Journal of Personalized Medicine

19 pages, 1112 KB

Open AccessArticle

Assessment of Oral Health-Related Quality of Life in Children with Leukemia and Gingival Inflammation

by Alina Adumitroaie, Vasilica Toma, Minerva Codruta Badescu, Daniel Cioloca, Aurelia Spinei, Nura Jdid, Mioara Florentina Trandafirescu, Carmen Ecaterina Leferman and Liliana Georgeta Foia

J. Pers. Med. 2026, 16(2), 84; https://doi.org/10.3390/jpm16020084 (registering DOI) - 2 Feb 2026

Abstract

Background/Objectives: Oral health-related quality of life (OHRQoL) is a complex topic, encompassing the medical, functional and psychosocial aspects of well-being, especially in the context of systemic conditions that can trigger oral cavity impairment. While this subject has been extensively investigated in adults, [...] Read more.

Background/Objectives: Oral health-related quality of life (OHRQoL) is a complex topic, encompassing the medical, functional and psychosocial aspects of well-being, especially in the context of systemic conditions that can trigger oral cavity impairment. While this subject has been extensively investigated in adults, evidence remains limited in pediatric populations, particularly in children with leukemia who are at high risk for oral complications related to the disease itself and its treatment. Moreover, children and parent perceptions of oral health are essential for guiding preventive and personalized therapeutic strategies, yet they are poorly explored in this clinical context. The objective of this study was to assess OHRQoL in children with leukemia and gingival inflammation, and compare it with that of children without this systemic condition. Methods: This observational, cross-sectional, case–control study was conducted on 99 subjects, divided into two groups: the study group n = 49 leukemia subjects and the control group n = 50 subjects without oncologic pathology. Clinical examination of all subjects was performed and oral health status was evaluated using Oral Health Index-Simplified (OHI-S) and Gingival Index (GI). Parents filled out a personalized exploratory questionnaire, adapted after established scales, designed to capture the child’s perceived impact of certain leukemia-related gingivo-periodontal alterations, including pain, ulcerations, gingival bleeding and xerostomia. Data were analyzed using descriptive statistics, Pearson’s Chi-square test and comparative graphical analyses (IBM SPSS Statistics 26). Results: Children with leukemia reported higher frequencies of xerostomia, ulcerations and gingival bleeding compared to children in the control group, with xerostomia showing a suggestive association to gingival inflammation. Oral hygiene status of children in the leukemia group was generally better among children receiving parental assistance during brushing or those practicing dental flossing. Comparative graphical analyses showed differences in symptom reporting and oral hygiene support between groups. Conclusions: The results suggest that xerostomia seemed to align with gingival inflammation in children with leukemia, while parental assistance and dental flossing seemed to be associated with better oral hygiene status. Our findings also support the need for developing standardized, disease-oriented scales of evaluating OHRQoL, as well as individualized oral care and continuous monitoring in order to improve oral health-related quality of life in this vulnerable pediatric population. Full article

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

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1 pages, 136 KB

Open AccessRetraction

RETRACTED: Lee et al. Machine-Learning-Based Survival Prediction in Castration-Resistant Prostate Cancer: A Multi-Model Analysis Using a Comprehensive Clinical Dataset. J. Pers. Med. 2025, 15, 432

by Jeong Hyun Lee, Jaeyun Jeong, Young Jin Ahn, Kwang Suk Lee, Jong Soo Lee, Seung Hwan Lee, Won Sik Ham, Byung Ha Chung and Kyo Chul Koo

J. Pers. Med. 2026, 16(2), 83; https://doi.org/10.3390/jpm16020083 (registering DOI) - 2 Feb 2026

Abstract

The journal retracts the article “Machine-Learning-Based Survival Prediction in Castration-Resistant Prostate Cancer: A Multi-Model Analysis Using a Comprehensive Clinical Dataset” [...] Full article

(This article belongs to the Section Personalized Medical Care)

11 pages, 224 KB

Open AccessArticle

Incidence and Predictors of Venous Thromboembolism Following Major Urologic Cancer Surgery: Toward Risk-Stratified, Personalized Prophylaxis Strategies

by Sri Saran Manivasagam, Alireza Aminsharifi and Jay D. Raman

J. Pers. Med. 2026, 16(2), 82; https://doi.org/10.3390/jpm16020082 (registering DOI) - 1 Feb 2026

Abstract

Background/Objectives: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), remains a significant postoperative complication following major urologic cancer surgeries. Despite widespread use of thromboprophylaxis, the real-world effectiveness of these strategies remains uncertain. Methods: We conducted a retrospective [...] Read more.

Background/Objectives: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), remains a significant postoperative complication following major urologic cancer surgeries. Despite widespread use of thromboprophylaxis, the real-world effectiveness of these strategies remains uncertain. Methods: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, including procedure-targeted data for radical cystectomy, radical prostatectomy, and radical nephrectomy from 2019 to 2022. Patients aged 18–90 years with complete data were included. Descriptive statistics and multivariate logistic regression analyses were performed to identify predictors of DVT and evaluate the impact of thromboprophylaxis strategies. Results: A total of 65,105 patients were analyzed: 28,805 prostatectomies, 28,414 cystectomies, and 7886 nephrectomies. The 30-day incidence of DVT and PE was 1.1% and 0.8%, respectively. Multivariate analysis identified prolonged hospital stay (>4 days), operative time (>180 min), and age > 75 years as independent predictors of DVT. Subgroup analyses confirmed these findings for cystectomy and prostatectomy but not for nephrectomy. Thromboprophylaxis was administered in 97.8% of patients; however, its use was not significantly associated with reduced DVT incidence, except for pharmacologic prophylaxis in cystectomy patients (OR 0.04, p = 0.03). Conclusions: Despite high adherence to thromboprophylaxis protocols, DVT remains a clinically relevant complication after urologic cancer surgery. Our findings highlight the importance of procedural factors in DVT risk and question the universal effectiveness of current prophylaxis strategies. These findings underscore the need for personalized, risk-stratified thromboprophylaxis protocols tailored to patient and procedural factors. Full article

