Journal of Personalized Medicine

22 pages, 900 KB

Open AccessArticle

Personalized Profiles of Autonomic Regulation in Elite Athletes: Analysis of Genetic and Cardiorespiratory Determinants Using Decision Tree Modeling

by Irina Bacheva, Lyazat Ibrayeva, Dina Rybalkina, Irina Kadyrova and Diana Zhumagaliyeva

J. Pers. Med. 2026, 16(4), 230; https://doi.org/10.3390/jpm16040230 - 21 Apr 2026

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Abstract

Backgrounds: The aim of this pilot study was to evaluate the hierarchical contribution of individual genetic polymorphisms to the variability of autonomic regulation parameters and respiratory function in athletes of different sport specializations using Classification and Regression Tree (CRT) analysis. Methods: [...] Read more.

Backgrounds: The aim of this pilot study was to evaluate the hierarchical contribution of individual genetic polymorphisms to the variability of autonomic regulation parameters and respiratory function in athletes of different sport specializations using Classification and Regression Tree (CRT) analysis. Methods: The study included athletes divided into two groups: hockey players (n = 48) and martial artists (n = 43). Heart rate variability (LF, HF) parameters and spirometric indices (FEV₁) were assessed. Genetic analysis included 8 single nucleotide polymorphisms (SNPs): IL6 rs1800795, VDR rs731236, KCNJ11 rs5219, ADRB2 rs1042713, ADRB2 rs1042714, TRHR rs16892496, MSTN rs1805086, UCP3 rs1800849. Results: In martial artists, the main predictors were genes responsible for adrenoreceptor sensitivity (ADRB2) and neuroimmune interactions (IL6). In hockey players, the most significant predictors were genes involved in muscle growth (MSTN), energy metabolism (UCP3), and neuroendocrine regulation (TRHR). These findings indicate that similar resting HRV parameters in athletes from different sports may be associated with different genetic polymorphisms, reflecting sport-specific physiological adaptations to training loads. Conclusions: The results highlight the sport-specific nature of genetic determinants of autonomic regulation. In martial artists, genes related to the immuno-adrenergic axis (IL6, ADRB2) appear to play a dominant role, whereas in hockey players neuroendocrine, muscle-metabolic, and mitochondrial factors (TRHR, MSTN, UCP3) demonstrate greater influence. The observed interactions between genotypes and FEV₁ emphasize the importance of transitioning from generalized approaches toward personalized monitoring strategies in sports science. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment in Sports Medicine)

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17 pages, 1219 KB

Open AccessReview

Personalized Diabetes Therapy Part 2—Individual Diabetes Treatment (Standard of Care Plus, SOC+)

by Julia Jantz and Andreas Pfützner

J. Pers. Med. 2026, 16(4), 229; https://doi.org/10.3390/jpm16040229 - 20 Apr 2026

Viewed by 283

Abstract

Conventional diabetes therapy primarily targets HbA1c using a standardized, stepwise approach, often neglecting individual clinical and diagnostic phenotypes. In this second part of our discussion, we present an alternative strategy. After phenotyping the patient, we initiate a targeted pharmacological combination therapy tailored to [...] Read more.

Conventional diabetes therapy primarily targets HbA1c using a standardized, stepwise approach, often neglecting individual clinical and diagnostic phenotypes. In this second part of our discussion, we present an alternative strategy. After phenotyping the patient, we initiate a targeted pharmacological combination therapy tailored to the individual’s underlying pathophysiology, alongside lifestyle modifications. Sulfonylureas are completely avoided in this approach. Instead, medications are selected based on their alignment with the patient’s phenotype and absence of contraindications. Early insulin therapy, for example, is particularly effective in patients with β-cell-dysfunction-driven diabetes, whereas GLP-1-supported weight reduction and glitazone therapy are more suitable for insulin-resistance-driven diabetes. For monitoring and determining when temporary therapy intensification may be necessary, we rely on a combination of functional biomarkers (intact proinsulin, adiponectin, hsCRP, and leptin) and conventional clinical parameters (HbA1c, BMI, lipids, blood pressure). Using this personalized strategy, we have consistently achieved long-term glycemic control—often maintaining normal HbA1c levels for up to 15 years in our patients so far. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives, 2nd Edition)

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12 pages, 684 KB

Open AccessReview

Machine Perfusion Across Marginal Liver Grafts: Benefits and Challenges

by Leandro Sierra, Maria Ortega Abad, Maria Saavedra-Martinez, Kanisha Bahierathan, Zainab Ifthikar, Ana Eliza Velez, Nikki Duong, Luis Antonio Diaz and Juan Pablo Arab

J. Pers. Med. 2026, 16(4), 228; https://doi.org/10.3390/jpm16040228 - 20 Apr 2026

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Abstract

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular [...] Read more.

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks. Full article

(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases—2nd Edition)

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1 pages, 122 KB

Open AccessExpression of Concern

Expression of Concern: Dellino et al. Effects of Oral Supplementation with Myo-Inositol and D-Chiro-Inositol on Ovarian Functions in Female Long-Term Survivors of Lymphoma: Results from a Prospective Case–Control Analysis. J. Pers. Med. 2022, 12, 1536

by Journal of Personalized Medicine Editorial Office

J. Pers. Med. 2026, 16(4), 227; https://doi.org/10.3390/jpm16040227 - 20 Apr 2026

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Abstract

With this notice, the Journal of Personalized Medicine Editorial Office and Editorial Board wishes to alert readers to concerns related to this article [...] Full article

12 pages, 1883 KB

Open AccessReview

Personalized Diabetes Therapy Part 1—Functional Phenotyping as a Conceptual Basis for Individualized Treatment

by Andreas Pfützner and Julia Jantz

J. Pers. Med. 2026, 16(4), 226; https://doi.org/10.3390/jpm16040226 - 18 Apr 2026

Viewed by 278

Abstract

The diagnosis of type 2 diabetes using classical clinical and laboratory biomarkers (HbA1c, glucose, lipids, BMI, and blood pressure) is a classification by symptoms and does not provide insight into the underlying pathophysiological disorders (insulin resistance, β-cell dysfunction, visceral adipose tissue hormonal secretion, [...] Read more.

The diagnosis of type 2 diabetes using classical clinical and laboratory biomarkers (HbA1c, glucose, lipids, BMI, and blood pressure) is a classification by symptoms and does not provide insight into the underlying pathophysiological disorders (insulin resistance, β-cell dysfunction, visceral adipose tissue hormonal secretion, and chronic systemic inflammation). A better understanding of these disorders may help in the selection of appropriate and potentially more successful personalized therapeutic interventions. Based on extensive clinical trial experience, a method for individual phenotyping and consecutive personalized diabetes therapy has been developed in our practice, which we have been using for more than 15 years and would like to share for discussion and debate. In this Part 1, the pathophysiological background and diagnostic approach to phenotyping is described. A consecutive Part 2 will present the translation of the phenotyping result into a personalized diabetes therapy, and another consecutive Part 3 will provide more comprehensive real-world patient observations when practicing this concept. This article is intended as a discussion/concept paper and does not present unpublished patient-level outcome data or formal effectiveness analyses. Prospective validation studies are needed to evaluate the clinical utility of this phenotype-based framework. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives, 2nd Edition)

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11 pages, 480 KB

Open AccessArticle

Body Mass Index Lacks Predictive Influence on Perioperative, Short-Term Follow-Up, and Patient-Reported Outcomes from Holmium Laser Enucleation of the Prostate

by Jack T. Peterson, Jenny N. Guo, Amir Patel, Nabila Khondakar, Perry Xu and Amy E. Krambeck

J. Pers. Med. 2026, 16(4), 225; https://doi.org/10.3390/jpm16040225 - 18 Apr 2026

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Abstract

Background/Objectives: Obesity has been associated with the development and severity of benign prostatic hyperplasia (BPH), yet its influence on outcomes following definitive surgical management, like holmium laser enucleation of the prostate (HoLEP), remains unclear. Furthermore, gradation of body mass index (BMI) severity [...] Read more.

