Journal of Personalized Medicine

13 pages, 657 KB

Open AccessArticle

Assessing Willingness to Pay for Genetic Testing Among Adults: A Cross-Sectional Study Using Data from the Omnibus Survey 2022

by Angelo Navas, Lauren Hendy and Megan Roberts

J. Pers. Med. 2026, 16(3), 154; https://doi.org/10.3390/jpm16030154 (registering DOI) - 7 Mar 2026

Abstract

Background: Population genetic screening (PGS) serves an essential role in identifying individuals at higher risk for hereditary cancer and cardiovascular disease. Nevertheless, the current lack of insurance coverage for screening costs might pose a barrier to its adoption. Health systems might contemplate covering [...] Read more.

Background: Population genetic screening (PGS) serves an essential role in identifying individuals at higher risk for hereditary cancer and cardiovascular disease. Nevertheless, the current lack of insurance coverage for screening costs might pose a barrier to its adoption. Health systems might contemplate covering these test expenses, but individuals covered by Medicaid and Medicare may not qualify for cost-free screening due to constraints related to the Beneficiary Inducement Statute. Methods: A cross-sectional online survey was administered to 602 US adults in January 2023. Andersen’s model guided variable selection. An ordered probit model was deployed to explore the association between insurance type and willingness to pay (WTP) for PGS, controlling for demographic and healthcare characteristics. Results: Among the 602 respondents, 524 (87%) were included in our analysis. Over 70% (n = 373) of participants expressed WTP for genetic testing. A similar proportion of respondents with Medicare and Medicaid expressed WTP for screening (68%, and 70%, respectively). Insurance type was not significantly associated with WTP for genetic testing. Notably, lower trust levels and absence of family cancer history were associated with a lower probability of expressing high WTP compared to the reference categories (high levels of trust and having a family cancer history). Conclusions: WTP for genetic testing was not significantly associated with insurance type. Almost 30% of our sample were unwilling to pay for PGS, suggesting variability in WTP for PGS and adding to the limited literature on how individuals value genomic screening tests. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases: 2nd Edition)

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12 pages, 841 KB

Open AccessArticle

The Role of Kidney Biopsy as a Tool for Personalized Treatment Decision-Making in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Nephritis

by Makoto Harada, Shotaro Aso, Takayuki Nimura, Kosuke Yamaka, Daiki Aomura, Aiko Yamada, Kosuke Sonoda, Akinori Yamaguchi, Yutaka Kamimura, Tohru Ichikawa, Mamoru Kobayashi, Koji Hashimoto and Yuji Kamijo

J. Pers. Med. 2026, 16(3), 153; https://doi.org/10.3390/jpm16030153 (registering DOI) - 7 Mar 2026

Abstract

Background/Objectives: Personalized treatment approaches are increasingly recognized as essential in the management of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), given the substantial heterogeneity in disease severity and patient characteristics. Kidney biopsy has the potential to serve as an effective tool for personalized treatment [...] Read more.

Background/Objectives: Personalized treatment approaches are increasingly recognized as essential in the management of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), given the substantial heterogeneity in disease severity and patient characteristics. Kidney biopsy has the potential to serve as an effective tool for personalized treatment decision-making in patients with AAV. This study aimed to investigate the association of kidney biopsy with intensive immunosuppressive therapy and clinical outcomes in patients with AAV and kidney impairment. Methods: In this retrospective study, propensity score overlap weighting was applied to compare intensive immunosuppressive therapy and clinical outcomes (ESKD, death, combined ESKD and death, and infectious complications) between patients with AAV who underwent kidney biopsy and those who did not. Results: Out of 74 patients with AAV, 38 underwent kidney biopsy. Overlap weight analysis revealed that kidney biopsy was significantly associated with intensive immunosuppressive therapy (risk difference [RD], 28.9%; 95% confidence interval [CI], 0.017 to 0.562). Kidney biopsy was not associated with combined ESKD and death (RD, −0.2%; 95% CI, −0.302 to 0.298), death (RD, −3.8%; 95% CI, −0.264 to 0.189), ESKD (RD, −7.3%; 95% CI, −0.353 to 0.207), and infectious complications (RD, −25.9%; 95% CI, −0.537 to 0.020). Conclusions: In this observational cohort, kidney biopsy was associated with intensification of immunosuppressive therapy. However, after adjustment using overlap weighting, no statistically significant difference in clinical outcomes was detected, and the reduced effective sample size limited statistical power. These findings should be interpreted cautiously, as causal inference regarding the prognostic impact of kidney biopsy remains limited. Full article

(This article belongs to the Special Issue Personalized Medicine for Rheumatic Diseases)

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15 pages, 1530 KB

Open AccessReview

Sex and Gender in Chronic Obstructive Pulmonary Disease: Does It Matter?

by Christos Kyriakopoulos, Georgios Hillas, Antonia Assioura, Anastasia Papanikolaou, Vasileios Angelopoulos, Konstantinos Kostikas and Athena Gogali

J. Pers. Med. 2026, 16(3), 152; https://doi.org/10.3390/jpm16030152 - 6 Mar 2026

Abstract

Chronic obstructive pulmonary disease (COPD) is a major contributor to global respiratory morbidity and exhibits substantial sex- and gender-related differences in incidence, phenotype, pathophysiology, and outcomes across the life course. Historically regarded as a predominantly male disease due to higher smoking rates, COPD [...] Read more.

