Journal of Personalized Medicine

15 pages, 386 KB

Open AccessArticle

Serum Albumin, Globulin and Albumin–Globulin Ratios as Biomarkers of Clinical Outcomes in COVID-19 Pneumonia

by Rauno Joks, Tamar Smith-Norowitz, Shawn Mathew, Mansi R. Kothari and Sairaman Nagarajan

J. Pers. Med. 2026, 16(6), 336; https://doi.org/10.3390/jpm16060336 - 22 Jun 2026

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Objective: Low serum albumin has been linked to morbidity and mortality in critically ill patients, including those with COVID-19. Whether serum globulin levels and albumin/globulin ratios (AGRs) can serve as biomarkers in COVID-19 is less well-characterized. This study assessed serum total protein, [...] Read more.

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

(This article belongs to the Section Disease Biomarkers)

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20 pages, 634 KB

Open AccessReview

Three-Dimensional Bronchovascular Modelling in Sublobar Pulmonary Resection: A Tool for Personalised Thoracic Surgery

by Victor A. Shahen and Cheng-Hon Yap

J. Pers. Med. 2026, 16(6), 335; https://doi.org/10.3390/jpm16060335 - 22 Jun 2026

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Abstract

Sublobar pulmonary resection has become an increasingly adopted approach for early-stage non-small cell lung cancer, driven by evidence that anatomical segmentectomy can achieve oncological outcomes comparable to lobectomy in selected patients. Safe execution of sublobar resection depends on accurate preoperative identification of segmental [...] Read more.

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

(This article belongs to the Special Issue Personalized Cardiothoracic Surgery: Treatment and Management)

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2 pages, 141 KB

Open AccessCorrection

Correction: Rao et al. Ensemble Deep-Learning-Based Prognostic and Prediction for Recurrence of Sporadic Odontogenic Keratocysts on Hematoxylin and Eosin Stained Pathological Images of Incisional Biopsies. J. Pers. Med. 2022, 12, 1220

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

J. Pers. Med. 2026, 16(6), 334; https://doi.org/10.3390/jpm16060334 - 22 Jun 2026

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Abstract

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

(This article belongs to the Special Issue Recent Advances and Personalized Treatment in Dental Health)

6 pages, 201 KB

Open AccessEditorial

New Advances and Perspectives in Ophthalmology: Progress and Modern Challenges Toward Personalized Eye Care

by Livio Vitiello

J. Pers. Med. 2026, 16(6), 333; https://doi.org/10.3390/jpm16060333 - 22 Jun 2026

Viewed by 550

Abstract

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

(This article belongs to the Special Issue New Advances and Perspectives in Ophthalmology: Progress and Modern Challenges)

21 pages, 673 KB

Open AccessReview

Bridging Ancestry-Stratified Bias in Pharmacogenomics AI: Toward Metabolomics-Inclusive Multi-Omics Precision Medicine

by Heayyean Lee, Khadijah Sajid and Dayeon Lee

J. Pers. Med. 2026, 16(6), 332; https://doi.org/10.3390/jpm16060332 - 20 Jun 2026

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Abstract

Pharmacogenomics AI offers significant potential for individualized drug therapy; however, its clinical benefits remain unevenly distributed. Models trained predominantly on European-ancestry data consistently underperform in non-European populations, with polygenic risk scores (PRS) showing an estimated 39–73% reduction in predictive accuracy in African-ancestry cohorts [...] Read more.

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

(This article belongs to the Section Omics/Informatics)

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19 pages, 597 KB

Open AccessReview

Hormone-Driven Growth Signaling as a Therapeutic Target in Acute Myeloid Leukemia: Implications for Drug-Resistant Disease

by Joel Costoya and Joaquin J. Jimenez

J. Pers. Med. 2026, 16(6), 331; https://doi.org/10.3390/jpm16060331 - 20 Jun 2026

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Abstract

Growth hormone-releasing hormone (GHRH) antagonists have displayed anti-neoplastic activity against a multitude of cancers in vitro, as well as in vivo, via xenografted tumors in nude mice. Following a successful demonstration of GHRH antagonists treating non-Hodgkin’s lymphoma and the discovery of GHRH mRNA [...] Read more.

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

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

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11 pages, 871 KB

Open AccessReview

Circulating Tumor DNA in Merkel Cell Carcinoma: A Precision Biomarker for Recurrence Detection and Therapeutic Guidance

by Joshua E. Chan and Lisa C. Zaba

J. Pers. Med. 2026, 16(6), 330; https://doi.org/10.3390/jpm16060330 - 20 Jun 2026

Viewed by 577

Abstract

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA [...] Read more.

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

(This article belongs to the Special Issue Cell-Free Nucleic Acids as Precision Biomarkers for Therapeutic Decision-Making Across Diseases)

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26 pages, 1143 KB

Open AccessReview

Pharmacogenomics and Epigenetic Regulation Transforming Pediatric Precision Therapeutics

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

J. Pers. Med. 2026, 16(6), 329; https://doi.org/10.3390/jpm16060329 - 19 Jun 2026

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Abstract

Pediatric drug therapy remains fundamentally challenged by profound interindividual variability driven by dynamic development, genetic, and environmental factors. Although dosing strategies based on age, body weight, or body surface area remain important starting points in pediatric pharmacotherapy, they may not fully capture ontogeny-dependent [...] Read more.

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

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

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21 pages, 618 KB

Open AccessReview

Nanomedicine in Cardiovascular Inflammation: Novel Diagnostic and Therapeutic Strategies

by Aikaterini-Eleftheria Karanikola, Agapi Ploussi, Dimitrios Tsiachris and Efstathios P. Efstathopoulos

J. Pers. Med. 2026, 16(6), 328; https://doi.org/10.3390/jpm16060328 - 18 Jun 2026

Viewed by 715

Abstract

Inflammation plays a central role in the pathogenesis and progression of cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. Despite advances in conventional diagnostic and therapeutic strategies, limitations in sensitivity, specificity and targeted drug delivery still remain. Nanomedicine has emerged as a [...] Read more.

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

(This article belongs to the Special Issue Personalized Prevention and Treatment of Cardiovascular Diseases)

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11 pages, 506 KB

Open AccessArticle

Factors Associated with Adverse Neonatal Outcomes in Complete Rupture of the Pregnant Uterus: A Single-Center Cohort Study

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

J. Pers. Med. 2026, 16(6), 327; https://doi.org/10.3390/jpm16060327 - 18 Jun 2026

Viewed by 495

Abstract

Objective: This study aimed to evaluate clinical characteristics and outcomes of complete uterine rupture during pregnancy and identify factors associated with adverse neonatal outcomes. Methods: This retrospective cohort study analyzed data from a single center between January 2008 and July 2024. [...] Read more.

