Journal of Personalized Medicine

16 pages, 588 KB

Open AccessReview

The Immune System and the Plural Autisms: A Narrative Review

by Paul Whiteley, Kevin Carr, Paul Shattock, Malcolm Hooper, Carol Stott, Karl Hardy, Ben Marlow, Chandoshi Rhea Mukherjee and Athena Whiteley

J. Pers. Med. 2026, 16(7), 379; https://doi.org/10.3390/jpm16070379 - 15 Jul 2026

Abstract

Plural autisms offer one important way of organising the massive heterogeneity that is currently included under the singular diagnostic label of autism spectrum disorder (ASD). Characterised exclusively by behavioural criteria related to social communication skills and restricted or repetitive patterns of symptoms, the [...] Read more.

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

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

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18 pages, 1063 KB

Open AccessArticle

A Randomized Controlled Pilot Trial Evaluating the Efficacy of Intravaginal and Extravaginal K-Laser Therapy as a Personalized Non-Hormonal Treatment for Genitourinary Syndrome of Menopause

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

J. Pers. Med. 2026, 16(7), 378; https://doi.org/10.3390/jpm16070378 - 15 Jul 2026

Abstract

Background/Objectives: Genitourinary Syndrome of Menopause (GSM) negatively affects quality of life in postmenopausal women, causing sexual dysfunction, vaginal atrophy, and pelvic discomfort. Personalized medicine highlights the need for individualized, non-hormonal therapeutic options for women with contraindications to or preferences against hormonal treatment. [...] Read more.

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

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

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34 pages, 5181 KB

Open AccessReview

Wearable Devices and Machine Learning in Cardiovascular Monitoring: Current Evidence and Future Directions for Precision Medicine

by Ayokunle Osonuga, Madhavi Dave, Ikponmwosa Jude Ogieuhi, David B. Olawade and Stergios Boussios

J. Pers. Med. 2026, 16(7), 377; https://doi.org/10.3390/jpm16070377 - 14 Jul 2026

Abstract

Cardiovascular disease remains the leading global health challenge, claiming approximately 19.8 million lives annually. The convergence of wearable technology and artificial intelligence represents a transformative shift in cardiovascular healthcare, enabling continuous real-time monitoring beyond conventional clinical settings. This narrative review synthesises current evidence [...] Read more.

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

(This article belongs to the Section Personalized Medical Care)

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25 pages, 2492 KB

Open AccessReview

Beyond Description: A Functional GIUS-Based Algorithm for Enteral Feeding Decisions in the ICU

by Nick Weidner, Christian von Löffelholz, Robert Patejdl, Jan Seyfferth and Heinrich Volker Groesdonk

J. Pers. Med. 2026, 16(7), 376; https://doi.org/10.3390/jpm16070376 - 14 Jul 2026

Abstract

Gastrointestinal dysfunction is common in critically ill patients and frequently compromises the delivery and tolerance of enteral nutrition. Traditional bedside markers such as gastric residual volume or nonspecific abdominal symptoms provide only limited diagnostic accuracy and often fail to capture dynamic alterations in [...] Read more.

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

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

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20 pages, 974 KB

Open AccessReview

TET Enzymes as Epigenetic Integrators in Intestinal Immunity, Inflammation, and Disease

by Dhirendra K. Singh, Yukihiro Yamaguchi, Lei Huang, Chieko Saito, Olivia G. Cassidy and Keita Nishiyama

J. Pers. Med. 2026, 16(7), 375; https://doi.org/10.3390/jpm16070375 - 14 Jul 2026

Abstract

DNA methylation plays a fundamental role in maintaining intestinal homeostasis, immune tolerance, and inflammatory balance. Active DNA demethylation, mediated by the ten-eleven translocation family of dioxygenases (TET1, TET2, and TET3), has emerged as an important epigenetic mechanism linking environmental and metabolic cues to [...] Read more.

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

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

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15 pages, 273 KB

Open AccessPerspective

From Association to Prediction: Translational Barriers in Pain Biomarker Research

by Gustavo Fabregat-Cid, Natalia Escrivá-Matoses and José De Andrés

J. Pers. Med. 2026, 16(7), 374; https://doi.org/10.3390/jpm16070374 - 13 Jul 2026

Abstract

Pain biomarkers have been proposed as potential tools to improve patient stratification, treatment selection, and individualized therapeutic strategies in chronic pain. However, despite an increasing volume of research across neuroimaging, electrophysiological, and molecular domains, their translation into clinical practice remains limited. A central [...] Read more.