Chronic obstructive pulmonary disease (COPD) is a major contributor to global respiratory morbidity and exhibits substantial sex- and gender-related differences in incidence, phenotype, pathophysiology, and outcomes across the life course. Historically regarded as a predominantly male disease due to higher smoking rates, COPD is now increasingly recognized among women, reflecting changing exposure patterns and enhanced diagnostic attention. Moreover, evidence indicates that women may be more biologically susceptible to the harmful effects of tobacco smoke and often develop COPD at younger ages. Clinical manifestations also differ, with women more frequently reporting dyspnea, anxiety, and depression, whereas men may exhibit more cough and sputum production. Imaging studies suggest that airway-predominant disease is more common in women, while men are more likely to demonstrate emphysema-predominant patterns. Furthermore, women face an increased risk of exacerbation, yet they are more likely to experience underdiagnosis or misdiagnosis. Treatment responses and comorbidity patterns also show sex- and gender-related variations. Despite these differences, most clinical guidelines and therapeutic strategies do not differentiate by sex and gender, highlighting a gap in personalized COPD management. Overall, growing evidence underscores the importance of incorporating sex and gender as biological and sociocultural variables in COPD research, diagnosis, and treatment. Recognizing sex/gender-specific risk profiles, symptom patterns, and disease phenotypes may improve early detection and enable more targeted, effective interventions. This narrative synthesis, derived from a meticulous search in PubMed and the critical selection of 74 articles from the 448 identified originally, integrates evidence from guideline statements, registry studies, mechanistic and preclinical research, imaging and physiology investigations, systematic reviews, and randomized controlled trials that report sex- and gender-disaggregated data. Full article

(This article belongs to the Special Issue Personalized Management in Chronic Obstructive Pulmonary Disease (COPD))

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18 pages, 395 KB

Open AccessReview

Low-Dose Naltrexone in Chronic Pain Management: Mechanisms, Evidence, and Clinical Implications

by Alyssa McKenzie, Tiffany Bittar, Rachel Dombrower, Dupinder Raman, Hatim Hussain, Nitchanan Theeraphapphong, Sophia M. McKenzie and Alaa Abd-Elsayed

J. Pers. Med. 2026, 16(3), 151; https://doi.org/10.3390/jpm16030151 - 6 Mar 2026

Abstract

Chronic pain imposes a substantial burden on global health and remains challenging to manage, despite ongoing advances in pharmacologic and interventional therapies. Recognition of chronic pain as a condition driven by central sensitization and neuroimmune dysregulation has prompted interest in therapies that target [...] Read more.

Chronic pain imposes a substantial burden on global health and remains challenging to manage, despite ongoing advances in pharmacologic and interventional therapies. Recognition of chronic pain as a condition driven by central sensitization and neuroimmune dysregulation has prompted interest in therapies that target these mechanisms rather than peripheral nociception alone. Low-dose naltrexone (LDN), administered at doses substantially lower than those used for opioid or alcohol use disorders, has emerged as a repurposed treatment with potential analgesic and anti-inflammatory properties. This review summarizes the pharmacologic characteristics of LDN, with emphasis on its proposed mechanisms involving transient opioid receptor blockade, modulation of microglial activation, Toll-like receptor signaling, and central neuroimmune pathways. Available clinical evidence evaluating LDN across a range of chronic pain conditions, such as fibromyalgia, neuropathic pain syndromes, inflammatory and autoimmune disorders, headache disorders, and other centralized pain states, is critically reviewed. Although early trials, observational studies, and case series suggest potential benefit in selected populations, the overall evidence base remains limited, heterogeneous, and characterized by variability in dosing strategies and outcome measures. Safety, tolerability, and practical considerations relevant to contemporary pain practice are discussed, including interactions with opioid therapy and challenges related to off-label use. Finally, key gaps in the current evidence and priorities for future research are highlighted, underscoring the need for larger, well-designed randomized trials and mechanism-informed studies to better define LDN’s role in multimodal chronic pain management. Full article

(This article belongs to the Section Mechanisms of Diseases)

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14 pages, 1189 KB

Open AccessArticle

A Five-Year Study on Treatment Changes in Hypoglycemia-Associated Medications: Towards Personalized Diabetes Management

by Amal Asiri, Indriastuti Cahyaningsih, Stijn de Vos, Jens H. J. Bos, Catharina C. M. Schuiling-Veninga, Eelko Hak, Sumaira Mubarik, Petra Denig and Katja Taxis

J. Pers. Med. 2026, 16(3), 150; https://doi.org/10.3390/jpm16030150 - 4 Mar 2026

Abstract

Background: Understanding patient-specific patterns of medication intensification and de-intensification is essential for personalizing diabetes management and minimizing hypoglycemia risk in patients with type 2 diabetes. Objectives: To assess treatment changes in hypoglycemia-associated medications over five years and explore patient characteristics associated [...] Read more.

Background: Understanding patient-specific patterns of medication intensification and de-intensification is essential for personalizing diabetes management and minimizing hypoglycemia risk in patients with type 2 diabetes. Objectives: To assess treatment changes in hypoglycemia-associated medications over five years and explore patient characteristics associated with these changes. Methods: We conducted a longitudinal cohort study using the IADB.nl database containing prescription data from Dutch community pharmacies. Individuals aged ≥35 years with at least two dispensations of glucose-lowering medications were identified. We estimated transition probabilities of changes in hypoglycemia-associated medications (sulfonylureas and/or insulin) using a Markov model for each year of follow-up. Associations with age, sex, and estimated hypoglycemia risk were explored with regression analysis. Results: Overall, 25,057 patients were included. Medication remained unchanged for the majority of the patients in the follow-up period. De-intensification increased from 4.7% (Year 1) to 6.5% (Year 5), while intensification decreased from 7.7% to 6.9% over the same period. Markov models showed that patients predominantly remained in a no change state over 5 years (transition probabilities: 0.92–0.94). High estimated hypoglycemia risk, age and being female were associated with intensification and/or de-intensification. Conclusions: While treatment regimens remained unchanged for most patients, de-intensification of hypoglycemia-associated medications increased modestly over five years. Factors like hypoglycemia risk, age and sex influenced changes. These findings support the need for personalized, risk-stratified approaches to diabetes medication management. Full article

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

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8 pages, 444 KB

Open AccessPerspective

Cervical Insufficiency Beyond Terminology: From Fixed Labels to Pregnancy-Specific Vulnerability in Personalized Maternal–Fetal Care

by Moon-Il Park and Yong-Jin Park

J. Pers. Med. 2026, 16(3), 149; https://doi.org/10.3390/jpm16030149 - 4 Mar 2026

Abstract

Over the past two decades, the term cervical incompetence has largely been replaced by cervical insufficiency in clinical guidelines, reflecting efforts to avoid pejorative language and to acknowledge functional variability. However, despite this terminological evolution, the underlying conceptual framework has remained largely static, [...] Read more.

