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Volume 15
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J. Pers. Med., Volume 15, Issue 10 (October 2025) – 56 articles

Cover Story (view full-size image): Psychedelics are gaining attention across disciplines for their profound psychological and neurobiological effects. Research highlights their efficacy in treating mood disorders, PTSD, and addiction by enhancing neuroplasticity and disrupting maladaptive cognitive patterns. From a psychological standpoint, psychedelics facilitate introspection, emotional processing, and therapeutic breakthroughs. Neuroscientific findings reveal altered brain network dynamics, while anthropological and philosophical perspectives contextualize their cultural and existential significance. In medicine, they offer interventions for chronic pain and palliative care. This review underscores the need for rigorous, ethically grounded research to explore psychedelics’ potential from a multidisciplinary perspective. View this paper
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10 pages, 1048 KB  
Article
Omission of Sentinel Lymph Node Biopsy in Early-Stage HER2+ and Triple-Negative Breast Cancer: A Retrospective Analysis
by Amandine Causse d’Agraives, Rebecca Allievi, Raquel Diaz and Piero Fregatti
J. Pers. Med. 2025, 15(10), 501; https://doi.org/10.3390/jpm15100501 - 17 Oct 2025
Abstract
Background: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in early-stage breast cancer. However, its necessity for some patient groups is being reevaluated. This change mainly arises from the procedure’s impact on quality of life and new evidence suggesting [...] Read more.
Background: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in early-stage breast cancer. However, its necessity for some patient groups is being reevaluated. This change mainly arises from the procedure’s impact on quality of life and new evidence suggesting that some patients can forgo it without affecting their overall survival. Objective: This study focuses on the omission of SLNB in elderly patients aged 80 and older with HER2-positive (HER2+) or triple-negative breast cancer (TNBC) who are clinically node-negative (cN0), comparing outcomes to other relevant studies. Methods: In this retrospective study, we analyzed 39 cN0 women aged 80 and older (mean age at surgery 85.8) with HER2+ or TNBC treated between 2016 and 2024. We assessed overall survival (OS), disease-free survival (DFS), and locoregional recurrence without performing SLNB. We used Kaplan–Meier estimates and Cox proportional hazards models to evaluate survival outcomes by subtype, tumor size, and Ki-67 index. Results: The median OS was 3.9 years (95% confidence interval [CI]: 3.1 years, not estimable [NE]); the 5-year OS was 43.4% (95% CI: 25.3–74.6). The 5-year DFS was 37.7% (95% CI: 21.5–66.2). The median follow-up was 36.5 months (approximately 3.0 years). Five recurrences (12.8%) and two complications (5.1%) occurred. Patients with TNBC had a 5-year OS of 58.2% compared with 35.9% in those with HER2+ disease (p = 0.414). Patients with a low Ki-67 index (≤25%) had a 5-year OS of 78.6% compared with 25.9% in those with higher Ki-67 (p = 0.080). Tumor size ≥pT2 was associated with a worse prognosis. Conclusions: In carefully selected elderly patients with HER2+ or TNBC and no clinical nodal involvement, omitting SLNB was not linked to significantly lower survival rates. The observed numerical differences according to Ki-67 and tumor size suggest that surgical de-escalation may be feasible in selected elderly patients to limit complications without compromising oncological safety. Full article
(This article belongs to the Special Issue Advances in Personalized Treatment of Breast Cancer)
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11 pages, 2216 KB  
Article
Innovative Approach to Embolization of Pelvic Varices Using Endovaginal Guidance: Methodology and Early Outcomes
by Eva Fourage-Jambon, Rayann Soueidan, Hamza Sawalha, Yassine Lamfichekh, Benjamin Linares, Hugo Hans, Mathieu David, Isabelle Molina-Andreo, Charlotte Douchez, Nicolas Pangon, Yann Le Bras, Rim Maaloum and Clément Marcelin
J. Pers. Med. 2025, 15(10), 500; https://doi.org/10.3390/jpm15100500 - 17 Oct 2025
Abstract
Objective: To retrospectively assess the safety and efficacy of endovaginal guidance for embolizing perivaginal varices associated with persistent localized symptoms, including dyspareunia and postcoital pain. Methods: From February 2024 to January 2025, 10 women (median age: 36 years, range: 23–45) underwent pelvic embolization [...] Read more.
Objective: To retrospectively assess the safety and efficacy of endovaginal guidance for embolizing perivaginal varices associated with persistent localized symptoms, including dyspareunia and postcoital pain. Methods: From February 2024 to January 2025, 10 women (median age: 36 years, range: 23–45) underwent pelvic embolization using endovaginal guidance. Eight patients had already undergone endovascular embolization, with persistent perivaginal varices that were inaccessible by this approach, accompanied by dyspareunia or postcoital pain. Primary efficacy was assessed three months post-embolization, defined as a Visual Analog Scale (VAS) score of <2 and a ≥50% decrease. Outcomes were assessed through clinical and imaging follow-up. Results: Technical efficacy was achieved in all procedures (100%). Embolization was performed using Glubran/Lipiodol in eight cases (80%) and Onyx® in two cases (20%). The primary efficacy of the procedures was 90.0% (9 out of 10 cases). A reduction in dyspareunia and postcoital pain was observed, with median VAS scores decreasing to one and zero, respectively, compared to initial scores of seven and seven (p = 0.002 and p = 0.016) and to scores after endovascular embolization to five and five (p = 0.004 and p = 0.016). No major complications were recorded. Imaging follow-up showed a significant reduction in perivaginal varicosities in all cases. Conclusions: Endovaginal guidance proves to be a fast and effective technique for the embolization of perivaginal varices, highlighting its integration into the principles of personalized medicine. Full article
(This article belongs to the Special Issue Exploring Interventional Radiology: New Advances and Prospects)
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20 pages, 588 KB  
Review
Inflammatory Phenotypes of Bronchiectasis
by Evangelia Koukaki, Georgia Papaiakovou, Argyri Klironomou, Efthymia Theofani, Andreas M. Matthaiou, Adamantia Liapikou, Nektarios Anagnostopoulos, Grigorios Stratakos, Petros Bakakos and Nikoletta Rovina
J. Pers. Med. 2025, 15(10), 499; https://doi.org/10.3390/jpm15100499 - 17 Oct 2025
Abstract
Bronchiectasis is a heterogeneous chronic airway disease traditionally viewed as neutrophil-driven. Emerging evidence demonstrates distinct complex inflammatory phenotypes influencing clinical outcomes, prognosis and therapeutic options. A narrative review was conducted, informed by a structured literature search on PubMed and Google Scholar databases, focusing [...] Read more.
Bronchiectasis is a heterogeneous chronic airway disease traditionally viewed as neutrophil-driven. Emerging evidence demonstrates distinct complex inflammatory phenotypes influencing clinical outcomes, prognosis and therapeutic options. A narrative review was conducted, informed by a structured literature search on PubMed and Google Scholar databases, focusing on inflammatory phenotypes in bronchiectasis. Based on the prevalent cellular population, four distinct phenotypes can be described. The most common is the neutrophilic phenotype, which is associated with frequent Pseudomonas infection, severe disease, exacerbations and poor prognosis. Targeted novel-agents for this group such as brensocatib (neutrophil protease inhibition) emerge. The eosinophilic phenotype is defined by elevated blood or sputum eosinophils and is associated with FeNO, IL-5/IL-13 signaling, a possible response to inhaled corticosteroids and biologic agents. The mixed phenotype demonstrates dual neutrophilic and Th2 inflammation. Paucigranulocytic phenotypes remain poorly characterized but with distinct characteristics. Finally, dysregulation of macrophages and lymphocytes as inflammation mediators needs to be studied further. Recent advances have introduced a variety of therapeutic strategies targeting specific inflammatory pathways. Bronchiectasis has a spectrum of inflammatory phenotypes with distinct biological and clinical implications. Recognition and better understanding of inflammatory phenotypes in bronchiectasis may enable opportunities for personalized precision medicine through the transition from empirical management to biomarker-guided, personalized care. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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11 pages, 2241 KB  
Article
Pulmonary Embolism Detection in Unenhanced CT Exams: A Radiomic-Based Classifier as a Promising Screening-Diagnostic Tool
by Diletta Cozzi, Alessio Gnerucci, Giulia Zantonelli, Matteo Benelli and Maurizio Bartolucci
J. Pers. Med. 2025, 15(10), 498; https://doi.org/10.3390/jpm15100498 - 17 Oct 2025
Abstract
Background: Pulmonary embolism (PE) is a life-threatening condition in which early diagnosis and prompt treatment are essential to reduce morbidity and mortality. Recent advances in radiomics have introduced software tools for PE detection on CT pulmonary angiography (CTPA), but their application to [...] Read more.