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

(This article belongs to the Special Issue Personalized Pain Medicine: Biomarkers and New Therapeutic Frontiers)

16 pages, 542 KB

Open AccessSystematic Review

Fibular Nonunion: A Systematic Review of Incidence, Diagnosis, and Treatment Outcomes

by Virginia Cinelli, Federico Moretti, Chiara Comisi, Antonio Mascio, Gloria Assegbede, Vincenzo La Vergata, Giulio Maccauro, Carlo Perisano and Tommaso Greco

J. Pers. Med. 2026, 16(7), 373; https://doi.org/10.3390/jpm16070373 - 10 Jul 2026

Abstract

Background: Fibular nonunion is an uncommon but clinically relevant complication following fractures or surgical procedures, often resulting in persistent pain and functional impairment. Due to its rarity, current evidence remains limited and no standardized treatment guidelines are available. Purpose: To systematically review the [...] Read more.

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

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

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21 pages, 1237 KB

Open AccessArticle

Depression and Mood Changes in People with Parkinson’s Disease over Time: A 5-Year Follow-Up Study

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

J. Pers. Med. 2026, 16(7), 372; https://doi.org/10.3390/jpm16070372 - 10 Jul 2026

Abstract

Background and Objective: Depression is frequent in Parkinson’s disease (PD), but it is unclear how mood changes and impacts patient’s quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) [...] Read more.

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

(This article belongs to the Special Issue Depression and Anxiety: Recent Advances in Personalized Treatment and Management)

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11 pages, 682 KB

Open AccessArticle

Causal Effect and Personalization of Intraoperative Hypotension Burden on Postoperative Acute Kidney Injury: A Doubly Robust Analysis of the VitalDB Cohort

by Seung-Bo Lee

J. Pers. Med. 2026, 16(7), 371; https://doi.org/10.3390/jpm16070371 - 10 Jul 2026

Abstract

Background: Intraoperative hypotension (IOH) is the leading modifiable contributor to postoperative acute kidney injury (AKI), yet most evidence is associational and the heterogeneity of its effect is unknown. We estimated the causal effect of IOH burden on AKI and tested whether the [...] Read more.

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

(This article belongs to the Section Personalized Preventive Medicine)

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9 pages, 5957 KB

Open AccessCase Report

Prevertebral Abscess Revealing a Rare Foreign Body: A Case Report

by Theresa Mally, Nina Rubicz and Paul Martin Zwittag

J. Pers. Med. 2026, 16(7), 370; https://doi.org/10.3390/jpm16070370 - 9 Jul 2026

Abstract

Background: Migrated foreign bodies in the prevertebral region represent a rare but potentially serious condition. This case underscores the importance of thorough visual and digital intraoperative exploration for successful foreign body retrieval and highlights the potential diagnostic and surgical challenges associated with migrated [...] Read more.

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

(This article belongs to the Special Issue Clinical Diagnosis and Personalized Treatment in Otolaryngology)

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19 pages, 5763 KB

Open AccessArticle

Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB

by Kathleen D. McDaniel, Neda Ghousifam, Rodney A. Bowling, Jr., Catherine Z. Chen, Wei Zheng and Zeenat A. Shyr

J. Pers. Med. 2026, 16(7), 369; https://doi.org/10.3390/jpm16070369 - 8 Jul 2026

Abstract

Background: Mucopolysaccharidosis type IIIB (MPSIIIB, Sanfilippo syndrome type B) is a rare lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU) enzyme, leading to progressive accumulation of heparan sulfate and severe neurological decline. MPSIIIB’s significant genetic heterogeneity presents a major barrier to developing [...] Read more.

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

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

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11 pages, 1129 KB

Open AccessArticle

Evaluation of Prophylactic Defibrotide Use in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multicenter Retrospective Cohort Study

by Archana Ramgopal, Tsuyoshi Fujita, Breana K. Goscicki, Shiva Sridar, Daniel Klein, Li Wang, Ramasubramanian Kalpatthi and Jignesh Dalal

J. Pers. Med. 2026, 16(7), 368; https://doi.org/10.3390/jpm16070368 - 7 Jul 2026

Abstract

Background/Objectives: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a serious complication of hematopoietic stem cell transplantation (HSCT), particularly in high and very high-risk pediatric patients. Despite known risk factors, U.S. data remain limited. The benefit of prophylactic defibrotide is [...] Read more.

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

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

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24 pages, 410 KB

Open AccessReview

Perioperative Arrhythmias: Pathophysiology, Risk Stratification, Management, and Emerging Technologies—A Narrative Review Toward Personalised Care

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

J. Pers. Med. 2026, 16(7), 367; https://doi.org/10.3390/jpm16070367 - 4 Jul 2026

Abstract

Cardiac arrhythmias complicate 20–50% of surgical procedures and contribute substantially to perioperative morbidity, mortality, and healthcare costs, with postoperative atrial fibrillation (POAF) being the most frequent form. Their genesis reflects the convergence of surgical stress, anaesthetic agents, autonomic imbalance, systemic inflammation, and electrolyte [...] Read more.