Background/Objectives: Obesity has been associated with the development and severity of benign prostatic hyperplasia (BPH), yet its influence on outcomes following definitive surgical management, like holmium laser enucleation of the prostate (HoLEP), remains unclear. Furthermore, gradation of body mass index (BMI) severity has yet to discern personalized outcome stratification. We evaluated BMI’s influence on perioperative, immediate, short-term follow-up, and patient-reported outcomes for HoLEP patients. Methods: We performed a retrospective review of a prospectively maintained database of patients undergoing HoLEP for BPH at a single institution between January 2021 and August 2025. Outcomes included operative characteristics, post-operative complications, and validated symptom score changes. Analyses treated BMI as both a continuous and categorical variable. Multivariable linear and logistic regression models adjusted for common colinear confounders. Results: Among 1445 patients, BMI was not associated with most immediate, three-month, or patient-reported outcomes. Surgical complications were low across all BMI categories, and post-operative reported outcomes indicating high success rate for HoLEP. Higher BMI correlated with a modest increase in enucleation time (β = 0.197; p = 0.0132), increased odds of dysuria (OR = 1.084; p < 0.001), and change in American Urological Association Symptom Score (β = 0.211; p = 0.0334). All other operative metrics, complication rates, continence outcomes, and symptom scores (17 other total) were independent of BMI. Conclusions: After adjustment for relevant confounders, BMI does not meaningfully predict surgical safety, functional recovery, or patient-reported benefit following HoLEP. BMI alone should not influence candidacy or risk stratification for HoLEP in patients with BPH, instead favoring personalized, risk-stratified approaches. Full article

(This article belongs to the Special Issue Personalized Urologic Surgery: Innovation and Strategies)

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17 pages, 903 KB

Open AccessArticle

Treatment of Severe Uncontrolled Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) with Mepolizumab or Dupilumab: A Preliminary Single-Center Study for Evaluation of Safety and Efficacy

by Melania Bertolini, Lorenzo Fucci, Luca Guastini, Carlo Conti, Gregorio Santori and Frank Rikki Mauritz Canevari

J. Pers. Med. 2026, 16(4), 224; https://doi.org/10.3390/jpm16040224 - 17 Apr 2026

Viewed by 905

Abstract

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the [...] Read more.

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

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

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12 pages, 226 KB

Open AccessArticle

Feasibility of a Short-Stay Lumboperitoneal Shunt Pathway Based on Perioperative Optimization and Individualized Discharge Decision-Making: A Pilot Before–After Study

by Tatsuya Tanaka, Eiichi Suehiro, Anh Tran Hue, Ryosuke Doi, Shunsuke Hatakenaka, Junpei Kato, Tomihiro Wakamiya, Kimihiro Nakahara, Takashi Agari, Masahiro Indo, Takashi Sugawara, Hiroshi Itokawa, Kazuaki Shimoji, Keisuke Onoda and Akira Matsuno

J. Pers. Med. 2026, 16(4), 223; https://doi.org/10.3390/jpm16040223 - 17 Apr 2026

Viewed by 255

Abstract

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding [...] Read more.

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding early complications, cerebrospinal fluid overdrainage, and discharge readiness in older adults. This study evaluated the feasibility and short-term safety of a perioperative optimization pathway for planned short-stay hospitalization after LP shunt surgery. Methods: This single-center retrospective before-and-after cohort study included 15 consecutive patients who underwent elective LP shunt surgery. Six patients were managed using a conventional hospitalization pathway, whereas nine patients were treated under a short-stay pathway targeting discharge after one postoperative night. Key perioperative modifications included a uniform higher initial programmable valve pressure (level 7), structured discharge education, scheduled postoperative analgesia, waterproof wound sealing permitting early showering, and early outpatient follow-up with head computed tomography for staged valve pressure adjustment. The primary outcome was 30-day safety, defined as readmission, reoperation, or major postoperative complications. Results: Baseline characteristics were generally comparable between groups, although the short-stay group was slightly older and had more frequent antithrombotic therapy. Mean hospital length of stay was shorter in the short-stay group than in the conventional group (3.7 ± 2.0 vs. 9.7 ± 0.8 days; median, 3 vs. 9.5 days). Orthostatic headache requiring valve adjustment occurred in three conventional cases but in none of the short-stay patients. No patients in the short-stay group required readmission or reoperation within 30 days. Conclusions: In this pilot before-and-after study, a short-stay LP shunt pathway incorporating perioperative optimization and individualized discharge decision-making was feasible and was not associated with an apparent increase in early adverse events. These findings should be interpreted as exploratory and may support further evaluation of short-stay management strategies for selected patients undergoing LP shunt surgery in Japan. Full article

(This article belongs to the Special Issue Personalized Approaches in Neurosurgery)

10 pages, 353 KB

Open AccessArticle

Clinical Application of Artificial Intelligence in Anesthesiology: A Multicenter Retrospective Comparison Between Human Anesthetic Decisions and Algorithmic Recommendations in Non-Cardiac Surgery

by Gilberto Duarte-Medrano, Natalia Nuño-Lámbarri, Octavio Gonzalez-Chon, Rebeca Garazi Elguezabal Rodelo, Carmelo Calvagna, Daniele Paternò, Luigi La Via and Massimiliano Sorbello

J. Pers. Med. 2026, 16(4), 222; https://doi.org/10.3390/jpm16040222 - 17 Apr 2026

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Abstract

Background: Artificial intelligence (AI) is progressively entering perioperative medicine; however, its role in preoperative anesthetic decision-making remains insufficiently characterized. We evaluated the concordance between anesthesiologist-selected anesthetic techniques and algorithm-generated recommendations in a cohort of adult patients undergoing non-cardiac surgery. Methods: This [...] Read more.

Background: Artificial intelligence (AI) is progressively entering perioperative medicine; however, its role in preoperative anesthetic decision-making remains insufficiently characterized. We evaluated the concordance between anesthesiologist-selected anesthetic techniques and algorithm-generated recommendations in a cohort of adult patients undergoing non-cardiac surgery. Methods: This retrospective observational study included adult patients (≥18 years) undergoing elective non-cardiac surgery between January 2024 and January 2025 at two international centers (Mexico and Italy). Clinical, demographic, and surgical variables were extracted from electronic medical records. For each case, a structured anonymized vignette was submitted to ChatGPT (version 5.0, medical configuration) to obtain an independent recommendation regarding anesthetic technique. Concordance between AI-generated and clinician-selected techniques was assessed using agreement analysis and stratified by country and surgical specialty. Results: A total of 1965 patients were analyzed. Overall concordance between ChatGPT recommendations and anesthesiologist-selected techniques was 84.6%. Agreement remained stable across centers (Mexico 84.3%; Italy 88.7%). Disagreement rates varied by surgical specialty, with the highest values observed in vascular and proctologic surgery (28.6%), followed by urology (21.1%) and thoracic surgery (18.8%). Orthopedic procedures—particularly shoulder arthroscopy—accounted for a relevant proportion of divergences, where AI frequently favored regional techniques over general anesthesia. No specialty demonstrated discordance exceeding 30%. Conclusions: AI-generated anesthetic recommendations demonstrated substantial concordance with expert clinical decision-making across heterogeneous surgical settings. These findings support the potential integration of AI within a hybrid decision-making framework, complementing—rather than replacing—anesthesiologist expertise in contemporary perioperative care. Full article

(This article belongs to the Special Issue Artificial Intelligence for Personalized Medicine: Bridging Innovative Technologies and Patient-Centric Care)

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6 pages, 175 KB

Open AccessEditorial

Bridging the Gap Between Pharmacogenomic Discovery and Clinical Implementation: Insights from Selected Studies on Inter-Individual Variability in Drug Response

by Su-Jun Lee

J. Pers. Med. 2026, 16(4), 221; https://doi.org/10.3390/jpm16040221 - 17 Apr 2026

Viewed by 389

Abstract

Inter-individual variability in drug efficacy and toxicity remains a major challenge in modern healthcare, particularly as aging populations are increasingly exposed to polypharmacy and complex treatment regimens [...] Full article

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

17 pages, 514 KB

Open AccessReview

Upper Tract Urothelial Carcinoma: An Update on Current Diagnostic Modalities and Emerging Biomarkers

by Konstantinos Kapriniotis, Ioannis Loufopoulos, Mohammad U. Sharif, Ioannis Manolitsis, Lazaros Tzelves, Amy Nagle and James S. A. Green

J. Pers. Med. 2026, 16(4), 220; https://doi.org/10.3390/jpm16040220 - 16 Apr 2026

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Abstract

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic [...] Read more.

