Journal of Personalized Medicine doi: 10.3390/jpm16050259

Authors: Hui-Leng Tan Athanasios Kaditis David Gozal

Pediatric obstructive sleep-disordered breathing encompasses a wide spectrum of diagnostic clusters, including primary snoring, upper airway resistance syndrome, mild, moderate, and severe obstructive sleep apnea, and obstructive hypoventilation. Even within these classifications, the symptomatic presentation involves a large array of variations, reflecting a wide phenotypic spectrum. Here, we aim to summarize current diagnostic criteria and explore the spectrum of disease, particularly highlighting the phenotypic variation and its potential relevance to therapeutic decisions and overall outcomes. It has become apparent that polysomnographic (PSG) indices do not correlate well with associated morbidities, even though one-night in-lab PSGs are considered the diagnostic gold standard. Novel approaches, including exploration of plasma and urine biomarkers and data-mining the physiological information embedded within the PSG, may enable the extraction of phenotypic information that can then be interpreted in conjunction with clinical data, including history, physical examination findings, risk factors, and associated disease morbidity, so that an individualized treatment plan can be optimally delineated.

Journal of Personalized Medicine doi: 10.3390/jpm16050258

Authors: Hadi Darawsheh Dmitry Leonov Sergey Dydykin Beatrice Volel Ellina Velichko Irina Usmanova Irina Lakman Anzhela Brago Seyedamirhossein Hosseini Evgeniy Sosnin Yuriy Vasil’ev

The safety of mandibular anesthesia is directly dependent on a precise understanding of the spatial relationships in the pterygomandibular space, particularly the risk of injury to the highly vascularized pterygoid venous plexus (PVP). In vivo studies of PVP displacement during mandibular movements face significant technical challenges. Objective: The study aims to study the spatial displacements of the pterygoid venous plexus during various physiological positions of the mandible using computer modeling with the finite-element method (FEM). Materials and Methods: A three-dimensional finite-element model was developed based on computed tomography data and the BodyParts3D anatomical atlas. The model included the bony structures of the skull, mandible, temporomandibular joint, masticatory muscles, and blood vessels. Simulations were performed for vertical displacements of the jaw at 15, 25, and 35 mm, as well as horizontal displacements of 5 mm to the left and right. Results: It was found that the magnitude of PVP displacement is proportional to the degree of mouth opening. The maximum total displacement (1.24 mm) was recorded at a 35 mm opening along the “posterior–medial–inferior” vector. Lateral excursions revealed asymmetry: displacement to the right caused plexus movement posteriorly, medially, and inferiorly (0.66 mm), while displacement to the left resulted in movement anteriorly, laterally, and superiorly (0.64 mm). Conclusions: This study demonstrates the significant mobility of the pterygoid venous plexus, which depends on the direction and amplitude of mandibular movements. The obtained data have important practical implications for planning regional anesthesia and minimizing the risk of iatrogenic complications. From a biomechanical perspective, maximum mouth opening produces the greatest displacement of the PVP, which may hypothetically reduce the risk of vascular puncture. Clinical studies are required to confirm this.

Journal of Personalized Medicine doi: 10.3390/jpm16050257

Authors: Antonio Giulio Napolitano Dania Nachira Gloria Santoro Eleonora Coviello Maria Teresa Congedo Marco Sanguigni Domenico Pourmolkara Chiara Scognamiglio Leonardo Petracca Ciavarella Adriana Nocera Maria Letizia Vita Felice Mucilli Jacopo Vannucci Elisa Meacci Francesco Puma Filippo Lococo Stefano Margaritora

Background: Contralateral recurrence following surgically treated primary spontaneous pneumothorax represents clinical concern yet remains poorly understood. This study aims to expand the current understanding by evaluating a large, multicenter cohort over a 10-year period and to determine the true incidence of contralateral recurrence assessing the potential role of clinical factors in risk stratification. Methods: A total of 479 patients surgically treated for PSP (2012–2024) across three Italian high-volume centers were retrospectively reviewed. Secondary pneumothorax, patients <18 years old, lung emphysema or intraparenchymal large bullae, and the thoracotomy approach were excluded. The association between categorical variables and contralateral recurrence was assessed using the chi-square (χ2) test, while the association with continuous variables was evaluated using the t-test. Time to recurrence was analyzed using Kaplan–Meier survival curves. Variables with a p-value < 0.05 were considered statistically significant. Results: We identified 59 patients who experienced contralateral recurrence: 45 were males, the mean age was 26.66 ± 12.32 and the mean BMI was 22.00 ± 2.92; only 13 were active smokers. Age (p < 0.001) and smoking history (p = 0.029) were significantly associated with contralateral recurrence in univariate analysis, though these were not confirmed in multivariate analysis. Among the cohort of recurrence, 53 patients only had a recurrence on the contralateral side, with a median time to recurrence of 139 days. The incidence rate ratio (IRR) of recurrence for patients with a mean age of < 34 years was 1.23, which translates to a 23% increased risk. No significant impact of age (p = 0.25), sex (p = 0.67), or smoking (p = 0.59) on the time to recurrence on the other side was observed through Kaplan–Meier analysis. The peak incidence for the first episode of PNX surgically treated and contralateral recurrence was observed in October, November and January. Conclusions: This study highlights a 12% contralateral recurrence rate after PSP surgery. Younger age is associated with earlier contralateral recurrence. Seasonality may influence recurrence patterns. Further studies should explore underlying mechanisms and preventive strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16050256

Authors: Gianluca Ferini Stefano Forte

The trajectory of modern oncology is increasingly defined by the convergence of two therapeutic paradigms that were once considered only marginally related: radiotherapy and immunotherapy [...]

Journal of Personalized Medicine doi: 10.3390/jpm16050255

Authors: Maria Sanchez-McNamara Maria-Jose Fernandez-Cotarelo Begoña Perez-de-Paz Lydia Rodriguez-Romero Esther Anton-Diaz Paz Rodriguez-Bolado Eva Griñan-Fernandez Victor Moreno Cesar Henriquez-Camacho

Background: COPD remains a leading cause of hospitalization and mortality worldwide. This study aimed to analyze trends in COPD patients in Spain from 2016 to 2023, compare outcomes between patients with COPD as a primary versus secondary diagnosis, and identify factors associated with in-hospital mortality. Methods: Retrospective observational study using the Spanish database CMBD. 711.799 patients were analyzed. Demographic characteristics, Charlson Comorbidity Index (CCI), complications, mortality, and hospitalization costs were also evaluated. Multivariate logistic regression was used to identify mortality risk factors. Results: The overall hospitalization rate was 20.02 per 1000 admissions. It decreased by 30% during 2020–2021 before rebounding to peak levels in 2023. The proportion of female patients increased from 19.9% (2016) to 26.4% (2023). Patients with COPD as a secondary diagnosis had higher mortality (13% vs. 5.4%, p < 0.001), greater comorbidity burden (mean CCI 3.5 vs. 2.8), and higher costs. While overall admissions dropped in 2020, mortality peaked at 11.7%, and the number of patients with extremely severe disease nearly doubled. Independent risk factors for mortality included sepsis, age ≥ 66 years, CCI ≥ 3, and COVID-19. Conclusions: Hospitalization involving COPD in Spain showed pandemic-related fluctuations with increasing clinical complexity and increasing female sex. The higher mortality and cost associated with secondary COPD diagnosis highlight the need for comprehensive risk stratification of comorbid conditions and multidisciplinary management of these patients. Early identification of sepsis and CCI scores is essential to improve clinical outcomes in the aging population.