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

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

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18 pages, 503 KB

Open AccessReview

Immune Cell Therapy Promises More Effective Cure for Medulloblastoma

by Marco Agostini, Pietro Traldi and Mahmoud Hamdan

J. Pers. Med. 2026, 16(6), 326; https://doi.org/10.3390/jpm16060326 - 18 Jun 2026

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Abstract

Medulloblastoma is one of the most prevalent pediatric brain tumors. Currently, existing therapies for this devastating type of cancer can only prolong survival time with severe side-effects and relapse. These therapies are not curative for almost a third of treated patients, while most [...] Read more.

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

(This article belongs to the Special Issue Novel Challenges and Advances in Neuro-Oncology)

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6 pages, 190 KB

Open AccessEditorial

Special Issue—Diabetes Mellitus: Current Research and Future Perspectives, 2nd Edition

by Evelina Maines and Roberto Franceschi

J. Pers. Med. 2026, 16(6), 325; https://doi.org/10.3390/jpm16060325 - 17 Jun 2026

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Abstract

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

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

17 pages, 275 KB

Open AccessReview

AI and Its Shifting Roles in the Therapeutic Relationship: Implications for Precision Medicine

by Michael Igoumenidis and Venetia-Sofia Velonaki

J. Pers. Med. 2026, 16(6), 324; https://doi.org/10.3390/jpm16060324 - 17 Jun 2026

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Abstract

The emergence and increasing use of artificial intelligence (AI) in healthcare have paved the way for highly personalized and time-saving approaches in the field of precision medicine. It can be applied to determine a prognosis, diagnosis, and recommended treatment, and may also be [...] Read more.

The emergence and increasing use of artificial intelligence (AI) in healthcare have paved the way for highly personalized and time-saving approaches in the field of precision medicine. It can be applied to determine a prognosis, diagnosis, and recommended treatment, and may also be used for patient monitoring. As AI applications become more widely available, reliable and easy to use, they are rapidly reshaping the traditional roles of professionals and patients in the therapeutic relationship. On the positive side, professionals may have more time to communicate with patients and provide individualized care, whereas patients may become more empowered and autonomous due to AI-facilitated personalized information and monitoring. On the negative side, AI applications threaten to reduce the role of professionals to a mediating one in clinical decision-making, provide patients with misinformation, and lead to misunderstandings that hinder patients’ autonomy. In this narrative review, we examine the main ethical issues related to the AI-induced shift in roles in the therapeutic relationship, within four inter-related themes: the validity of claims that algorithms outperform humans in certain tasks; the ways in which AI saves time for health professionals but also takes time to properly explain and implement; the issues of trust and accountability, especially if AI suggestions lead to patient harm; and what AI’s alleged cost-effectiveness means for professionals’ employment and remuneration. Across the three roles, we find a common pattern: AI tends to absorb the technical and data-processing parts of clinical work while leaving its relational core to humans. Physicians move toward oversight and interpretation, nurses retain the attentiveness and responsiveness that define care, and patients gain tools for self-management that can widen autonomy or, left unguided, erode it. Whether the overall effect is benign depends less on the technology than on how outperformance is evidenced, how the freed time is used, how trust and accountability are anchored in people, and how cost pressures are managed. The article concludes with some suggestions for prudent use of AI in healthcare, indicating the appropriate measures that can be used to harness the power of AI without damaging the traditional cornerstones of the therapeutic relationship. Full article

(This article belongs to the Special Issue Bioethics in Personalized Medicine and Precision Medicine)

12 pages, 805 KB

Open AccessArticle

Systemic Immune–Inflammation Index (SII) as a Predictive Biomarker of Therapeutic Response in Psoriasis: A Retrospective Comparative Analysis of Anti-TNF, Anti-IL-17, and Anti-IL-23 Agents

by Emanuele Trovato, Francesca La Marca, Benedetta Simonini, Martina Dragotto, Enrico Calandra, Francesca Lussana, Alessandra Cartocci and Pietro Rubegni

J. Pers. Med. 2026, 16(6), 323; https://doi.org/10.3390/jpm16060323 - 16 Jun 2026

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Abstract

Background/Objectives: The Systemic Immune–Inflammation Index (SII), derived from routine blood counts, has emerged as a potential marker of systemic inflammation in psoriasis. However, its longitudinal behavior across different systemic and biologic therapies remains poorly characterized. This study aimed to evaluate changes in SII [...] Read more.

Background/Objectives: The Systemic Immune–Inflammation Index (SII), derived from routine blood counts, has emerged as a potential marker of systemic inflammation in psoriasis. However, its longitudinal behavior across different systemic and biologic therapies remains poorly characterized. This study aimed to evaluate changes in SII over time, assess its relationship with Psoriasis Area and Severity Index (PASI) scores, and compare SII trajectories among different treatment classes. Methods: A retrospective single-center study included 210 adults with psoriasis treated for 12 months with cyclosporine, anti-TNF-α, anti-IL-17, or anti-IL-23 agents. SII and PASI were recorded at baseline, 16, 36, and 52 weeks. Correlations between SII and PASI were assessed using Spearman’s analysis. Longitudinal changes were evaluated using the Friedman test, and treatment-group differences were assessed using Kruskal–Wallis analysis. An adjusted multivariable linear regression model including age, sex, body mass index, psoriatic arthritis, baseline PASI, and treatment group was performed to identify factors associated with Δ%SII. Results: SII correlated with PASI at baseline (ρ = 0.406, p < 0.001) and at 52 weeks (ρ = 0.186, p = 0.007), whereas no significant associations were observed at intermediate timepoints. Longitudinal analyses demonstrated significant differences in SII trajectories among treatment groups (p < 0.001). SII increased over time in the cyclosporine and anti-TNF-α groups, while anti-IL-17 and anti-IL-23 therapies were associated with marked and sustained reductions. In the adjusted model, anti-IL-17 (β = −90.7, 95% CI −119.6 to −61.8, p < 0.001) and anti-IL-23 therapies (β = −97.9, 95% CI −126.2 to −69.6, p < 0.001) remained independently associated with greater reductions in SII compared with cyclosporine, whereas anti-TNF therapy showed no significant difference. Conclusions: SII is a dynamic marker of systemic inflammatory changes in psoriasis and exhibits distinct longitudinal patterns according to treatment class. The pronounced reductions observed with IL-17 and IL-23 inhibitors support the potential value of SII as an adjunctive measure of systemic inflammation. However, prospective studies are required to clarify its clinical utility and determine its role in routine patient management. Full article

(This article belongs to the Special Issue Personalized Medicine in Dermatology: Current Status and Challenges)

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30 pages, 4486 KB

Open AccessReview

Cardiovascular Imaging for the Early Detection of Cardiotoxicity from Emerging Cancer Therapies: Mechanistic Insights Across the Pediatric and Adult Spectrum

by Camilla Calvieri, Isabella Leo, Jessica Ielapi, Giulia Guglielmi, Gian Luca Ragazzoni, Vincenzo D’Ambrosio, Leonie Luedke and Sara Moscatelli

J. Pers. Med. 2026, 16(6), 322; https://doi.org/10.3390/jpm16060322 - 15 Jun 2026

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Abstract

Cancer therapies have significantly improved survival but are frequently limited by cancer therapy-related cardiovascular toxicity (CTR-CVT). Cardiovascular imaging plays a central role in baseline risk stratification, surveillance during therapy and long-term follow-up. Transthoracic echocardiography (TTE) remains the first-line imaging modality; however, conventional parameters [...] Read more.