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic biomarkers to overcome these limitations. Methods: We carried out a narrative review of the literature searching for research articles on diagnostic and prognostic biomarkers for upper tract urothelial carcinoma (UC) and underlined the limitations of current diagnostic modalities. Results: CT urogram (CTU) is the imaging modality of choice in suspected upper tract UC with sensitivity and specificity exceeding 90% but with limitations in smaller lesions. Urine cytology has an excellent specificity for high-grade UC but is limited by low sensitivity leading to a high number of diagnostic ureteroscopies with significant associated risks. Adjuncts such as Fluorescence In Situ Hybridization (FISH) technology and urine DNA methylation markers have shown promising results but need further validation in large cohorts of upper tract UC. Finally, circulation tumour DNA (ctDNA) is a novel approach with great potential in risk stratification and monitoring of minimal residual disease post radical surgery; however, larger prospective studies are required to validate its role similarly to the recent bladder UC trials. Conclusions: There is an urgent need for non-invasive biomarkers that can reliably replace diagnostic ureteroscopies, identify high-risk/invasive disease and select patients for radical surgery or kidney sparing procedures. Full article

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

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17 pages, 685 KB

Open AccessReview

Beyond the Gut: Extra-Enteric Digestive Manifestations of Inflammatory Bowel Disease—A Personalized Medicine Perspective and Comprehensive Review

by Maria Rogalidou, Maria-Veatriki Christodoulou, Alexandros Skamnelos and Dimitrios K. Christodoulou

J. Pers. Med. 2026, 16(4), 219; https://doi.org/10.3390/jpm16040219 - 16 Apr 2026

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Abstract

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, [...] Read more.

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

(This article belongs to the Special Issue Advancing Personalized Medicine in Inflammatory Disorders of the Gut)

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16 pages, 1066 KB

Open AccessReview

A Decade of Artificial Intelligence in Stroke Care (2015–2025): Trends, Clinical Translation, and the Precision Medicine Frontier—A Narrative Review

by Mian Urfy and Mariam Tariq Mir

J. Pers. Med. 2026, 16(4), 218; https://doi.org/10.3390/jpm16040218 - 16 Apr 2026

Viewed by 611

Abstract

Background/Objectives: Stroke generates 157 million disability-adjusted life-years (DALYs) annually, making it the leading neurological cause of global disease burden. Artificial intelligence (AI) and machine learning (ML) have emerged as transformative technologies across the stroke care continuum. This narrative review maps the trajectory of [...] Read more.

Background/Objectives: Stroke generates 157 million disability-adjusted life-years (DALYs) annually, making it the leading neurological cause of global disease burden. Artificial intelligence (AI) and machine learning (ML) have emerged as transformative technologies across the stroke care continuum. This narrative review maps the trajectory of AI in stroke medicine over the decade from 2015 to 2025. Methods: We conducted a narrative review with a structured, pre-specified search strategy across eight pre-specified thematic clusters using PubMed/MEDLINE (January 2015–December 2025), identifying 8549 records and including 1335 studies after screening. Inclusion criteria encompassed primary research articles, systematic reviews, meta-analyses, and RCTs reporting quantitative performance metrics or clinical outcome data for AI/ML in stroke. Results: Stroke imaging AI is the most commercially mature domain, with over 30 FDA-cleared tools. Automated ASPECTS scoring reduced radiologist reading time by 74.8% (AUC 84.97%; 95% CI: 83.1–86.8%). The only triage AI RCT demonstrated an 11.2 min reduction in door-to-groin time without significant improvement in 90-day functional independence (OR 1.3, 95% CI 0.42–4.0). Brain–computer interface rehabilitation showed significant upper limb recovery in a 17-center RCT (FMA-UE mean difference +3.35 points, 95% CI 1.05–5.65; p = 0.0045). AF detection AI is FDA-cleared and RCT-validated. LLMs and federated learning are pre-regulatory but growing exponentially. Conclusions: AI in stroke has achieved diagnostic maturity but therapeutic immaturity. Bridging algorithmic performance to patient outcomes, addressing equity gaps, and building the economic evidence base for scalable deployment are the defining challenges of the next decade. Full article

(This article belongs to the Special Issue Advances in Ischemic Stroke Management: Toward Precision Medicine)

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15 pages, 2483 KB

Open AccessPerspective

Personalized Medicine, Storied Past, Contentious Present, Promising Future

by Kenneth P. H. Pritzker and Arash Samari

J. Pers. Med. 2026, 16(4), 217; https://doi.org/10.3390/jpm16040217 - 16 Apr 2026

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Abstract

Personalized Medicine has been a central aspiration of medical practice and has guided the direction of medical advances from ancient times to the present. This narrative review highlights some of the most significant past advances and present practices, discusses issues currently limiting Personalized [...] Read more.

Personalized Medicine has been a central aspiration of medical practice and has guided the direction of medical advances from ancient times to the present. This narrative review highlights some of the most significant past advances and present practices, discusses issues currently limiting Personalized Medicine and proposes activities necessary for Personalized Medicine to have a promising future. Throughout history, Personalized Medicine has developed along with the evolution of science and societal concepts. Notable advances paralleled the growth in what an individual person is and how experimental science can apply to medical practice. In the twentieth century, the study of inborn errors of metabolism and pharmacogenetics broadened the horizons of what Personalized Medicine could be. Presently, Personalized Medicine is challenged by different perspectives on its scope, by the various clinical scientific activities which can inadvertently or by misinterpretation serve to depersonalize medicine, and by the difficulties involved in integrating the massive amount of available scientific data to optimize medical practice centered on the individual. The conditions necessary for Personalized Medicine to have a promising future include developing broader, deeper, and more dynamic knowledge of disease processes, new methods to identify anomalous, singular disease-contributing characteristics in individuals, and improving data quality in research and medical practice. Advancing Personalized Medicine requires developing new perspectives for research, healthcare education, medical practice, and healthcare governance, as well as deploying medical advances at scale across populations. Full article

(This article belongs to the Special Issue Selected Papers from 1st International Online Conference on Personalized Medicine (IOCPM 2025))

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13 pages, 820 KB

Open AccessArticle

Clinical Risk Management and Postoperative Outcomes After Colorectal Resection: A Retrospective Observational Study

by Laura Ambrosi, Giorgio Ammerata, Maurizio Mastrapasqua, Gianmarco Sirago, Valentina Cianci, Biagio Solarino, Alessandro Dell’Erba, Davide Ferorelli and Michele Simone

J. Pers. Med. 2026, 16(4), 216; https://doi.org/10.3390/jpm16040216 - 15 Apr 2026

Viewed by 381

Abstract

Background: Postoperative complications after colorectal cancer surgery imply challenges to patient safety, recovery, and healthcare resources. Clinical Risk Management (CRM) is vital for reducing complications. This study aims to provide a comprehensive overview of short-term outcomes in a high-volume hospital over four [...] Read more.