Journal of Personalized Medicine doi: 10.3390/jpm16050253

Authors: Raoul Saggini Domiziano Tarantino Claudia Barbato Raffaello Pellegrino Francesco Pegreffi Rosa Grazia Bellomo

Background: Early recovery after total hip (THA) and total knee arthroplasty (TKA) is often limited by pain and impaired antigravity function. Mechano-acoustic vibration therapy (VT) may enhance neuromuscular activation and analgesia, but evidence in arthroplasty is scarce. Methods: A total of 380 patients aged ≥65 years were retrospectively identified within 3 ± 1 days after primary unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA). All patients underwent standard inpatient physiotherapy; in the VT group, mechano-acoustic vibration therapy (ViSS®, 30 min/day for 5 days at 200–300 Hz) was added as an adjunct treatment, whereas the control group received standard physiotherapy alone. Pain (VAS, McGill), muscle strength (MRC), thigh circumferences, and 10 s Sit-to-Stand were assessed at baseline (T0), end of treatment (T1), and 3-day follow-up (T2). Results: VT produced large, early and sustained improvements in both cohorts. In THA patients, VAS decreased from 7.1 ± 1.1 to 3.8 ± 0.6 at T1 and 3.0 ± 0.7 at T2 and Sit-to-Stand repetitions increased from 3.7 ± 1.9 to 6.3 ± 1.7 at T2, with significant gains in strength and circumferences. TKA VT patients showed similar patterns. Control groups reported smaller pain reductions and no clinically relevant changes in the reported outcomes. Conclusions: integrating a short cycle of mechano-acoustic VT into early inpatient rehabilitation after THA or TKA significantly enhances pain relief and restoration of antigravity function compared with standard physiotherapy alone. VT represents a promising adjunct to conventional rehabilitation strategies and may contribute to optimizing postoperative recovery pathways in major joint replacement.

Journal of Personalized Medicine doi: 10.3390/jpm16050254

Authors: Abdelrahman Hafez Juan M. Farina Kamal Awad Milagros Pereyra Pietri Isabel G. Scalia Hesham Sheashaa Fatmaelzahraa E. Abdelfattah Mahshad Razaghi Sherif Ahmed Ramzi Ibrahim David Simper Steven J. Lester Balaji Tamarappoo Chadi Ayoub Reza Arsanjani

Coronary microvascular dysfunction (CMD) has emerged as a crucial contributor to cardiovascular morbidity and mortality, particularly in patients with ischemia and non-obstructive coronary arteries (INOCA). The condition arises from a complex interplay of structural and functional abnormalities within the small coronary vessels, driven by underlying molecular mechanisms including endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and chronic inflammation. Lipid metabolism plays a central role in this pathology, especially in the setting of elevated low-density lipoprotein cholesterol (LDL-C). Furthermore, the protective capacity of high-density lipoprotein (HDL) is increasingly understood to depend on its functionality rather than absolute levels, as it can become dysfunctional and pro-inflammatory in pathological states. Emerging evidence has identified lipoprotein(a) [Lp(a)] and triglyceride-rich lipoproteins as significant, independent contributors to microvascular injury. Comprehensive clinical assessment of microvascular dysfunction therefore requires integration of advanced lipid profiling, including apolipoprotein B (ApoB), [Lp(a)], and the triglyceride-glucose (TyG) index with invasive and non-invasive measures of coronary flow reserve to more precisely stratify risk. In this narrative review, we synthesize current observational, mechanistic, and early interventional data linking diverse lipid phenotypes to coronary microvascular dysfunction. We propose a concept of lipid-driven CMD endotypes, such as ApoB-/particle overload, dysfunctional HDL, Lp(a)-mediated risk, and metabolic/TyG-high states, and map these to a practical, mechanism-informed management framework. While intensive LDL-C lowering with high-intensity statins and combination therapy remains guideline-directed care for high-risk patients, evidence for dedicated microvascular benefit from newer lipid and cardiometabolic agents is still largely hypothesis-generating. A personalized approach that aligns lipid phenotyping, CMD endotyping, and existing guideline-based therapies may help refine risk assessment and inform future trials.

Journal of Personalized Medicine doi: 10.3390/jpm16050252

Authors: Linda Carli Federico Fattorini Marco Di Battista Lorenzo Esti Cosimo Cigolini Marta Mosca Andrea Delle Sedie

Background: Central sensitization (CS) has been held responsible for both persistent pain and high disease activity scores in Spondyloarthritis (SpA). The Central Sensitization Inventory (CSI) is a questionnaire used to determine CS frequency: a score of at least 40 is associated with a high likelihood of CS. Objectives: To investigate the prevalence of CS in our cohort and its association with clinical characteristics of patients and their quality of life. Methods: Adult patients with a diagnosis of Psoriatic Arthritis (PsA) or Axial Spondyloarthritis (AxSpA) who were also classifiable according to ClASsification criteria for Psoriatic Arthritis (CASPAR) and Assessment of SpondyloArthritis international Society (ASAS) criteria respectively, and regularly followed at the SpA outpatient clinic of our Unit were consecutively enrolled from April to November 2023. Their epidemiologic, clinical and clinimetric data were collected, as well as patient-reported outcome measures (PROMs) [CSI, Health Assessment Questionnaire (HAQ), FACIT-Fatigue (FACIT-F), SHORT-FORM 36 (SF-36), and Hospital Anxiety and Depression Scale (HADS)]. Considering the definition of “difficult-to-treat” rheumatoid arthritis, we defined as “multi-failure” those patients who were treated with more than two biologic disease-modifying anti-rheumatic drugs (bDMARDs) with different mechanisms of action. Intergroup comparisons were assessed by using Chi-square, t-test and ANOVA. p-values < 0.05 were considered significant. Results: A total of 100 patients were enrolled, 46 male (46.0%) and 54 female (54.0%), with a mean age of 59.4 ± 9.8 years and a mean disease duration of 14.8 ± 10.1 years; 79 patients (79%) had a diagnosis of PsA and 21 (21%) of AS. Forty-two patients (42.0%) had a CSI score ≥ 40. Significant correlations were found between a CSI score ≥ 40 and female sex (p = 0.004), the occurrence of enthesitis (p = 0.05), DAPSA-CRP (p = 0.02) and ASDAS scores (p = 0.03), a multi-failure condition (p = 0.01), fibromyalgia (FM) (p = 0.004), thyroid disease (p = 0.016) and obesity (p = 0.047). Regarding PROMs, significant correlations were found between CSI and values of HADS (both anxiety and depression), FACIT-F, HAQ and all the domains of SF-36 (p-value < 0.0001). Conclusions: Our data confirmed that more than 40% of SpA patients had CSI values ≥ 40 and underlined how CS could widely impair their disease burden. A routinary evaluation of CS and a multifactorial biopsychosocial perspective in the diagnosis and management of chronic pain in patients with SpA could help rheumatologists in improving their quality of care.