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

(This article belongs to the Special Issue Advances in Atrial Fibrillation and Cardiac Arrhythmias: Mechanisms, Diagnosis, and Therapy)

23 pages, 1389 KB

Open AccessReview

Integration of Precision Medicine into ERAS Pathways: A Conceptual Framework, Current Feasibility and Challenges

by Berkan Aliev and Boyko Atanasov

J. Pers. Med. 2026, 16(7), 366; https://doi.org/10.3390/jpm16070366 - 4 Jul 2026

Abstract

Enhanced Recovery After Surgery (ERAS) pathways have improved perioperative outcomes by standardizing evidence-based interventions across the surgical continuum. However, substantial variability in postoperative recovery persists, even within well-implemented ERAS programs. This heterogeneity reflects differences in clinical risk, functional reserve, biological response to surgical [...] Read more.

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

(This article belongs to the Section Personalized Medical Care)

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13 pages, 4135 KB

Open AccessReview

Enhancing Precision in Lumbar Spine Surgery Through Spinal Endoscopy: A Narrative Review with Expert Opinion

by Bradley C. Nelson and Mark J. Lambrechts

J. Pers. Med. 2026, 16(7), 365; https://doi.org/10.3390/jpm16070365 - 4 Jul 2026

Abstract

Technological advances in spine surgery have allowed for significantly improved precision. Perhaps no technology has allowed for more personalized and precise surgery than endoscopic spine surgery. Although this technology has been around for decades, advancements in camera resolution have led to enhanced magnification [...] Read more.

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

(This article belongs to the Special Issue Precision Medicine in Spine Surgery: Updates and Challenges)

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15 pages, 1702 KB

Open AccessArticle

Implementation of Video Consultations Within a Personalized Hybrid Care Model for Children and Adolescents with Type 1 Diabetes Using Automated Insulin Delivery Systems: A Real-World Descriptive Study

by Isolina Riaño-Galan, Corsino Rey, María Bogaerts Marquez, Laura Muñoz, Rebeca García, César Bazó and Julián Rodríguez

J. Pers. Med. 2026, 16(7), 364; https://doi.org/10.3390/jpm16070364 - 4 Jul 2026

Abstract

Background: Telemedicine complements traditional healthcare delivery and may improve access, continuity of care, and patient engagement, particularly in chronic conditions requiring regular follow-up. Video consultation is a widely adopted telemedicine modality and is increasingly integrated into hybrid care models. Methods: This real-world implementation [...] Read more.

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

(This article belongs to the Section Personalized Medical Care)

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30 pages, 1072 KB

Open AccessReview

Towards a Multidimensional Model of Neurocognitive Disorders (MOND Model): Integrating Evidence from a Critical Review into a Model for Future Research

by Joana O. Pinto, Bruno Peixoto, Artemisa R. Dores and Fernando Barbosa

J. Pers. Med. 2026, 16(7), 363; https://doi.org/10.3390/jpm16070363 - 3 Jul 2026

Abstract

The main purpose of this work is to critically review the literature on neurocognitive disorders (ND) diagnosis. A critical review was conducted in PubMed, Scopus, and EBSCO. Systematic reviews and meta-analyses focusing on ND diagnosis were included. The selected studies were critically analyzed [...] Read more.

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

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

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18 pages, 3375 KB

Open AccessArticle

Real-World Phenotypic Profiles and Longitudinal Lung Function Outcomes in Severe Asthma Treated with Biologic Therapies

by Ourania S. Kotsiou, Georgios I. Barkas, Konstantinos I. Gourgoulianis and Zoe Daniil

J. Pers. Med. 2026, 16(7), 362; https://doi.org/10.3390/jpm16070362 - 3 Jul 2026

Abstract

Background: Biologic therapies have transformed severe asthma management, but real-world evidence comparing phenotypes, lung function trajectories, and persistence across biologic classes remains limited. Objective: To characterize a real-world cohort of biologic-treated severe asthma patients, focusing on baseline phenotypes, longitudinal post-bronchodilator spirometry (including a [...] Read more.

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

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14 pages, 2688 KB

Open AccessArticle

Deep Learning Prediction of Retinal Thickness from Near-Infrared Fundus Photography: Toward Decentralized Quantitative Assessment of Diabetic Macular Edema

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

J. Pers. Med. 2026, 16(7), 361; https://doi.org/10.3390/jpm16070361 - 2 Jul 2026

Abstract

Objective: To predict pixel-wise retinal thickness maps from near-infrared (NIR) fundus images using deep learning (DL), and to identify image features in NIR fundus photographs serving as surrogate markers of retinal thickness, with implications for decentralized diabetic macular edema (DME) screening, progression monitoring, [...] Read more.

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

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