(This article belongs to the Special Issue Urological Diseases: Updates and Challenges on Personalized Diagnosis, Treatment, and Management)

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Graphical abstract

10 pages, 344 KB

Open AccessArticle

Towards a Personalized Vestibular Assessment in Older Patients with Cochlear Implant

by Tiziana Di Cesare, Pasqualina Maria Picciotti, Walter Di Nardo, Daniela Rodolico and Jacopo Galli

J. Pers. Med. 2026, 16(2), 81; https://doi.org/10.3390/jpm16020081 (registering DOI) - 1 Feb 2026

Abstract

Background: Age-related vestibular decline frequently accompanies presbycusis, and older adults undergoing cochlear implantation (CI) may be particularly vulnerable to postoperative dizziness due to a reduced compensatory capacity and a higher burden of comorbidities. Although CI is an effective treatment for severe-to-profound sensorineural [...] Read more.

Background: Age-related vestibular decline frequently accompanies presbycusis, and older adults undergoing cochlear implantation (CI) may be particularly vulnerable to postoperative dizziness due to a reduced compensatory capacity and a higher burden of comorbidities. Although CI is an effective treatment for severe-to-profound sensorineural hearing loss in the elderly, its impact on vestibular function remains a critical concern. This study aimed to compare pre and postoperative vestibular performance in older patients (≥65 years) versus younger adults undergoing CI in order to identify the risk factors for postoperative vestibular deterioration and critical issues that characterize this category and carry out personalized preoperative counseling. Methods: In this monocentric observational study, adults undergoing CI were divided into two groups: older patients (OPS, ≥65 years) and younger patients (YPS, <65 years). Vestibular function was assessed preoperatively and one month postoperatively through a Dizziness Handicap Inventory (DHI), history of recurrent falls, clinical examination, video head impulse test (VHIT), bithermal caloric testing, and computerized dynamic posturography (Sensory Organization Test, SOT). Risk factors for postoperative vestibular worsening were analyzed using ANOVA test and chi-square statistics, with significance set at p < 0.05. Results: A total of 63 patients were included, with 18 surgeries involving OPS and 45 involving YPS. Preoperatively, OPS showed significantly higher rates of vestibular abnormalities on caloric testing (55.5% vs. 17.7% bilateral hyporeflexia, p < 0.05) and a higher prevalence of recurrent falls (33.3% vs. 4.4%, p < 0.05). Early postoperative dizziness (DHI¹) increased significantly in both groups, but age ≥ 65 was a risk factor for ≥10% worsening (OR 2.2, p < 0.05). At one month, YPS returned to baseline DHI values, whereas OPS showed persistent dizziness with significantly higher DHI² scores (29.2 vs. 12.9, p < 0.05). Vestibular worsening was identified in 33.3% of VHIT assessments and 44.4% of caloric tests in OPS, with caloric testing proving more sensitive than VHIT. Implantation on the better-functioning vestibular side and the presence of ≥3 comorbidities increased the likelihood of persistent postoperative dizziness. Conclusions: Older age is a significant risk factor for persistent dizziness and vestibular impairment one month after CI. Given the reduced compensatory capacity typical of older adults, vestibular assessment should play a central role in preoperative decision-making, particularly for side selection. Bithermal caloric stimulation is recommended as the most sensitive tool for detecting clinically relevant vestibular changes. Preoperative counseling for older CI candidates should include a detailed discussion of vestibular risks and the possible need for postoperative rehabilitation. Full article

(This article belongs to the Special Issue Personalized Medicine for Otolaryngology (ENT))

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15 pages, 415 KB

Open AccessReview

Molecular-Guided Precision Oncology in Cancer of Unknown Primary: A State-of-the-Art Perspective

by Vivek Subbiah, Elie Rassy and Frank A. Greco

J. Pers. Med. 2026, 16(2), 80; https://doi.org/10.3390/jpm16020080 (registering DOI) - 1 Feb 2026

Abstract

Cancer of unknown primary (CUP) is evolving from a diagnosis of exclusion treated with empirical chemotherapy to a molecularly defined entity amenable to precision-based interventions. This heterogeneous entity, comprising 2–3% of all metastatic malignancies, encompasses diverse cancers with clinically occult primary sites at [...] Read more.

Cancer of unknown primary (CUP) is evolving from a diagnosis of exclusion treated with empirical chemotherapy to a molecularly defined entity amenable to precision-based interventions. This heterogeneous entity, comprising 2–3% of all metastatic malignancies, encompasses diverse cancers with clinically occult primary sites at diagnosis after a thorough workup. Recent landmark trials including CUPISCO and Fudan CUP-001 have demonstrated significant survival improvements with molecularly guided therapies compared to empirical chemotherapy, fundamentally enhancing and complementing traditional organ-centric treatment paradigms. This review synthesizes the current evidence supporting molecular diagnostics, tumor-agnostic therapies, and precision-based approaches in CUP management. We examine the clinical utility of comprehensive genomic profiling, gene expression profiling, and liquid biopsy technologies, while addressing implementation challenges and future directions. The integration of molecular tumor boards and the emergence of tissue/tissue-of-origin agnostic therapies herald a new era where CUP transitions from therapeutic nihilism to personalized oncology. As molecular technologies advance and targeted therapies proliferate, CUP may no longer represent a diagnosis of exclusion but rather an opportunity for molecularly informed precision care. Full article

