolactone demonstrated mixed effects on cognition. In healthy participants, it improved spatial memory under stress and prevented stress-related suppression of medial temporal activity, but impaired working memory and selective attention. In patients with psychiatric conditions, spironolactone reduced cognitive empathy deficits in major depressive disorder and improved working memory in bipolar I disorder. In cardiovascular patients, spironolactone improved cognitive scores and hippocampal memory but had no effect on non-hippocampal memory. Conclusions: Spironolactone exhibits potential cognitive benefits across diverse populations. However, its effects on cognition are mixed, highlighting the need for further research to understand its mechanisms and therapeutic potential, particularly in patients with heart failure and other related conditions. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 853 KB

Open AccessEditor’s ChoiceSystematic Review

Enhanced Lymph Node Detection in Colon Cancer Using Indocyanine Green Fluorescence: A Systematic Review of Studies from 2020 Onwards

by Roxana Loriana Negrut, Adrian Cote, Bogdan Feder, Florian Dorel Bodog and Adrian Marius Maghiar

J. Pers. Med. 2025, 15(2), 54; https://doi.org/10.3390/jpm15020054 - 29 Jan 2025

Cited by 5 | Viewed by 3030

Abstract

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for [...] Read more.

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for enhancing lymph node visualization during surgical intervention. The high rates of local recurrence in colon cancer patients require innovative methods to improve lymphatic mapping and lymph node dissection. This review evaluates the clinical utility and efficacy of ICG imaging in enhancing lymph node accuracy in colon cancer surgery. Materials and methods: A systematic search was conducted in October 2024 (last day of consulting the database was 16 November) across Web of Science, Scopus, and PubMed to identify studies published from 2020 onwards focusing on the use of indocyanine green in colon cancer surgeries. The search terms used were “indocyanine green”, “ICG”, “fluorescent imaging”, “near-infrared imaging”, “colon cancer”, “colorectal cancer”, “colon carcinoma”,” colon neoplasms”, “surgery”, “surgical procedure”, “surgical resection”, surgical precision”. The search followed PRISMA guidelines. The records underwent a two-phase independent screening process conducted by the authors, first based on the title and abstract, followed by full record evaluation. Articles were excluded following certain exclusion criteria: non-human studies; restricted access publications; other publication type than article (review, meta-analysis, questionnaire-based study, case report, etc.), studies focusing on other diseases or studies that focused on the surgical treatment of metastasis from colon cancer; foreign language (non-English); no data of interest for the current review; studies that focused on rectal cancer and that grouped rectal and colon cancer. Data extraction involved both quantitative and qualitative data, such as detection rates, sensitivity, specificity, and other surgical outcomes. Risk of bias was assessed using ROBINS-I, J Joanna Briggs Institute (JBI) Critical Appraisal Checklist, and the Newcastle–Ottawa Scale, depending on study type. The study was not preregistered in PROSPERO. However, to ensure methodological rigor and transparency, it was retrospectively registered in Open Science Framework (OSF). Results: From the 3300 records initially identified, 9 studies were included in this review. Detection rates varied from 55% to 100%, with the highest rate reported in robot-assisted surgeries. The studies showed an improved lymph node detection and lymphatic flow accuracy using ICG fluorescence. Discussion: ICG fluorescence demonstrated substantial benefits, improving staging accuracy and potentially reducing recurrence rates by guiding the lymphadenectomy. The variability observed in detection rates is largely attributed to differences in ICG administration, cancer stage, and surgical approaches. Conclusions: ICG-guided surgery for colon cancer represents a promising advancement, enhancing lymph node detection and staging accuracy. Large-scale randomized trials are essential to establish standardized protocols and validate the efficacy in improving surgical outcomes. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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22 pages, 297 KB

Open AccessEditor’s ChoiceReview

The Development and Application of Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma

by Laura Sun and Jason T. Romancik

J. Pers. Med. 2025, 15(2), 51; https://doi.org/10.3390/jpm15020051 - 28 Jan 2025

Cited by 10 | Viewed by 4965

Abstract

T-cell-engaging bispecific antibodies (BsAbs) are monoclonal antibodies that redirect the cytotoxic activity of T-cells to target malignant neoplasms. B-cell non-Hodgkin lymphoma (B-NHL) is a heterogenous group of aggressive and indolent malignancies with significant therapeutic challenges due to high relapse rates and limited options [...] Read more.