Over the past two decades, the term cervical incompetence has largely been replaced by cervical insufficiency in clinical guidelines, reflecting efforts to avoid pejorative language and to acknowledge functional variability. However, despite this terminological evolution, the underlying conceptual framework has remained largely static, continuing to treat cervical insufficiency as a fixed anatomic defect inferred from obstetric history or single-point measurements. This Perspective argues that such a model inadequately explains the substantial clinical heterogeneity observed across and within pregnancies, limiting its usefulness for individualized clinical interpretation and study design. Drawing on contemporary guideline frameworks, systematic reviews, and international disease classification systems, this article highlights the limitations of static, anatomy-centered approaches and proposes an alternative conceptualization of cervical insufficiency as a dynamic, pregnancy-specific vulnerability. Within this framework, cervical behavior is understood as time-dependent and context-sensitive, shaped by the interplay of mechanical load, biological processes, and gestational timing rather than predetermined structural failure. This conceptualization is intended to inform interpretation across diverse clinical contexts, rather than to redefine diagnostic criteria or existing guideline recommendations. By shifting emphasis from fixed diagnostic labels to trajectories of cervical vulnerability, this Perspective situates cervical insufficiency within the broader continuum of spontaneous preterm birth and aligns its interpretation with the principles of personalized medicine. This conceptual reframing positions cervical insufficiency as a model condition for personalized maternal–fetal care, emphasizing time- and context-aware risk assessment and trajectory-informed clinical decision-making, while providing a coherent foundation for individualized surveillance and future research aimed at improving maternal–fetal outcomes. Full article

(This article belongs to the Special Issue Personalized Medicine in Maternal–Fetal Care: From Cervical Insufficiency to Preterm Birth and Beyond)

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Graphical abstract

15 pages, 2515 KB

Open AccessArticle

Double Staining Immunohistochemistry and Digital Pathology: Moving Towards Standardization of the Proliferative Index Evaluation in Meningiomas

by Viscardo Paolo Fabbri, Giuseppe Broggi, Giovanna Attolini, Vincenzo L’Imperio, Fabio Pagni, Angela Guerriero, Stefano Marletta, Francesco Fiorentino, Stefania Caramaschi, Claudia Malagoli, Albino Eccher and Rosario Caltabiano

J. Pers. Med. 2026, 16(3), 148; https://doi.org/10.3390/jpm16030148 - 4 Mar 2026

Abstract

Background: Although Ki-67 is not included among the grading criteria in the current WHO Classification of Tumours of the Central Nervous System (CNS), it provides valuable, albeit limited, prognostic information. Immunohistochemistry for Ki-67 can reveal uneven proliferation patterns and assist in the assessment [...] Read more.

Background: Although Ki-67 is not included among the grading criteria in the current WHO Classification of Tumours of the Central Nervous System (CNS), it provides valuable, albeit limited, prognostic information. Immunohistochemistry for Ki-67 can reveal uneven proliferation patterns and assist in the assessment of mitotic counts. Several studies indicate that meningiomas with a proliferation index > 4% show recurrence rates comparable to CNS WHO grade 2 (atypical) tumors, while tumors with an index > 20% are associated with mortality rates similar to CNS WHO grade 3 (anaplastic) meningiomas. Issues related to Ki-67 assessment include interobserver variability, the use of different cut-off values among pathologists, and the presence of a complex inflammatory tumour microenvironment, which may lead to an overestimation of the proliferative index (PI). Methods: In this study, we describe how Double Staining Immunohistochemistry (dIHC) with EMA/Ki-67 better highlights neoplastic meningothelial cells compared with single-stain evaluation. Furthermore, the application of Digital Pathology provides quantitative digital data that allow a more accurate assessment of proliferation. Results: Ki-67 expression varied by grade, with digital image analysis (dIHC) showing high agreement with manual assessments. dIHC improved accuracy in evaluating diagnostic and proliferative markers within tumor samples. Conclusions: dIHC combined with DP can support and standardize the evaluation of the proliferative index in meningiomas in routine diagnostic practice. Full article

(This article belongs to the Special Issue Current Status and Future Prospects of Histopathology in Cancer Diagnosis)

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44 pages, 1322 KB

Open AccessReview

From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma

by Mislav Mokos and Mirna Šitum

J. Pers. Med. 2026, 16(3), 147; https://doi.org/10.3390/jpm16030147 - 3 Mar 2026

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) play a key role in the immune response against melanoma. They act as both markers of an active tumor environment and as treatments in adoptive cell therapy. This narrative review covers what is currently known about TIL biology, their [...] Read more.