(This article belongs to the Section Precision Oncology)

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34 pages, 1093 KB

Open AccessReview

Redox–Genomic Crosstalk: Linking Oxidative Stress, Sperm DNA Fragmentation, and Epigenetics in Personalized Management of Male Infertility

by Pallav Sengupta, Sulagna Dutta, Mohamed AlaaEldein Elsuity and Ramadan Saleh

J. Pers. Med. 2026, 16(2), 79; https://doi.org/10.3390/jpm16020079 (registering DOI) - 1 Feb 2026

Abstract

Male infertility is increasingly recognized as a complex, multifactorial disorder that extends beyond abnormalities in conventional semen parameters. A growing body of evidence highlights oxidative stress, sperm DNA fragmentation (SDF), and epigenetic alterations as tightly interconnected mechanisms contributing to sperm dysfunction and impaired [...] Read more.

Male infertility is increasingly recognized as a complex, multifactorial disorder that extends beyond abnormalities in conventional semen parameters. A growing body of evidence highlights oxidative stress, sperm DNA fragmentation (SDF), and epigenetic alterations as tightly interconnected mechanisms contributing to sperm dysfunction and impaired fertility. Reactive oxygen species, though vital for sperm maturation and signaling, can inflict extensive genomic and chromatin damage when their levels exceed the antioxidant capacity of the testis and seminal plasma. These redox-driven lesions not only compromise fertilization potential but may also influence embryonic development and offspring health. Clinical studies and meta-analyses consistently report that elevated SDF and redox imbalance are associated with reduced pregnancy and live birth rates, particularly in assisted reproductive technologies (ARTs). The use of testicular sperm in men with high ejaculated SDF appears to improve ART outcomes, although long-term safety data remain limited. Advances in redox and genomic diagnostics, including assays for oxidation–reduction potential, SDF, and sperm epigenetic profiling, have opened new avenues for precision-based andrology, enabling targeted antioxidant, metabolic, and surgical interventions. Nonetheless, methodological variability, lack of assay standardization, and insufficient longitudinal follow-up constrain the full clinical translation of these findings. This review synthesizes evidence linking OS, SDF, and epigenetic alterations, highlighting their mechanistic crosstalk and translational relevance in the personalized management of male infertility. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Therapy in Diseases)

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18 pages, 546 KB

Open AccessReview

Arteriolar Collapse and Haemodynamic Incoherence in Shock: Rethinking Critical Closing Pressure

by Ashley Miller, Philippe Rola, Rory Spiegel and Korbin Haycock

J. Pers. Med. 2026, 16(2), 78; https://doi.org/10.3390/jpm16020078 (registering DOI) - 1 Feb 2026

Abstract

Critical closing pressure (CCP) and the vascular waterfall have long been used to explain perfusion failure in shock, yet their physiological meaning has been inconsistently interpreted. CCP is frequently treated as a continuous downstream pressure and inserted into formulas such as mean arterial [...] Read more.

Critical closing pressure (CCP) and the vascular waterfall have long been used to explain perfusion failure in shock, yet their physiological meaning has been inconsistently interpreted. CCP is frequently treated as a continuous downstream pressure and inserted into formulas such as mean arterial pressure (MAP) − CCP, implying that a collapse threshold behaves like an opposing pressure even when vessels remain open. Drawing on classical vascular mechanics, whole-bed flow studies, microvascular models, and contemporary clinical physiology, we show that this interpretation is incorrect. Tone-dependent arteriolar collapse does not behave as a Starling resistor: CCP is a threshold at which smooth-muscle tension exceeds intraluminal pressure and vessels close, not a pressure governing flow in patent vessels. Perfusion becomes heterogeneous because different vascular beds reach their collapse thresholds at different pressures (via excessive tone, extrinsic compression, or profound hypotension), disconnecting macro-haemodynamics from microcirculatory flow. This explains why systemic variables such as MAP and systemic vascular resistance (SVR) may appear adequate even while tissues are under-perfused, a phenomenon now termed haemodynamic incoherence. Reframing CCP as a binary collapse threshold resolves longstanding contradictions in the literature, clarifies why MAP-centred targets often fail, and unifies the behaviour of shock states within a four-interface model of circulatory coupling. Therapeutically, the aim is not to “restore a waterfall” but to reopen closed vascular territories by lowering excessive tone, relieving external pressure, or raising truly low arterial inflow. This mechanistic reinterpretation provides a more coherent, physiologically grounded approach to personalised perfusion management in critical illness. Full article

(This article belongs to the Section Mechanisms of Diseases)

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17 pages, 469 KB

Open AccessReview

Neurological Complications After Thoracic Endovascular Repair (TEVAR): A Narrative Review of the Incidence, Mechanisms and Strategies for Prevention and Management

by Francesca Miceli, Marta Ascione, Rocco Cangiano, Antonio Marzano, Alessia Di Girolamo, Giovanni Gagliardo, Luca di Marzo and Wassim Mansour

J. Pers. Med. 2026, 16(2), 77; https://doi.org/10.3390/jpm16020077 (registering DOI) - 1 Feb 2026

Abstract

Background: Thoracic endovascular aortic repair (TEVAR) has evolved the management of descending thoracic aortic disease, but neurological complications—particularly spinal cord ischemia (SCI), stroke, and postoperative delirium—remain among the most feared adverse events, adversely affecting survival, quality of life, and functional independence. Objectives [...] Read more.