T-cell-engaging bispecific antibodies (BsAbs) are monoclonal antibodies that redirect the cytotoxic activity of T-cells to target malignant neoplasms. B-cell non-Hodgkin lymphoma (B-NHL) is a heterogenous group of aggressive and indolent malignancies with significant therapeutic challenges due to high relapse rates and limited options for relapsed/refractory disease. BsAbs function by simultaneously binding to CD3 on endogenous T-cells and a tumor-associated antigen, creating an immunologic synapse which results in the death of the target cell. The widespread T-cell activation that occurs with BsAb administration can result in cytokine release syndrome and neurological adverse events. Mosunetuzumab, epcoritamab, and glofitamab are CD20-targeting BsAbs that have demonstrated promising single-agent activity in both indolent and aggressive B-NHL. BsAbs are now being evaluated in combination with other anti-lymphoma agents and in earlier lines of treatment, and the results of ongoing clinical trials involving these agents have the potential to reshape the treatment landscape for B-NHL. In this review, we describe the structural features, clinical data, and toxicity profile associated with the BsAbs currently used to treat B-NHL and then discuss ongoing studies and future directions for this exciting new class of therapeutic agents. Full article

(This article belongs to the Special Issue Precision Medicine for Hematological Malignancies)

18 pages, 713 KB

Open AccessEditor’s ChoiceReview

Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy

by Taranatee Khan, Manojavan Nagarajan, Irene Kang, Chunjing Wu and Medhi Wangpaichitr

J. Pers. Med. 2025, 15(2), 50; https://doi.org/10.3390/jpm15020050 - 27 Jan 2025

Cited by 12 | Viewed by 5715

Abstract

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis to oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also [...] Read more.

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis to oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also contribute to immune evasion through mechanisms such as reactive oxygen species (ROS) generation and the upregulation of immune checkpoint molecules like PD-L1. This review explores the potential of targeting metabolic weaknesses in drug-resistant cancers to enhance therapeutic efficacy. Key metabolic pathways involved in resistance, including glycolysis, glutamine metabolism, and the kynurenine pathway, are discussed. The combination of metabolic inhibitors with immune checkpoint inhibitors (ICIs), particularly anti-PD-1/PD-L1 therapies, represents a promising approach to overcoming both metabolic and immune evasion mechanisms. Clinical trials combining metabolic and immune therapies have shown early promise, but further research is needed to optimize treatment combinations and identify biomarkers for patient selection. In conclusion, targeting cancer metabolism in combination with immune checkpoint blockade offers a novel approach to overcoming drug resistance, providing a potential pathway to improved outcomes in cancer therapy. Future directions include personalized treatments based on tumor metabolic profiles and expanding research to other tumor types. Full article

(This article belongs to the Special Issue Exploiting Metabolic Weaknesses: A Novel Approach to Overcome Drug Resistance in Cancer Therapy)

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24 pages, 1484 KB

Open AccessEditor’s ChoiceReview

Precision Medicine in Myeloid Neoplasia: Challenges and Opportunities

by Michael J. Hochman, Joshua P. Muniz and Nikolaos Papadantonakis

J. Pers. Med. 2025, 15(2), 49; https://doi.org/10.3390/jpm15020049 - 26 Jan 2025

Cited by 4 | Viewed by 3017

Abstract

High-risk myeloid neoplasms encompass a group of hematologic malignancies known to cause significant cytopenias, which are accompanied by the risk of end-organ damage. They tend to have an aggressive clinical course and limit life expectancy in the absence of effective treatments. The adoption [...] Read more.