Background: Pulmonary embolism (PE) is a life-threatening condition in which early diagnosis and prompt treatment are essential to reduce morbidity and mortality. Recent advances in radiomics have introduced software tools for PE detection on CT pulmonary angiography (CTPA), but their application to non-contrast chest CT remains unexplored. Methods: We retrospectively identified 57 CTPA examinations performed between January 2020 and March 2023. Patients were randomly assigned to training and validation cohorts; an additional 14 PE-negative patients were included in the validation cohort. Spherical regions of interest (ROIs) were manually placed within emboli and within normal-flow pulmonary arteries. From each ROI, 836 radiomic features were extracted. Statistically significant features were identified using the Wilcoxon test. A logistic regression classifier was then developed to discriminate between embolus and control ROIs based on their radiomic signatures. Results: Of the 836 features, 242 (all derived from wavelet-filtered images) showed significant differences between embolus and normal-flow ROIs on unenhanced CT. The classifier demonstrated high diagnostic performance in the validation cohort, with an AUC of 0.87 (95% CI: 0.86–0.88) and an accuracy of 0.77 (95% CI: 0.76–0.79), with only a limited number of misclassified ROIs. Conclusions: This preliminary study demonstrates the potential of radiomics to identify thrombi on unenhanced chest CT scans, offering a promising avenue for the early detection of acute PE. The proposed model showed satisfactory diagnostic accuracy with low few misclassifications, supporting further validation in larger cohorts. Full article
(This article belongs to the Section Omics/Informatics)
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18 pages, 2177 KB  
Article
Differentially Expressed Genes Identify FIGO Stage II Cervical Cancer Patients with a Higher Risk of Relapse in a Small Cohort
by Carolina P. S. Melo, Angelo B. Melo, Fábio R. Queiroz, Álvaro P. Costa, Laurence R. Amaral, Ramon A. Pereira, Izabela F. G. Amorim, Jorge G. G. Ferreira, Wander J. Jeremias, Pedro L. L. Bertarini, Matheus S. Gomes, Letícia C. Braga and Paulo G. O. Salles
J. Pers. Med. 2025, 15(10), 497; https://doi.org/10.3390/jpm15100497 - 16 Oct 2025
Abstract
Background/Objectives: Most studies investigating prognostic biomarkers in cervical cancer (CC) analyze patients irrespective of FIGO stage, potentially masking molecular features that underlie the aggressiveness of some FIGO II tumors. To address this, we investigated differential gene expression in a FIGO II CC [...] Read more.
Background/Objectives: Most studies investigating prognostic biomarkers in cervical cancer (CC) analyze patients irrespective of FIGO stage, potentially masking molecular features that underlie the aggressiveness of some FIGO II tumors. To address this, we investigated differential gene expression in a FIGO II CC cohort to identify a gene signature predictive of progression-free survival (PFS) within five years of treatment initiation. Methods: Tumor samples from 15 CC patients were analyzed using RNA sequencing, bioinformatics, and machine learning to identify differentially expressed genes (DEGs) associated with prognosis. Findings were validated in an independent CC cohort (n = 174). Results: High expression of B3GALT1 (HR = 5.11), GTF3C2-AS1 (HR = 18.73), and ZKSCAN4 (HR = 5.18) was significantly associated with an increased risk of recurrence in our cohort. Elevated expression of these transcripts is also associated with shorter PFS in the external dataset. Notably, GTF3C2-AS1 expression alone was sufficient to classify all fifteen patients into their respective prognostic groups using a decision tree model, achieving 93.3% accuracy in leave-one-out cross-validation (LOOCV). Additional candidates, including RCAN2-DT, MYH9-DT, IGKC, IGHG1, and IGHG3, were associated with PFS in our cohort but could not be externally validated due to a lack of available data. Conclusions: Transcriptomic profiling revealed potential biomarkers that refine prognostic stratification in cervical cancer beyond FIGO staging. Among them, GTF3C2-AS1 consistently emerged as a potential predictor of recurrence risk. Additional candidates, including B3GALT1, ZKSCAN4, and immunoglobulin transcripts, provided complementary insights but require further validation. These preliminary results highlight intra-stage heterogeneity in FIGO II CC and underscore the promise of molecular markers to improve risk assessment. Full article
(This article belongs to the Special Issue Novel Biomarkers in the Diagnostics of Cancer)
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10 pages, 364 KB  
Article
Laterocervical Lymph Node Metastases in Papillary Thyroid Carcinoma: Predictive Factors for Recurrence and Oncological Outcome
by Andrea Migliorelli, Marianna Manuelli, Agnese Maria Tringali, Claudio Moretti, Virginia Corazzi, Matteo Geminiani, Andrea Ciorba, Francesco Stomeo, Stefano Pelucchi and Chiara Bianchini
J. Pers. Med. 2025, 15(10), 496; https://doi.org/10.3390/jpm15100496 - 16 Oct 2025
Abstract
Background/Objectives: Papillary cancer is the most common thyroid cancer. The development of lateral cervical lymph node metastases (I–V levels) is considered a major cause of recurrence. The aim of this study is to investigate the potential predictive factors for lateral cervical lymph [...] Read more.
Background/Objectives: Papillary cancer is the most common thyroid cancer. The development of lateral cervical lymph node metastases (I–V levels) is considered a major cause of recurrence. The aim of this study is to investigate the potential predictive factors for lateral cervical lymph node metastasis and disease recurrence, in order to tailor the clinical approach to these patients. An ROC (Receiver Operating Characteristic) curve has been set to search out a cut-off value for the lymph node ratio (LNR), a ratio of involved lymph nodes-to-examined lymph nodes, that could serve as an index of tumor recurrence. Methods: This was an observational retrospective study. The clinical charts of 43 patients with histopathological diagnosis of papillary thyroid cancer who underwent thyroidectomy with lateral and central neck dissection have been reviewed. These results have also been compared with those who underwent total thyroidectomy alone that served as a control group. Results: Extrathyroidal extension (p-value < 0.001), tumor size (p-value = 0.015), number of lymph nodes involvement (p-value = 0.022), and LNR (p-value = 0.004) were identified as potential predictors of tumor recurrence. The ROC curve revealed that an LNR value exceeding 0.205 is indicative of disease recurrence, with an Area Under the Curve (AUC) of 0.818, a sensitivity of 82%, and a specificity of 81%. Furthermore, fT4 value (p-value = 0.008), tumor size (p-value = 0.019), and alcohol consumption (p-value < 0.001) may serve as potential predictors of lymph node metastasis. Conclusions: Extrathyroidal extension, vascular invasion, tumor size, number of pathological lymph nodes, and LNR are associated with recurrence of papillary thyroid carcinoma; in particular, the lymph node ratio can be considered an effective indicator of recurrence risk. Full article
(This article belongs to the Section Personalized Medical Care)
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10 pages, 238 KB  
Review
The Neuro-Ophthalmologic Manifestations of SPG7-Associated Disease
by Ruben Jauregui, Christian Diaz Curbelo, Steven L. Galetta and Scott N. Grossman
J. Pers. Med. 2025, 15(10), 495; https://doi.org/10.3390/jpm15100495 - 16 Oct 2025
Abstract
The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg [...] Read more.