Cancer therapies have significantly improved survival but are frequently limited by cancer therapy-related cardiovascular toxicity (CTR-CVT). Cardiovascular imaging plays a central role in baseline risk stratification, surveillance during therapy and long-term follow-up. Transthoracic echocardiography (TTE) remains the first-line imaging modality; however, conventional parameters such as left ventricular ejection fraction (LVEF) often fail to detect early myocardial injury. Myocardial deformation imaging, particularly global longitudinal strain (GLS), has emerged as a sensitive marker of subclinical dysfunction across multiple cardiotoxic phenotypes. Cardiac magnetic resonance (CMR) further enhances diagnostic accuracy through tissue characterization techniques, enabling the detection of myocardial edema, inflammation, and fibrosis before overt functional decline. Different anticancer therapies induce distinct pathophysiological mechanisms of injury, each associated with characteristic imaging patterns. Emerging imaging biomarkers and multimodality approaches may improve early detection, the spatial characterization of myocardial injury and individualized surveillance strategies. Pediatric patients represent a uniquely vulnerable population due to their myocardial immaturity, altered pharmacokinetics and prolonged post-treatment life expectancy, resulting in a higher cumulative lifetime cardiovascular risk. In conclusion, a mechanism-based multimodality imaging approach integrating echocardiography, CMR and emerging data-driven technologies is essential to optimize early detection, risk stratification and long-term cardiovascular outcomes in both adult and pediatric cardio-oncology populations. Full article

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

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16 pages, 1139 KB

Open AccessArticle

Twelve-Month Real-World Outcomes of Tezepelumab in Severe Asthma: Clinical Remission, Biomarker Changes, and Trigger Burden—A SANI Multicenter Cohort

by Stefania Nicola, Simone Negrini, Fulvia Ribolla, Giuseppe Guida, Rocco Francesco Rinaldo, Benedetta Bondi, Iuliana Badiu, Federica Corradi, Anna Quinternetto, Ilaria Vitali, Luca Lo Sardo, Benedetta Crida, Linda Mhimid, Sofia Luisa Tocci, Marcelo Teocchi, Asia Milione, Marta Marengo, Enrico Heffler, Giorgio Walter Canonica, Francesco Blasi, Pierluigi Paggiaro, Marzia Boem, Stefania Basiglio, Lucrezia Alessi, Fulvio Braido, Fabio Luigi Massimo Ricciardolo, Paolo Solidoro, Diego Bagnasco, Luisa Brussino and on behalf of the SANI Study Group Show full author list Hide full author list

J. Pers. Med. 2026, 16(6), 321; https://doi.org/10.3390/jpm16060321 - 15 Jun 2026

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Abstract

Background/Objectives: Tezepelumab targets thymic stromal lymphopoietin and has broad efficacy in severe asthma, yet real-world evidence on patient-reported trigger burden remains limited. We assessed 12-month outcomes after tezepelumab, focusing on clinical remission, biomarkers, and trigger profiling as complementary dimensions of response. Methods [...] Read more.

Background/Objectives: Tezepelumab targets thymic stromal lymphopoietin and has broad efficacy in severe asthma, yet real-world evidence on patient-reported trigger burden remains limited. We assessed 12-month outcomes after tezepelumab, focusing on clinical remission, biomarkers, and trigger profiling as complementary dimensions of response. Methods: In this multicenter longitudinal real-world observational cohort based on routine clinical follow-up and Severe Asthma Network in Italy (SANI) registry data, 43 adults with severe asthma treated with tezepelumab at four Italian SANI reference centers were evaluated at baseline and, when available, after 1, 3, 6, and 12 months. Outcomes included exacerbations, lung function, type 2 biomarkers, the Asthma Control Test, SNOT-22, trigger categories, Asthma Trigger Inventory (ATI) scores, and SANI-defined clinical remission. Results: Among 22 patients with 12-month follow-up data, mean annualized exacerbations decreased from 4.30 ± 2.77 to 0.36 ± 0.49 (p < 0.001), and 14/22 (63.6%) were exacerbation-free. Asthma control improved, whereas FEV1 remained stable. FeNO and blood eosinophils decreased at selected time points. The number of reported trigger categories was lower at 6 months (p < 0.001), and physical exertion, smoke, irritants, and infection-related ATI domains improved longitudinally. Complete clinical remission was achieved in 5/22 patients (22.7%). Conclusions: Tezepelumab was associated with reduced exacerbations, improved asthma control, and lower patient-reported trigger burden. Structured trigger profiling may provide an exploratory patient-centered dimension for assessing treatment response in severe asthma. Full article

(This article belongs to the Special Issue Mechanisms of Airway Inflammation in Asthma)

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14 pages, 1935 KB

Open AccessArticle

Layer-Specific Retinal Perfusion as a Personalized Biomarker: Evaluating the Subclinical Microanatomical Effects of Intracameral Cefuroxime After Routine Cataract Surgery

by Chia-Yu Wang, Chun-Yao Cheng and Yi-Jie Peng

J. Pers. Med. 2026, 16(6), 320; https://doi.org/10.3390/jpm16060320 - 15 Jun 2026

Viewed by 419

Abstract

Background/Objectives: The objective of this study was to evaluate macular perfusion changes after intracameral injection (ICI) of cefuroxime at the end of phacoemulsification. Methods: Patients who underwent routine phacoemulsification were enrolled. Subjects in the case group had ICI 1 mg/0.1 mL [...] Read more.