Journal of Personalized Medicine doi: 10.3390/jpm16050251

Authors: Patricia Piñeiro Francisco Sánchez Alberto Calvo María Tudela Silvia Ramos Sergio García Pilar Benito Isabel Solchaga Raquel Vela Claudia Menéndez Eneko Cabezuelo Ignacio Garutti

Background: Esophagectomy is associated with substantial postoperative morbidity, with infectious complications remaining a leading cause of mortality. Septic shock represents the most severe infectious complication; however, data on its perioperative predictors and long-term impact after esophagectomy are limited. Methods: We conducted a retrospective observational study including consecutive adult patients who underwent esophagectomy with curative intent for esophageal cancer between January 2015 and December 2024 at a tertiary referral center. Postoperative septic shock was defined according to Sepsis-3 criteria. Demographic, clinical, surgical, laboratory, and oncological variables were analyzed. Independent risk factors for septic shock were identified using multivariate logistic regression. Overall survival was assessed using Kaplan–Meier analysis. Results: Among 106 patients, 19 (17.9%) developed postoperative septic shock. These patients had a lower body mass index, reduced preoperative and postoperative albumin levels, and a higher incidence of advanced lymph node involvement. Septic shock was strongly associated with severe postoperative complications, including anastomotic leakage, hemorrhagic shock, acute respiratory distress syndrome, acute kidney failure, and increased rates of PICU readmission. In multivariate analysis, lower albumin levels at PICU admission (OR 0.54; 95% CI 0.29–0.99) and advanced nodal stage (OR 4.98; 95% CI 1.36–18.3) were independently associated with the development of septic shock. Patients who developed septic shock had significantly higher in-hospital mortality (31.6% vs. 1.1%, p < 0.001) and markedly reduced long-term survival, even among those discharged alive. Conclusions: Postoperative septic shock after esophagectomy is a devastating complication with a profound negative impact on both short- and long-term survival. Hypoalbuminemia and advanced lymph node involvement are independent predictors of septic shock. These findings support the integration of simple clinical and laboratory markers into personalized perioperative risk stratification models, enabling individualized management strategies to reduce severe postoperative complications.

Journal of Personalized Medicine doi: 10.3390/jpm16050249

Authors: Kai-Uwe Lewandrowski

Personalized spine care is increasingly understood as more than the use of custom implants, robotics, navigation, or advanced imaging alone [...]

Journal of Personalized Medicine doi: 10.3390/jpm16050250

Authors: Eleni M. Domouzoglou Evangelia E. Ntzani Michail I. Papafaklis Anastasios Serbis Ekaterini Siomou Flora Bacopoulou Assimina Galli-Tsinopoulou

Background: Early diagnosis of obesity in adolescents is crucial for the prevention of severe health consequences. Different criteria for the diagnosis of obesity may lead to variations in prevalence. We aimed to compare the three most widely used international definitions (by WHO, IOTF and CDC) for overweight/obesity in adolescents in Northwestern Greece. Methods: A total of 403 adolescents aged 10–17 years were included. Agreement metrics and assessment of marginal heterogeneity and asymmetry were used for the comparison of the definitions. Results: In the total population, high agreement was observed among all definitions (Krippendorff’s alpha: 0.931, 95% CI 0.913–0.949). However, there was significant marginal heterogeneity (p < 0.001) and asymmetry (p < 0.001) for each pairwise comparison. WHO definition consistently yielded higher prevalence of obesity (WHO: 23.1%, IOTF: 15.4%, CDC: 21.6%). There were no significant differences in agreement (p = 0.247 for the comparison) between males and females, with more prominent marginal heterogeneity and asymmetry in males. Agreement among definitions was numerically lower in young adolescents aged < 14 years versus older ones (alpha: 0.919 vs. 0.953, p = 0.082), and systematic bias (p < 0.001) and asymmetry (p < 0.001) were present only in young adolescents without any significant difference in older ones. Conclusions: Although agreement was very high among definitions, they are not interchangeable, yielding different prevalence rates, particularly in young adolescents. IOTF criteria resulted in a reduced diagnosis of obesity and could lead to undertreatment; in contrast, WHO and CDC criteria may lead to overdiagnosis in our population. Caution is required when interpreting international criteria for overweight/obesity in various populations.

Journal of Personalized Medicine doi: 10.3390/jpm16050248

Authors: Eszter Györke Gábor Benyó Kristóf Balázs Árvai Csaba Bödör László Kereskai Hajnalka Ábrahám Barbara Réger Bálint Egyed Gábor Ottóffy

Background: The etiological diagnosis of chronic thrombocytopenia in children remains challenging and is often established by exclusion. In this article, we present the case of a patient in whom we used whole-exome sequencing (WES) to help identify the underlying cause and determine the appropriate treatment. Methods: Whole-exome sequencing was performed to clarify the genetic background of the disease. Based on the results, transmission electron microscopy (TEM) was also carried out to confirm or exclude the pathogenic role of the identified NBEAL2 gene variant and to assess the presence of gray platelet syndrome. Results: In this patient, despite the presence of the NBEAL2 gene variant, neither gray platelet syndrome nor a pathogenic role of the variant could be confirmed. However, the genetic findings identified by WES led to numerous additional investigations, causing a considerable burden on both the patient and the family. Conclusions: Our case highlights that WES testing, which is emerging in pediatric hematology practice, offers not only diagnostic advantages but also pitfalls. Whole-exome sequencing has recently emerged as a new diagnostic tool and has been available nationwide in pediatric hematology-oncology care in Hungary for just over two years. While personalized treatment strategies for benign hematologic diseases increasingly rely on high-throughput genetic testing, the clinical application of WES requires a cautious, critical evaluation of results. Despite the method’s promise, the heterogeneity of the findings underscores the need to interpret WES results carefully and to place them in a clinical context in every case.