Background: Tumor-infiltrating lymphocytes (TILs) play a key role in the immune response against melanoma. They act as both markers of an active tumor environment and as treatments in adoptive cell therapy. This narrative review covers what is currently known about TIL biology, their prognostic and predictive value, and the use of TIL-based adoptive cell therapy (TIL-ACT) in advanced melanoma. Methods: We searched PubMed/MEDLINE, Web of Science and clinicaltrials.gov through January 2026 using terms related to melanoma, TILs, adoptive cell therapy, immune checkpoint inhibitors, neoantigens, T-cell receptor clonality, and spatial transcriptomics. We included original research, major clinical trials, translational studies and key reviews. Results: Melanoma often has many neoantigens, which leads to a high number of tumor-resident TILs. These TILs, their arrangement, and their interactions with myeloid cells influence how well they fight tumors. Features of TILs seen under the microscope and through other tests can help predict patient outcomes, even before treatment. Studies show that TIL-ACT leads to objective responses in about 30–50% of patients whose melanoma did not respond to immune checkpoint inhibitors. Some patients achieve lasting complete remissions, though the treatment can cause significant, mostly short-term side effects from lymphodepletion and interleukin-2. New research points to factors related to the patient, tumor, and TIL product that affect treatment success, supporting the use of biomarkers and combination strategies. Conclusions: TIL-based adoptive cell therapy is now a promising, personalized treatment for advanced melanoma after anti-PD-1 therapy has failed. Future studies should focus on identifying reliable biomarkers, improving TIL products, combining therapies to change the tumor environment, and making manufacturing more efficient to ensure more patients can safely access TIL therapy. Full article

(This article belongs to the Special Issue Translational Research and Novel Therapeutics in Cutaneous Melanoma)

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35 pages, 4111 KB

Open AccessReview

Global Burden of Deep Neck Space Abscesses: Epidemiology, Challenges, and Outcomes

by Antonino Maniaci, Francesco Chiari, Pierre Guarino, Luigi La Via, Mario Lentini, Salvatore Lavalle, Paolo Boscolo-Rizzo, Luigi Angelo Vaira and Jerome Rene Lechien

J. Pers. Med. 2026, 16(3), 146; https://doi.org/10.3390/jpm16030146 - 3 Mar 2026

Abstract

Background/Objectives: Deep neck space abscesses (DNSAs), representing severe suppurative infections, continue to pose a significant global health challenge due to their morbidity, mortality, and evolving epidemiology. This review synthesizes existing knowledge regarding DNSA definitions, anatomic basis, epidemiological trends, microbiology, clinical presentation, diagnostic [...] Read more.

Background/Objectives: Deep neck space abscesses (DNSAs), representing severe suppurative infections, continue to pose a significant global health challenge due to their morbidity, mortality, and evolving epidemiology. This review synthesizes existing knowledge regarding DNSA definitions, anatomic basis, epidemiological trends, microbiology, clinical presentation, diagnostic strategies, treatment paradigms, outcomes, health system challenges, and disparities to guide global efforts in DNSA prevention, management, and research. Methods: A structured narrative review was performed following SANRA guidelines. PubMed/MEDLINE and the Cochrane Library were searched from January 2000 to May 2025, retrieving 1102 records. After screening, 49 studies met the inclusion criteria. Data were extracted using standardized templates and synthesized thematically. Results: During the period 2004–2015, annual case increases were reported in a Finnish population-based retrospective cohort (n = 277), going from 14 to 24 subjects, and for a UK tertiary center retrospective series, going from 1 to 15 cases annually (2006–2015) (Pearson’s correlation, r = 0.9; p = 0.00019). The microbiological environment is mostly polymicrobial, composed of group streptococci and staphylococcus strains and anaerobes. Factors associated with poor outcomes include diabetes mellitus (adjusted hazard ratio of 10.7 [95% CI 6.0–19.1] in a retrospective, population-based cohort of 12,738 diabetic patients compared to 50,952 individuals without diabetes), immunosuppressed state, elderly age, and multispace involvement. Diagnosis relies on contrast-enhanced CT imaging (sensitivity > 90%), and treatment consists of early multidisciplinary intervention combining empiric broad-spectrum antibiotics with surgical drainage in 60–97% of cases. Mortality ranges from 1.6% to 7.6%, with higher rates in cases complicated by mediastinitis (up to 40%). Conclusions: DNSAs demonstrate a clear upward incidence trend across high-income and resource-limited settings. Establishing standardized DNSA registries, validating risk-stratification tools, reinforcing antimicrobial stewardship to address rising resistance, and implementing early detection protocols in primary care remain critical priorities. While emerging technologies, including rapid molecular diagnostics and AI-based decision support, represent promising research directions, current DNSA management relies fundamentally on conventional clinical assessment, prompt imaging, and coordinated multidisciplinary care. Full article

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

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9 pages, 218 KB

Open AccessArticle

Serum Chitinase 3-like-1 (CHI3L1) Has Good Correlation with Fecal Calprotectin Levels in Pregnant IBD Patients

by Hagai Schweistein, Rachel Gingold-Belfer, Adi Rave, Ahinoam Glusman-Bendersky, Hadar Amir-Barak, Jacob E. Ollech and Ariella Bar-Gil Shitrit

J. Pers. Med. 2026, 16(3), 145; https://doi.org/10.3390/jpm16030145 - 3 Mar 2026

Abstract

Background: Monitoring inflammatory bowel disease (IBD) during pregnancy is challenging due tolimited use of invasive tools. While fecal calprotectin is considered reliable, its use is limited by patient adherence and availability. Blood-based markers, such as serum chitinase-3-like-1 (CHI3L1), offer a promising alternative. [...] Read more.