High-risk myeloid neoplasms encompass a group of hematologic malignancies known to cause significant cytopenias, which are accompanied by the risk of end-organ damage. They tend to have an aggressive clinical course and limit life expectancy in the absence of effective treatments. The adoption of precision medicine approaches has been limited by substantive diversity in somatic mutations, limited fraction of patients with targetable genetic lesions, and the prolonged turnaround times of pertinent genetic tests. Efforts to incorporate targeted agents into first-line treatment, rapidly determine pre-treatment molecular or cytogenetic aberrations, and evaluate functional vulnerabilities ex vivo hold promise for advancing the use of precision medicine in these malignancies. Given the relative accessibility of malignant cells from blood and bone marrow, precision medicine strategies hold great potential to shape future standard-of-care approaches to patients with high-risk myeloid malignancies. This review aims to summarize the development of the targeted therapies currently available to treat these blood cancers, most notably acute myeloid leukemia, and also evaluate future opportunities and challenges related to the integration of personalized approaches. Full article

(This article belongs to the Special Issue Precision Medicine for Hematological Malignancies)

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17 pages, 1527 KB

Open AccessEditor’s ChoiceArticle

Impact of Whole-Body Cryotherapy on Pain, Sleep Quality, Functional Status, and Quality of Life in Multiple Sclerosis: A Comparative Study with Follow-Up

by Ewa Zielińska-Nowak, Anna Lipert, Łukasz Kikowski and Elżbieta Miller

J. Pers. Med. 2025, 15(2), 46; https://doi.org/10.3390/jpm15020046 - 26 Jan 2025

Cited by 5 | Viewed by 8383

Abstract

Background/Objectives: Whole-body cryotherapy (WBC) is widely recognized for its analgesic and anti-inflammatory effects. Despite growing interest in its therapeutic potential, the impact of WBC on functional performance, pain perception, sleep quality, and quality of life among individuals with multiple sclerosis (MS) remains underexplored. [...] Read more.

Background/Objectives: Whole-body cryotherapy (WBC) is widely recognized for its analgesic and anti-inflammatory effects. Despite growing interest in its therapeutic potential, the impact of WBC on functional performance, pain perception, sleep quality, and quality of life among individuals with multiple sclerosis (MS) remains underexplored. This study aimed to assess the effects of a 10-session WBC protocol on functional and psychological parameters in patients with MS and compare them with individuals without neurological disorders. Methods: A total of 73 participants divided into two groups, non-neurological individuals (non-MS, n = 43) and patients with MS (MS, n = 30), underwent 10 WBC sessions (−120 °C to −130 °C) over 2 weeks. Assessments included the Numerical Rating Scale (NRS), 30-Second Chair Stand Test (30CST), Timed Up and Go (TUG) test, and Pittsburgh Sleep Quality Index, with the WHOQOL-BREF conducted pre-treatment, post-treatment, and at a 10-day follow-up. Results: In the MS group, significant improvements were observed post-treatment in the NRS, 30CST, WHOQOL-1, and PSQI. However, only the CST and WHOQOL-3 maintained improvements during follow-up. In the non-MS group, statistically significant improvements were observed post-treatment across most parameters, except for the NRS and WHOQOL-3, with most effects diminishing by the follow-up. No deterioration in any assessed parameters was observed in either group. Conclusions: WBC demonstrates potential benefits for managing MS symptoms, particularly pain and sleep quality, with no observed deterioration in parameters and some effects emerging only during follow-ups, underscoring its safety and the need for further research on long-term outcomes. Full article

(This article belongs to the Special Issue Cold Perspectives: Advancements and Applications of Cryotherapy in Clinical Settings)

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14 pages, 1355 KB

Open AccessEditor’s ChoiceArticle

Dupilumab Effectiveness in Patients with Severe Allergic Asthma Non-Responsive to Omalizumab

by Diego Bagnasco, Benedetta Bondi, Luisa Brussino, Stefania Nicola, Paolo Cameli, Angelica Tiotiu, Giuseppe Guida, Chiara Gollinucci, Dina Visca, Antonio Spanevello, Laura Pini, Marco Caminati, Gianenrico Senna, Cristiano Caruso, Rikki Frank Canevari, Melania Bertolini, Sara Fedele, Marcello Mincarini, Giorgio Walter Canonica, Fulvio Braido and on behalf of the SANI group Show full author list Hide full author list

J. Pers. Med. 2025, 15(2), 43; https://doi.org/10.3390/jpm15020043 - 23 Jan 2025

Cited by 6 | Viewed by 4597

Abstract

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab [...] Read more.