Journal of Personalized Medicine doi: 10.3390/jpm16050247

Authors: Mehdi Abouzari

The practice of medicine has long aspired to treat the individual rather than the disease, yet it has only been in recent decades that the scientific and technological tools required to fulfill this aspiration have begun to mature [...]

Journal of Personalized Medicine doi: 10.3390/jpm16050246

Authors: Lucia Buccarello Costanza Montagna Sabina Di Matteo Renata Mangione Giuseppe Carota Jay Sibbitts Romana Jarosova Susan M. Lunte Giacomo Lazzarino Giuseppe Caruso

Nitric oxide (NO) plays an important role in neuronal communication, synaptic plasticity and vascular regulation. Due to its important function in neuronal homeostasis, NO imbalance is associated with neurodegeneration. Specifically, in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and frontotemporal lobar degeneration (FTLD), an excessive amount of NO, mostly produced by inducible NO synthase (iNOS), reacts with superoxide to form peroxynitrite, driving oxidative/nitrosative stress, mitochondrial dysfunction, and aberrant protein modifications. In AD, NO dysregulation promotes amyloid-β (Aβ) accumulation, tau hyperphosphorylation and synaptic loss, creating a self-perpetuating cycle of neuronal damage. NO’s dual role, protective at physiological levels but harmful if overproduced, underscores the therapeutic potential of antioxidant compounds that restore the balance of NO/NOS (especially iNOS) while preserving physiological functions. However, despite the emerging role of antioxidant-based therapeutic approaches, clinical translation is limited by the complexity of NO signaling and the absence of safe, specific NOS inhibitors. By targeting the molecular switch from protective to toxic, NO activity may offer new personalized treatment avenues for neurodegenerative diseases.

Journal of Personalized Medicine doi: 10.3390/jpm16050245

Authors: Saleh Alsulami Youn Soo Jung Kari Nadeau Perdita Permaul Longxiang Li Petros Koutrakis Jonathan M. Gaffin Wanda Phipatanakul Tina M. Banzon

Background/Objectives: Radon exposure has recently been associated with asthma morbidity, including increased airway inflammation and school absenteeism in children, though limited data on underlying biological mechanisms exist. Interleukin-6 (IL-6), a pleiotropic cytokine implicated in both Type 2-low airway inflammation and radon-related lung carcinogenesis, may represent a key mechanistic link between radon exposure and asthma morbidity. We aimed to evaluate the association between indoor radon exposure and plasma IL-6 levels in children with asthma and whether this relationship differs by allergic sensitization status. Methods: We analyzed baseline data from the School Inner-City Asthma Study, a prospective cohort of children aged 4–13 years with persistent asthma. Monthly indoor radon concentrations at each participant’s residential ZIP Code Tabulation Area were estimated using a validated spatiotemporal prediction model. Plasma IL-6 was measured from baseline blood samples. Multivariable linear mixed-effects models with random intercepts for school were used to assess the association between radon exposure and IL-6, adjusting for demographic, clinical, and socioeconomic covariates. Effect modification by allergic sensitization was evaluated using an interaction term. Results: Among 144 participants, 62.5% were allergen-sensitized. The median home radon concentration was 46.6 Bq/m3 (range 30.7–99.9), and the mean plasma IL-6 was 0.22 pg/mL (SD 0.41). A significant interaction was observed between radon exposure and allergic sensitization status (β-interaction = –0.012; p = 0.014), indicating differential effects by phenotype. Among non-sensitized children, higher radon exposure was associated with increased IL-6 levels (β = 0.0088; p = 0.044), corresponding to a 0.32 pg/mL rise in IL-6 per 37 Bq/m3 increase in radon. No significant association was observed among sensitized children. Conclusions: Indoor radon exposure is associated with higher plasma IL-6 levels in non-sensitized children with asthma, suggesting a potential IL-6–mediated pathway linking radon exposure to asthma morbidity in the Type 2-low phenotype. These findings highlight heterogeneity in environmental asthma responses and support further investigation into radon mitigation as a modifiable factor to improve asthma outcomes. IL-6 may serve as a biomarker to identify children most susceptible to radon-related airway inflammation, guiding personalized mitigation strategies and targeted interventions to improve asthma outcomes. Future studies should incorporate direct home radon measurements, comprehensive endotyping panels, and longitudinal biomarker sampling to validate these findings and elucidate whether IL-6 trans-signaling pathways mediate radon-induced airway injury in non-allergic asthma.

Journal of Personalized Medicine doi: 10.3390/jpm16050244

Authors: Simonetta Masieri Elona Begvarfaj Pasquale Frisina Carlo Cavaliere Antonella Loperfido Francesca Lombardi Marcella Bugani Daniela Messineo

Background/Objectives: The therapeutic effectiveness of chronic rhinosinusitis with nasal polyposis (CRSwNP) depends on an accurate diagnosis that identifies disease characteristics, evaluates sinus patency, and detects paranasal sinus obliteration. This study aims to assess a novel artificial intelligence (AI) system integrated with radiomic analysis for the radiological evaluation of CRSwNP, developing a reliable and predictive clinical-radiological scoring system. Methods: This study retrospectively evaluates CT scans of patients with CRSwNP. Image analysis was performed using Radiomica LifeX (Local Image Features Extraction) version 7.5. The extracted densitometric volumes were compared to the Lund-Mackay Score (LMS) to develop a novel scoring system (P-ABCD score) and assess its radiomic predictive capability. Results: Twenty patients with CRSwNP undergoing Dupilumab therapy participated in this study. The P-ABCD score, derived from sinus CT imaging data, served as a valuable objective measure of clinical improvement following CRSwNP treatment. Conclusions: Advanced radiomic imaging techniques of the sinus cavity provide precise volumetric data combined with texture analysis. These techniques offer high sensitivity by accurately quantifying the true extent of inflammatory involvement in the paranasal sinuses, enabling effective disease stratification.