Background: Thoracic endovascular aortic repair (TEVAR) has evolved the management of descending thoracic aortic disease, but neurological complications—particularly spinal cord ischemia (SCI), stroke, and postoperative delirium—remain among the most feared adverse events, adversely affecting survival, quality of life, and functional independence. Objectives: The aim of this study was to provide a contemporary narrative synthesis (2000–2025) of the incidence, mechanisms, risk factors, prevention, and management of neurological complications after TEVAR, emphasizing how current evidence supports individualized and risk-adapted strategies for prevention and management. Methods: A narrative, non-systematic search (PubMed/MEDLINE, Scopus, Cochrane Library; 2000–2025) was conducted using terms related to TEVAR, SCI, cerebrovascular events, delirium, and cognitive dysfunction. Priority was given to large registries, cohort studies, and systematic reviews in adult TEVAR populations. Results: Perioperative stroke occurs in ~2–6% of TEVAR cases, with higher rates in arch/zone 0–2 procedures and when the left subclavian artery (LSA) is covered without revascularization. SCI incidence ranges from ~2–9%, influenced by aortic extent and urgency; Vascular Quality Initiative data report SCI in 3.7% of procedures, with markedly reduced 1-year survival. Major SCI risk factors include extensive thoracic coverage, prior aortic repair, vertebral or hypogastric occlusion, emergency presentation, low perioperative mean arterial pressure, anemia, and chronic kidney disease. Postoperative delirium occurs in ~13% of TEVAR-treated type B dissections and correlates with longer hospitalization and early complications. Emerging nomograms for SCI and delirium enable individualized risk stratification. Conclusions: Neurological complications after TEVAR remain clinically significant. Contemporary evidence supports personalized prevention—selective cerebrospinal fluid (CSF) drainage, LSA revascularization, staging, neuromonitoring, and tailored hemodynamic targets—guided by anatomical complexity, comorbidities, collateral network integrity, and prior aortic history. Further research should refine prediction tools, standardize definitions, and evaluate individualized neuroprotective bundles. Full article

(This article belongs to the Special Issue Complications in Vascular Surgery: Current Updates and Perspectives)

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13 pages, 741 KB

Open AccessReview

Model-Informed Precision Dosing: Conceptual Framework for Therapeutic Drug Monitoring Integrating Machine Learning and Artificial Intelligence Within Population Health Informatics

by Jennifer Le, Hien N. Le, Giang Nguyen, Rebecca Kim, Sean N. Avedissian, Connie Vo, Ba Hai Le, Thanh Hai Nguyen, Dua Thi Nguyen, Dylan Huy Do, Brian Le, Austin-Phong Nguyen, Tu Tran, Chi Kien Phung, Duong Anh Minh Vu, Karandeep Singh and Amy M. Sitapati

J. Pers. Med. 2026, 16(2), 76; https://doi.org/10.3390/jpm16020076 (registering DOI) - 31 Jan 2026

Abstract

Background/Objective: Traditional therapeutic drug monitoring is limited by manual interpretation and specific constraints like sampling at steady-state and requiring a minimum of two drug concentrations. The integration of model-informed precision dosing (MIPD) into population health informatics represents a promising approach to address [...] Read more.

Background/Objective: Traditional therapeutic drug monitoring is limited by manual interpretation and specific constraints like sampling at steady-state and requiring a minimum of two drug concentrations. The integration of model-informed precision dosing (MIPD) into population health informatics represents a promising approach to address drug safety and efficacy. This article explored the integration of MIPD within population health informatics and evaluated its potential to enhance precision dosing using artificial intelligence (AI), machine learning (ML), and electronic health records (EHRs). Methods: PubMed and Embase searches were conducted, and all relevant peer-reviewed studies in English published between 1958 and December 2024 were included if they pertained to MIPD and population-level health, with the use of AI/ML algorithms to predict individualized drug dosing requirements. Emphasis was placed on vulnerable populations such as critically-ill, geriatric, and pediatric groups. Results: MIPD with the Bayesian method represents a scalable innovation in precision medicine, with significant implications for population health informatics. By combining AI/ML with comprehensive electronic health records (EHRs), MIPD can offer real-time, precise dosing adjustments. This integration has the potential to improve patient safety, optimize therapeutic outcomes, and reduce healthcare costs, especially for vulnerable populations where evidence is limited. Successful implementation requires collaboration among clinicians, pharmacists, and health informatics professionals, alongside secure data management and interoperability solutions. Conclusions: Further research is needed to define, implement, and evaluate practical applications of AI/ML. This insight may help develop standards and identify drugs for MIPD to advance personalized medicine within population health informatics. Full article

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

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Graphical abstract

28 pages, 1932 KB

Open AccessReview

Drug-Coated Balloons in Coronary Bifurcation Disease: A State-of-the-Art Review

by Saad M. Ezad, Natasha Khullar, Peter O’Kane and Jonathan Hinton

J. Pers. Med. 2026, 16(2), 75; https://doi.org/10.3390/jpm16020075 (registering DOI) - 31 Jan 2026

Abstract

Coronary bifurcation disease remains one of the more challenging lesion subsets to treat with percutaneous coronary intervention due to bifurcation geometry and increased risk of target lesion failure. Whilst a provisional approach is preferred in most bifurcations, two-stent techniques may be required where [...] Read more.