Background: Monitoring inflammatory bowel disease (IBD) during pregnancy is challenging due tolimited use of invasive tools. While fecal calprotectin is considered reliable, its use is limited by patient adherence and availability. Blood-based markers, such as serum chitinase-3-like-1 (CHI3L1), offer a promising alternative. Aim: To evaluate whether serum CHI3L1 reflects disease activity in pregnant IBD patients, compared to standard markers and clinical questionnaires. Methods: Pregnant IBD patients were recruited from a multidisciplinary clinic. Blood samples were collected to assess inflammatory markers. Stool samples were used to measure calprotectin levels. Each visit was classified as a distinct sample for analysis. Correlations between CHI3L1 and disease activity markers were examined. Results: A total of 124 samples from 80 pregnant IBD patients were analyzed: 90 from Crohn’s disease (CD) patients and 34 from ulcerative colitis (UC) patients. CHI3L1 levels showed a significant positive correlation with fecal calprotectin (r_p = 0.366, p = 0.008), ESR (r_p = 0.358, p = 0.001), CRP (r_p = 0.478, p < 0.001) and standardized clinical scoring questionnaires. Elevated CHI3L1 (>56.6 ng/mL) is a risk factor for active disease (OR 8.78, 95% CI 1.54–49.83, p = 0.014). Conclusions: Serum CHI3L1 is positively associated with established markers of inflammation and may serve as a useful non-invasive biomarker for monitoring IBD activity during pregnancy, a medical condition in which invasive procedures are not recommended. Based on CHI3L1 levels, personalized treatment for pregnant IBD patients can be tailored. However, further validation is recommended. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Diagnosis and Personalized Treatment)

10 pages, 752 KB

Open AccessArticle

Flexor Tendon Repair Using a New Looped Six- and Eight-Strand Technique—A Biomechanical Analysis

by Lucas G. de Groot, Caroline A. Hundepool, Jaimy E. Koopman, Pierluigi Tos and Jelle M. Zuidam

J. Pers. Med. 2026, 16(3), 144; https://doi.org/10.3390/jpm16030144 - 3 Mar 2026

Abstract

Background/Objectives: Tendon injuries are a common cause of emergency department presentation and impose a substantial socioeconomic burden. Despite advances in surgical techniques, rupture rates after primary repair remain at 3.1–11.7%. Contemporary repairs typically combine at least four core strands with epitenon sutures to [...] Read more.

Background/Objectives: Tendon injuries are a common cause of emergency department presentation and impose a substantial socioeconomic burden. Despite advances in surgical techniques, rupture rates after primary repair remain at 3.1–11.7%. Contemporary repairs typically combine at least four core strands with epitenon sutures to achieve sufficient tensile strength while limiting bulk. Increasing the number of core strands improves strength but may impair gliding and healing. Looped core sutures increase the effective strand number without additional knots or passes, potentially allowing omission of the epitenon suture and thus limiting repair complexity and bulk. The objective was to determine whether six- or eight-strand looped core suture techniques provide sufficient tensile strength to allow omission of an epitenon suture without excessive repair bulk, compared with a conventional four-strand Adelaide repair. Methods: One hundred and twenty human flexor digitorum profundus tendons were harvested from fresh-frozen anatomical specimens and allocated to six groups: Adelaide (four-strand) ± epitenon suture, six-strand ± epitenon suture, and eight-strand ± epitenon suture. Repairs were performed in zone II. The cross-sectional area (CSA) was measured before and after repair to quantify bulkiness. Tendons were tested to failure using axial tensile loading, and the failure mode was recorded. Results: The Adelaide with epitenon suture, six-strand with epitenon suture, and eight-strand with epitenon suture demonstrated significantly higher load to failure than the Adelaide without epitenon suture. The eight-strand without epitenon suture achieved a load to failure comparable to the Adelaide with epitenon suture, while also resulting in a smaller increase in CSA. The Adelaide with epitenon suture showed the greatest increase in CSA, while the six-strand without epitenon suture showed the smallest increase in CSA. Suture breakage was the predominant failure mode. Conclusions: An eight-strand looped core suture without epitenon suture provides comparable tensile strength to the conventional Adelaide repair with epitenon suture while minimizing repair bulk. The six-strand with epitenon suture demonstrated similar tensile strength to higher-strand techniques and may represent a mechanically adequate alternative with less tissue manipulation. These findings support a more individualized approach to flexor tendon repair, in which the choice of repair construct can be tailored to biomechanical demands and clinical context rather than applying a single uniform technique. Full article

(This article belongs to the Section Personalized Medical Care)

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29 pages, 1303 KB

Open AccessReview

Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors

by Ilaria Poli, Gaia Rachele Oliva, Ginevra Mongelli, Angelachiara Rotondi, Valentina Frescura, Giorgia Arcuri, Giovanna Garufi, Letizia Pontolillo, Luca Mastrantoni, Elena Di Monte, Noemi Maliziola, Maria Antonia Fucile, Francesca Salvatori, Rita Mondello, Antonella Palazzo, Alessandra Fabi, Emilio Bria, Giampaolo Tortora and Armando Orlandi

J. Pers. Med. 2026, 16(3), 143; https://doi.org/10.3390/jpm16030143 - 3 Mar 2026

Abstract

HER2-positive/hormone-receptor-positive breast cancer represents approximately 10% of all breast cancer cases and constitutes a distinct biological entity with unique therapeutic challenges. The complex crosstalk between HER2 and estrogen receptor signaling pathways contributes to both primary and acquired resistance to anti-HER2 therapies, and the [...] Read more.