Background/Objectives: Severe allergic asthma is usually treated with omalizumab; however, this drug may not be effective for every patient. By its action, dupilumab could be an alternative in these patients. The objective of this study was to evaluate the efficacy of dupilumab in patients with severe allergic asthma, non-responsive to omalizumab, according to the maintenance of their oral corticosteroid (OCS) dose, an exacerbation rate decrease, or poor control of the disease, despite optimized treatment. Methods: A retrospective analysis of data from severe asthma clinics was performed, observing the efficacy of the switch to dupilumab in patients who experienced a failed treatment with omalizumab. Results: Forty-two patients were included. Dupilumab proved to be effective in patients who experienced a failed omalizumab treatment, with a significant reduction in the exacerbation number and OCS use. Furthermore, remission of the disease, according to the Severe Asthma Network of Italy (SANI) criteria, was achieved in 35 patients, with complete remission in 19 (45%) and partial remission in 16 (38%). The analysis of the predictors of the success of dupilumab therapy in achieving clinical remission, through univariate analysis of the data at baseline, showed that complete remission was more easily reached in patients with concomitant aspirin (ASA) intolerance or in those with nasal polyposis. Conclusions: Dupilumab is an effective drug for the treatment of patients with severe asthma with an allergic component, with better benefits in patients with an ASA intolerance or nasal polyposis. Full article

(This article belongs to the Section Molecular Targeted Therapy)

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15 pages, 5044 KB

Open AccessEditor’s ChoiceReview

Navigating the Uncertainty of B3 Breast Lesions: Diagnostic Challenges and Evolving Management Strategies

by Sabatino D’Archi, Beatrice Carnassale, Alejandro Martin Sanchez, Cristina Accetta, Paolo Belli, Flavia De Lauretis, Enrico Di Guglielmo, Alba Di Leone, Antonio Franco, Stefano Magno, Francesca Moschella, Maria Natale, Lorenzo Scardina, Marta Silenzi, Riccardo Masetti and Gianluca Franceschini

J. Pers. Med. 2025, 15(1), 36; https://doi.org/10.3390/jpm15010036 - 18 Jan 2025

Cited by 3 | Viewed by 5663

Abstract

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia [...] Read more.

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia (FEA), radial scars (RSs), lobular neoplasia (LN), and phyllodes tumors (PTs), occupy a “grey zone” between benign and malignant pathologies, making their management complex and often controversial. This article explores the diagnostic difficulties associated with B3 lesions, focusing on the limitations of current imaging techniques, including mammography, ultrasound, and magnetic resonance imaging (MRI), as well as the challenges in histopathological interpretation. Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are widely used for diagnosis, but both methods have inherent limitations, including sampling errors and the inability to determine malignancy in some cases definitively. The therapeutic approach to B3 lesions is nuanced, with treatment decisions strongly influenced by factors such as the lesion size, radiological findings, histopathological characteristics, and patient factors. While some lesions can be safely monitored with watchful waiting, others may require vacuum-assisted excision (VAE) or surgical excision to rule out malignancy. The decision-making process is further complicated by the discordance between the BI-RADS score and biopsy results, as well as the presence of additional risk factors, such as microcalcifications. This review provides an in-depth analysis of the current diagnostic challenges and treatment strategies for B3 lesions, emphasizing the importance of a multidisciplinary approach to management. By synthesizing the most recent research, this article aims to provide clinicians with a clearer understanding of the complexities involved in diagnosing and treating B3 breast lesions while highlighting areas for future research, such as artificial intelligence and genomics, to improve the diagnostic accuracy and patient outcomes. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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66 pages, 1373 KB

Open AccessEditor’s ChoiceReview

Concussion and the Autonomic, Immune, and Endocrine Systems: An Introduction to the Field and a Treatment Framework for Persisting Symptoms

by Jon L. Pertab, Tricia L. Merkley, Holly Winiarski, Kelly M. J. Cramond and Alex J. Cramond

J. Pers. Med. 2025, 15(1), 33; https://doi.org/10.3390/jpm15010033 - 17 Jan 2025

Cited by 6 | Viewed by 11787

Abstract

A significant proportion of patients who sustain a concussion/mild traumatic brain injury endorse persisting, lingering symptoms. The symptoms associated with concussion are nonspecific, and many other medical conditions present with similar symptoms. Medical conditions that overlap symptomatically with concussion include anxiety, depression, insomnia, [...] Read more.