Journal of Personalized Medicine doi: 10.3390/jpm16050243

Authors: Dimitra V. Peristeri Dimitrios N. Raptis Ioannis Mantzoros Dimitrios Schizas Alexandros-Georgios I. Asimakopoulos Eirini Papadopoulou Georgios D. Lianos Thomas Papaziogas Vasileios Papaziogas

Introduction: Robotic gastrectomy is increasingly used in the surgical management of gastric cancer. Indocyanine green (ICG) near-infrared fluorescence imaging has emerged as a technique that enables real-time visualization of lymphatic drainage pathways, potentially facilitating more precise and individualized lymph node dissection. However, the clinical value of ICG-guided fluorescent lymphography during robotic gastrectomy remains incompletely established. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and the Cochrane Library were searched from database inception to 31 January 2026 for comparative studies evaluating ICG-guided fluorescent lymphography versus standard robotic gastrectomy for gastric cancer. Statistical analyses were performed using R (version 4.4.2) and the meta package. Results: Six studies, including 406 patients, met the inclusion criteria. Use of ICG was associated with a higher number of retrieved lymph nodes (mean difference [MD] 8.48; 95% CI 4.61–12.36; p = 0.001; I2 = 55.5%). Operative time was modestly shorter in the ICG group (MD −10.84 min; 95% CI −21.08 to −0.61; p = 0.038). There were no significant differences in intraoperative blood loss (MD −4.02 mL; p = 0.289), length of hospital stay (MD −0.82 days; p = 0.131), or postoperative complications (odds ratio 0.83; 95% CI 0.46–1.49; p = 0.534). Conclusions: ICG-guided fluorescence imaging during robotic gastrectomy is associated with increased lymph node retrieval and a small reduction in operative time without evidence of increased perioperative morbidity. Larger prospective studies are required to confirm these findings and to evaluate long-term oncologic outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16050242

Authors: Kelly Olvany Annie Aitken Elysa J. Marco Neil Hattangadi Kevin A. Shapiro

Purpose: The purpose of this study was to examine the effects of a medically centered, interdisciplinary treatment model on adaptive behavior in children with Autism Spectrum Disorder (ASD). The Cortica model involves a comprehensive program including behavioral and developmental therapies, overseen by a neurodevelopmental physician. Here, we investigated how adaptive behaviors change over time during care at Cortica. Methods: We analyzed changes in the Vineland Adaptive Behavior Scales over the course of Cortica care compared to a community sample comprising longitudinal data from the National Database for Autism Research (NDAR). Results: Using propensity score weights to match cohorts based on baseline functioning, multilevel growth curve models showed significant Cohort × Time interactions for the Adaptive Behavior Composite (ABC) score and all subscale scores, indicating increased growth in adaptive behavior skills for children in the Cortica cohort relative to NDAR. Conclusions: Results of this study highlight the importance of using adaptive behaviors as a primary outcome in clinical research studies and suggest that a personalized, multidisciplinary approach to intervention can result in improved adaptive behavior skills over time.

Journal of Personalized Medicine doi: 10.3390/jpm16050240

Authors: Barbara Pala Mariagrazia Piscione Francesco Cribari Paola Gualtieri Marco Alfonso Perrone Laura Di Renzo

Growing evidence indicates that myocardial infarction (MI) is the clinical manifestation of heterogeneous plaque substrates with distinct molecular, cellular, and biomechanical mechanisms. Acute coronary thrombosis (ACT) most commonly arises from plaque rupture (PR), plaque erosion (PE), and calcified nodules (CNs), each associated with different inflammatory profiles, thrombus composition, clinical presentation, and prognosis. This comprehensive review provides a clinician-oriented synthesis of the pathophysiological mechanisms underlying these three principal plaque phenotypes and discusses their implications for the contemporary management of acute coronary syndromes (ACS). We examine the molecular and cellular determinants of plaque instability and highlight how systemic factors such as plaque burden, impaired healing responses, and myocardial jeopardy modulate clinical risk. The role of intracoronary and non-invasive imaging is discussed primarily as a tool to elucidate plaque biology with direct clinical relevance rather than merely as a procedural guide. Building on these insights, we propose a conceptual framework for integrating plaque biology into clinical decision-making across the acute phase, secondary prevention, and long-term follow-up. In particular, recognizing the biological heterogeneity of plaque substrates may support more personalized therapeutic strategies, enabling clinicians to tailor pharmacological and interventional approaches according to the underlying plaque phenotype and patient-specific risk profile. Finally, we briefly address emerging perspectives, including the potential role of artificial intelligence (AI) in refining plaque characterization, risk stratification, and precision cardiovascular prevention. Overall, recognition of PR, PE, and CNs as biologically distinct entities supports a shift toward mechanism-informed and personalized management of MI, aligning advances in plaque biology with the principles of precision cardiovascular medicine.

Journal of Personalized Medicine doi: 10.3390/jpm16050241

Authors: Debora Emanuela Torre Carmelo Pirri

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg–Strauss syndrome, is a rare necrotizing vasculitis characterized by asthma, eosinophilia, and systemic granulomatosis vasculitis. Perioperative risk is primarily driven by airway hyperreactivity, potential cardiac disease, chronic immunosuppressive therapy, and reported alterations in plasma cholinesterase activity. Evidence specifically addressing anesthetic management remains scarce and largely limited to case-based reports. Methods: A focused narrative review was conducted by searching MEDLINE (via PubMed), Scopus, and Embase from inception to January 2026 for publications reporting perioperative anesthetic management in patients with EGPA/Churg–Strauss syndrome. Case reports and case-based descriptions providing explicit anesthetic details were qualitatively synthesized. Results: Available evidence consists predominantly of isolated case reports across heterogeneous surgical settings, including ENT, abdominal, orthopedic, ambulatory, pediatric, and rare cardiac procedures. Recurring perioperative principles include optimization of bronchial disease and continuation of inhaled therapy; minimization of airway stimulation and avoidance of histamine-releasing drugs; selection of induction agents preserving hemodynamic stability in the presence of myocardial involvement; preference for non-depolarizing neuromuscular blockade with quantitative monitoring (and consideration for sugammadex when appropriate); individualized corticosteroid management and multimodal, opioid-sparing analgesia, often supported by regional techniques. Conclusions: In the absence of dedicated perioperative guidelines, anesthetic care for EGPA should be individualized based on clinical phenotype and organ involvement. A structured approach targeting airway protection, cardiovascular stability, safe neuromuscular management, and opioid-sparing analgesia may represent a pragmatic risk-mitigation framework. These considerations are illustrated by an institutional experience in mitral valve surgery.