HER2-positive/hormone-receptor-positive breast cancer represents approximately 10% of all breast cancer cases and constitutes a distinct biological entity with unique therapeutic challenges. The complex crosstalk between HER2 and estrogen receptor signaling pathways contributes to both primary and acquired resistance to anti-HER2 therapies, and the convergence of these pathways on cell cycle regulation, particularly through the cyclin D1-CDK4/6-Rb axis, has provided a compelling rationale for combining CDK4/6 inhibitors with anti-HER2 therapy. This scoping review aimed to map preclinical and clinical evidence evaluating combinations of CDK4/6 inhibitors with HER2-targeted therapy in HER2+/HR+ disease. Eligible sources included preclinical models and clinical studies assessing CDK4/6 inhibitor-based combinations with anti-HER2 therapy, identified through searches of PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. Data were charted and synthesized descriptively according to PRISMA-ScR guidelines. Preclinical studies have demonstrated synergistic antitumor activity when CDK4/6 inhibitors are combined with trastuzumab, pertuzumab, or newer HER2-targeted agents across multiple HER2+ breast cancer models. In the metastatic setting, phase II trials including MonarcHER and PATRICIA II have shown encouraging efficacy signals, while the phase III PATINA trial demonstrated a clinically meaningful 15.2-month progression-free survival benefit with palbociclib plus anti-HER2 therapy and endocrine therapy. In the neoadjuvant setting, trials including NA-PHER2 and MUKDEN-01 demonstrated marked Ki67 suppression and promising pathologic responses, supporting the exploration of chemotherapy de-escalation strategies. Despite these advances, key challenges remain including the identification of predictive biomarkers, optimal treatment sequencing, and the integration of emerging HER2-targeted agents such as trastuzumab deruxtecan. Novel CDK4/6 inhibitors including dalpiciclib and next-generation agents are expanding therapeutic options, while combination strategies incorporating CDK7 inhibition represent future therapeutic frontiers. The evolving landscape of HER2+/HR+ breast cancer treatment increasingly emphasizes precision medicine approaches that leverage cell cycle control mechanisms to overcome resistance and improve patient outcomes across all disease stages. Full article

(This article belongs to the Special Issue Breast Cancer: Current Trends and Future Challenges in Evaluation and Treatment)

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18 pages, 1304 KB

Open AccessReview

The Polyphenol–Microbiota Axis: Molecular Mechanisms, Metabolic Pathways, and Therapeutic Perspectives in Human Health

by Andrea Ballini, Simona Nicole Barile, Alfredo De Rosa, Maria Eleonora Bizzoca, Mariarosaria Boccellino, Salvatore Scacco, Stefania Cantore, Lorenzo Lo Muzio, Francesco Massimo Lasorsa and Roberto Arrigoni

J. Pers. Med. 2026, 16(3), 142; https://doi.org/10.3390/jpm16030142 - 2 Mar 2026

Abstract

Polyphenols are a diverse class of bioactive phytochemicals increasingly recognized for their ability to modulate human physiology through extensive interactions with the gut microbiota. This review provides a comprehensive and updated synthesis of the bidirectional polyphenol–microbiota relationship, emphasizing how dietary polyphenols reshape microbial [...] Read more.

Polyphenols are a diverse class of bioactive phytochemicals increasingly recognized for their ability to modulate human physiology through extensive interactions with the gut microbiota. This review provides a comprehensive and updated synthesis of the bidirectional polyphenol–microbiota relationship, emphasizing how dietary polyphenols reshape microbial community structure while intestinal microorganisms metabolize polyphenols into smaller, more bioavailable derivatives. These microbial metabolites—such as urolithins, phenolic acids, and dihydroresveratrol—exert amplified biological activities compared to their parent molecules, acting on key molecular pathways linked to oxidative stress, inflammation, energy homeostasis, and metabolic regulation. Through integration of mechanistic studies, multi-omics analyses, and emerging clinical evidence, this review outlines the potential of the polyphenol–microbiota–metabolite axis as a target for precision nutrition and microbiota-informed therapeutic interventions. The manuscript highlights ongoing challenges, including inter-individual variability in polyphenol metabolism, and proposes future research directions to advance the field of personalized nutrition. Full article

(This article belongs to the Section Omics/Informatics)

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13 pages, 1857 KB

Open AccessArticle

Soft-Palate Changes After Orthognathic Surgery: A Three-Dimensional Assessment of Positioning and Morphology

by Orion Luiz Haas Junior, René de Jesús Quiñones Ravelo, Rubens Martins Bastos, Bibiana Mello da Rosa, Rogério Belle de Oliveira, Pedro Gomes de Oliveira and Robson Capasso

J. Pers. Med. 2026, 16(3), 141; https://doi.org/10.3390/jpm16030141 - 2 Mar 2026

Abstract

Background/Objectives: This study evaluated, by cone-beam computed tomography, the role of soft-palate morphology and positioning in upper airway volume and minimum cross-sectional area (mCSA) after orthognathic surgery at three time points: one week before surgery (T0); 4–6 months after surgery (T1); and [...] Read more.

Background/Objectives: This study evaluated, by cone-beam computed tomography, the role of soft-palate morphology and positioning in upper airway volume and minimum cross-sectional area (mCSA) after orthognathic surgery at three time points: one week before surgery (T0); 4–6 months after surgery (T1); and 12–36 months after surgery (T2). Methods: Patients (N = 91) were divided into five groups according to maxillary surgical movement: 1: maxillary advancement; 2: maxillary advancement and counterclockwise rotation with anterior upward movement; 3: maxillary advancement and counterclockwise rotation with posterior downward movement; 4: maxillary advancement and clockwise rotation with anterior downward movement; and 5: maxillary advancement and clockwise rotation with posterior upward movement. Results: Time was an important predictor of change for almost all volume and mCSA parameters (p < 0.05), except for mCSA-nasopharynx (p = 0.114). Groups 1 and 5 showed recurrence of oropharynx volume and minimum cross-sectional area at 12–36 months, while Group 3 had 85% of vertical soft palate morphology and no oblique morphology at 12–36 months. Conclusions: Soft palate angulation did not change at any time or with any type of surgical movement. Maxillary counterclockwise rotation with posterior downward movement seems to be the preferred surgical movement of the maxilla to increase pharyngeal dimensions and improve soft-palate morphology. Full article

(This article belongs to the Special Issue Personalized Medicine in Dental and Oral Health)

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15 pages, 1037 KB

Open AccessArticle

Serum-Soluble Receptor for Advanced Glycation End Products as a Potential Biomarker in Lung Cancer Patients

by Emmanouil Panagiotou, Anastasia Georganta, Efstathios Garoflos, Eleftheria Karaviti, Dimitra Karaviti, Athanasios Kontogiannis, Sofia Chorianopoulou, Elias Kotteas, Nikolaos Syrigos and Melpomeni Peppa

J. Pers. Med. 2026, 16(3), 140; https://doi.org/10.3390/jpm16030140 - 2 Mar 2026

Abstract

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Soluble receptor for advanced glycation end products (sRAGE) has emerged as a candidate biomarker in metabolic, inflammatory, and malignant diseases, although its prognostic significance in LC remains uncertain. Methods: Serum sRAGE [...] Read more.