The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg weakness and spasticity) and complex (with additional neurologic features including cerebellar signs and optic atrophy) forms. Now identified as one of the most common causes of HSP, SPG7-associated disease has been linked to additional neuro-ophthalmologic features, including isolated dominant optic atrophy, cerebellar eye signs (various forms of nystagmus, dysmetric saccades), progressive external ophthalmoplegia (PEO), and supranuclear vertical palsy. This review describes in detail the various neuro-ophthalmologic presentations of SPG7-associated disease, illustrating the role of mitochondrial dysfunction in the pathophysiology of these different entities. Knowledge of the different manifestations of SPG7-associated disease is crucial for both neurologists and ophthalmologists, and SPG7 should be considered in the work-up of patients presenting with entities such as optic atrophy, PEO, and cerebellar eye signs. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
3 pages, 295 KB  
Correction
Correction: Liem et al. High Ocular Disease Burden and Increased Referral Needs in Patients with Chronic Kidney Disease: A Step Toward Personalized Care. J. Pers. Med. 2025, 15, 204
by Yulia Liem, Pavitra Thyagarajan, Miao Li Chee, Cynthia Ciwei Lim, Boon Wee Teo and Charumathi Sabanayagam
J. Pers. Med. 2025, 15(10), 494; https://doi.org/10.3390/jpm15100494 - 15 Oct 2025
Viewed by 34
Abstract
Error in Figure and Table [...] Full article
(This article belongs to the Special Issue Clinical Advances in Diagnosis and Personalized Treatments of Chronic Kidney Diseases)
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6 pages, 188 KB  
Editorial
Special Issue: Emergency Medicine: Clinical Advances and Challenges in Diagnosis and Treatment, 2nd Edition
by Carmen Gabriela Williams, Daian-Ionel Popa and Ovidiu Alexandru Mederle
J. Pers. Med. 2025, 15(10), 493; https://doi.org/10.3390/jpm15100493 - 14 Oct 2025
Viewed by 104
Abstract
The development of emergency medicine brings both challenges and opportunities [...] Full article
(This article belongs to the Special Issue Emergency Medicine: Clinical Advances and Challenges in Diagnosis and Treatment, 2nd Edition)
41 pages, 7020 KB  
Review
Recent Insights into Organoid-Derived Extracellular Vesicles and Their Biomedical Applications
by Ahmed Abdal Dayem, Yeonjoo Kwak, Hyemin Jeun and Ssang-Goo Cho
J. Pers. Med. 2025, 15(10), 492; https://doi.org/10.3390/jpm15100492 - 14 Oct 2025
Viewed by 348
Abstract
Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication by transporting functionally active molecules, including proteins, lipids, and nucleic acids. While extensive research has focused on EVs generated from traditional two-dimensional (2D) monolayer cultures (2D-EVs), the emergence of three-dimensional (3D) organoid systems [...] Read more.
Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication by transporting functionally active molecules, including proteins, lipids, and nucleic acids. While extensive research has focused on EVs generated from traditional two-dimensional (2D) monolayer cultures (2D-EVs), the emergence of three-dimensional (3D) organoid systems has led to the development of organoid-derived EVs (OEVs), which more closely mimic the physiological conditions of native tissues. In contrast to 2D cultures, 3D systems offer improved EV yield and cargo specificity, enhancing their translational potential. This review discusses the distinctive features of OEVs, including their enhanced tissue relevance, diverse molecular composition, and promising therapeutic applications in areas like disease modeling, regenerative therapies, and targeted drug delivery. We also present an overview of the current organoid-based platforms used to produce OEVs, recent innovations in EV modification and bioengineering, and the practical barriers to their clinical adoption. By comparing the strengths and limitations of OEVs with those of 2D-EVs, we provide a comprehensive perspective on their future role in precision healthcare, biomarker identification, and advanced therapeutic strategies. Full article
(This article belongs to the Section Disease Biomarkers)
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10 pages, 592 KB  
Article
Lateral Intercostal Artery Perforator (LICAP) Flap for Level II Oncoplastic Breast Reconstruction: Our Initial Experience
by Gianluca Marcaccini, Claudia Biagini, Benedetta Daicampi, Simone Miccoli, Pietro Susini, Ishith Seth, Warren M. Rozen, Roberto Cuomo, Luca Grimaldi and Leonardo Barellini
J. Pers. Med. 2025, 15(10), 491; https://doi.org/10.3390/jpm15100491 - 14 Oct 2025
Viewed by 128
Abstract
Background: Breast-conserving surgery (BCS) combined with radiotherapy achieves oncologic outcomes comparable to mastectomy while preserving breast integrity. However, resections of more than 20% of breast volume or those in challenging quadrants may compromise cosmetic results. Level II oncoplastic techniques using volume replacement flaps [...] Read more.
Background: Breast-conserving surgery (BCS) combined with radiotherapy achieves oncologic outcomes comparable to mastectomy while preserving breast integrity. However, resections of more than 20% of breast volume or those in challenging quadrants may compromise cosmetic results. Level II oncoplastic techniques using volume replacement flaps aim to address this. The lateral intercostal artery perforator (LICAP) flap is a reliable, muscle-sparing option for lateral and central–lateral breast defects. This study reports our initial experience with LICAP in Level II oncoplastic breast reconstruction. Methods: A retrospective review was conducted of women undergoing BCS with LICAP reconstruction between March 2024 and March 2025. The primary outcome was flap-related complications within 90 days. Secondary outcomes included operative time, hospital stay, donor-site morbidity, and six-month aesthetic results using the Harvard scale and BREAST-Q® module. Results: Nine women underwent LICAP reconstruction. All tumours were ≤pT2 with negative margins. Mean operative time was 128 min, and the median hospital stay was 2 days. One minor flap-related complication (seroma, 11%) occurred, which was managed conservatively without re-operation or delay in adjuvant therapy. At six months, all patients achieved good or excellent Harvard scores. The mean BREAST-Q® satisfaction score was 79 ± 12. Conclusions: LICAP reconstruction is safe, efficient, and provides reliable early aesthetic and patient-reported outcomes. Its low complication rate, high satisfaction, and minimal morbidity support its broader adoption, while larger prospective studies are needed to assess long-term results and refine indications. These findings also underline the role of LICAP reconstruction as part of a personalized surgical strategy, where the choice of technique is tailored to individual anatomy and expectations. Full article
(This article belongs to the Special Issue Clinical Advances and Innovations in Reconstructive and Plastic Surgery)
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11 pages, 243 KB  
Review
Next-Generation Anticoagulants: Precision Strategies for Patient-Centered Thromboprophylaxis
by Abdulrahman Nasiri, Manal Alshammari, Rawan Alqahtani, Omar Alshaer, Eysa Alsolamy, Hamad Alghethber and Reem Alkharras
J. Pers. Med. 2025, 15(10), 490; https://doi.org/10.3390/jpm15100490 - 14 Oct 2025
Viewed by 215
Abstract
Thrombosis remains a leading preventable cause of global morbidity and mortality, with conditions like venous thromboembolism and atrial fibrillation affecting millions worldwide. Traditional anticoagulants (heparins, vitamin K antagonists) require careful monitoring due to narrow therapeutic windows. Direct oral anticoagulants (DOACs) greatly improved convenience [...] Read more.