Background: Postoperative complications after colorectal cancer surgery imply challenges to patient safety, recovery, and healthcare resources. Clinical Risk Management (CRM) is vital for reducing complications. This study aims to provide a comprehensive overview of short-term outcomes in a high-volume hospital over four years, evaluating the impact of complications through the lens of CRM. Methods: A retrospective cohort study was conducted on 483 patients (332 colon tumors, 151 rectal tumors) who underwent surgical resection. Data were extracted from the internal database, including demographic characteristics, diagnoses, surgical approaches, types of anastomoses, histological grades, and postoperative outcomes. Complications were categorized using the Clavien–Dindo system (grades I–V). Statistical analyses examined the link between clinical variables and complications. Results: Postoperative complications occurred in 44 (9.1%) patients in 483 cases. Among the 44 patients with postoperative complications, the most frequent events were anastomotic leakage (AL) (9/44, 20.5%; 9/483, 1.9% of the total cohort) and postoperative hemorrhage (POH) (8/44, 18.2%; 8/483, 1.7% of the total cohort). Moreover, complications were accompanied by an extended hospital stay and a higher in-hospital mortality (15.9% vs. 0%). The number of recorded postoperative follow-up visits differed significantly across complication severity categories. The overall in-hospital survival rate was 98.6%. Conclusions: The low rates of complications and in-hospital mortality observed in this cohort were documented within a hospital operating under a mandatory institutional CRM framework. However, due to the retrospective single-arm design, these findings should be interpreted as descriptive and hypothesis-generating rather than causal. The Clavien–Dindo system provided a useful tool for grading complication severity and supporting postoperative management. These findings support continued refinement of perioperative care pathways and further comparative studies on CRM implementation. Full article

(This article belongs to the Special Issue Advances in Colorectal Cancer: Diagnosis and Personalized Treatment)

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46 pages, 4300 KB

Open AccessSystematic Review

Toward Personalized Psychoeducational Interventions for Psychophysical Health: A Systematic Review and Meta-Analysis for Tailored Intervention Selection

by Evgenia Gkintoni and Apostolos Vantarakis

J. Pers. Med. 2026, 16(4), 215; https://doi.org/10.3390/jpm16040215 - 14 Apr 2026

Viewed by 957

Abstract

Background: Psychoeducational interventions are increasingly implemented to promote psychological and physical health, yet evidence guiding personalized intervention selection remains limited. This systematic review and meta-analysis quantifies the effectiveness of psychoeducational interventions across five settings and identifies empirically derived moderator patterns to inform [...] Read more.

Background: Psychoeducational interventions are increasingly implemented to promote psychological and physical health, yet evidence guiding personalized intervention selection remains limited. This systematic review and meta-analysis quantifies the effectiveness of psychoeducational interventions across five settings and identifies empirically derived moderator patterns to inform the selection of tailored interventions. Methods: Systematic searches of PubMed/MEDLINE, PsycINFO, Scopus, Web of Science, ERIC, the Cochrane Library, and Google Scholar were conducted to identify eligible studies published between January 2015 and December 2024. A two-tier analytical approach was employed: a random-effects meta-analysis of k = 53 studies reporting extractable effect-size data, and a direction-of-effect narrative synthesis of all 186 included studies (N = 50,328 verified from 124 studies reporting sample sizes), following SWiM guidelines. Results: The quantitative meta-analysis yielded a significant medium-to-large pooled effect (g = 0.66, 95% CI [0.50, 0.82], p < 0.001) with substantial heterogeneity (I² = 96.1%). Effects varied across settings: clinical/vulnerable populations showed the largest effect (g = 0.91), followed by university programs (g = 0.62), school-based (g = 0.60), mindfulness/positive psychology (g = 0.55), and community-based (g = 0.49). The broader narrative synthesis confirmed near-universal effectiveness: 131 studies (70.4%) reported significant positive effects, 51 (27.4%) reported mixed results, and none reported null effects—yielding 97.8% favorable outcomes across the full evidence base. Direction-of-effect moderator patterns indicated a stepped severity gradient (indicated 100% favorable, selective 98.6%, universal 95.6%), and that programs exceeding 8 weeks (99.0% vs. 96.6%), theory-based interventions (98.2% vs. 95.2%), and guided digital delivery were consistently associated with the most favorable outcomes. Publication bias assessment confirmed robustness (fail-safe N = 22,942; leave-one-out range: 0.61–0.67). GRADE evidence quality was rated Moderate for four of five research questions. Conclusions: This systematic review and meta-analysis provide converging quantitative and direction-of-effect evidence supporting the effectiveness of psychoeducational interventions. The near-universal favorable direction across 186 studies, combined with a medium-to-large pooled effect in the quantitative subset, provides a preliminary empirical foundation for personalized intervention matching. A preliminary four-phase implementation framework is proposed as a hypothesis-generating heuristic; prospective validation through a meta-analysis of individual participant data is needed before prescriptive application. Full article

(This article belongs to the Special Issue Personalized Therapy for Psychophysical Health: An Integrative Approach)

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11 pages, 988 KB

Open AccessArticle

Personalized Vestibular Rehabilitation in Persistent Postural–Perceptual Dizziness (PPPD), Unilateral and Bilateral Vestibular Dysfunction: A Comparative Study

by Pasqualina Maria Picciotti, Rolando Rolesi, Giorgia Rossi, Giuseppe Oliveto and Jacopo Galli

J. Pers. Med. 2026, 16(4), 214; https://doi.org/10.3390/jpm16040214 - 13 Apr 2026

Viewed by 730

Abstract

Background: In the last few decades, a growing body of evidence has confirmed that vestibular rehabilitation (VR) can improve the symptoms of many unilateral and bilateral vestibular disorders, by facilitating vestibular compensation mechanisms, such as adaptation, substitution, and habituation. However, the usefulness of [...] Read more.

Background: In the last few decades, a growing body of evidence has confirmed that vestibular rehabilitation (VR) can improve the symptoms of many unilateral and bilateral vestibular disorders, by facilitating vestibular compensation mechanisms, such as adaptation, substitution, and habituation. However, the usefulness of the vestibular rehabilitation approach in Persistent Postural–Perceptual Dizziness (PPPD) is currently highly debated and unclear. The aim of the present study was to evaluate the efficacy of VR using computerized dynamic posturography in PPPD patients as a single treatment and without other associated psychological or pharmacological therapies. Results were compared with patients with unilateral and bilateral vestibular disfunction, in order to define the role of our rehabilitation model within a framework of personalized therapy for different disorders. Methods: We evaluated 44 patients (23 F, 21 M; ranged from 28 to 82 years; mean age 63.72) affected by unilateral vestibular vestibulopathy (UVP) (n = 19), bilateral vestibular vestibulopathy (BVP) (n = 10) and PPPD (n = 15). For each patient, a comprehensive clinical bedside vestibular assessment was carefully performed by expert clinicians, as well as Bithermal caloric tests with videonystagmography (VNG), Video Head Impulse Test (vHIT) and Computed Dynamic Posturography (CDP). The impact of dizziness on quality of life (QoL) was assessed by the Italian Dizziness Handicap Inventory (DHI). All subjects evaluated in this study underwent five rehabilitative therapy sessions in our centre, once a week for 45 min and exercised daily for 30 min at home. All the exercises progressively became more difficult each week. Results: Our study showed that vestibular rehabilitation improved quality of life and reduced the level of self-perceived handicap in patients affected by unilateral and bilateral vestibular dysfunction, with significant improvement in DHI total score and posturographic parameters. In PPPD patients, rehabilitation did not significantly modify posturographic performances and the improvement in total DHI score did not reach statistical significance, although a significant change was observed in the functional sub-score. Conclusions: Vestibular rehabilitation confirmed its effectiveness in unilateral and bilateral peripheral vestibulopathies. In patients with PPPD, rehabilitation performed with computerized dynamic posturography may reduce subjective handicap and improve some aspects of daily functioning, although the small sample size and the absence of a control group do not allow definitive conclusions about its efficacy. Full article

(This article belongs to the Section Personalized Medical Care)

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25 pages, 798 KB

Open AccessReview

Personalised Approach to the Management of Older People with Type 2 Diabetes Mellitus—A Comprehensive Narrative Review

by Alan Sinclair, Mohammed Al-Banna, Roxana Tutunariu and Ahmed H. Abdelhafiz

J. Pers. Med. 2026, 16(4), 213; https://doi.org/10.3390/jpm16040213 - 13 Apr 2026

Viewed by 549

Abstract

The global population is ageing due to increased life expectancy, and the prevalence of diabetes is proportionally increasing. With advancing age, diabetes in older people is a complex condition due to associated morbidities and geriatric syndromes. As a result, the management of diabetes [...] Read more.