Coronary bifurcation disease remains one of the more challenging lesion subsets to treat with percutaneous coronary intervention due to bifurcation geometry and increased risk of target lesion failure. Whilst a provisional approach is preferred in most bifurcations, two-stent techniques may be required where there is a high risk of side branch compromise or a bailout; however, this further increases procedure complexity. Drug-coated balloons (DCBs) are emerging as a promising alternative that allow vessel healing without leaving behind a permanent metallic implant by delivering antiproliferative medication directly to the vessel wall and simplifying procedures. This state-of-the-art review summarises the current evidence and the evolving role of DCBs in the management of coronary bifurcation lesions with a focus on patient- and lesion-specific factors that might influence the treatment strategy choice. Full article

(This article belongs to the Special Issue Complex and High-Risk Coronary Interventional Procedures)

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12 pages, 764 KB

Open AccessArticle

Particularities in Surgical Results Following Obstetrical and Gynecological Surgery Using Pharmacological, Anesthesiological and Genetic Markers

by Gabriel Valentin Tănase, Manuela Ciocoiu, Adina Elena Tănase and Ciprian Gavrila Ilea

J. Pers. Med. 2026, 16(2), 74; https://doi.org/10.3390/jpm16020074 (registering DOI) - 31 Jan 2026

Abstract

Aim: Finding innovative paraclinical parameters is necessary for advancing clinical research, in obstetrics and gynecology for subjective symptoms such as pain, especially in patients with a weakened immune system, following, for example, different obstetrical and gynecological surgeries. The purpose of this study [...] Read more.

Aim: Finding innovative paraclinical parameters is necessary for advancing clinical research, in obstetrics and gynecology for subjective symptoms such as pain, especially in patients with a weakened immune system, following, for example, different obstetrical and gynecological surgeries. The purpose of this study was to analyze if genetic markers can correlate with the postoperative outcome and surgical results in obstetrics and gynecology. We wanted to analyze whether patients carrying the G gene responsible for the A11G polymorphism of the OPRM1 receptor really have a higher need for analgesic doses for postoperative pain control, depending on the histopathological results, benign or malignant tumors, dimensions of tumors, type of incision performed, and hospitalization period. Materials and Methods: We analyzed 111 patients, including both obstetrical and gynecological cases. Blood samples (2 mL) for DNA analysis were obtained before surgery in a tube containing EDTA as an anticoagulant and immediately stored at −20 °C until required for further use. The blood samples, which were collected at the time of intravenous cannulation before surgery, were analyzed for the presence of SNP 118AG. Results: We examined the mutation of the opioid receptor called OPRM1 for the polymorphism noted with AG with a plus sign (+) (present) in 24.3% of the patients, with a minus sign (−) (AA) (absent) in 66.7% of the patients, and with a result with both genes modified (GG) in 9%. We correlated the data obtained in histopathology and clinical anamnesis with these results. The OPRM1(+) morphine receptor mutation was more frequently encountered in patients with biopsy uterine curettage (60%) with benign results in anatomopathology, uterine myomectomy of at least 5 cm fibromas with benign results in anatomopathology (50%), Madden mastectomy (50%), interventional hysteroscopy (33.3%) with extraction of benign tumors such as polyps or endometrial hyperplasia, caesarean section-associated surgeries (20.7%), and ovarian cystectomy (20%) (p = 0.048) that had a final benign anatomopathology result. Conclusions: Pain management in the postoperative phase is difficult for clinicians because of the response of patients to opioid therapy. Some of this variability in pain response may result from single nucleotide polymorphisms (SNPs) in the human opioid receptor mu-1 (OPRM1) that alter receptor binding or signal transduction. Part of the difficulty in identifying genes and variants that affect postsurgical pain is the inconsistent findings and poor replicability of results. Full article

(This article belongs to the Special Issue Personalized Medicine in Gynecology and Obstetrics)

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14 pages, 297 KB

Open AccessArticle

The Role of Chronic Endometritis in Endometriosis: A Personalized Diagnostic Tool?

by María Luna Arana, Augusto Pereira Sánchez, Gema Vaquero Argüello, Eva Tejerina González, Milagros Alonso-Iniesta and Tirso Pérez Medina

J. Pers. Med. 2026, 16(2), 73; https://doi.org/10.3390/jpm16020073 (registering DOI) - 31 Jan 2026

Abstract

(1) Background: Endometriosis and chronic endometritis (CE) are pathologies that are positively correlated and have similar paracrine and immunological alterations. This leads us to wonder whether their interrelationship plays a role in the etiopathogenesis or progression of endometriosis. The purpose of this [...] Read more.

(1) Background: Endometriosis and chronic endometritis (CE) are pathologies that are positively correlated and have similar paracrine and immunological alterations. This leads us to wonder whether their interrelationship plays a role in the etiopathogenesis or progression of endometriosis. The purpose of this study is to evaluate whether patients with endometriosis and CE have a more advanced stage of the disease, higher rates of pain, a poorer response to treatment, and a greater association with other pathologies compared to women with endometriosis without CE. (2) Methods: This is a cross-sectional pilot design study of 37 women with endometriosis who underwent endometrial aspiration for the diagnosis of CE and were followed up at the Puerta de Hierro Hospital. (3) Results: All patients with CE in this study had adenomyosis (p = 0.004). There was a relatively homogeneous distribution of CE in the different endometriosis phenotypes. The group of patients with endometriosis and CE indicated higher rates of pain during ovulation and less pain during defecation and sexual intercourse. (4) Conclusions: A high prevalence of CE was observed in patients with endometriosis, as well as a trend suggesting a relationship between CE and adenomyosis that should be studied. The following article attempts to reflect a link found between endometriosis and chronic endometritis, which would be important when prescribing personalized medicine, as it forces us to look for a specific disease in a specific patient profile. Full article

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

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27 pages, 6214 KB

Open AccessReview

Gastric-Type Cervical Adenocarcinoma: Clinicopathologic Features, Molecular Landscape, and Therapeutic Challenges

by Hiroshi Yoshida, Daiki Higuchi, Waku Takigawa, Nao Kikkawa, Taro Yamanaka, Ayaka Nagao, Mayumi Kobayashi-Kato, Masaya Uno, Mitsuya Ishikawa and Kouya Shiraishi

J. Pers. Med. 2026, 16(2), 72; https://doi.org/10.3390/jpm16020072 - 31 Jan 2026

Abstract

Endocervical adenocarcinoma is now classified within an etiologic framework based on the presence or absence of high-risk human papillomavirus (HPV) infection. Gastric-type endocervical adenocarcinoma (GAS) is the prototypical HPV-independent subtype, accounting for up to 25% of endocervical adenocarcinomas and showing a particularly high [...] Read more.