Background/Objectives: The objective of this study was to evaluate macular perfusion changes after intracameral injection (ICI) of cefuroxime at the end of phacoemulsification. Methods: Patients who underwent routine phacoemulsification were enrolled. Subjects in the case group had ICI 1 mg/0.1 mL cefuroxime at the end of surgery. Using optical coherence tomography angiography (OCT-A), macular perfusions were assessed at T0 (before surgery), T1, T10, T30, and T90 (days after surgery). Perfusion parameters were calculated in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Independent t-tests were used to compare the changes from baseline in each parameter between groups. Results: A total of 33 eyes in the case group and 27 eyes in the control group were enrolled. After surgery, the case group showed a less pronounced reduction in the foveal avascular zone (FAZ) in the DCP at T10 (−0.06 ± 0.23 vs. −0.18 ± 0.18 mm², p = 0.041) and T30 (−0.04 ± 0.20 vs. −0.16 ± 0.24 mm², p = 0.050). At T90, there was no statistically significant difference in the FAZ change in the DCP between the groups. The postoperative changes in the vessel density, skeleton density, and acircularity index of the FAZ in the SCP and DCP, central retinal thickness, and best-corrected visual acuity were similar between the groups in all 3 months. Conclusions: Our findings indicate that intraoperative ICI low-dose cefuroxime is associated with a temporary deceleration in FAZ reduction in the DCP during the first postoperative month. From a personalized medicine perspective, these layer-specific microanatomic variations suggest that, while prophylactic cefuroxime is globally safe—demonstrating no evidence of inducing capillary dropout, aggravating macular thickening, or compromising visual outcomes within this cohort—preoperative and postoperative OCT-A monitoring can serve as an individualized screening framework to track subclinical perfusion dynamics, especially in patients with compromised retinal baselines. Full article

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13 pages, 502 KB

Open AccessReview

Sulforaphane as a Photoprotective Agent Against UV-Induced Skin Damage and Carcinogenesis: A Scoping Review

by Marco Di Filippo, Giovanni Paolino, Matteo Riccardo Di Nicola, Norbert Kiss, András Bánvölgyi, Giulio Bortone, Steven Paul Nisticò, Elia Zampini, Giovanni Pellacani and Carmen Cantisani

J. Pers. Med. 2026, 16(6), 319; https://doi.org/10.3390/jpm16060319 - 14 Jun 2026

Viewed by 977

Abstract

Background/Objectives: Ultraviolet (UV) radiation is a major environmental carcinogen responsible for skin damage through oxidative stress, DNA damage, and inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a central role in regulating cellular antioxidant defences against UV-induced damage. This [...] Read more.

Background/Objectives: Ultraviolet (UV) radiation is a major environmental carcinogen responsible for skin damage through oxidative stress, DNA damage, and inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a central role in regulating cellular antioxidant defences against UV-induced damage. This scoping review aims to evaluate the potential role of sulforaphane (SFN), a known Nrf2 inducer, in protecting against UV-induced skin damage and photocarcinogenesis. Methods: A literature search was conducted in PubMed and Scopus from inception to 27 January 2026, to identify original experimental studies investigating SFN, glucoraphanin, or broccoli sprout extracts in the context of UV-induced skin damage. Eligible studies included in vitro, ex vivo, in vivo, and human models assessing outcomes related to oxidative stress, inflammation, molecular signalling pathways, and tumour development. Following screening and eligibility assessment, twelve studies were included in the qualitative synthesis. Results: The included studies suggest that SFN exerts photoprotective effects across multiple experimental models. In murine studies, SFN and SFN-rich extracts were associated with a reduction in tumour incidence, multiplicity, and volume following UV exposure. In human studies, topical SFN application reduced UV-induced erythema and induced cytoprotective enzyme expression, although clinical evidence remains limited. Mechanistically, SFN consistently activated the Nrf2 pathway, leading to increased expression of antioxidant and phase II detoxifying enzymes, and was associated with modulation of inflammatory responses and inhibition of MAPK/AP-1 signalling. Emerging evidence also indicates potential effects on UV-induced metabolic and epigenetic alterations. Conclusions: Current evidence supports a potential role for sulforaphane in mitigating UV-induced skin damage through activation of endogenous defence pathways. However, the available data are predominantly preclinical, and further well-designed clinical studies are needed to clarify its efficacy and translational relevance in humans. Full article

(This article belongs to the Special Issue Personalized Prevention, Diagnosis and Treatment of Skin Disorders)

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13 pages, 794 KB

Open AccessReview

An Individualized Right-to-Left Tunneling “Bail-Out” for Complex ICD Upgrade in a Pacemaker-Dependent Patient: A Case Report and Literature Review

by Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Sotiria G. Giotaki, Christos Piperis, Maria S. Kousta, Ioannis Anagnostopoulos, Christos Karavasilis, Gerasimos Deftereos, Georgios Giannopoulos, Sotirios Patsilinakos, Gerasimos Siasos and Spyridon Deftereos

J. Pers. Med. 2026, 16(6), 318; https://doi.org/10.3390/jpm16060318 - 14 Jun 2026

Viewed by 589

Abstract

Inadequate vein access is a frequent obstacle during cardiac implantable electronic device (CIED) upgrade procedures; thus, bail-out strategies are employed. A 71-year-old male with dilated cardiomyopathy bearing a 7-year-old right-sided dual-chamber pacemaker was scheduled for upgrade to an implantable cardioverter defibrillator. The case [...] Read more.

Inadequate vein access is a frequent obstacle during cardiac implantable electronic device (CIED) upgrade procedures; thus, bail-out strategies are employed. A 71-year-old male with dilated cardiomyopathy bearing a 7-year-old right-sided dual-chamber pacemaker was scheduled for upgrade to an implantable cardioverter defibrillator. The case presented two main challenges—first, pacemaker dependency, and second, an occluded right subclavian vein. In a shared decision-making approach, the decision was made to “abandon” the right-sided ventricular lead in situ, reposition the right-sided atrial lead by tunneling over the sternum into the left pectoral area, and implant a new left-sided defibrillator lead. During the 2-year follow-up our patient remained clinically stable and the CIED fully functional. Herein, beyond case presentation we also elaborate on individualized alternative treatment strategies for patients with venous access site occlusion in a literature review. Full article

(This article belongs to the Special Issue New Insights into Cardiac Electrophysiology and Personalized Medicine)

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14 pages, 631 KB

Open AccessReview

Non-Operative Management of Esophageal Cancer with Complete Clinical Response After Neoadjuvant Therapy: Current Status and Future Directions

by Sofia Bertona, Javier Castillo and Francisco Schlottmann

J. Pers. Med. 2026, 16(6), 317; https://doi.org/10.3390/jpm16060317 - 13 Jun 2026

Viewed by 778

Abstract

Introduction: Esophagectomy has traditionally been considered mandatory after neoadjuvant therapy for locally advanced esophageal cancer. However, recent evidence has challenged this paradigm and motivated interest in organ-preservation strategies with active surveillance in patients achieving clinical complete response (cCR). Methods: A literature [...] Read more.