The global population is ageing due to increased life expectancy, and the prevalence of diabetes is proportionally increasing. With advancing age, diabetes in older people is a complex condition due to associated morbidities and geriatric syndromes. As a result, the management of diabetes in old age is challenging. Due to the wide heterogeneity of older people, diabetes management in this age group should be personalised. While strict targets are accepted in fit individuals, relaxed targets should be considered in patients with multiple morbidities and a high risk of hypoglycaemia. The development of frailty changes the metabolic profile of older people, and their insulin resistance and diabetes trajectory, which will have an impact on the choice of glucose-lowering agents and the goals of therapy. For example, intensive therapy, the use of SGLT-2 inhibitors and GLP-1RA, and tight targets should be continued in frail, sarcopenic, obese individuals due to their increased insulin resistance and cardiovascular risk. On the other hand, relaxed targets and deintensification of therapy should be considered in anorexic, malnourished, frail individuals with significant weight loss due to their low insulin resistance, low prevalence of cardiovascular risk factors, and high risk of hypoglycaemia. Annual reviews of older people with diabetes should include screening for frailty, depression and dementia for early diagnosis, and appropriate interventions. The introduction of continuous glucose monitoring is increasingly used in older people with diabetes and has the potential to reduce the incidence of hypoglycaemia. With the expectation of a continued increase in the prevalence of older people with diabetes, the use of mobile health may allow care delivery on a wider scale without the need for face-to-face appointments. In addition, there is a promising scope for artificial intelligence to achieve better diabetes outcomes. Future research is still required to expand the use of these technologies in older age groups. Full article

(This article belongs to the Special Issue Personalized Management and Treatment in Geriatrics)

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12 pages, 238 KB

Open AccessArticle

Early Postnatal Hypocapnia and Hypercapnia in Ventilated Preterm Infants: Incidence and Associations with Adverse Outcomes

by Ilias Chatziioannidis, Angeliki Kontou, Eleni Agakidou, Theodora Stathopoulou, Kostantia Tsoni, Christos Paschaloudis, William Chotas and Kosmas Sarafidis

J. Pers. Med. 2026, 16(4), 212; https://doi.org/10.3390/jpm16040212 - 12 Apr 2026

Viewed by 351

Abstract

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their [...] Read more.

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO₂ in the first 72 h were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD. Full article

(This article belongs to the Section Personalized Medical Care)

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11 pages, 465 KB

Open AccessSystematic Review

Clinical Impact of Rare Subtypes of Parathyroid Adenoma: A Systematic Review

by Maurizio Martiradonna, Rossella Mazzilli, Virginia Zamponi, Daniela Prosperi, Massimiliano Mancini and Antongiulio Faggiano

J. Pers. Med. 2026, 16(4), 211; https://doi.org/10.3390/jpm16040211 - 10 Apr 2026

Viewed by 416

Abstract

Background: Parathyroid lipoadenoma, oncocytic parathyroid adenoma, and water-clear cell parathyroid adenoma (WCCA) are exceptionally rare subtypes of parathyroid adenoma, whose real clinical impact remains unclear. Methods: We performed a literature review and comparison of these uncommon subtypes of parathyroid adenoma, as these [...] Read more.

Background: Parathyroid lipoadenoma, oncocytic parathyroid adenoma, and water-clear cell parathyroid adenoma (WCCA) are exceptionally rare subtypes of parathyroid adenoma, whose real clinical impact remains unclear. Methods: We performed a literature review and comparison of these uncommon subtypes of parathyroid adenoma, as these lesions may be associated with distinct clinical, pathological and radiological phenotypes. Results: The three groups were comparable in terms of age and gender, mainly affecting middle-aged women. As for the biochemical findings, although PTH level did not show statistically significant differences among the three adenomas, in the two-tail comparison between WCCAs and lipoadenomas, there was a trend towards higher PTH values (p = 0.058). However, serum calcium levels differed significantly, with higher levels in WCCAs than in lipoadenomas (12.1 vs. 11.3 mg/dL; p = 0.002). From a preoperative point of view, ultrasound positivity was significantly higher in WCCAs than in lipoadenomas and oncocytic adenomas (97% vs. 50% vs. 55.3%, p < 0.001), compared to scintigraphy positivity, which was comparable between subtypes and relatively suboptimal (66.7% vs. 64.3% vs. 61.3%; p = 0.825); WCCAs also had an overall more voluminous morphological phenotype. Conclusions: This review, although limited by its reliance primarily on case reports and small case series, confirms that lipoadenoma, oxyphilic adenoma, and WCCAs are rare but clinically relevant subtypes of parathyroid adenoma. These entities may be associated with atypical presentations of primary hyperparathyroidism (including difficult preoperative localization and clinicopathological features raising suspicion of malignancy) and should be recognized as a potential source of diagnostic difficulty. A better understanding of these rare subtypes may improve clinicopathological interpretation, increase awareness of potential diagnostic pitfalls and support a more personalized diagnostic and surgical approach in the future. Full article

(This article belongs to the Special Issue Personalized Approaches in Endocrine Surgical Innovation)

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25 pages, 835 KB

Open AccessArticle

Personalised Blood Glucose Time Series Forecasting in Type 1 Diabetes: Deep Collaborative Adversarial Learning

by Heydar Khadem, Hoda Nemat, Jackie Elliott and Mohammed Benaissa

J. Pers. Med. 2026, 16(4), 210; https://doi.org/10.3390/jpm16040210 - 8 Apr 2026

Cited by 1 | Viewed by 569

Abstract

Background/Objectives: Blood glucose prediction (BGP) for individuals with type 1 diabetes (T1D) is a clinically essential yet highly challenging task in time series forecasting (TSF) and an important problem in personalised medicine. Accurate bespoke BGP is crucial for individualised T1D management, reducing complications, [...] Read more.

Background/Objectives: Blood glucose prediction (BGP) for individuals with type 1 diabetes (T1D) is a clinically essential yet highly challenging task in time series forecasting (TSF) and an important problem in personalised medicine. Accurate bespoke BGP is crucial for individualised T1D management, reducing complications, and supporting patient-specific glycaemic risk mitigation. However, the pronounced volatility of glycaemic fluctuations in T1D, combined with the need for mathematical rigor and clinical relevance, hampers reliable prediction. This complexity underscores the demand to explore and enhance more advanced techniques. While adversarial learning is adept at modelling intricate data variability, its potential for BGP remains largely untapped. Methods: This work presents a novel approach for BGP by addressing a key limitation in conventional adversarial learning when applied to this task. Typically, these methods optimise prediction accuracy within a set horizon by minimising adversarial loss. This focus overlooks how predictions align with longer-term patterns, which are critical for clinical relevance in BGP, thereby yielding suboptimal results. To overcome this limitation, we introduce collaborative augmented adversarial learning, designed to improve the model’s temporal awareness. Incorporating collaborative interaction optimisation, this approach enables the model to reflect extended time dependencies beyond the immediate horizon, thereby improving both the clinical reliability of predictions and overall predictive performance. We develop and evaluate four learning systems for BGP: independent learning, adversarial learning, collaborative learning, and adversarial collaborative learning. The proposed systems were evaluated for two clinically relevant prediction horizons, namely 30 min and 60 min ahead. Results: The interdependent collaboratively augmented learning frameworks, validated using the well-established Ohio T1D datasets, demonstrate statistically significant superior performance in both clinical and mathematical evaluations. Conclusions: Beyond advancing BGP accuracy and clinical reliability, the proposed approach supports personalised medicine by improving subject-specific glucose forecasting from CGM data, with potential relevance for more individualised diabetes monitoring and decision support. The proposed approach also opens new avenues for advancements in other complex TSF domains, as outlined in our future work. Full article

(This article belongs to the Special Issue Integrating Mathematical Modeling and Data Analysis in Personalized Medical Research)

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52 pages, 5024 KB

Open AccessArticle

In Silico Psycho-Oncology: Understanding Resilience Pathways in Breast Cancer—Determinants of Longitudinal Depression and Quality-of-Life Trajectories

by Eleni Kolokotroni, Paula Poikonen-Saksela, Ruth Pat-Horenczyk, Berta Sousa, Albino J. Oliveira-Maia, Ketti Mazzocco, Haridimos Kondylakis and Georgios S. Stamatakos

J. Pers. Med. 2026, 16(4), 209; https://doi.org/10.3390/jpm16040209 - 7 Apr 2026

Viewed by 670

Abstract

Background/Objectives: Patients with breast cancer show substantial heterogeneity in terms of psychological adjustment following diagnosis. We aimed to characterize longitudinal trajectories of quality of life (QoL) and depressive symptoms during the first 18 months post-diagnosis and to identify robust clinical, psychosocial, and behavioral [...] Read more.