Endocervical adenocarcinoma is now classified within an etiologic framework based on the presence or absence of high-risk human papillomavirus (HPV) infection. Gastric-type endocervical adenocarcinoma (GAS) is the prototypical HPV-independent subtype, accounting for up to 25% of endocervical adenocarcinomas and showing a particularly high frequency in East Asia. GAS is typically diagnosed at a more advanced stage than usual-type HPV-associated endocervical adenocarcinoma (UEA); exhibits deep stromal and parametrial invasion, lymphovascular space invasion, and a strong propensity for ovarian and peritoneal metastasis; and is associated with markedly worse survival, even in stage I disease. Radiological evaluation is challenging because of diffuse infiltrative growth, prominent mucin production, and frequent underestimation of extra-cervical spread. Histologically, GAS shows gastric-type (pyloric) differentiation, ranging from minimal deviation adenocarcinoma to poorly differentiated forms, and often overlaps with precursor lesions such as atypical lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma in situ. Immunophenotypically, GAS is typically p16-negative, ER/PR-negative, and frequently exhibits mutant-type p53 and expression of gastric markers including MUC6, HIK1083, and claudin 18.2. Recent next-generation sequencing and multi-omics studies have revealed recurrent alterations in TP53, CDKN2A, STK11, KRAS, ARID1A, KMT2D, and homologous recombination-related genes, together with the activation of PI3K/AKT, WNT/β-catenin, TGF-β, and EMT pathways and characteristic metabolic reprogramming. GAS is highly resistant to conventional chemotherapy and radiotherapy, and its current management follows guidelines for squamous and usual-type adenocarcinoma. Emerging data support precision-medicine approaches targeting HER2/HER3, PD-1/PD-L1, and claudin 18.2, and suggest a role for PARP inhibition and other genotype-directed therapies in selected subsets. Given its aggressive biology and rising relative incidence in the HPV-vaccination era, GAS represents a critical unmet need in gynecologic oncology. Future progress hinges on developing reliable diagnostic biomarkers, refining imaging protocols, and validating targeted therapies through international clinical trials. Full article

(This article belongs to the Special Issue Molecular Pathology in Cancer Research)

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20 pages, 942 KB

Open AccessReview

Artificial Intelligence in Minimally Invasive and Robotic Gastrointestinal Surgery: Major Applications and Recent Advances

by Matteo Pescio, Francesco Marzola, Giovanni Distefano, Pietro Leoncini, Carlo Alberto Ammirati, Federica Barontini, Giulio Dagnino and Alberto Arezzo

J. Pers. Med. 2026, 16(2), 71; https://doi.org/10.3390/jpm16020071 - 31 Jan 2026

Abstract

Artificial intelligence (AI) is rapidly reshaping gastrointestinal (GI) surgery by enhancing decision-making, intraoperative performance, and postoperative management. The integration of AI-driven systems is enabling more precise, data-informed, and personalized surgical interventions. This review provides a state-of-the-art overview of AI applications in GI surgery, [...] Read more.

Artificial intelligence (AI) is rapidly reshaping gastrointestinal (GI) surgery by enhancing decision-making, intraoperative performance, and postoperative management. The integration of AI-driven systems is enabling more precise, data-informed, and personalized surgical interventions. This review provides a state-of-the-art overview of AI applications in GI surgery, organized into four key domains: surgical simulation, surgical computer vision, surgical data science, and surgical robot autonomy. A comprehensive narrative review of the literature was conducted, identifying relevant studies of technological developments in this field. In the domain of surgical simulation, AI enables virtual surgical planning and patient-specific digital twins for training and preoperative strategy. Surgical computer vision leverages AI to improve intraoperative scene understanding, anatomical segmentation, and workflow recognition. Surgical data science translates multimodal surgical data into predictive analytics and real-time decision support, enhancing safety and efficiency. Finally, surgical robot autonomy explores the progressive integration of AI for intelligent assistance and autonomous functions to augment human performance in minimally invasive and robotic procedures. Surgical AI has demonstrated significant potential across different domains, fostering precision, reproducibility, and personalization in GI surgery. Nevertheless, challenges remain in data quality, model generalizability, ethical governance, and clinical validation. Continued interdisciplinary collaboration will be crucial to translating AI from promising prototypes to routine, safe, and equitable surgical practice. Full article

(This article belongs to the Special Issue New Technologies and Personalized Medicine in Gastrointestinal Surgery)

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13 pages, 2282 KB

Open AccessSystematic Review

Primary Clitoral Melanoma: Personalized Therapeutic Strategies Informed by Clinical Evidence and Systematic Review

by Anna Pitsillidi, Laura Vona, Guglielmo Stabile and Günter Noé

J. Pers. Med. 2026, 16(2), 70; https://doi.org/10.3390/jpm16020070 - 31 Jan 2026

Abstract

Introduction: Mucosal melanomas are rare, and vulvar melanoma is typically diagnosed at an advanced stage with aggressive behavior and poor prognosis. The clitoral region adds challenges due to its functional importance and lack of a dedicated staging system, requiring individualized management. This review [...] Read more.