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Soluble receptor for advanced glycation end products (sRAGE) has emerged as a candidate biomarker in metabolic, inflammatory, and malignant diseases, although its prognostic significance in LC remains uncertain. Methods: Serum sRAGE levels were prospectively measured at baseline and prior to the second cycle of treatment in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Associations of sRAGE with overall survival (OS), progression-free survival (PFS), clinical features, and other biomarkers were analyzed. Results: In total, 42 patients were enrolled in this study. sRAGE was detected in 16 patients (38.1%) at baseline and in 15 patients (37.5%) after the first cycle of treatment. Pre-treatment sRAGE levels were strongly correlated with post-treatment levels (Pearson’s r = 0.78; 95% CI, 0.61–0.88; p = 4.1 × 10⁻⁹) and moderately correlated with PD-L1 tumor proportion score in NSCLC patients (Spearman’s ρ = 0.4, p = 0.049). Pre-treatment sRAGE levels tended to be higher in patients with indeterminate/high risk of liver fibrosis compared to patients with low risk (Wilcoxon rank-sum test, p = 0.041). Post-treatment change in sRAGE levels was correlated with whole blood cell count-derived inflammatory markers. A preliminary association between decreased sRAGE and overall survival in SCLC patients was observed. Conclusions: Serum sRAGE shows potential as a blood-based biomarker reflecting metabolic, immune, and inflammatory status in lung cancer, warranting further investigation to clarify its prognostic and therapeutic relevance. Full article

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26 pages, 1257 KB

Open AccessReview

Precision Medicine in Inflammatory Bowel Disease: The Emerging Role of Metabolic Dysfunction

by Aditya Kotha, Arun J. Sanyal and Raseen Tariq

J. Pers. Med. 2026, 16(3), 139; https://doi.org/10.3390/jpm16030139 - 2 Mar 2026

Abstract

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract with a rapidly increasing global prevalence. In parallel, metabolic comorbidities including obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and sarcopenia are becoming [...] Read more.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract with a rapidly increasing global prevalence. In parallel, metabolic comorbidities including obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and sarcopenia are becoming increasingly common among patients with IBD and are now recognized as important modifiers of disease course and outcomes. As the therapeutic landscape of IBD continues to evolve, these intersecting trends create an opportunity to advance precision medicine through more individualized approaches to care. This review synthesizes established and emerging evidence on the role of metabolic dysfunction in IBD, focusing on epidemiology, risk factors, and prognostic implications. We highlight key domains relevant to personalized care, including metabolic phenotypes, energy metabolism, circulating biomarkers, and nutrition, and discuss how these factors may complement traditional inflammatory markers in risk stratification and longitudinal disease monitoring. Collectively, the available evidence suggests that metabolic comorbidities are not merely coincidental but represent clinically meaningful phenotypes that influence treatment response, complications, and long-term outcomes in IBD. Integrating metabolic assessment into routine IBD care may enable more precise, patient-centered management strategies and help address the growing heterogeneity of IBD in the era of precision medicine. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Diagnosis and Personalized Treatment)

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17 pages, 961 KB

Open AccessReview

Volatile Anesthesia in Contemporary Cardiac Surgery: Clinical Implications, Organ Protection and Perspectives for Personalized Perioperative Care

by Debora Emanuela Torre and Carmelo Pirri

J. Pers. Med. 2026, 16(3), 138; https://doi.org/10.3390/jpm16030138 - 1 Mar 2026

Abstract

Background: Interest in inhalational anesthesia in cardiac surgery has resurged as volatile anesthetics exert biological effects extending beyond hypnosis. Sevoflurane and desflurane activate mitochondrial cytoprotective signaling pathways, modulate inflammatory and endothelial responses and may attenuate ischemia–reperfusion injury during cardiopulmonary bypass, potentially influencing [...] Read more.

Background: Interest in inhalational anesthesia in cardiac surgery has resurged as volatile anesthetics exert biological effects extending beyond hypnosis. Sevoflurane and desflurane activate mitochondrial cytoprotective signaling pathways, modulate inflammatory and endothelial responses and may attenuate ischemia–reperfusion injury during cardiopulmonary bypass, potentially influencing postoperative organ function and recovery. Methods: This narrative review critically examines experimental and clinical evidence on the use of volatile anesthetics in cardiac anesthesia. The current literature was analyzed to elucidate mechanistic foundations of myocardial and extracardiac organ protection, hemodynamic and metabolic effects, and the influence of patient-specific vulnerability profiles on perioperative outcomes. Results: Preclinical studies consistently demonstrate that volatile anesthetics trigger mitochondrial protective pathways, including K-ATP channel activation, controlled reactive oxygen species signaling and inhibition of the mitochondrial permeability transition pore. Clinical studies suggest potential benefits in myocardial protection and modulation of systemic inflammatory and microcirculatory responses. However, translation into consistent clinical outcome improvement remains heterogeneous, influenced by variability in surgical procedures, anesthetic protocols and patient risk stratification. Conclusions: Volatile anesthetics exhibit mechanistic properties supporting a potential role in organ protection during cardiac surgery. Nevertheless, clinical evidence remains inconclusive, underscoring the need for refined patient stratification and precision-based perioperative strategies. Identifying knowledge gaps and research priorities may facilitate rational, individualized integration of inhalational anesthesia into contemporary cardiac surgical practice. Full article