Background/Objectives: Patients with breast cancer show substantial heterogeneity in terms of psychological adjustment following diagnosis. We aimed to characterize longitudinal trajectories of quality of life (QoL) and depressive symptoms during the first 18 months post-diagnosis and to identify robust clinical, psychosocial, and behavioral predictors associated with distinct adjustment pathways. Methods: Women (N = 538; mean age 55.4 years; range 40–70) with operable breast cancer (stages I–III) were drawn from the multicenter BOUNCE cohort. QoL (Global Health Status/QoL scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and depressive symptoms (depression subscale of the Hospital Anxiety and Depression Scale) were assessed at baseline and months 3, 6, 9, 12, 15 and 18. Latent class growth analysis and growth mixture modeling identified distinct trajectory classes. Associations between early predictors and trajectory membership were examined using logistic regression combined with elastic net regularization. Results: Depression trajectories demonstrated heterogeneity, with groups characterized by persistent resilience (59.7%), stable moderate/high (25.3%), delayed onset (5.0%), and recovery (10.0%). QoL trajectories ranged from stable excellent (13.2%) and stable high (40.7%) to moderate (31.4%) and persistent low/deteriorating (6.9%), as well as a distinct recovering trajectory (7.8%). Trajectory differentiation was primarily driven by psychological resources, symptom burden, functional status, and coping processes, alongside specific contributions from clinical factors. Conclusions: Distinct subgroups of women with breast cancer follow divergent adjustment pathways. These findings highlight the multidimensional nature of resilience and support the need for tailored interventions that promote long-term well-being beyond simple risk reduction. Full article

(This article belongs to the Special Issue Personalized Medicine for Clinical Psychology)

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17 pages, 2489 KB

Open AccessReview

Extracellular Vesicles in Osteonecrosis of the Femoral Head: An Integrated Review of Experimental and Bioinformatic Evidence

by Elvira Immacolata Parrotta, Giorgia Lucia Benedetto, Giovanni Cuda, Umile Giuseppe Longo, Arianna Carnevale, Olimpio Galasso, Giorgio Gasparini and Michele Mercurio

J. Pers. Med. 2026, 16(4), 208; https://doi.org/10.3390/jpm16040208 - 7 Apr 2026

Viewed by 439

Abstract

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive condition characterized by bone necrosis, impaired vascularization, and immune dysregulation, often resulting in femoral head collapse. Effective strategies to halt disease progression are limited. Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular [...] Read more.

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive condition characterized by bone necrosis, impaired vascularization, and immune dysregulation, often resulting in femoral head collapse. Effective strategies to halt disease progression are limited. Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication and influence osteogenesis, angiogenesis, and immune responses. This review summarizes current evidence on EVs in ONFH and their translational potential. Methods: A structured narrative review of PubMed, Scopus, Web of Science, and Cochrane Central databases was conducted, including in vitro, preclinical, and clinical studies on EVs in ONFH. Data on EV sources, molecular cargo, signaling pathways, functional effects, and translational implications were qualitatively synthesized. No pooled statistical analysis was performed because the extracted data were heterogeneous. Bioinformatic analyses such as Gene Ontology, KEGG enrichment, and protein–protein interaction networks were also summarized. Results: In vitro, EVs from bone marrow mesenchymal stem cells, endothelial cells, and M2 macrophages modulate osteogenic differentiation, angiogenesis, and inflammation. Preclinical studies demonstrate that EV administration reduces femoral head necrosis, improves trabecular structure, and enhances neovascularization. Clinical studies have identified EV-associated molecules (SAA1, C4A, RPS8) linked to disease stage and the risk of femoral head collapse. Bioinformatic analyses connect EV cargo to pathways regulating bone formation, vascularization, immunity, and metabolism. Conclusions: EVs appear to play key roles in ONFH pathogenesis and may represent promising candidates for diagnostic and therapeutic applications. However, current clinical evidence remains limited and requires validation in larger studies. Nonetheless, heterogeneity and limited clinical data require standardized, longitudinal studies to validate their translational relevance. Full article

(This article belongs to the Special Issue Personalized Medicine in Orthopedics and Traumatology: Updates and Challenges)

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11 pages, 980 KB

Open AccessStudy Protocol

Rationale and Design of a Randomised Proof-of-Concept Trial to Assess the Safety of Early Discharge Using Index Microcirculatory Resistance in Patients with Acute Myocardial Infarction: SECURE Study

by Muntaser Omari, Mohamed Ali, Luke Spray, Adam McDiarmid and Mohammad Alkhalil

J. Pers. Med. 2026, 16(4), 207; https://doi.org/10.3390/jpm16040207 - 7 Apr 2026

Viewed by 352

Abstract

Background: Current guidelines acknowledge that early discharge is not associated with late mortality and that in-hospital length of stay (LOS) of 48–72 h should be considered following successful primary percutaneous coronary intervention (PPCI) in low-risk patients. Recent studies have highlighted the safety [...] Read more.

Background: Current guidelines acknowledge that early discharge is not associated with late mortality and that in-hospital length of stay (LOS) of 48–72 h should be considered following successful primary percutaneous coronary intervention (PPCI) in low-risk patients. Recent studies have highlighted the safety of very early discharge after PPCI in highly selected low-risk patients; however, objective tools to guide discharge timing remain limited. The Index of Microcirculatory Resistance (IMR) offers a quantitative assessment of microvascular function and may help identify patients suitable for very early discharge. We aimed to evaluate the feasibility of using IMR to guide very early discharge in patients who underwent uncomplicated PPCI. Study design and objectives: The Safety of Early Discharge Using Index Microcirculatory Resistance in Patients with Acute Myocardial Infarction (SECURE) study is designed to assess the feasibility of using IMR, measured immediately following successful PPCI, to guide early discharge from hospital within 24 h. The SECURE study is a prospective, proof-of-concept, functional non-inferiority, single-centre, randomised, open-label trial to determine if patients with low IMR can be safely discharged when compared to standard discharge policy. The SECURE study will recruit 82 patients with low IMR following successful PPCI. Participants will be 1:1 randomised to either standard discharge timing or very early discharge (within 24 h). The left ventricle ejection fraction will be assessed using cardiac magnetic resonance imaging. A telephone follow-up at 3 months will be arranged. Clinical events are collected as secondary and exploratory safety endpoints. Conclusions: The SECURE study will provide proof-of-concept data about the feasibility of using IMR to guide very early discharge following PPCI. If successful, this study will provide data to plan for a larger study to determine the safety of this personalised approach. Full article

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

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15 pages, 497 KB

Open AccessArticle

An Assessment of GPT-3.5 and GPT-4.0 Responses to Scoliosis FAQs

by Tu-Lan Vu-Han, Enikö Regényi, Vikram Sunkara, Paul Köhli, Friederike Schömig, Alexander P. Hughes, Michael Putzier, Matthias Pumberger and Thilo Khakzad

J. Pers. Med. 2026, 16(4), 206; https://doi.org/10.3390/jpm16040206 - 7 Apr 2026

Viewed by 399

Abstract

Background: ChatGPT is a large language model (LLM) online chatbot developed by OpenAI and launched in November 2022. Early adoption studies have shown high readiness to use this technology for health-related questions and self-diagnosis. However, the quality and clinical adequacy of health-related [...] Read more.