Introduction: Mucosal melanomas are rare, and vulvar melanoma is typically diagnosed at an advanced stage with aggressive behavior and poor prognosis. The clitoral region adds challenges due to its functional importance and lack of a dedicated staging system, requiring individualized management. This review evaluates current evidence on prognosis with emphasis on clitoral involvement and highlights diagnostic and therapeutic challenges, underscoring the need for personalized strategies and prospective multicentre studies. Materials and Methods: A systematic review, registered in PROSPERO (CRD420251151187), was conducted per PRISMA guidelines across PubMed, Scopus, Embase, and Web of Science, including English-language case reports and series of primary clitoral melanoma published until August 2025, with no historical limits. Results: 15 cases from 10 studies were identified. The mean patient age was 60 years, with most tumors presenting at advanced stages (median Breslow thickness of 8 mm, frequent ulceration). Immunohistochemical markers and gene mutations are rarely investigated in reported cases. All patients underwent surgery, with variable lymph node assessment; adjuvant therapy was rarely used. Recurrence occurred in nearly one-third of cases, sometimes more than 10 years after initial treatment. Conclusions: Primary clitoral melanoma is extremely rare and often diagnosed late, underscoring the need for heightened clinical awareness. Wide local excision with organ preservation is preferred, and bilateral sentinel lymph-node biopsy can improve staging. The absence of a dedicated staging system and limited systemic evidence highlight the need for standardized protocols. Emerging molecular and immunologic approaches are promising, but prospective multicentre studies are essential to guide management. Full article

(This article belongs to the Special Issue Personalized Medicine in Gynecological Oncology: Update and Challenge)

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32 pages, 27435 KB

Open AccessReview

Artificial Intelligence in Adult Cardiovascular Medicine and Surgery: Real-World Deployments and Outcomes

by Dimitrios E. Magouliotis, Noah Sicouri, Laura Ramlawi, Massimo Baudo, Vasiliki Androutsopoulou and Serge Sicouri

J. Pers. Med. 2026, 16(2), 69; https://doi.org/10.3390/jpm16020069 - 30 Jan 2026

Abstract

Artificial intelligence (AI) is rapidly reshaping adult cardiac surgery, enabling more accurate diagnostics, personalized risk assessment, advanced surgical planning, and proactive postoperative care. Preoperatively, deep-learning interpretation of ECGs, automated CT/MRI segmentation, and video-based echocardiography improve early disease detection and refine risk stratification beyond [...] Read more.

Artificial intelligence (AI) is rapidly reshaping adult cardiac surgery, enabling more accurate diagnostics, personalized risk assessment, advanced surgical planning, and proactive postoperative care. Preoperatively, deep-learning interpretation of ECGs, automated CT/MRI segmentation, and video-based echocardiography improve early disease detection and refine risk stratification beyond conventional tools such as EuroSCORE II and the STS calculator. AI-driven 3D reconstruction, virtual simulation, and augmented-reality platforms enhance planning for structural heart and aortic procedures by optimizing device selection and anticipating complications. Intraoperatively, AI augments robotic precision, stabilizes instrument motion, identifies anatomy through computer vision, and predicts hemodynamic instability via real-time waveform analytics. Integration of the Hypotension Prediction Index into perioperative pathways has already demonstrated reductions in ventilation duration and improved hemodynamic control. Postoperatively, machine-learning early-warning systems and physiologic waveform models predict acute kidney injury, low-cardiac-output syndrome, respiratory failure, and sepsis hours before clinical deterioration, while emerging closed-loop control and remote monitoring tools extend individualized management into the recovery phase. Despite these advances, current evidence is limited by retrospective study designs, heterogeneous datasets, variable transparency, and regulatory and workflow barriers. Nonetheless, rapid progress in multimodal foundation models, digital twins, hybrid OR ecosystems, and semi-autonomous robotics signals a transition toward increasingly precise, predictive, and personalized cardiac surgical care. With rigorous validation and thoughtful implementation, AI has the potential to substantially improve safety, decision-making, and outcomes across the entire cardiac surgical continuum. Full article

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

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16 pages, 696 KB

Open AccessArticle

Impact of Comorbid Generalized Anxiety Disorder on rTMS/iTBS Clinical Outcomes in Major Depression: A Multicenter Registry-Based Observational Study

by Yoshihiro Noda, Ryota Osawa, Yuya Takeda, Keiko Fujita, Takumi Tsuji and Ryosuke Kitahata

J. Pers. Med. 2026, 16(2), 68; https://doi.org/10.3390/jpm16020068 - 30 Jan 2026

Abstract

Background: Major depressive disorder (MDD) is often accompanied by generalized anxiety disorder (GAD), a comorbidity linked to greater illness burden and potentially poorer outcomes. Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are established treatments for MDD, yet the impact of [...] Read more.