Introduction: Esophagectomy has traditionally been considered mandatory after neoadjuvant therapy for locally advanced esophageal cancer. However, recent evidence has challenged this paradigm and motivated interest in organ-preservation strategies with active surveillance in patients achieving clinical complete response (cCR). Methods: A literature search was performed using PubMed/MEDLINE, ScienceDirect, and Embase databases to identify relevant studies related to non-operative management (NOM) of esophageal cancer. Evidence was synthesized qualitatively with a critical focus on the biological rationale of NOM, diagnostic limitations of response-assessment, oncologic outcomes associated with surveillance strategies and the evolving role of molecular biomarkers. Results: The safety of NOM with active surveillance is tightly linked to the diagnostic accuracy of response assessment. Although structured multimodal response assessment protocols combining endoscopy, endoscopic ultrasound, and PET-CT have shown acceptable performance, residual clinically undetectable disease might persist in some patients. Evidence from the SANO trial has suggested non-inferior short-term survival outcomes of NOM compared with immediate esophagectomy in carefully selected patients with cCR after neoadjuvant chemoradiotherapy treated within specialized centers. Nevertheless, long-term oncologic outcomes remain unknown, and uncertainty persists regarding the broader applicability of this strategy outside specialized multidisciplinary settings. Emerging biomarker-driven approaches including PD-L1 expression, microsatellite instability, and circulating tumor DNA (ctDNA) may further refine response assessment and help identify patients most suitable for organ-preservation strategies. Conclusions: Active surveillance represents a promising alternative to immediate esophagectomy in selected patients with cCR after neoadjuvant therapy. However, further studies with longer follow-up and standardized surveillance protocols are still needed to safely implement this strategy outside trial settings. Full article

(This article belongs to the Special Issue Personalized Oncology in Gastrointestinal Cancer: Emerging Therapies and Challenges)

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19 pages, 3846 KB

Open AccessReview

Extrachromosomal DNA Amplification as a Prognostic Factor for Cancer

by Filip Gajewski, Joanna Pec, Jakub Kleinrok, Weronika Pająk, Katarzyna Pacyna, Agata Tokarzewska and Paweł Krawczyk

J. Pers. Med. 2026, 16(6), 316; https://doi.org/10.3390/jpm16060316 - 12 Jun 2026

Viewed by 812

Abstract

Background: Extrachromosomal DNA (ecDNA) amplification represents a distinct mechanism of genomic instability in cancer, increasingly recognized for its role in aggressive disease progression. This review examines how ecDNA drives tumour evolution and assesses its potential as both a prognostic marker and therapeutic target. [...] Read more.

Background: Extrachromosomal DNA (ecDNA) amplification represents a distinct mechanism of genomic instability in cancer, increasingly recognized for its role in aggressive disease progression. This review examines how ecDNA drives tumour evolution and assesses its potential as both a prognostic marker and therapeutic target. Methods: The authors integrate findings from multiple detection platforms—including FISH, whole-genome sequencing, and specialized reconstruction algorithms—and present data across diverse cancer types; no preregistration is noted, and no animal studies are included. Results: ecDNA consists of circular, acentric DNA elements carrying high-copy oncogene amplifications (such as EGFR, MYC, MDM2, and CDK4). Unlike chromosomal DNA, ecDNA segregates unevenly during cell division, generating intratumoral heterogeneity, accelerating adaptation to selective pressures, and promoting resistance to therapy. Pan-cancer surveys summarized here reveal ecDNA in a significant subset of tumours, with particularly high frequencies in liposarcoma, glioblastoma, and HER2-positive breast cancer, and consistent associations with worse clinical outcomes. Conclusions: The authors conclude that ecDNA amplification serves as a credible adverse prognostic indicator and holds promise for refining risk stratification and guiding treatment strategies. However, they stress that clinical adoption remains constrained by the absence of standardized, scalable, and reproducible detection. Full article

(This article belongs to the Special Issue Current Trends of Precision Medicine in Oncology)

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37 pages, 1403 KB

Open AccessReview

A Pressure-Centered Mechanistic Framework for Precision Otology: The Neuro–Vascular–Mechanical–Inflammatory–Autonomic (NVMIA) Regulatory Architecture

by Hee-Young Kim

J. Pers. Med. 2026, 16(6), 315; https://doi.org/10.3390/jpm16060315 - 12 Jun 2026

Viewed by 520

Abstract

Eustachian tube dysfunction (ETD) and related pressure-mediated otologic disorders often present with fluctuating auditory, vestibular, and pressure-related symptoms that are difficult to explain using static structural or symptom-based diagnostic labels alone. This conceptual review proposes the Neuro–Vascular–Mechanical–Inflammatory–Autonomic (NVMIA) framework as a hypothesis-generating architecture [...] Read more.

Eustachian tube dysfunction (ETD) and related pressure-mediated otologic disorders often present with fluctuating auditory, vestibular, and pressure-related symptoms that are difficult to explain using static structural or symptom-based diagnostic labels alone. This conceptual review proposes the Neuro–Vascular–Mechanical–Inflammatory–Autonomic (NVMIA) framework as a hypothesis-generating architecture for organizing such variability. Within this framework, middle ear pressure (MEP) is interpreted as a clinically measurable physiologic variable through which interacting neural, vascular, mechanical, inflammatory, and autonomic influences may become mechanically expressed and clinically observable. The framework does not present NVMIA-based patterns as validated diagnostic categories, clinical decision tools, or treatment algorithms. Rather, it proposes provisional regulatory patterns that may help generate testable hypotheses regarding pressure-regulatory instability, cross-axis coupling, symptom fluctuation, and physiologic reversibility. Mechanical impedance may function as an accessible reference plane for future empirical assessment, while neural, vascular, inflammatory, and autonomic domains are conceptualized as modulatory axes that may alter symptom expression and response variability. The review further outlines future validation needs, including dynamic MEP measurement, patient-reported outcome integration, longitudinal response assessment, and cautious computational modeling. By reframing ETD as a model of state-dependent regulatory instability, the NVMIA framework provides a conceptual basis for future studies in precision otology while emphasizing that prospective validation is required before clinical implementation. Full article

(This article belongs to the Special Issue Precision Medicine in Otorhinolaryngology: From Diagnostics to Personalized Therapy)

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18 pages, 2592 KB

Open AccessArticle

Knee Osteoarthritis Severity Grading Using Contrastive Learning Image Pre-Training

by Sedigh Abdalla Bashir, Rabeeah S. Altarhouni, Mohamed Burid Milad, Fauzia Ali Abuhtna, Mansor Masaud Wafi, Ellafi. A. Elbahri, Esam Alsadiq Alshareef, Mohammad Khaleel Sallam Ma’aitah, Esraa Alsariera and Ainur Toigozhinova

J. Pers. Med. 2026, 16(6), 314; https://doi.org/10.3390/jpm16060314 - 12 Jun 2026

Viewed by 771

Abstract

Background/Objectives: Accurate evaluation of knee osteoarthritis (KOA) severity is critical for optimal patient care, yet manual radiographic grading remains subject to observer variability. This study aims to evaluate the performance of a fine-tuned contrastive language–image pre-training (CLIP) framework designed to assist clinicians [...] Read more.