Journal of Personalized Medicine doi: 10.3390/jpm16050239

Authors: Antonio Borzelli Francesco Giurazza Luigi Basile Fabio Corvino Felice D’Antuono Francesco Pane Milena Coppola Alessandro Punzi Gianluca Cangiano Antonio Corvino Raffaella Niola

Background: Femoral pseudoaneurysms are clinically heterogeneous, with substantial variability in anatomical features and patient-related bleeding risk. Standard treatment algorithms may be inadequate, particularly in patients receiving anticoagulation or presenting with altered coagulation profiles. A personalized, risk-adapted interventional strategy may optimize outcomes while preserving procedural safety. This study compares ultrasound-guided compression with endovascular and percutaneous therapies and evaluates the safety of minimally invasive approaches across different risk profiles to support individualized management. Methods: This single-center retrospective cohort study included 65 consecutive patients treated for femoral pseudoaneurysms between January 2019 and May 2025. Treatment modalities comprised ultrasound-guided compression, endovascular embolization (coils, covered stents, NBCA–Lipiodol), percutaneous glue injection, and hybrid approaches. Primary endpoints were technical and clinical success. Safety was assessed using pre- and post-procedural INR, platelet count, and hemoglobin levels. High-risk status was defined as ongoing anticoagulation or antiplatelet therapy, INR > 1.5, or platelet count <50 × 109/L. Results: Endovascular and percutaneous approaches achieved significantly higher technical (100% vs. 68.5%, p = 0.006) and clinical success rates (100% vs. 77.8%, p = 0.009) compared with ultrasound-guided compression. In minimally invasive cohorts, INR and platelet counts remained stable after treatment, while hemoglobin showed an expected post-procedural decrease (p < 0.001). High-risk patients demonstrated technical success rates comparable to standard-risk patients, with no significant differences in laboratory trends. Favorable outcomes were observed across different embolic materials. Conclusions: Endovascular and percutaneous therapies provide superior effectiveness compared with ultrasound-guided compression while maintaining a reassuring safety profile, even in patients at increased bleeding risk. These findings support a personalized, patient-tailored interventional approach based on individual anatomical and clinical characteristics.

Journal of Personalized Medicine doi: 10.3390/jpm16050238

Authors: Katelynn Murray Whelan Gerard Anthony Sheridan Kenneth Joyce Alan Hussey Jason S. Hoellwarth Justina Baltrunaite

Background: Peri-prosthetic joint infection (PJI) following total knee arthroplasty complicated by soft tissue compromise presents a major reconstructive challenge. Successful management requires the eradication of infection while restoring durable soft tissue coverage and limb function. This study reports the outcomes of a patient-specific, multidisciplinary orthoplastic approach to complex knee PJI. Methods: We retrospectively reviewed five patients with complex infected knee arthroplasty and associated soft tissue compromise managed at our institution between 2021 and 2025 by a single orthopaedic surgeon and two plastic reconstructive surgeons. All cases required personalized management, including the use of custom spacers, patient-specific orthopaedic reconstruction, and individualized soft tissue reconstruction techniques. Data collected included patient demographics, infection characteristics, reconstructive techniques, and functional outcomes. Results: All patients achieved durable soft tissue coverage and infection eradication at final follow-up. Of the five patients, one underwent primary closure of a persistent sinus, one required a local axial bi-pedicled flap for sinus control and soft tissue closure, two were managed with medial gastrocnemius flaps, and one complex case with an associated bone defect required a custom-designed spacer to achieve stability and dead-space management. Conclusions: In this retrospective case series, we aim to demonstrate that complex knee PJI with associated soft tissue defects may be successfully managed with an individualized, multidisciplinary strategy. We aim to demonstrate the feasibility of such an approach in a tertiary referral centre and to highlight the importance of customisation in achieving infection control and limb preservation.

Journal of Personalized Medicine doi: 10.3390/jpm16050237

Authors: Haye H. Glas Tom L. Zwijnenberg Johan Jansma Rutger H. Schepers

Background/Objectives: Inferior alveolar nerve injury is a common complication of Bilateral Sagittal Split Osteotomy. Preoperative three-dimensional tracing of the mandibular nerve canal using Cone-beam CT may help reduce this risk. We reconstructed the nerve course in 428 consecutively planned BSSO cases and developed a statistical model that quantifies population-level canal position to guide safe, evidence-based osteotomy planning. Methods: Traceable mandibular nerve canal CBCTs from 440 BSSO candidates (2023–2025) were retained. The mandibles and 2.5 mm diameter canals were segmented in Mimics and fused with intraoral scans. Next, the meshes were aligned non-rigidly to a template. A k-nearest-neighbour analysis mapped the outer mandibular surface to canal distances of all the patients on the template mandible model. Results: After excluding 12 scans because the nerve could not be traced, 428 mandibles were studied. The canal’s position varied, with regions near the vertical ramus and premolar regions frequently showing fewer than 3 mm of buccal bone covering the mandibular nerve. In contrast, a preferred safe zone was identified in the second molar region, where more than 97.8% of patients had greater than 5 mm of buccal bone clearance. A population-based colour map was generated to visualise the risk areas and confidence intervals for outer cortex-to-canal distances. Conclusions: This study provides the first high-resolution, population-based 3D map of nerve clearance in BSSO patients. Routine use of CBCT with patient-specific nerve tracing is recommended to reduce the risk of nerve injury.

Journal of Personalized Medicine doi: 10.3390/jpm16050236

Authors: Lucia Scurto Ottavia Borghese Giovanni Tinelli Guido Rindi Roberto Pola Yamume Tshomba

Background: Reliable preoperative identification of carotid plaque instability remains challenging. Although duplex ultrasound allows early detection of carotid stenosis, it does not consistently predict plaque biological behavior. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been implicated in atherosclerotic progression and plaque destabilization. The tissue-level expression of miRNAs in carotid plaques and their relationship with histological vulnerability remain incompletely defined. Methods: This exploratory, pilot, hypothesis-generating study included patients undergoing carotid endarterectomy for asymptomatic high-grade carotid stenosis (>75% NASCET). Plaque vulnerability was assessed using a multiparametric approach combining preoperative duplex ultrasound features (including Gray Scale Median, GSM), intraoperative macroscopic evaluation, and a validated histological scoring system; only plaques with concordant classification across all three modalities were retained for molecular analysis. Total RNA including small RNA was extracted from plaque tissue and miRNA expression was measured by qRT-PCR on a panel of 47 candidate miRNAs. Data were analyzed descriptively. Results: Twenty-eight patients were initially enrolled; after application of strict vulnerability criteria, five plaques (three unstable, two stable) were selected for miRNA profiling. Among the 47 miRNAs assayed, miR-122 and miR-197 showed a consistent descriptive trend toward higher expression in plaques classified as unstable; these plaques also displayed histological features of vulnerability (lipid-rich necrotic cores and inflammatory infiltrates). Given the extremely limited sample size, no inferential statistical comparisons or multiple-testing corrections were performed. Conclusions: In this small, tissue-based exploratory analysis, miR-122 and miR-197 were more highly expressed in plaques with histological features of instability. Due to the small sample size, the effect estimates are unstable, and the findings should be used solely to inform the design and power calculations of future studies. We outline the need of a clear, pragmatic validation pathway based on replication in independent, larger cohorts with standardized tissue handling and blinded assessment and parallel evaluation of circulating miRNA levels to assess noninvasive biomarker potential. Indeed, these findings are preliminary and strictly hypothesis-generating; validation in larger, prospectively collected cohorts and integration with circulating biomarkers and imaging data are required before clinical application.