Thrombosis remains a leading preventable cause of global morbidity and mortality, with conditions like venous thromboembolism and atrial fibrillation affecting millions worldwide. Traditional anticoagulants (heparins, vitamin K antagonists) require careful monitoring due to narrow therapeutic windows. Direct oral anticoagulants (DOACs) greatly improved convenience and reduced certain hemorrhagic complications (notably intracranial hemorrhage) compared to warfarin, but bleeding, drug–drug interactions, and unmet needs in special populations persist. This review highlights emerging strategies to decouple antithrombotic efficacy from bleeding risk. Novel agents targeting factor XI or XII (small molecules, antibodies, antisense oligonucleotides) have shown in early trials robust thromboembolism prevention with low bleeding. Advances in pharmacogenomics, biomarker-guided dosing, artificial intelligence risk prediction, and digital monitoring promise to personalize therapy. We discuss optimized approaches for high-risk subgroups (cancer-associated thrombosis, extremes of body weight, renal/hepatic dysfunction, pregnancy, perioperative care, and COVID-19) with citations to current evidence. Finally, we outline critical systems-level considerations, including drug accessibility, cost-effectiveness, and educational strategies, that are necessary to realize precision anticoagulation. Our synthesis is grounded in recent peer-reviewed literature and emphasizes innovations likely to improve safety and efficacy of thromboprophylaxis. Full article
(This article belongs to the Section Pharmacogenetics)
13 pages, 453 KB  
Article
Prediction of Mortality in Hemodialysis Patients Using Inflammation- and Nutrition-Based Indices
by Umit Cakmak, Nurgul Sevimli, Suleyman Akkaya and Ozgur Merhametsiz
J. Pers. Med. 2025, 15(10), 489; https://doi.org/10.3390/jpm15100489 - 13 Oct 2025
Viewed by 140
Abstract
Background and Objectives: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are characterized by persistent inflammation, malnutrition, and immune dysfunction, all of which contribute to poor outcomes in hemodialysis (HD) patients. The C-reactive protein albumin lymphocyte (CALLY) index has been proposed as [...] Read more.
Background and Objectives: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are characterized by persistent inflammation, malnutrition, and immune dysfunction, all of which contribute to poor outcomes in hemodialysis (HD) patients. The C-reactive protein albumin lymphocyte (CALLY) index has been proposed as a novel biomarker that integrates these mechanisms. This study aimed to evaluate the prognostic value of the CALLY index together with established markers, including the C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) for all-cause mortality in HD patients. Materials and Methods: This retrospective cohort study was conducted on 106 patients undergoing HD. Demographic, clinical, and laboratory parameters were obtained three months after the effects of HD initiation was reviewed. Results: During a median follow-up of 24.5 months, 29 patients (27.3 percent) died. Non-survivors were significantly older (65.3 vs. 52.5 years, p < 0.001), had a higher prevalence of coronary artery disease (31 percent vs. 2.6 percent, p < 0.001), or shorter dialysis duration (14 vs. 27 months, p < 0.001). They also showed lower hemoglobin (9.2 vs. 10.1 g/dL, p = 0.007), creatinine (5.3 vs. 6.3 mg/dL, p = 0.048), and albumin levels (28 vs. 34 g/L, p = 0.001), as well as a higher MLR (0.329 vs. 0.254, p = 0.014). In multivariate analysis, age, CAR, and NLR independently predicted mortality, explaining 83.8% of the variation. ROC analysis identified age and MLR as significant predictors, with MLR showing a high negative predictive value (83.9%). The CALLY index did not demonstrate independent prognostic value. Conclusions: Age, CAR, NLR, and MLR were independent predictors of mortality in HD patients, whereas the CALLY index was not prognostic in this cohort. Among these markers, MLR may be a practical biomarker with strong negative predictive power. Larger prospective studies are needed to validate these findings. Full article
(This article belongs to the Special Issue Precision Medicine in Kidney Disease)
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12 pages, 761 KB  
Article
Measurement of Indocyanine Green as a Predictor of Liver Failure After Hepatic Resection, Contributing to Risk Stratification in Personalized Medicine
by Víctor Baladrón González, David Padilla Valverde, María del Carmen Gasco García, Pedro Juan Villarejo Campos, María Jesús Pardo Mora, Natalia Bejarano Ramírez, Omar Montenegro Herrera, Patricia Faba Martín, Rubén Villazala González and Francisco Javier Redondo Calvo
J. Pers. Med. 2025, 15(10), 488; https://doi.org/10.3390/jpm15100488 - 13 Oct 2025
Viewed by 150
Abstract
Background: Most of the advances in liver surgery have been achieved in the last few decades. The development of new diagnostic and therapeutic techniques has aided diagnosis and has facilitated more efficient and personalized resections for liver disorders. The estimation of the [...] Read more.
Background: Most of the advances in liver surgery have been achieved in the last few decades. The development of new diagnostic and therapeutic techniques has aided diagnosis and has facilitated more efficient and personalized resections for liver disorders. The estimation of the hepatic reserve has gained great importance because it marks the limit for more aggressive liver resections. It was hypothesized that determination of hepatic reserve by measuring plasma clearance of indocyanine green—following hepatic parenchymal liver resection—could provide earlier and more accurate knowledge of hepatic reserve and thus allow for more personalized therapy. Methods: A prospective observational post-authorization study was performed. Results: Applying ROC curves and the area under the curve (AUC) for the evaluation of the different tests as predictors of liver failure, favorable data were obtained in relation to bilirubin (AUC = 0.922) and prothrombin time (AUC = 1), and for postoperative PDR (AUC = 0.879) and GOT (AUC = 0.857), but not for preoperative PDR (AUC = 0.667) or GPT (AUC = 0.6). Conclusions: The gold standard for predicting early liver failure (the 50:50 criterion at on postoperative day 5) has a very good relationship with the plasma clearance rate of indocyanine green on postoperative day 1 and therefore has the potential to support earlier and more personalized therapeutic interventions, pending further validation. Full article
(This article belongs to the Special Issue Liver Diseases: Diagnosis and Treatment in the Era of Personalized Medicine)
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12 pages, 3340 KB  
Article
Navigating the Decision to Discontinue Intravitreal Injection Therapy in End-Stage Neovascular Age-Related Macular Degeneration
by Justin Bennie and David J. Ramsey
J. Pers. Med. 2025, 15(10), 487; https://doi.org/10.3390/jpm15100487 - 13 Oct 2025
Viewed by 267
Abstract
Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of [...] Read more.
Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of anti-VEGF therapy. Results: Long-term management of nAMD with intravitreal injections of agents targeting vascular endothelial growth factor (VEGF) is crucial for slowing progression of the disease and is generally well-tolerated. However, vision often declines as the disease progresses over time, even with treatment. This article presents strategies for aligning therapeutic goals with their expected visual outcome when an eye has reached end-stage disease. It addresses considerations for how and when to stop treatment when vision becomes limited, taking into consideration the visual status of the fellow eye and incorporating input from low vision specialists who can better assess best-corrected visual acuity (BCVA) and optimize the visual function of patients. We also acknowledge the potential benefits of switching either the dose or the agent that targets VEGF to alter the long-term visual outcome of treatment. Finally, we discuss the importance of taking into consideration related manifestations of the disease, such as macular scarring, geographic atrophy, or other retinal or optic nerve diseases which may limit vision and thus the utility of continued nAMD treatment. Conclusions: Building a strong patient–physician relationship is essential for navigating the shared decision-making process of when to stop treatment for nAMD. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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12 pages, 1926 KB  
Article
Tracking False Lumen Remodeling with AI: A Variational Autoencoder Approach After Frozen Elephant Trunk Surgery
by Anja Osswald, Sharaf-Eldin Shehada, Matthias Thielmann, Alan B. Lumsden, Payam Akhyari and Christof Karmonik
J. Pers. Med. 2025, 15(10), 486; https://doi.org/10.3390/jpm15100486 - 11 Oct 2025
Viewed by 184
Abstract
Objective: False lumen (FL) thrombosis plays a key role in aortic remodeling after Frozen Elephant Trunk (FET) surgery, yet current imaging assessments are limited to categorical classifications. This study aimed to evaluate an unsupervised artificial intelligence (AI) algorithm based on a variational autoencoder [...] Read more.