Background: ChatGPT is a large language model (LLM) online chatbot developed by OpenAI and launched in November 2022. Early adoption studies have shown high readiness to use this technology for health-related questions and self-diagnosis. However, the quality and clinical adequacy of health-related responses remain incompletely characterized. This study aimed to explore responses generated by ChatGPT-3.5 and ChatGPT-4.0 to common patient questions regarding scoliosis. Methods: Ten scoliosis-related frequently asked questions (FAQs) were selected from a larger pool of over 250 patient-facing questions compiled from 17 publicly available FAQ webpages and informed by a Google Trends analysis. Questions were harmonized, grouped by theme, and then reduced by rule-based expert review to a final set intended to represent common patient concerns. Results: The median ratings of ChatGPT-3.5 and ChatGPT-4.0 responses ranged from satisfactory, requiring minimal (2) to moderate clarification (3). Across the ten matched questions, no statistically detectable difference was found between models in this study setting (W = 8.0, p = 0.59; Cliff’s δ = −0.12 [95% CI −0.58, 0.40]); however, given the small question set, unblinded rating process, and poor inter-rater reliability, this should not be interpreted as evidence of equivalence, non-inferiority, or comparable model performance. The results apply only to the 10–15 April 2024, online snapshots of ChatGPT-3.5 and ChatGPT-4.0 and should not be generalized to later model iterations. Conclusions: This study should be interpreted as a clinically oriented observational report, intended to inform physician awareness and patient-physician communication rather than validate chatbot accuracy or safety. In this 10–15 April 2024, sample, both model outputs frequently required clinician clarification. Given the small FAQ set, low inter-rater reliability, unblinded design, and single-sample outputs, the findings do not establish equivalence or superiority and apply only to the specific 10–15 April 2024, model snapshots and evaluated questions. Full article

(This article belongs to the Special Issue AI and Precision Medicine: Innovations and Applications)

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14 pages, 2424 KB

Open AccessArticle

Personalized Prediction of Postoperative Recurrence in Lung Squamous Cell Carcinoma: Integrating AI-Based Nuclear Morphometry and Clinical Data

by Tomokazu Omori, Akira Saito, Yoshihisa Shimada, Yujin Kudo, Jun Matsubayashi, Toshitaka Nagao, Masahiko Kuroda and Norihiko Ikeda

J. Pers. Med. 2026, 16(4), 205; https://doi.org/10.3390/jpm16040205 - 6 Apr 2026

Viewed by 426

Abstract

Background: This study employed artificial intelligence (AI) to analyze quantitative nuclear morphological features obtained from digital pathology images to predict postoperative recurrence in patients with lung squamous cell carcinoma (LSQCC). We aimed to develop a prediction model that contributes to the realization of [...] Read more.

Background: This study employed artificial intelligence (AI) to analyze quantitative nuclear morphological features obtained from digital pathology images to predict postoperative recurrence in patients with lung squamous cell carcinoma (LSQCC). We aimed to develop a prediction model that contributes to the realization of ‘personalized postoperative management’ tailored to individual tumor biology by integrating AI-extracted morphological features with clinical information. Methods: A total of 185 of the 253 surgically resected LSQCC cases were included; 136 were randomly assigned to the training set and 49 to the test set. Nuclear features from manually selected regions of interest were extracted and used to build AI-based prediction models. Three recurrence models were developed: recurrence within 2 years, within 5 years, and a three-category model (≤2 years, 3–5 years, >5 years or no recurrence). Support vector machine (SVM) and random forest (RF) algorithms were applied to each, yielding six predictive models. An ensemble approach was used to calculate AI-based risk scores, and a “total risk score” was developed by integrating these with the pathologic stage. Results: All six AI models demonstrated stable predictive performance, with AUC values ranging from 0.76 to 0.91. Kaplan–Meier analysis showed that the total risk score provided the most precise risk stratification (p < 0.005), with clearer separation between risk groups than the AI-based risk score alone. Conclusions: The integration of AI-based nuclear morphology analysis and clinical data provides an objective and practical tool for personalized postoperative management in LSQCC. This approach enables tailored clinical decision-making by identifying patients at high risk for early recurrence and customizing postoperative treatment plans to meet the specific needs of each individual. Full article

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14 pages, 1395 KB

Open AccessArticle

Does Provider Identity at Triage Improve Machine Learning Prediction of Hospital Admission? A Comparative Analysis of Ten Supervised Classifiers with SHAP Explainability

by Adam E. Brown, Chance W. Marostica and Wayne A. Martini

J. Pers. Med. 2026, 16(4), 204; https://doi.org/10.3390/jpm16040204 - 5 Apr 2026

Viewed by 415

Abstract

Background/Objectives: Machine learning (ML) models can predict hospital admission from emergency department (ED) triage data with areas under the receiver operating characteristic curve (AUC) exceeding 0.85. Whether incorporating the assigned provider’s identity—as a proxy for unmeasured practice variation—improves prediction has not been systematically [...] Read more.

Background/Objectives: Machine learning (ML) models can predict hospital admission from emergency department (ED) triage data with areas under the receiver operating characteristic curve (AUC) exceeding 0.85. Whether incorporating the assigned provider’s identity—as a proxy for unmeasured practice variation—improves prediction has not been systematically studied. We aimed to compare 10 supervised ML classifiers for predicting hospital admission at ED triage, with and without provider identity, and to characterize model reasoning using SHapley Additive exPlanations (SHAP). Methods: We conducted a retrospective cohort study of 186,094 ED visits (2020–2023, training) and 58,151 visits (2024, temporal holdout test) at one academic tertiary-care ED. Ten classifiers spanning linear, distance-based, tree-based, ensemble, probabilistic, and neural network families were each trained in two conditions: baseline (23 triage features) and with provider identity appended. SHAP TreeExplainer was applied to the top-performing models (CatBoost and XGBoost). Results: The admission rate was 31.3% (training) and 31.7% (test). CatBoost achieved the highest baseline AUC of 0.8906 (0.8878–0.8933). Adding provider identity produced negligible AUC changes across all models (ΔAUC range: −0.0029 to +0.0015; all DeLong p > 0.05). SHAP analysis identified ESI level, respiratory rate, temperature, complaint category, and age as the dominant predictors, with clinically intuitive directionality. Conclusions: Provider identity does not meaningfully improve ML prediction of hospital admission beyond standard triage variables. The observed 28-percentage-point variation in provider admission rates is explained by patient case-mix differences than with independent practice pattern effects on prediction. SHAP provides transparent, clinically interpretable explanations suitable for bedside decision support. Full article

(This article belongs to the Special Issue AI and Precision Medicine: Innovations and Applications)

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13 pages, 776 KB

Open AccessArticle

Soluble Isoforms of PD-1 and PD-L1 in Non-Small Cell Lung Cancer: Correlation with Tumor Stage, Longitudinal Analysis and Prognostic Implications

by Konstantinos Vachlas, Dimitra Grapsa, Stylianos Gaitanakis, Anna Papadopoulou, Paraskevi Moutsatsou, Nikolaos Syrigos and Ioannis P. Trontzas

J. Pers. Med. 2026, 16(4), 203; https://doi.org/10.3390/jpm16040203 - 4 Apr 2026

Viewed by 455

Abstract

Background: Soluble immune checkpoint molecules, including soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), have emerged as potential minimally invasive biomarkers in non-small cell lung cancer (NSCLC). However, their diagnostic, kinetic, and prognostic significance across different disease settings remains unclear. This prospective study evaluated [...] Read more.