Background/Objectives: Accurate evaluation of knee osteoarthritis (KOA) severity is critical for optimal patient care, yet manual radiographic grading remains subject to observer variability. This study aims to evaluate the performance of a fine-tuned contrastive language–image pre-training (CLIP) framework designed to assist clinicians in grading KOA severity in plain radiographs using the Kellgren–Lawrence (KL) classification system (Grades 0–4). Methods: The model operates by projecting visual features from radiographs and standard textual clinical descriptions into a shared embedding space. Training was conducted using 8260 posterior–anterior (PA) fixed-flexion X-ray images from the Osteoarthritis Initiative (OAI) dataset. For robust external evaluation across distinct data distributions, the model was tested on an independent dataset consisting of 1650 plain radiographs. Results: When evaluated on the external validation dataset, the fine-tuned CLIP model achieved an accuracy of 76.94% and an F1-score of 76.66%. Comparative analysis demonstrates that these aligned vision-language representations provide competitive, stable diagnostic capabilities even when applied to an entirely independent data distribution. Conclusions: Fine-tuned CLIP architectures offer a viable and valuable foundation for semantically transparent, computer-aided evaluation of KOA. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Personalized Medicine: Diagnosis and Treatment)

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12 pages, 242 KB

Open AccessArticle

Personalized Combination of a Ketogenic Diet and Low-Dose Semaglutide for Cardiometabolic Health: A Retrospective Case Series

by Genevieve Parker, Madeline D. Morris, Jeter R. Heggie, Ella F. Cooper-Leavitt, Cameron J. Clark, Asher P. Reynolds, Holly A. Smith, Carlie P. Wendel, William J. Jensen, Tyson J. Morris, Paul R. Reynolds and Benjamin T. Bikman

J. Pers. Med. 2026, 16(6), 313; https://doi.org/10.3390/jpm16060313 - 12 Jun 2026

Viewed by 3856

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated efficacy for weight loss in obesity; however, up to 40% of weight lost may derive from lean body mass. The ketogenic diet independently improves insulin sensitivity and promotes fat oxidation while preserving [...] Read more.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated efficacy for weight loss in obesity; however, up to 40% of weight lost may derive from lean body mass. The ketogenic diet independently improves insulin sensitivity and promotes fat oxidation while preserving lean tissue. This study aimed to describe changes in body composition, insulin sensitivity, and cardiometabolic markers in patients who followed a personalized ketogenic dietary protocol while receiving low-dose semaglutide over a 6-month insulin resistance reversal program. Methods: Seven analyzed adults (six female, one male) with overweight or obesity (baseline BMI 25.6–47.2 kg/m²) participated in a clinician-supervised 6-month program combining a whole-food ketogenic diet with semaglutide (≤1.0 mg/week). Body composition and fasting metabolic markers were assessed at 1, 3, and 6 months. Results: Mean total weight loss was 21.9 kg, of which a mean of 92% was attributable to BIA-estimated fat mass. Skeletal muscle mass was largely preserved as measured by BIA (mean loss 1.2 kg), and one patient gained lean tissue. Fasting insulin declined by a mean of 15.6 µIU/mL. Visceral fat decreased by a mean of 37.0%. Six of seven patients showed reductions in high-sensitivity C-reactive protein. Triglycerides decreased in six of seven patients, and HDL cholesterol increased in all seven. LDL cholesterol responses were heterogeneous. Conclusions: In this small, uncontrolled case series, combining a ketogenic diet with low-dose semaglutide was associated with substantial fat loss, apparent preservation of lean mass as measured by BIA, and improvements in insulin sensitivity and cardiometabolic markers. Because the semaglutide dose and dietary protocol were individualized to each patient’s response, the program illustrates a personalized approach to insulin resistance. These preliminary findings are hypothesis-generating and warrant confirmation in controlled prospective studies. Full article

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

11 pages, 499 KB

Open AccessArticle

Pancreatic Stone Protein as an Early Predictor of Adverse Events in Patients with Infection Presenting to the Emergency Department: A Pilot Study

by Louiza Mpoumi, Georgia Sarantos, Vasiliki Bistola, Sofia Bezati, Christos Verras, Ioanna Rita, Sotirios Tsiodras, John Parissis and Effie Polyzogopoulou

J. Pers. Med. 2026, 16(6), 312; https://doi.org/10.3390/jpm16060312 - 11 Jun 2026

Viewed by 568

Abstract

Background: Pancreatic stone protein (PSP) has recently emerged as a novel biomarker with diagnostic and prognostic potential in sepsis. The present study aimed to investigate its role as an early prognosticator in patients presenting to the Emergency Department (ED) with various types [...] Read more.

Background: Pancreatic stone protein (PSP) has recently emerged as a novel biomarker with diagnostic and prognostic potential in sepsis. The present study aimed to investigate its role as an early prognosticator in patients presenting to the Emergency Department (ED) with various types of infection. Methods: Point-of-care PSP was measured in 102 consecutive patients (59.8% male) with mean age of 62.7 (±23.4) years, presenting to the ED with suspected or confirmed infection. We examined the utility of PSP to predict adverse events including death, development of septic shock or need for repeated medical evaluation due to persistence or worsening of initial symptoms during a 10-day follow-up period. Results: Respiratory tract infections were the most common (50%) followed by urinary tract infections (17.6%), sepsis of unknown origin (4.9%) and other infections (27.5%). PSP exhibited intermediate performance in predicting short-term adverse outcomes with an AUC of 0.734 (p < 0.001). In contrast, other inflammatory biomarkers such as procalcitonin, C-reactive protein (CRP) and White Blood Cells (WBCs) did not predict adverse outcomes (procalcitonin: AUC 0.680, p = 0.059; CRP: AUC 0.593, p = 0.072; WBC: AUC 0.635, p = 0.074). Conclusions: PSP appears to be a promising biomarker reflecting the severity of infection. Point-of-care PSP evaluation may serve as an early predictor of adverse events in patients presenting with infection to the ED. Full article

(This article belongs to the Section Disease Biomarkers)

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13 pages, 1145 KB

Open AccessArticle

Clinical and Serological Characteristics of Idiopathic Inflammatory Myopathies According to the Presence of Interstitial Lung Disease and Initial Evaluating Medical Specialty: A Single-Center Experience

by Christina Koukouvitaki, Sofia Flouda, Theofanis Karageorgas, Stelios Loukides, Dimitrios T. Boumpas, Antonis Fanouriakis, Aggelos Banos and Vasilios Tzilas

J. Pers. Med. 2026, 16(6), 311; https://doi.org/10.3390/jpm16060311 - 8 Jun 2026

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Abstract

Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with [...] Read more.

Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with the goal of advancing personalized medicine. Methods: A computer-assisted search was conducted to identify patients with a diagnosis of IIM seen at Attikon University Hospital, from January 2010 to December 2025. Medical records were reviewed for clinical, laboratory and serological features. Results: We identified 140 patients with IIM; 96 (68.6%) were female with a mean age at diagnosis of 55.8 years (SD 15.7). ILD was present in 75 patients (53.6%), being more common among males (30/44, 68.2% vs. 45/96 females, 46.9%, p = 0.019). Patients in the ILD subgroup were older at diagnosis (mean age 60.2 years vs. 50.7 years, p < 0.001) and presented more often with dyspnea (41 vs. 1, p < 0.001), higher CRP (median 5.95 mg/L vs. 2.9 mg/L, p = 0.024), and lower CPK (median 103 vs. 580, p < 0.001). Patients first seen by a pulmonologist were more likely to be older (mean age 60.5 years vs. 53 years, p = 0.002) and to present with dyspnea (33 vs. 9, p < 0.001) and ILD (48 vs. 27, p < 0.001). By contrast, skin involvement (61% vs. 27%, p = 0.04), muscle weakness (53 vs. 15, p < 0.001) and elevated CPK (median 301.5 vs. 103.5, p = 0.013) were less frequent in these patients as compared to patients first evaluated by a rheumatologist. Anti-tRNA synthetase, anti-Ro52 and anti-Pm/Scl antibodies were more frequent in the ILD subgroup. Anti-tRNA antibodies were also more frequent in patients first seen by a pulmonologist. Conclusions: Patients with IIM-ILD are more likely to present without overt clinical or biochemical characteristics of muscle involvement, thereby increasing the likelihood of initial evaluation by pulmonologists. Full article

(This article belongs to the Special Issue Advancing Respiratory Care Through Personalized Medicine)

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16 pages, 1994 KB

Open AccessArticle

Personalized Selection of Inferior Turbinate Surgery Based on Structural Phenotyping: A Structured Narrative Review and Proposed Decision-Making Framework

by Alessia Pennacchi, Basile N. Landis, Michael B. Soyka, Roberto Spasiano and Matteo Trimarchi

J. Pers. Med. 2026, 16(6), 310; https://doi.org/10.3390/jpm16060310 - 8 Jun 2026

Viewed by 1025

Abstract

Background: Inferior turbinate hypertrophy is a major cause of chronic nasal obstruction and can be treated with several surgical techniques. However, current surgical decision-making is often not personalized to the dominant anatomical and functional substrate of obstruction. No widely adopted structural classification of [...] Read more.

Background: Inferior turbinate hypertrophy is a major cause of chronic nasal obstruction and can be treated with several surgical techniques. However, current surgical decision-making is often not personalized to the dominant anatomical and functional substrate of obstruction. No widely adopted structural classification of the inferior turbinate exists, and no standardized algorithm links individual anatomical phenotypes to targeted surgical strategies. Methods: A structured narrative review of PubMed and Scopus was performed from database inception to 1 February 2026, using predefined search terms and eligibility criteria. Studies were selected if they addressed inferior turbinate anatomy, histopathology, imaging morphology, endoscopic grading, nasal valve or septal anatomy, surgical techniques, postoperative outcomes, complications, or patient-reported outcomes. Randomized and prospective trials, histopathological studies, CT morphometric analyses, and validated endoscopic grading systems were considered. Four phenotypes of inferior turbinate hypertrophy were identified and linked to preferred surgical options within a clinically oriented decision algorithm integrating endoscopy, functional testing, and selective CT imaging. This framework was developed to support individualized treatment planning and shared decision-making. Results: Four structural phenotypes were defined: (i) predominantly cavernous/mucosal hypertrophy; (ii) predominantly bony hypertrophy; (iii) anterior nasal valve-turbinate conflict; and (iv) mixed hypertrophy. For mucosal-dominant disease, radiofrequency ablation and laser turbinoplasty are preferred first-line, mucosa-preserving options. For bony hypertrophy, mucosa-preserving powered inferior turbinoplasty is favored for the mid/posterior turbinate, whereas endoscopic pyriform aperture turbinoplasty is preferred for anterior valve-level conflict. Mixed phenotypes are best managed with combined skeletal and mucosal procedures. The algorithm aims to avoid mismatched treatments, such as mucosal-only techniques for rigid bony hypertrophy or extensive skeletal reduction in purely mucosal disease. Perioperative variables relevant to shared decision-making, including type of anesthesia, postoperative morbidity, recovery profile, and expected limitations, were summarized for each technique. Conclusions: This phenotype-guided algorithm provides a structured, evidence-informed framework for the personalized selection of inferior turbinate surgery, emphasizing mucosal preservation, anatomical specificity, patient-centered decision-making, and avoidance of mismatched procedures. It is intended to support, not replace, clinical judgment and to guide future prospective validation studies in personalized rhinologic surgery. Full article

(This article belongs to the Special Issue Personalized Medicine in Otolaryngology: New Challenges and Future Perspectives)

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17 pages, 519 KB

Open AccessSystematic Review

Sleep Disorders in Patients with Tics: Towards Personalized Care for Tourette Syndrome

by Kashish K. Qureshi and Andrea E. Cavanna

J. Pers. Med. 2026, 16(6), 309; https://doi.org/10.3390/jpm16060309 - 6 Jun 2026

Viewed by 1144

Abstract

Background/Objectives: Tourette syndrome and other chronic tic disorders are neurodevelopmental conditions characterized by intermittent motor/phonic tics and frequent behavioral comorbidity. Poor sleep quality is often reported by patients with tic disorders; however, little is known about the prevalence and clinical correlates of [...] Read more.