Objective: False lumen (FL) thrombosis plays a key role in aortic remodeling after Frozen Elephant Trunk (FET) surgery, yet current imaging assessments are limited to categorical classifications. This study aimed to evaluate an unsupervised artificial intelligence (AI) algorithm based on a variational autoencoder (VAE) for automated, continuous quantification of FL thrombosis using serial computed tomography angiography (CTA). Methods: In this retrospective study, a VAE model was applied to axial CTA slices from 30 patients with aortic dissection who underwent FET surgery. The model encoded each image into a structured latent space, from which a continuous “thrombus score” was developed and derived to quantify the extent of FL thrombosis. Thrombus scores were compared between postoperative and follow-up scans to assess individual remodeling trajectories. Results: The VAE successfully encoded anatomical features of the false lumen into a structured latent space, enabling unsupervised classification of thrombus states. A continuous thrombus score was derived from this space, allowing slice-by-slice quantification of thrombus burden across the aorta. The algorithm demonstrated robust reconstruction accuracy and consistent separation of fully patent, partially thrombosed, and completely thrombosed lumen states without the need for manual annotation. Across the cohort, 50% of patients demonstrated an increase in thrombus score over time, 40% a decrease, and 10% remained unchanged. Despite these individual differences, no statistically significant change in overall thrombus burden was observed at the group level (p = 0.82), emphasizing the importance of individualized longitudinal assessment. Conclusions: The VAE-based method enables reproducible, annotation-free quantification of FL thrombosis and captures patient-specific remodeling patterns. This approach may enhance post-FET surveillance and supports the integration of AI-driven tools into personalized aortic imaging workflows. Full article
(This article belongs to the Special Issue New Insights into Personalized Medicine for Cardiac Surgery: Clinical Advances in Diagnosis, Treatment, and Prognosis)
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14 pages, 730 KB  
Article
Surgical Outcomes of Craniocervical Junction Fractures in Elderly Patients: A Retrospective Single-Center Series
by Nicola Montemurro, Stefano Carnesecchi, Riccardo Morganti, Antonella De Carlo and Ardico Cocciaro
J. Pers. Med. 2025, 15(10), 485; https://doi.org/10.3390/jpm15100485 - 10 Oct 2025
Viewed by 206
Abstract
Background: Fractures of the first and second cervical vertebrae are common in both young and elderly patients. Surgical management of C1–C2 fractures in elderly patients is controversial. The aim of this study is to report the rate of fusion in elderly patients who [...] Read more.
Background: Fractures of the first and second cervical vertebrae are common in both young and elderly patients. Surgical management of C1–C2 fractures in elderly patients is controversial. The aim of this study is to report the rate of fusion in elderly patients who underwent surgery for C1 or C2 fractures. Methods: A retrospective review of all patients over the age of 65 years old who underwent surgical treatment for C1 or C2 fracture was reported. Visual analog scale (VAS) and neck disability index (NDI) were used to assess patients’ clinical outcome at 1 year follow-up. Cervical spine computer tomography (CT) scans were performed in all cases before surgery and at 1 year follow-up to evaluate the long-term postoperative rate of fusion, according to Lenke fusion grade. Results: From 2019 to 2023, 105 patients with cervical craniocervical junction (CCJ) fracture underwent surgical treatment in our Pisana University Hospital. Among all these, 74 patients (70.5%) were over 65 years old. The mean age of the study population was 76.9 years old (12.2% aged 65–70, 51.4% aged 70–79, and 36.5% over 80). According to the AO Spine Upper Cervical Injury Classification System, 6 (8.1%) patients presented a type II fracture and 68 (91.9%) patients presented a type III fracture. At admission, neurological examination resulted in American Spinal Injury Association (ASIA) E in 97.3% of cases. Over 60% of all patients underwent C1–C2 posterior fixation. Postoperative complications occurred in 12.25% of patients. According to the criteria described by Lenke, a good rate of fusion (A-B grade) was obtained in 71.6% of patients. Conclusions: In elderly patients with CCJ fractures, precision medicine can help identify those at higher risk for complications and guide personalized treatment strategies. Surgical treatment of CCJ fractures in elderly patients, although not always associated with bone fusion, can be performed with an acceptable incidence of mortality and morbidity, allowing rapid mobilization and return to pre-trauma levels of independence. Full article
(This article belongs to the Special Issue New Insight into Aging and Geriatric Syndromes: Clinical Updates and Perspectives)
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15 pages, 282 KB  
Review
Left Ventricular Non-Compaction Cardiomyopathy: A Review of the Pathophysiology, Epidemiology, Diagnosis, Genetics, and Clinical Management
by Luis Elias Martínez-Tittonel, Florin Radu Ciorba, Xavier Bayona-Huguet and Edgardo Kaplinsky
J. Pers. Med. 2025, 15(10), 484; https://doi.org/10.3390/jpm15100484 - 10 Oct 2025
Viewed by 272
Abstract
Left ventricular non-compaction cardiomyopathy (LVNC) is an uncommon myocardial phenotype characterized by prominent trabeculae and deep blood-filled recesses. The expanding use of cardiac magnetic resonance (CMR) has increased detection, yet uncertainty persists about whether LVNC is a distinct disease or a phenotype that [...] Read more.
Left ventricular non-compaction cardiomyopathy (LVNC) is an uncommon myocardial phenotype characterized by prominent trabeculae and deep blood-filled recesses. The expanding use of cardiac magnetic resonance (CMR) has increased detection, yet uncertainty persists about whether LVNC is a distinct disease or a phenotype that overlaps with other cardiomyopathies. LVNC expression reflects the interplay among genotype, sex, ancestry, and hemodynamic load and thus serves as a model for precision cardiology. We conducted a narrative review of literature published between January 2000 and April 2025 in major databases. We included clinical studies with at least 10 patients, meta-analyses, reviews, and consensus statements addressing pathophysiology, genetics, diagnosis, prognosis, and treatment. Sarcomeric variants account for a substantial fraction of cases and connect LVNC with dilated and hypertrophic cardiomyopathies. Echocardiographic and CMR criteria identify the phenotype but blur the boundary between physiological and pathological hypertrabeculation. Fibrosis on late gadolinium enhancement and systolic dysfunction are consistently associated with worse outcomes. Current management largely adapts heart-failure strategies, including neurohormonal blockade, SGLT2 inhibitors, and implantable cardioverter-defibrillators in selected high-risk patients. Optimal care integrates clinical, imaging, and genetic information. The lack of universal diagnostic criteria highlights the need for prospective studies and consensus to standardize diagnosis and treatment. Future algorithms that combine multi-omics, quantitative imaging, and AI-based risk prediction could individualize surveillance, pharmacotherapy, and device therapy. Full article
(This article belongs to the Special Issue Cardiology and Vascular Health: Pathophysiology, Therapeutics and Epidemiology)
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11 pages, 466 KB  
Article
Polytrauma Cases in the Emergency Department of a Community Hospital in Croatia
by Ivana Herak, Ante Mihanović, Andrea Cvitković Roić, Anita Lukic, Sonja Obranić, Denis Grgurović, Ines Kalinić, Valentina Vincek, Ivo Dumić-Čule and Marijana Neuberg
J. Pers. Med. 2025, 15(10), 483; https://doi.org/10.3390/jpm15100483 - 10 Oct 2025
Viewed by 143
Abstract
Background: The purpose of this study was to quantify the incidence of polytrauma cases at a single-center county hospital in Croatia and evaluate the therapeutic approaches currently in use. Methods: Patient data for 54 individuals diagnosed with polytrauma between 2019 and [...] Read more.
Background: The purpose of this study was to quantify the incidence of polytrauma cases at a single-center county hospital in Croatia and evaluate the therapeutic approaches currently in use. Methods: Patient data for 54 individuals diagnosed with polytrauma between 2019 and 2022 were retrospectively reviewed using the hospital’s medical records system. The analysis encompassed several aspects, including injury mechanisms, injury timing, Glasgow Coma Scale scores, alcohol levels, therapies, triage classifications, and hospital stay durations. Results: In this study, patient age was not significantly associated with clinical presentation, treatment approach, or outcomes. However, gender showed significant associations with GCS, triage category, and discharge status, with female patients presenting more frequently with severe impairment (GCS 3–8) and higher triage urgency. Blood alcohol levels were more frequently elevated in male patients but showed no association with clinical severity or outcomes. Additionally, lower GCS scores were significantly linked to poorer outcomes, including higher in-hospital mortality, while surgical intervention was associated with longer hospital stays. Conclusions: Collectively, gender and level of consciousness significantly influenced triage urgency and outcomes, highlighting the need for targeted prevention and management strategies. Full article
(This article belongs to the Section Personalized Medical Care)
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12 pages, 1520 KB  
Article
Real-World Outcomes of Robotic Total Knee Arthroplasty: Five Years’ Experience in a Non-Academic Center
by Joost Burger, Wei Fan, Sandy Gansiniec, Casper Reinders, Scarlette Kienzle, Clemens Gwinner, Adrianus den Hertog and Arne Kienzle
J. Pers. Med. 2025, 15(10), 482; https://doi.org/10.3390/jpm15100482 - 9 Oct 2025
Viewed by 301
Abstract
Background: Robotic-assisted systems have transformed total knee arthroplasty (TKA), promising improved accuracy and intraoperative consistency, yet real-world data from non-academic centers remain limited. Objective: This study evaluates five-year clinical integration of a semi-autonomous, CT-based, robotic-arm-assisted TKA at a tertiary non-teaching hospital in Germany, [...] Read more.