(This article belongs to the Special Issue New Insights into Personalized Medicine for Anesthesia and Pain)

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20 pages, 535 KB

Open AccessArticle

Perceived Risk Perception of Future Cardiovascular Disease and Diabetes in the Postpartum Period

by Amin Heidarikakolaki, Siew Lim, Maureen Makama, Mingling Chen, Melinda J. Hutchesson, Cheryce L. Harrison, Helen Skouteris, Helena Teede and Lisa J. Moran

J. Pers. Med. 2026, 16(3), 137; https://doi.org/10.3390/jpm16030137 - 1 Mar 2026

Abstract

Background/Objectives: Risk perception of future disease may play a role in supporting lifestyle change to prevent diabetes mellitus (DM) and cardiovascular disease (CVD). It is unknown how women in the postpartum period with different cardiometabolic conditions perceive their future risk of DM [...] Read more.

Background/Objectives: Risk perception of future disease may play a role in supporting lifestyle change to prevent diabetes mellitus (DM) and cardiovascular disease (CVD). It is unknown how women in the postpartum period with different cardiometabolic conditions perceive their future risk of DM and CVD, and whether this perception influences engagement in a healthy lifestyle. Methods: Cross-sectional study of women who delivered in the past five years (n = 497) living in Australia. Logistic regression analyses examined associations between history of pregnancy (gestational diabetes mellitus (GDM), gestational hypertension (GHP), pre-eclampsia, spontaneous preterm birth (PTB), small-for-gestational-age (SGA) infants), and non-pregnancy (polycystic ovary syndrome (PCOS), infertility) conditions with perceived risk of DM or CVD, and with lifestyle behaviours (physical activity, sedentary behaviour, and diet). Results: Overall, most participants had a low perceived risk of developing future DM (73.4%) and CVD (75.2%), which varied by condition type. History of GDM and GHP were associated with higher DM risk perception (OR 1.83, 95% CI 1.06, 3.15; OR 2.73, 95% CI 1.28, 5.84), whereas history of pre-eclampsia and DM were associated with higher CVD risk perception (OR 4.48, 95% CI 1.88, 10.62; OR 3.78, 95% CI 1.20, 11.88). History of PTB, SGA infant, PCOS, infertility, and lifestyle behaviours were not consistently associated with perceived risk of DM and CVD. Conclusions: Postpartum risk perception of developing future DM and CVD was low, even in the presence of female-specific cardiometabolic conditions. This highlights the need for greater postpartum support to enhance risk awareness and support a healthy lifestyle. Full article

(This article belongs to the Special Issue Advances and Challenges in Personalized Medicine for Reproductive Health)

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13 pages, 883 KB

Open AccessArticle

From Preparticipation Screening to Diagnosis: Long-Term Outcomes of Athletes with Ventricular Repolarization Abnormalities and Normal Echocardiography

by Massimiliano Bianco, Fabrizio Sollazzo, Stefania Manes, Andrea Giovanni Cristaudo, Gloria Modica, Riccardo Monti, Michela Cammarano, Paolo Zeppilli and Vincenzo Palmieri

J. Pers. Med. 2026, 16(3), 136; https://doi.org/10.3390/jpm16030136 - 1 Mar 2026

Abstract

Background/Objectives: Ventricular repolarization abnormalities (VRA) represent a grey area in athlete screening: some patterns are physiological, while others are precursors to heart disease. Objective: to clarify the natural history of VRA and the associated factors of structural diagnosis. Methods: Retrospective observational [...] Read more.

Background/Objectives: Ventricular repolarization abnormalities (VRA) represent a grey area in athlete screening: some patterns are physiological, while others are precursors to heart disease. Objective: to clarify the natural history of VRA and the associated factors of structural diagnosis. Methods: Retrospective observational single-center study of athletes with resting or stress VRA at the first evaluation, with normal echocardiography; minimum follow-up of 2 years. Clinical data, resting and stress ECG, echocardiography, and selective advanced imaging throughout follow-up were collected. Primary outcome: cardiovascular diagnosis at follow-up; time-to-event analysis and associations between ECG characteristics and diagnosis. Results: Fifty-three athletes (mean age 22.2 ± 9.2 years; 92.5% male) were included; 60.4% had resting VRA, and 100% had exercise-induced VRA at baseline. Over 7.3 ± 4.5 years, 28/53 (52.8%) received a diagnosis; median time-to-detection was 7.0 years (95% CI 6.0–not reached); RMST10 was 6.7 years (95% CI 5.7–7.7). Diagnoses included hypertrophic cardiomyopathy (24.5%), non-ischaemic left-ventricular scar (11.3%), myocardial bridging (7.5%), hypertensive remodelling (5.7%), coronary anomaly (1.9%), and ventricular pre-excitation (1.9%). Persistence of resting VRA from baseline to follow-up was more frequent in athletes with a final diagnosis (p = 0.01), whereas topography and exercise-induced abnormalities did not discriminate groups. Advanced imaging contributed substantially to case ascertainment. No major adverse cardiovascular events have been identified throughout follow-up. Conclusions: In athletes with screening-detected VRA and normal echocardiography, persistence of resting VRA was associated with higher detection of a cardiovascular diagnosis, while exercise-induced changes alone show limited diagnostic yield. The long median time-to-detection supports prolonged, pre-planned surveillance, with priority for advanced imaging in profiles with persistent abnormalities. These findings align with a risk-adapted, personalized management strategy in sports cardiology. Full article

(This article belongs to the Special Issue Sports Cardiology and Health Promotion Through Personalized Exercise Prescription)

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