Background: Soluble immune checkpoint molecules, including soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), have emerged as potential minimally invasive biomarkers in non-small cell lung cancer (NSCLC). However, their diagnostic, kinetic, and prognostic significance across different disease settings remains unclear. This prospective study evaluated baseline levels, longitudinal fluctuations, and clinical associations of sPD-1 and sPD-L1 in early- and advanced-stage NSCLC. Methods: Three cohorts were prospectively enrolled: early-stage NSCLC patients undergoing curative surgery (n = 25), advanced-stage NSCLC patients receiving pembrolizumab-based immunotherapy (n = 55), and non-oncological controls (n = 16). Serum sPD-1 and sPD-L1 were measured by ELISA at baseline and at four months post-surgery (early stage) or six months post-treatment (advanced stage). Baseline comparisons, longitudinal changes, correlation with tumor PD-L1 expression (TPS), and associations with recurrence (early stage) or 6-month objective response (advanced stage) were assessed. Results: Baseline sPD-1 and sPD-L1 levels did not differ significantly among controls, early-stage, and advanced-stage cohorts. In early-stage patients, sPD-L1 increased post-operatively (p = 0.006) while sPD-1 decreased (p < 0.001). In advanced-stage disease, sPD-1 declined during immunotherapy (p < 0.001), whereas sPD-L1 remained unchanged (p = 0.37). Baseline levels and continuous percent changes were not predictive of most outcomes. However, a ≥20% postoperative increase in sPD-L1 was strongly associated with recurrence in early-stage NSCLC (OR = 10.29; 95% CI: 1.40–215.20; p = 0.019). No sPD-1/PD-L1 metric predicted response in advanced disease. Baseline sPD-L1 showed no correlation with tumor PD-L1 expression (ρ = −0.09, p = 0.53) in the advanced-stage cohort. Conclusions: sPD-1 and sPD-L1 demonstrate distinct kinetic patterns across NSCLC settings. A postoperative >20% surge in sPD-L1 may identify early-stage patients at elevated risk of recurrence, whereas soluble checkpoints were not predictive of treatment response in advanced disease. These findings support further investigation of soluble checkpoint dynamics as complementary biomarkers in NSCLC management in larger cohorts. Full article

(This article belongs to the Special Issue From Biomarkers to Breakthroughs: Advancing Lung Cancer Research)

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17 pages, 1826 KB

Open AccessReview

Integrating AI Segmentation, Simulated Digital Twins, and Extended Reality into Medical Education: A Narrative Technical Review and Proof-of-Concept Case Study

by Parhesh Kumar, Ingharan Siddarthan, Catharine Kelsh Keim, Daniel K. Cho, John E. Rubin, Robert S. White and Rohan Jotwani

J. Pers. Med. 2026, 16(4), 202; https://doi.org/10.3390/jpm16040202 - 3 Apr 2026

Viewed by 751

Abstract

Background/Objectives: Simulation digital twins (DT) models that integrate patient-specific imaging with artificial intelligence (AI)-based segmentation and extended reality (XR) technologies are rapidly increasing in relevance in personalized medicine. While their clinical applications are expanding, their role as reusable educational tools and the [...] Read more.

Background/Objectives: Simulation digital twins (DT) models that integrate patient-specific imaging with artificial intelligence (AI)-based segmentation and extended reality (XR) technologies are rapidly increasing in relevance in personalized medicine. While their clinical applications are expanding, their role as reusable educational tools and the technical pipeline utilized for their development remain incompletely characterized. This narrative review examines current approaches to digital twin creation and XR integration, illustrated by a scoliosis-specific proof-of-concept educational case study. Methods: A narrative technical review was conducted by identifying relevant search keywords within the fields of AI-based image segmentation, extended reality in medicine, and medical education based on the authors’ expertise and familiarity with the subject. PubMed, Google Scholar, and Scopus were searched for English-language studies published primarily between 2015 and 2025 addressing patient-specific three-dimensional modeling, AI-driven segmentation, and XR applications in spine, orthopedic, anesthesiology, and interventional care. A de-identified case of scoliosis is used to present a proof-of-concept example of this process of creating a simulated digital twin for the purpose of medical education in a recorded XR format. Results: Prior studies demonstrated benefits of patient-specific 3D models for anatomical understanding and procedural planning, while highlighting limitations in segmentation accuracy and workflow integration. Nevertheless, while DTs have traditionally served clinical roles in surgical planning or pre-procedural rehearsal, their pedagogical potential remains under-explored. In the proof-of-concept case study, AI-assisted segmentation enabled rapid creation of an anatomically detailed scoliosis digital twin that was incorporated into XR and used to produce a reusable, spatially anchored instructional experience focused on neuraxial access. Conclusions: AI-enabled digital twin models integrated with XR represent a promising approach for personalized, anatomy-driven medical education. Further evaluation is needed to assess educational outcomes, scalability, and integration into clinical training workflows. Full article

(This article belongs to the Special Issue Artificial Intelligence for Personalized Medicine: Bridging Innovative Technologies and Patient-Centric Care)

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14 pages, 379 KB

Open AccessArticle

Role of Cardiovascular Magnetic Resonance in Post-Heart Transplant Surveillance: Integrating Evidence with Prospective Cohort Data

by Ricardo Carvalheiro, Vera Vaz Ferreira, Ana Raquel Santos, Isabel Cardoso, António Valentim Gonçalves, Rita Ilhão Moreira, Tiago Pereira da Silva, Sílvia Aguiar Rosa and Rui Cruz Ferreira

J. Pers. Med. 2026, 16(4), 201; https://doi.org/10.3390/jpm16040201 - 3 Apr 2026

Viewed by 387

Abstract

Background: Heart transplantation remains the definitive therapy for selected patients with end-stage heart failure, but outcomes are limited by acute rejection, chronic allograft injury, and cardiac allograft vasculopathy. Endomyocardial biopsy (EMB) remains the reference standard for rejection surveillance but is invasive and [...] Read more.

Background: Heart transplantation remains the definitive therapy for selected patients with end-stage heart failure, but outcomes are limited by acute rejection, chronic allograft injury, and cardiac allograft vasculopathy. Endomyocardial biopsy (EMB) remains the reference standard for rejection surveillance but is invasive and imperfectly captures diffuse myocardial injury. Cardiovascular magnetic resonance (CMR) offers noninvasive, multiparametric assessment of graft structure, function, tissue composition, and perfusion. We aimed to review current evidence supporting CMR in post-heart transplant surveillance and to evaluate the performance of serial CMR for acute cellular rejection in a prospective cohort. Methods: We performed a focused narrative review of the literature on CMR for detection of acute rejection, assessment of chronic allograft injury and prognosis, and evaluation of cardiac allograft vasculopathy and microvascular disease. In parallel, we conducted a prospective observational study of adult heart transplant recipients undergoing early post-transplant CMR (CMR1) and follow-up CMR (CMR2) with temporally matched EMB. Multiparametric CMR included cine imaging, native T1 and T2 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Clinically significant acute cellular rejection was defined as ISHLT grade ≥ 2R. Results: Eighteen recipients were included (median 53 days to CMR1 and 192 days to CMR2). Baseline CMR parameters correlated with invasive hemodynamic and biomarkers. Two patients had biopsy-proven ≥2R rejection at follow-up. T2 values at CMR2 were significantly higher in rejection versus non-rejection patients (59.0 ± 1.4 ms vs. 51.1 ± 1.9 ms; p = 0.015), with greater LGE burden in rejection (p = 0.029). In longitudinal analyses, rejection was associated with divergent patterns of cardiac remodelling and tissue characterization, including increases in indexed ventricular volumes and T2 over time, whereas non-rejection patients demonstrated stable ventricular volumes and a decline in T2. Conclusions: Multiparametric CMR, anchored by T2 mapping, provides clinically meaningful, non-invasive information for acute rejection surveillance after heart transplantation and complements EMB within a personalized, risk-adapted follow-up framework. Establishing individualized baseline CMR phenotypes and monitoring longitudinal changes may support more personalized, less invasive graft surveillance strategies. Larger multicentre prospective studies are needed to define standardized implementation pathways. Full article

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

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J. Pers. Med., Volume 16, Issue 4 (April 2026) – 57 articles

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