Background: Robotic-assisted systems have transformed total knee arthroplasty (TKA), promising improved accuracy and intraoperative consistency, yet real-world data from non-academic centers remain limited. Objective: This study evaluates five-year clinical integration of a semi-autonomous, CT-based, robotic-arm-assisted TKA at a tertiary non-teaching hospital in Germany, focusing on planning accuracy, gap balancing, and intraoperative outcomes. Methods: We retrospectively analyzed all patients (n = 457) who underwent MAKO-assisted TKA from 2020 to 2025, performed by three orthopedic surgeons using a standardized subvastus approach. We assessed preoperative deformities, intraoperative alignment, implant sizing, and gap balancing. Surgical plans were adapted intraoperatively when indicated. Pre- vs. post-implantation values were compared using slopes to evaluate execution consistency. Results: Median patient age was 67.0 years (IQR: 60.0–75.0), with varus in 84.1% (7.0°, IQR: 4.0°–10.0°), valgus in 13.2% (3.0°, IQR: 1.5°–5.8°), and neutral alignment in 2.7%. Flexion contracture occurred in 80.4% (6.0°, IQR: 3.0–10.0%), hyperextension in 12.7% (2.0°, IQR: 1.5°–5.0°). Planning-to-execution consistency was high, even with plan adaptations. Slope values for alignment parameters were: tibial rotation in degrees (slope value: 1.0), femoral sagittal angle in degrees (0.8), tibial sagittal angle in degrees (0.9), coronal posterior condylar angle in degrees (0.9), femoral component size (1.0), tibial component size (1.0). Over 95% of cases showed ≤3.0° deviation between planned and final values. Bone resection concordance showed moderate agreement, with slopes from 0.8 (posterior medial femoral cut in mm) to 0.5 (lateral tibial cut in mm). Gap balancing improved at all stages, with reduced variability in medial/lateral extension and flexion gaps (all p < 0.05). Functional reconstruction showed significant improvements in extension, flexion, and deformities (all p < 0.001). Conclusions: Semi-autonomous, CT-based, robotic-arm-assisted TKA was successfully implemented in this non-academic setting, demonstrating acceptable intraoperative and functional reconstruction outcomes, supporting the feasibility of robotic-assisted surgery outside academic centers. Full article
(This article belongs to the Special Issue Precision Orthopedics: Evolving Shoulder, Hip, and Knee Surgery Through Intelligent Technology and Personalized Clinical Care)
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14 pages, 1438 KB  
Article
Pharmacogenomics in Diabetes: Population-Specific Insights from Colombia
by David A. Hernandez-Paez, Johana Galván-Barrios, Kevin Fernando Montoya-Quintero and Indiana Luz Rojas Torres
J. Pers. Med. 2025, 15(10), 481; https://doi.org/10.3390/jpm15100481 - 9 Oct 2025
Viewed by 238
Abstract
Background: Pharmacogenomics offers critical insights into interindividual variability in drug response, especially in complex diseases such as diabetes mellitus. However, most pharmacogenomic evidence is derived from populations of European ancestry, limiting its applicability in admixed and underrepresented populations. In Colombia, the lack of [...] Read more.
Background: Pharmacogenomics offers critical insights into interindividual variability in drug response, especially in complex diseases such as diabetes mellitus. However, most pharmacogenomic evidence is derived from populations of European ancestry, limiting its applicability in admixed and underrepresented populations. In Colombia, the lack of population-specific data hampers the implementation of precision medicine strategies in diabetes care. The aim of this study was to identify pharmacogenomic variants significantly associated with diabetes and exhibiting differential allele frequencies between Colombian populations of African and European ancestry. Methods: We extracted 115 variant annotations related to diabetes from PharmGKB and filtered them for statistical significance and availability of allele frequency data. Fourteen single-nucleotide polymorphisms (SNPs) were compared across five Colombian populations using the CÓDIGO genomic diversity database. Principal component analysis (PCA) was performed to assess genetic clustering, and Pearson correlation coefficients were used to assess pharmacogenomic similarity. Results: PCA revealed distinct genetic clustering patterns that aligned with geographical distribution and ancestral origins. Pharmacogenomic divergence was observed between African and European ancestry groups in Colombia, with certain SNPs (e.g., rs8192675-C for metformin, rs7754840-C for DPP-4 inhibitors) showing 2- to 3-fold higher frequency in African ancestry populations. The bibliometric analysis revealed that 76.1% of studies originated from high-income countries and 68.4% of participants were of European ancestry. No studies originated from Africa or low-income countries. Conclusions: Marked ancestry-based differences in pharmacogenomic variant frequencies in Colombian populations may impact drug efficacy and risk of diabetes. The global literature shows a strong geographic and economic bias, underscoring the need for inclusive, population-specific pharmacogenomic research. These findings offer a foundation for implementing precision diabetes therapies in Latin America and advancing equitable genomic medicine. Full article
(This article belongs to the Special Issue New Trends and Challenges in Pharmacogenomics Research)
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17 pages, 312 KB  
Review
Current Applications and Future Directions of Technologies Used in Adult Deformity Surgery for Personalized Alignment: A Narrative Review
by Janet Hsu, Taikhoom M. Dahodwala, Noel O. Akioyamen, Evan Mostafa, Rami Z. AbuQubo, Xiuyi Alexander Yang, Priya K. Singh, Daniel C. Berman, Rafael De la Garza Ramos, Yaroslav Gelfand, Saikiran G. Murthy, Jonathan D. Krystal, Ananth S. Eleswarapu and Mitchell S. Fourman
J. Pers. Med. 2025, 15(10), 480; https://doi.org/10.3390/jpm15100480 - 3 Oct 2025
Viewed by 476
Abstract
Patient-specific technologies within the field of adult spinal deformity (ASD) aid surgeons in pre-surgical planning, accurately help identify anatomical landmarks, and can project optimal post-surgical sagittal alignment. This narrative review aims to discuss the current uses of patient-specific technologies in ASD and identify [...] Read more.
Patient-specific technologies within the field of adult spinal deformity (ASD) aid surgeons in pre-surgical planning, accurately help identify anatomical landmarks, and can project optimal post-surgical sagittal alignment. This narrative review aims to discuss the current uses of patient-specific technologies in ASD and identify new innovations that may very soon be integrated into patient care. Pre-operatively, machine learning or artificial intelligence helps surgeons to simulate post-operative alignment and provide information for the 3D-printing of pre-contoured rods and patient-specific cages. Intraoperatively, robotic surgery and intraoperative guides allow for more accurate positioning of implants. Implant materials are being developed to allow for better osseointegration and patient outcome monitoring. Despite the significant promise of these technologies, work still needs to be performed to ensure their accuracy, safety, and cost efficacy. Full article
(This article belongs to the Special Issue Personalized Approaches in Spinal Deformity: Innovations in Diagnosis and Treatment)
20 pages, 6167 KB  
Article
ICU Readmission and In-Hospital Mortality Rates for Patients Discharged from the ICU—Risk Factors and Validation of a New Predictive Model: The Worse Outcome Score (WOScore)
by Eleftherios Papadakis, Athanasia Proklou, Sofia Kokkini, Ioanna Papakitsou, Ioannis Konstantinou, Aggeliki Konstantinidi, Georgios Prinianakis, Stergios Intzes, Marianthi Symeonidou and Eumorfia Kondili
J. Pers. Med. 2025, 15(10), 479; https://doi.org/10.3390/jpm15100479 - 3 Oct 2025
Viewed by 457
Abstract
Background: Intensive Care Unit (ICU) readmission and in-hospital mortality are critical indicators of patient outcomes following ICU discharge. Patients readmitted to the ICU often face worse prognosis, higher healthcare costs, and prolonged hospital stays. Identifying high-risk patients is essential for optimizing post-ICU [...] Read more.