Background/Objectives: Tourette syndrome and other chronic tic disorders are neurodevelopmental conditions characterized by intermittent motor/phonic tics and frequent behavioral comorbidity. Poor sleep quality is often reported by patients with tic disorders; however, little is known about the prevalence and clinical correlates of disruption in sleep physiology. Methods: We conducted a systematic literature review of clinical studies evaluating sleep using at least one validated sleep outcome (questionnaire, polysomnography, or coded clinical diagnosis). Results: Despite high heterogeneity in age ranges, diagnostic formulations, outcome measures, and confounder handling, converging evidence across designs indicated a significantly higher prevalence of sleep disturbance in patients with Tourette syndrome and other chronic tic disorders compared to controls. Specifically, registries showed significantly greater insomnia rates (aOR 6–7); case–control studies revealed a 9-fold increase in night-waking, bedtime resistance, parasomnias, and daytime drowsiness; polysomnography studies demonstrated sleep fragmentation, with decreased efficiency, longer latency, and more awakenings. Conclusions: Sleep disorders are relatively common in patients with Tourette syndrome and other chronic tic disorders, with clinical implications for both arousal instability and sleep initiation/maintenance issues. Further research is needed to better understand the complex interplay between altered sleep patterns and tic expression, as well as the impact of behavioral comorbidities. Our findings highlight a need for personalized treatment interventions focusing on sleep problems in the context of tic disorders. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment for Neurological Diseases)

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26 pages, 1187 KB

Open AccessFeature PaperArticle

Ethical Considerations in Health Technology Assessment for Precision Medicine: A Delphi Study in a Greek Setting

by Nikolaos Veskoukis, Nikos Stefanopoulos, Panagiota Naoum and Kostas Athanasakis

J. Pers. Med. 2026, 16(6), 308; https://doi.org/10.3390/jpm16060308 - 5 Jun 2026

Viewed by 666

Abstract

Background/Objectives: Precision medicine has moved into routine practice, but its evaluation through Health Technology Assessment (HTA) remains ethically underdeveloped. Existing instruments do not address the distinctive ethical demands of genomic profiling, AI-based clinical decision-support, and the equitable distribution of benefits from high-cost targeted [...] Read more.

Background/Objectives: Precision medicine has moved into routine practice, but its evaluation through Health Technology Assessment (HTA) remains ethically underdeveloped. Existing instruments do not address the distinctive ethical demands of genomic profiling, AI-based clinical decision-support, and the equitable distribution of benefits from high-cost targeted therapies. Methods: A modified two-round Delphi study was conducted with a multidisciplinary panel of 18 Greek experts in bioethics, HTA, genomic medicine, nursing, and health policy. In Round 1, 32 candidate ethical statements across seven thematic domains were rated on a three-point scale; retention required a Content Validity Ratio (CVR) ≥ 0.42 and ≥80% agreement. Retained statements were re-evaluated in Round 2 with consensus defined as median ≥ 2.0 and ≥80% agreement. Reporting follows ACCORD guidelines. Results: Fifteen of 32 statements satisfied retention criteria. In Round 2, all 15 achieved consensus with a median of 3.0 and agreement of 94.4–100% (interquartile range, IQR = 0.00). Five domains constituted the final framework: fundamental ethical principles; transparency, stakeholder participation, and institutional accountability; equity and access; digital health and artificial intelligence (AI); and pandemic preparedness and system resilience. Domains addressing environmental sustainability and social acceptability did not meet the threshold. Conclusions: This study presents, to our knowledge, one of the first empirically grounded ethical frameworks for precision medicine HTA developed within an EU Member State through a formal Delphi process. The framework is operationalised through a ready-to-use ethics checklist designed for direct integration into national HTA submission and appraisal processes. Conducted in Greece—a late-aligning EU Member State—the study provides a transferable methodological template for comparable health systems across Europe. Full article

(This article belongs to the Special Issue Bioethics in Personalized Medicine and Precision Medicine)

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23 pages, 1638 KB

Open AccessArticle

Deep Dyspareunia One Year After Nerve-Sparing Endometriosis Surgery: An Observational Study Highlighting Undesirable Outcomes

by Nilton de Nadai Filho, Claudio Peixoto Crispi, Jr., Bruna Rafaela Santos de Oliveira, Claudio Peixoto Crispi and Marlon de Freitas Fonseca

J. Pers. Med. 2026, 16(6), 307; https://doi.org/10.3390/jpm16060307 - 5 Jun 2026

Viewed by 630

Abstract

Background/Objectives: This study evaluates the 1-year follow-up outcomes after minimally invasive nerve-sparing surgery for the complete excision of deep endometriosis (DE), with a specific focus on deep dyspareunia. Cases with undesirable outcomes were explored in detail to better understand the evolution of this [...] Read more.

Background/Objectives: This study evaluates the 1-year follow-up outcomes after minimally invasive nerve-sparing surgery for the complete excision of deep endometriosis (DE), with a specific focus on deep dyspareunia. Cases with undesirable outcomes were explored in detail to better understand the evolution of this cornerstone endometriosis-related symptom. This approach supports personalized medicine initiatives by seeking to stratify patients into likely surgical responders and non-responders. Methods: This is an interdisciplinary retrospective observational study assessing 195 consecutive cases. Inclusion criteria comprised women with an established diagnosis of DE who had been sexually active in the 6 months prior to surgery. Because pregnancy and postpartum can interfere with the longitudinal assessment of deep dyspareunia, women in these phases during follow-up were excluded. Additionally, individuals who had not been sexually active in the preceding 6 months for reasons unrelated to deep dyspareunia were excluded. Deep dyspareunia was measured using an 11-point (0–10) self-reported Numerical Rating Scale (NRS). Hierarchical clusters were established based on preoperative scores: NONE (NRS = 0), MILD (1 ≤ NRS ≤ 3), MODERATE (4 ≤ NRS ≤ 6), and SEVERE (NRS ≥ 7). Results: In the SEVERE cluster, 82.2% (95% CI: 72.4–92.0) of women improved by ≥3 points. In the NONE cluster, 70.1% (95% CI: 60.3–79.2) remained asymptomatic. Although improvements in deep dyspareunia were statistically significant across the total sample, individual trajectories were not uniform; the response was considered undesirable in 34 cases (17.4%; 95% CI: 12.1–22.8). The frequency of preoperatively asymptomatic women (NRS = 0) developing De Novo deep dyspareunia (NRS ≥ 3) at the 1-year follow-up was estimated at 14.9% (95% CI: 8.0–22.7). These results highlight the marked phenotypic and clinical heterogeneity in patient trajectories and the inherent unpredictability of adverse responses. Conclusions: Postoperative pain outcomes likely result from a complex interplay among surgical, myofascial, neurological, psychological, inflammatory, and hormonal factors. While surgery remains an effective and safe approach for treating pain, our findings underscore that even preoperatively asymptomatic patients should receive targeted counseling regarding the unexpected risk of developing postoperative deep dyspareunia. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology and Women's Health—2nd Edition)

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J. Pers. Med., Volume 16, Issue 6 (June 2026) – 61 articles

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