A significant proportion of patients who sustain a concussion/mild traumatic brain injury endorse persisting, lingering symptoms. The symptoms associated with concussion are nonspecific, and many other medical conditions present with similar symptoms. Medical conditions that overlap symptomatically with concussion include anxiety, depression, insomnia, chronic pain, chronic fatigue, fibromyalgia, and cervical strain injuries. One of the factors that may account for these similarities is that these conditions all present with disturbances in the optimal functioning of the autonomic nervous system and its intricate interactions with the endocrine system and immune system—the three primary regulatory systems in the body. When clinicians are working with patients presenting with persisting symptoms after concussion, evidence-based treatment options drawn from the literature are limited. We present a framework for the assessment and treatment of persisting symptoms following concussion based on the available evidence (treatment trials), neuroanatomical principles (research into the physiology of concussion), and clinical judgment. We review the research supporting the premise that behavioral interventions designed to stabilize and optimize regulatory systems in the body following injury have the potential to reduce symptoms and improve functioning in patients. Foundational concussion rehabilitation strategies in the areas of sleep stabilization, fatigue management, physical exercise, nutrition, relaxation protocols, and behavioral activation are outlined along with practical strategies for implementing intervention modules with patients. Full article

(This article belongs to the Special Issue Clinical Advances in Traumatic Brain Injury and Concussion)

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13 pages, 1208 KB

Open AccessEditor’s ChoiceArticle

Robotic Versus Sternotomy, Thoracotomy and Video-Thoracoscopy Approaches for Thymoma Resection: A Comparative Analysis of Short-Term Results

by Beatrice Trabalza Marinucci, Matteo Tiracorrendo, Camilla Vanni, Fabiana Messa, Giorgia Piccioni, Alessandra Siciliani, Silvia Fiorelli, Mohsen Ibrahim, Erino A. Rendina and Antonio D’Andrilli

J. Pers. Med. 2025, 15(1), 34; https://doi.org/10.3390/jpm15010034 - 17 Jan 2025

Cited by 7 | Viewed by 2628

Abstract

OBJECTIVE. The optimal surgical approach for thymoma resection is still an object of debate. The increasing experience in robotic-assisted thoracic surgery (RATS) has led to the progressive affirmation of this technique as a valid alternative to Sternotomy, Thoracotomy and Video-Assisted Thoracic Surgery [...] Read more.

OBJECTIVE. The optimal surgical approach for thymoma resection is still an object of debate. The increasing experience in robotic-assisted thoracic surgery (RATS) has led to the progressive affirmation of this technique as a valid alternative to Sternotomy, Thoracotomy and Video-Assisted Thoracic Surgery (VATS) in this setting. The present study aims to compare the post-operative and short-term results of RATS Thymectomy for thymoma with those of other main surgical approaches (sternotomy, thoracotomy and VATS) from a high-volume single center. METHODS. Between May 2021 and September 2023, 40 consecutive patients underwent RATS Thymectomy for stage I to limited-stage III thymoma in our center. Three homogenous groups of patients who received thymoma resection through main alternative approaches (sternotomy, thoracotomy, VATS) over the last 5 years, were identified in order to perform a comparative analysis. Data including surgery duration, associated resections, conversion rate, overall morbidity, tumor size, radicality of resection, post-operative pain, length of hospital stay and cosmetic results were retrospectively collected and compared between the RATS and each control group. RESULTS. Mean tumor size was higher in the sternotomy group, but not significantly. The mean operative time of RATS interventions was significantly lower than that of sternotomy and VATS. It was significantly shorter compared to thoracotomy if excluding docking-undocking time. A higher rate of associated adjacent structures resection was reported in the sternotomy group (p = 0.005). Conversion rate was significantly higher in the VATS group (p = 0.026) compared to RATS. Post-operative pain at 24 and 48 h was significantly lower in the RATS group compared to the others. Improved cosmetics results were reported after RATS compared to sternotomy (p = 0.0001) and thoracotomy (p = 0.001) groups, with a trend towards better results compared to VATS (p = 0.05). Length of hospital stay was shorter in the RATS group with a significant difference vs. the sternotomy group (p < 0.001). CONCLUSIONS. These results from a single center confirm the safety and efficacy of RATS for the treatment of limited stage thymoma. An advantage in terms of operative outcomes, post-operative pain, cosmetic results and hospital stay was observed if compared to the alternative approaches. The short-term oncologic outcome was excellent based on the high complete resection rate of the tumor. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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