Journal of Personalized Medicine doi: 10.3390/jpm16050235

Authors: Bastien Chalamet Jean-Baptiste Pialat Anthony Viste Didier Defez Pierre-Adrien Bolze Nicolas Stacoffe

Objectives: Management of unstable pelvic fractures during pregnancy presents a major therapeutic challenge, requiring careful multidisciplinary evaluation to balance maternal benefits and fetal radiation risks. Methods: We report the case of a 32-year-old patient who presented with a pelvic fracture due to a road traffic accident at three months of pregnancy. A left sacroiliac osteosynthesis was performed to treat a left sacroiliac diastasis with pelvic osteosynthesis using a trans-iliosacral approach under cone-beam CT (CBCT) guidance using a very-low-dose protocol. Radiation parameters and fetal dose estimates were calculated in advance in collaboration with a medical physicist. Tight beam collimation, a reduced field of view, and minimization of fluoroscopic checks were applied to keep fetal exposure as low as reasonably achievable. This article aims to demonstrate the feasibility of managing a complex pelvic fracture using interventional radiology and to review the literature on management options and gestational age-dependent fetal risks. Results: The estimated cumulative fetal dose from initial imaging, open surgery, and CBCT-guided osteosynthesis remained below 70 mGy using a pregnant phantom (Duke Organ Dose–Dosewatch–General Electric system), which is below thresholds associated with deterministic effects. The procedure achieved optimal screw positioning with less than 40 s of fluoroscopy. Maternal postoperative recovery was favorable, and follow-up revealed normal fetal development. Conclusions: This case demonstrates that CBCT-guided percutaneous iliosacral screw fixation can be safely performed during pregnancy with meticulous planning, dose-reduction strategies, and multidisciplinary collaboration, maintaining fetal radiation exposure below accepted safety thresholds.

Journal of Personalized Medicine doi: 10.3390/jpm16050234

Authors: Carlota Abbad-Jaime De Aragón María Davo-Mogica Pablo de la Cruz-Anaya Emilio Berna-Rico Inés Díaz-Ruiz Inés Perales-Sánchez Nicholas D. Brownstone Pedro Jaén Lluis Puig Andrew Blauvelt Alvaro González-Cantero

Background/Objectives: Despite substantial progress in the management of psoriasis, evidence on as-needed dosing strategies for biologic therapies remains scarce. In this context, the present study aimed to assess the effectiveness of a previously defined as-needed bimekizumab (BKZ) dosing regimen in a larger cohort of patients with psoriasis, as well as to identify clinical factors associated with treatment response. Methods: In this retrospective study, medical records of 64 patients with moderate-to-severe psoriasis treated with BKZ between May 2023 and November 2025 at a specialized psoriasis unit in Madrid, Spain, were reviewed. Patients followed an off-label, as-needed dosing regimen, consisting of two initial 320 mg doses at Weeks 0 and 4, with subsequent administrations only upon loss of a PASI 90 response. The primary outcome was the proportion of patients achieving and maintaining optimal disease control (PASI 90) over time. The duration of treatment effect was defined as the interval between the second dose and loss of PASI90 in the absence of further treatment. Safety outcomes were also evaluated. Results: A total of 59 out of 64 patients achieved a PASI 90 response after the initial two BKZ doses, and all maintained disease control with the as-needed dosing strategy over time. On average, patients received approximately one-third of the doses expected under the standard dosing regimen. The mean duration of treatment effect following the second dose was approximately 24 weeks. Systemic and bio-naïve patients presented the longest treatment effect duration under the as-needed dosing regimen. Oral candidiasis was reported in two patients and resolved without complications. Conclusions: This study reinforces previous evidence supporting the effectiveness of an as-needed BKZ dosing strategy, particularly in patients naïve to systemic and biologic therapies for psoriasis. Nevertheless, larger prospective studies are required to confirm these findings.

Journal of Personalized Medicine doi: 10.3390/jpm16050233

Authors: Ilaria Benevento Angela Solazzo Luciana Rago Antonietta Montagna Barbara D'Andrea Fabrizio Sanna Salvatrice Campoccia Antonella Bianculli Raffaele Tucciariello Alessia Telesca Vito Metallo Francesco Marino Carmen Linda Ginetti Buccino Mario Ferrara Irene Schirò Teresa Virgilio Anna Zeccola Grazia Lazzari

Whole breast radiotherapy in adjuvant breast cancer (BC) treatment has been commonly delivered in supine positioning for more than 50 years. Its widespread use is related to the broad availability of simple and common breast board immobilization devices, which exploit the natural recumbent position of the body with arms above the head, the good match with linac tables and well-established set up procedures. However, in scenarios like painful arm discomfort in patients with post-surgery arm or arthritic limitation, unfavorable chest geometry like pectus excavatum (PE), large and pendulous breasts in obese women and cardiac morbidity in left sided BC, supine position seems very uncomfortable for patients and troublesome for radiation oncologists. The question is how to proceed when supine IMRT or DIBH are ineffective strategies? Alternative positions have been analyzed over the past twenty years, starting with a lot of trials testing prone positioning variants with and without DIBH, lateral decubitus or upright standing radiotherapy. A better recognition of new treatment position options in BC adjuvant therapy may provide more opportunities for personalized radiotherapy in this population, to ensure they receive an appropriate, safe and comfortable treatment.

Journal of Personalized Medicine doi: 10.3390/jpm16050232

Authors: Aleksandra Paripović Nikola Ilić Marina Perić Slavica Ostojić Danijela Radivojević Luka Nikolić Adrijan Sarajlija