Background: Major depressive disorder (MDD) is often accompanied by generalized anxiety disorder (GAD), a comorbidity linked to greater illness burden and potentially poorer outcomes. Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are established treatments for MDD, yet the impact of comorbid GAD and concomitant medications remains unclear. This study aimed to compare rTMS/iTBS treatment outcomes between patients with MDD with and without comorbid GAD, and to examine the association between concomitant psychotropic medication use, stimulation protocol, and treatment response in a real-world clinical setting. Methods: We conducted a retrospective observational analysis using registry data from 108 patients (MDD + GAD: n = 36; MDD only: n = 72). Patients received either Left-iTBS or Right-rTMS. Baseline severity, percentage change in Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAMD-17) scores, response, and remission were assessed. Logistic and linear regression models adjusted for age, sex, and baseline severity were applied. Sensitivity analyses stratified by stimulation protocol and benzodiazepine (BDZ) use were performed. Results: Baseline severity did not differ between groups. MADRS reduction was numerically lower in the comorbid GAD group (48.3% vs. 52.7%, p = 0.09), whereas HAMD-17 reduction was comparable. Response and remission rates did not differ significantly. Medication use and stimulation protocol did not show statistically significant independent associations with outcomes. Sensitivity analyses confirmed equivalent outcomes between Left-iTBS and Right-rTMS. BDZ users showed a non-significant trend toward lower MADRS improvement and remission. Conclusions: rTMS/iTBS produced substantial clinical improvement and was well tolerated in both patients with MDD and those with MDD comorbid with GAD. Although comorbid anxiety showed a modest tendency to attenuate MADRS score reduction, overall response and remission rates were comparable between groups. Neither concomitant medications nor stimulation protocol significantly affected treatment outcomes, while the potential influence of BDZ exposure warrants further investigation. Full article

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

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12 pages, 679 KB

Open AccessArticle

Patient Perception of Lower-Limb Straightness at One Week After Unrestricted Kinematically Aligned Total Knee Arthroplasty: Exploring the Concept of “Inherent Straightness”

by Toshiya Kano, Yoshinori Soda, Kimihiro Inoue and Mitsuhiro Nakamura

J. Pers. Med. 2026, 16(2), 67; https://doi.org/10.3390/jpm16020067 - 30 Jan 2026

Abstract

Background/Objectives: Mechanical neutrality has long been regarded as the principal alignment target in total knee arthroplasty (TKA). However, radiographic neutrality does not necessarily reflect physiological morphology or patient perception. This study aimed to evaluate one-week postoperative patient-perceived lower-limb straightness after unrestricted kinematic alignment [...] Read more.

Background/Objectives: Mechanical neutrality has long been regarded as the principal alignment target in total knee arthroplasty (TKA). However, radiographic neutrality does not necessarily reflect physiological morphology or patient perception. This study aimed to evaluate one-week postoperative patient-perceived lower-limb straightness after unrestricted kinematic alignment (KA) TKA and to examine its relationship with radiographic alignment parameters and functional findings. Methods: A total of 175 patients (203 knees) who underwent unrestricted KA-TKA were retrospectively reviewed. Pre- and postoperative radiographs, clinical assessments, and a study-specific, non-validated questionnaire were analyzed one week postoperatively. Patient perception of straightness was assessed using the Straightness Visual Analog Scale (S-VAS) and the Straightness Satisfaction Visual Analog Scale (SS-VAS). Radiographic parameters included the hip–knee–ankle angle (HKAA), the medial proximal tibial angle (MPTA), the mechanical lateral distal femoral angle (mLDFA), the joint line convergence angle (JLCA), and Coronal Plane Alignment of the Knee (CPAK) patterns. Correlative analyses between VAS scores and radiographic and clinical parameters were examined. Results: Preoperatively, 85% of knees were perceived as bowed, and all were reported as straight after surgery. Among knees not perceived as bowed preoperatively, 60% were newly perceived as straight postoperatively, while 40% remained perceived as straight. Postoperative satisfaction was high (S-VAS 88.9 ± 11.6; SS-VAS 92.3 ± 12.9). Associations between S-VAS/SS-VAS and HKAA were weak but statistically significant, whereas both showed moderate positive correlations with postoperative knee extension (S-VAS r = 0.54; SS-VAS r = 0.59). Conclusions: At one week after surgery, patients tended to perceive lower-limb straightness as being associated with restoration of physiological morphology and improved knee extension rather than with radiographic mechanical neutrality. Patient-perceived straightness reflects an individualized and natural sense of limb alignment (“inherent straightness”) and should be interpreted as an exploratory, patient-centered concept based on an early postoperative test, supporting a personalized framework for alignment evaluation in unrestricted KA-TKA. Full article

(This article belongs to the Section Personalized Medical Care)

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25 pages, 2817 KB

Open AccessArticle

Genetic Burden and APOE Methylation in a Korean Multi-Generational Alzheimer’s Disease Family: An Exploratory Multi-Omics Case Study

by Je-Hyun Eom, Mu-Yeol Cho, Ji-Won Kim, Yunwoo Kim, Seung-Jo Yang, Jiyoung Hwang, Dahye Lee, Hye-Sung Kim, Young-Youn Kim and Hanseung Baek

J. Pers. Med. 2026, 16(2), 66; https://doi.org/10.3390/jpm16020066 - 29 Jan 2026

Abstract

Background/Objectives: Alzheimer’s disease (AD) exhibits high heritability (60–80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean [...] Read more.

Background/Objectives: Alzheimer’s disease (AD) exhibits high heritability (60–80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with higher genetic burden (51–61 alleles) remained cognitively healthy. J-003 also exhibited lower APOE methylation (β = 0.495) compared to the family mean (β = 0.523). CR1 contributed the most risk alleles across the family, followed by PICALM. Conclusions: This single-case observation cannot establish causality, generalizability, or biological significance. The affected individual’s lower APOE methylation may represent a causal factor, disease consequence, or coincidental variation—scenarios that cannot be distinguished from this dataset. Validation in larger cohorts with multiple affected individuals is required to determine whether integrated multi-omics approaches can inform personalized risk assessment in familial contexts. Full article

(This article belongs to the Special Issue Genetic Counseling and Genome Sequencing in Pediatrics)

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