Background: Intensive Care Unit (ICU) readmission and in-hospital mortality are critical indicators of patient outcomes following ICU discharge. Patients readmitted to the ICU often face worse prognosis, higher healthcare costs, and prolonged hospital stays. Identifying high-risk patients is essential for optimizing post-ICU care and resource allocation. Methods: This two-phase study included the following: (1) a retrospective analysis of ICU survivors in a mixed medical–surgical ICU to identify risk factors associated with ICU readmission and in-hospital mortality, and (2) a prospective validation of a newly developed predictive model: the Worse Outcome Score (WOScore). Data collected included demographics, ICU admission characteristics, severity scores (SAPS II, SAPS III, APACHE II, SOFA), interventions, complications and discharge parameters. Results: Among 1.190 ICU survivors, 126 (10.6%) were readmitted to the ICU, and 192 (16.1%) died in hospital after ICU discharge. Key risk factors for ICU readmission included Diabetes Mellitus, SAPS III on admission, and ICU-acquired infections (Ventilator-Associated Pneumonia (VAP) and Catheter-Related Bloodstream Infection, (CRBSI)). Predictors of in-hospital mortality were identified: medical admission, high SAPS III score, high lactate level on ICU admission, tracheostomy, reduced GCS at discharge, blood transfusion, CRBSI, and Acute Kidney Injury (AKI) during ICU stay. The WOScore, developed based on the results above, demonstrated strong predictive ability (AUC: 0.845 derivation, 0.886 validation). A cut-off of 20 distinguished high-risk patients (sensitivity: 88.1%, specificity: 73.0%). Conclusions: ICU readmission and in-hospital mortality are influenced by patient severity, underlying comorbidities, and ICU-related complications. The WOScore provides an effective, easy-to-use risk stratification tool that can guide clinicians in identifying high-risk patients at ICU discharge and guide post-ICU interventions, potentially improving patients’ outcomes and optimizing resource allocation. Further multi-center studies are necessary to validate the model in diverse healthcare settings. Full article
(This article belongs to the Section Personalized Medical Care)
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17 pages, 1756 KB  
Review
Neuroanatomical and Functional Correlates in Depressive Spectrum: A Narrative Review
by Giulio Perrotta, Anna Sara Liberati and Stefano Eleuteri
J. Pers. Med. 2025, 15(10), 478; https://doi.org/10.3390/jpm15100478 - 2 Oct 2025
Viewed by 479
Abstract
Depressive spectrum disorders are considered among the most common in the general population. Major depressive disorder and persistent depressive disorder (or dysthymia) are the most recognized, but other depressive disorders exist with varying or no specificity. The main difference between major depressive disorder [...] Read more.
Depressive spectrum disorders are considered among the most common in the general population. Major depressive disorder and persistent depressive disorder (or dysthymia) are the most recognized, but other depressive disorders exist with varying or no specificity. The main difference between major depressive disorder and dysthymia lies in the duration and intensity of symptoms. Improving our understanding of its etiology and pathogenesis must be a priority for health and safety. Given the complexity of the evidence in the literature, it was deemed useful to provide a comprehensive summary of the neuroanatomical dysfunctions currently identified, with particular attention to the anterior and medial cingulate cortex, dorsolateral and ventromedial prefrontal cortex, posterior parietal cortex, insula, amygdala, and hippocampus. Significant neural network alterations include hyperconnectivity of the default mode network (DMN), impairment of the executive control network (ECN), and dysfunction of the salience network (Salience Network). Neurophysiological markers reveal frontal alpha asymmetries and front-striatal metabolic alterations. Studying neural correlates is essential to deepen our understanding of the depressive spectrum and the development of personalized therapeutic interventions, including noninvasive neurostimulation techniques and target-specific pharmacological therapies, opening new avenues for translational research in neuropsychiatric settings. Full article
(This article belongs to the Special Issue Depression and Anxiety: Recent Advances in Personalized Treatment and Management)
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15 pages, 1409 KB  
Article
External Validation and Comparative Performance of the T.O.HO. and S.T.O.N.E. Scoring Systems for Predicting Stone-Free Outcomes Following Flexible Ureteroscopy: Toward Personalized Preoperative Counseling
by Yuka Sugizaki, Takanobu Utsumi, Rino Ikeda, Naoki Ishitsuka, Takahide Noro, Yuta Suzuki, Shota Iijima, Takatoshi Somoto, Ryo Oka, Takumi Endo, Naoto Kamiya and Hiroyoshi Suzuki
J. Pers. Med. 2025, 15(10), 477; https://doi.org/10.3390/jpm15100477 - 2 Oct 2025
Viewed by 205
Abstract
Background/Objectives: The attainment of a stone-free (SF) condition is a fundamental indicator of successful outcomes after flexible ureteroscopy (fURS) for urinary stone disease. External confirmations of preoperative scores remain limited. We externally validated the T.O.HO. and S.T.O.N.E. scores in an independent Japanese [...] Read more.
Background/Objectives: The attainment of a stone-free (SF) condition is a fundamental indicator of successful outcomes after flexible ureteroscopy (fURS) for urinary stone disease. External confirmations of preoperative scores remain limited. We externally validated the T.O.HO. and S.T.O.N.E. scores in an independent Japanese cohort and examined calibration, decision curve utility, and threshold-guided use to support personalized planning. Methods: We retrospectively analyzed 361 consecutive patients treated with fURS from March 2018 to August 2023. Postoperative SF status was defined as the absence of residual calculi greater than 2 mm on non-contrast computed tomography performed within three months of surgery. Independent determinants of SF were identified using multivariable logistic regression, predictive performance was quantified by receiver operating characteristic analyses with DeLong’s test, and model calibration and decision curve analysis were additionally assessed. Results: Among the 361 patients, 255 (70.6%) achieved an SF state. A larger stone diameter, the presence of lower-pole calculi, and preoperative pyuria (positive urine WBC) were significant independent predictors of residual fragments. T.O.HO. demonstrated superior discrimination (AUC 0.86) compared with S.T.O.N.E. (AUC 0.77; p < 0.01) and surpassed individual predictors. Both scores showed acceptable calibration. Decision curve analysis demonstrated higher net benefit for T.O.HO. across clinically relevant thresholds. We provide clinically useful cut-offs (e.g., T.O.HO. ≤5: high SF probability; 6: trade-off discussion; ≥7: higher residual risk) to align actions with patient priorities. Conclusions: Beyond discrimination, a calibrated, threshold-aware use of T.O.HO. enables personalized preoperative counseling and shared decision-making, potentially reducing unnecessary staging and enhancing routine fURS planning. Full article
(This article belongs to the Section Personalized Medical Care)
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13 pages, 1292 KB  
Article
Development and Internal Validation of Machine Learning Algorithms to Predict 30-Day Readmission in Patients Undergoing a C-Section: A Nation-Wide Analysis
by Audrey Andrews, Nadia Islam, George Bcharah, Hend Bcharah and Misha Pangasa
J. Pers. Med. 2025, 15(10), 476; https://doi.org/10.3390/jpm15100476 - 2 Oct 2025
Viewed by 331
Abstract
Background/Objectives: Cesarean section (C-section) is a common surgical procedure associated with an increased risk of 30-day postpartum hospital readmissions. This study utilized machine learning (ML) to predict readmissions using a nationwide database. Methods: A retrospective analysis of the National Surgical Quality [...] Read more.
Background/Objectives: Cesarean section (C-section) is a common surgical procedure associated with an increased risk of 30-day postpartum hospital readmissions. This study utilized machine learning (ML) to predict readmissions using a nationwide database. Methods: A retrospective analysis of the National Surgical Quality Improvement Project (2012–2022) included 54,593 patients who underwent C-sections. Random Forests (RF) and Extreme Gradient Boosting (XGBoost) models were developed and compared to logistic regression (LR) using demographic, preoperative, and perioperative data. Results: Of the cohort, 1306 (2.39%) patients were readmitted. Readmitted patients had higher rates of being of African American race (17.99% vs. 9.83%), diabetes (11.03% vs. 8.19%), and hypertension (11.49% vs. 4.68%) (p < 0.001). RF achieved the highest performance (AUC = 0.737, sensitivity = 72.03%, specificity: 61.33%), and a preoperative-only RF model achieved a sensitivity of 83.14%. Key predictors included age, BMI, operative time, white blood cell count, and hematocrit. Conclusions: ML effectively predicts C-section readmissions, supporting early identification and interventions to improve patient outcomes and reduce healthcare costs. Full article
(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Maternal Fetal Medicine)
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14 pages, 1236 KB  
Article
Temporal Validation of a Plasma Diagnosis Approach for Early Alzheimer Disease Diagnosis in a Cognitive Disorder Unit
by Aleix Martí-Navia, Alejandro López, Lourdes Álvarez-Sánchez, Laura Ferré-González, Angel Balaguer, Miguel Baquero and Consuelo Cháfer-Pericás
J. Pers. Med. 2025, 15(10), 475; https://doi.org/10.3390/jpm15100475 - 2 Oct 2025
Viewed by 320
Abstract
Background: Nowadays, there is a lack of reliable and minimally invasive diagnosis methods for the early detection of Alzheimer’s disease. The development and validation of such tools could significantly reduce the dependence on more invasive and costly confirmatory procedures, such as cerebrospinal [...] Read more.
Background: Nowadays, there is a lack of reliable and minimally invasive diagnosis methods for the early detection of Alzheimer’s disease. The development and validation of such tools could significantly reduce the dependence on more invasive and costly confirmatory procedures, such as cerebrospinal fluid biomarkers analysis and neuroimaging techniques. Objectives: The main objective of this study is to validate the clinical performance of a previously developed diagnosis model based on plasma biomarkers from patients in a cognitive disorder unit. Methods: A new cohort of patients was recruited from the same cognitive disorder unit (n = 93). Specifically, demographic data (gender, age, and educational level), plasma biomarkers levels, and genotype (glial fibrillary acidic protein, phosphorylated Tau 181, amyloid-beta42/amyloid-beta40, apolipoprotein E) were collected to evaluate both approaches of the previous diagnosis model (one-cut-off, two-cut-off). Results: The one-cut-off approach showed a sensitivity of 74.3%, a specificity of 89.5%, and an area under the curve of 0.888, while the values for the two-cut-off approach were sensitivity of 66.7%, specificity of 99.9%, and area under the curve of 0.867. Conclusions: A multivariate diagnostic tool was temporally validated for implementation in a clinical unit. In fact, satisfactory results were obtained from both approaches (one-cut-off, two-cut-offs), but the two cut-offs approach was more consistent in correctly identifying non-Alzheimer’s disease cases, allowing us to identify a large number of cases with high specificity. Full article
(This article belongs to the Special Issue New Insight into Aging and Geriatric Syndromes: Clinical Updates and Perspectives)
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30 pages, 915 KB  
Review
Personalizing DNA Cancer Vaccines
by Annie A. Wu, Kaiqi Peng, Melanie Vukovich, Michelle Zhu, Yuki Lin, Arindam Bagga, TC Wu and Chien-Fu Hung
J. Pers. Med. 2025, 15(10), 474; https://doi.org/10.3390/jpm15100474 - 2 Oct 2025
Viewed by 494
Abstract
Recent progress in tumor immunotherapy highlights the important role of the immune system in combating various cancers. Traditionally designed to protect against infectious diseases, vaccines are now being adapted to stimulate immune responses against tumor-specific neoantigens. Both preclinical studies and clinical trials have [...] Read more.
Recent progress in tumor immunotherapy highlights the important role of the immune system in combating various cancers. Traditionally designed to protect against infectious diseases, vaccines are now being adapted to stimulate immune responses against tumor-specific neoantigens. Both preclinical studies and clinical trials have explored innovative approaches for identifying neoantigens and optimizing vaccine design, advancing the field of personalized oncology. Among these, DNA-based vaccines have become a particularly attractive approach for cancer immunotherapy. This evolution has been driven by improvements in molecular biology techniques, including more precise methods for detecting tumor-specific mutations, computational tools for predicting immunogenic antigens, and novel platforms for delivering nucleic acid vaccines. Personalized DNA vaccines are typically developed through a complex, multi-step process that involves sequencing a patient’s tumor, computational analysis to identify potential targets, and custom vaccine production. In this review, we examine the use of both shared tumor antigens and individualized neoantigens in cancer vaccine development. We outline strategies for neoantigen identification that provide insights into tumor-specific alterations. Furthermore, we highlight recent advances in DNA vaccine technologies, address the current limitations facing cancer vaccines, propose strategies to overcome these challenges, and consider key clinical and technical factors for successful implementation. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
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13 pages, 866 KB  
Article
Phenotype-Guided Outpatient Levosimendan as a Bridge-to-Transplant in Low-Output Advanced Heart Failure: A Single-Center Cohort
by Ricardo Carvalheiro, Ana Raquel Santos, Ana Rita Teixeira, João Ferreira Reis, António Valentim Gonçalves, Rita Ilhão Moreira, Tiago Pereira da Silva, Valdemar Gomes, Pedro Coelho and Rui Cruz Ferreira
J. Pers. Med. 2025, 15(10), 473; https://doi.org/10.3390/jpm15100473 - 2 Oct 2025
Viewed by 254
Abstract
Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant [...] Read more.
Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article
(This article belongs to the Special Issue Personalized Treatment for Heart Failure)
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Review
Cardiac Amyloidosis: Tribulations and New Frontiers
by Darren M. Nguyen, Noyan Ramazani, Gurpreet Sodhi and Tahir Tak
J. Pers. Med. 2025, 15(10), 472; https://doi.org/10.3390/jpm15100472 - 2 Oct 2025
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Abstract
This review article aims to provide an overview of the pathophysiology, diagnosis, and contemporary management of cardiac amyloidosis (CA) as well as identify the knowledge gaps and areas of potential research. CA can be divided into two main groups: transthyretin cardiac amyloidosis (ATTR-CA) [...] Read more.
This review article aims to provide an overview of the pathophysiology, diagnosis, and contemporary management of cardiac amyloidosis (CA) as well as identify the knowledge gaps and areas of potential research. CA can be divided into two main groups: transthyretin cardiac amyloidosis (ATTR-CA) and light chain cardiac amyloidosis (AL-CA). The former further separates into wild-type transthyretin (ATTRwt) and hereditary transthyretin (ATTRv). African Americans, males, and people older than 75 are the most common demographics affected by this disease. Thanks to an increased understanding of this disease combined with better diagnostic techniques, there is growing awareness and a surge of clinical trials aimed at improving outcomes of CA. The diagnosis and treatment of CA is multifaceted and complex, relying on multiple imaging modalities and the cooperation of specialists to deliver effective treatments. While some disease-modifying agents have been introduced recently, their extraordinary cost limits their benefit or they are supported by limited evidence. Other agents are currently undergoing phase 3 trials. To date, there is scarce data surrounding optimal diagnostic and treatment strategies, including a potential role for combination therapies. Critically, it is imperative that physicians develop close relationships with the patient that addresses not only their individual health needs but also their unique psychosocial situation. Therefore, more clinical trials, protocols and patient resources are needed to better inform and guide providers managing these complex patient needs. Full article
(This article belongs to the Section Mechanisms of Diseases)
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