Background: Chronic kidney disease (CKD) in children is frequently associated with underlying genetic etiologies, particularly in cases with early onset, congenital anomalies, or multisystem involvement. The integration of molecular diagnostics into routine nephrological practice represents an important step toward personalized medicine in pediatric CKD. Methods: This retrospective observational study included 50 pediatric patients with CKD stages 2–5 and suspected hereditary etiology evaluated at a tertiary pediatric center. All patients underwent genetic testing using next-generation sequencing and/or chromosomal microarray analysis. Clinical characteristics, CKD stage, extrarenal manifestations, and disease progression were analyzed in relation to genetic findings. Associations between clinical variables and genetic diagnosis were assessed using appropriate statistical tests, including multivariable logistic regression. Results: A positive genetic diagnosis was identified in 28 patients (56%), including 21 monogenic disorders detected by next-generation sequencing and 7 pathogenic copy number variants identified by chromosomal microarray analysis. Extrarenal manifestations were present in 48% of patients and were significantly associated with a higher diagnostic yield (75% vs. 42.3%; OR = 4.09; 95% CI: 1.23–13.61; p = 0.007). Psychomotor delay was strongly associated with pathogenic copy number variants (p < 0.001). Patients with confirmed genetic etiologies exhibited significantly higher rates of CKD progression compared with genetically negative individuals (82.1% vs. 22.7%; OR = 15.64; 95% CI: 3.90–62.7; p < 0.001). In multivariable analysis, genetic diagnosis shows association with disease progression after adjustment for age and baseline renal function. Conclusions: Genetic testing provided a molecular diagnosis in more than half of children with CKD and suspected hereditary etiology. Extrarenal manifestations were strongly associated with a higher diagnostic yield, while confirmed genetic etiologies may be associated with CKD progression. These findings support the early integration of genetic diagnostics into the evaluation of pediatric CKD to improve prognostic assessment and enable more personalized management strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16050231

Authors: Carter W. Elggren Charles H. Iverson Madeline D. Morris Ella F. Cooper-Leavitt Genevieve Parker Andrew W. Richardson Asher P. Reynolds Paul M. Cortes Benjamin T. Bikman Paul R. Reynolds

Background: Testosterone is the most abundant biologically active sex steroid in women, yet the therapeutic implications of its age-related decline remain undercharacterized. Published trials have focused predominantly on sexual function, leaving gaps in understanding how testosterone replacement therapy (TRT) affects broader symptom domains and metabolic biomarkers in women. Objective: To investigate whether individualized, biomarker-guided TRT in women is associated with improvements across multiple symptom domains and favorable hormonal, hematologic, and cardiometabolic biomarker changes, and to examine whether symptomatic benefit varies with treatment duration. Methods: In this retrospective observational study, women (n = 332; ages 27 to 78; mean 45.7 ± 7.1 years) receiving TRT as part of routine clinical care through a telehealth-based platform completed a structured survey at a single post-treatment time point assessing eight symptom domains: energy/fatigue, memory, concentration, irritability, depression, anhedonia, sexual interest, and relationship satisfaction. Respondents were stratified by TRT duration (1 month to >12 months) and a subset (n = 120) underwent paired biomarker assessment at baseline and 12 weeks for total testosterone, free testosterone, SHBG, hemoglobin, and triglycerides. Results: Improvement was reported across all eight domains, with energy/fatigue showing the strongest response (84.3% improved). Depression, irritability, anhedonia, and sexual interest each exceeded 65% improvement. Cognitive domains showed a delayed trajectory, with meaningful gains emerging at 4 to 6 months. Quality of life improvement was reported by 89.7%, with significant improvement rising from 5.4% at 1 month to 51.5% at greater than 12 months. Energy/fatigue (64.2%) and mood (49.7%) ranked above sexual desire (41.3%) as self-identified areas of greatest benefit. All five biomarkers changed favorably: total testosterone +151.8% (d = 3.60), free testosterone +216.7% (d = 3.01), hemoglobin +5.5% (d = 2.03), SHBG −13.3% (d = 1.57), and triglycerides −12.6% (d = 1.28). Conclusions: Individualized TRT in women was associated with broad symptomatic improvement spanning energy/fatigue, depression, irritability, anhedonia, cognitive function, and sexual interest, with duration-dependent gains and favorable biomarker changes across all five markers assessed. These findings suggest that the value of testosterone in women extends beyond sexual function and supports the need for larger controlled trials with extended follow-up.

Journal of Personalized Medicine doi: 10.3390/jpm16040230

Authors: Irina Bacheva Lyazat Ibrayeva Dina Rybalkina Irina Kadyrova Diana Zhumagaliyeva

Backgrounds: The aim of this pilot study was to evaluate the hierarchical contribution of individual genetic polymorphisms to the variability of autonomic regulation parameters and respiratory function in athletes of different sport specializations using Classification and Regression Tree (CRT) analysis. Methods: The study included athletes divided into two groups: hockey players (n = 48) and martial artists (n = 43). Heart rate variability (LF, HF) parameters and spirometric indices (FEV1) were assessed. Genetic analysis included 8 single nucleotide polymorphisms (SNPs): IL6 rs1800795, VDR rs731236, KCNJ11 rs5219, ADRB2 rs1042713, ADRB2 rs1042714, TRHR rs16892496, MSTN rs1805086, UCP3 rs1800849. Results: In martial artists, the main predictors were genes responsible for adrenoreceptor sensitivity (ADRB2) and neuroimmune interactions (IL6). In hockey players, the most significant predictors were genes involved in muscle growth (MSTN), energy metabolism (UCP3), and neuroendocrine regulation (TRHR). These findings indicate that similar resting HRV parameters in athletes from different sports may be associated with different genetic polymorphisms, reflecting sport-specific physiological adaptations to training loads. Conclusions: The results highlight the sport-specific nature of genetic determinants of autonomic regulation. In martial artists, genes related to the immuno-adrenergic axis (IL6, ADRB2) appear to play a dominant role, whereas in hockey players neuroendocrine, muscle-metabolic, and mitochondrial factors (TRHR, MSTN, UCP3) demonstrate greater influence. The observed interactions between genotypes and FEV1 emphasize the importance of transitioning from generalized approaches toward personalized monitoring strategies in sports science.

Journal of Personalized Medicine doi: 10.3390/jpm16040229

Authors: Julia Jantz Andreas Pfützner

Conventional diabetes therapy primarily targets HbA1c using a standardized, stepwise approach, often neglecting individual clinical and diagnostic phenotypes. In this second part of our discussion, we present an alternative strategy. After phenotyping the patient, we initiate a targeted pharmacological combination therapy tailored to the individual’s underlying pathophysiology, alongside lifestyle modifications. Sulfonylureas are completely avoided in this approach. Instead, medications are selected based on their alignment with the patient’s phenotype and absence of contraindications. Early insulin therapy, for example, is particularly effective in patients with β-cell-dysfunction-driven diabetes, whereas GLP-1-supported weight reduction and glitazone therapy are more suitable for insulin-resistance-driven diabetes. For monitoring and determining when temporary therapy intensification may be necessary, we rely on a combination of functional biomarkers (intact proinsulin, adiponectin, hsCRP, and leptin) and conventional clinical parameters (HbA1c, BMI, lipids, blood pressure). Using this personalized strategy, we have consistently achieved long-term glycemic control—often maintaining normal HbA1c levels for up to 15 years in our patients so far.

Journal of Personalized Medicine doi: 10.3390/jpm16040228

Authors: Leandro Sierra Maria Ortega Abad Maria Saavedra-Martinez Kanisha Bahierathan Zainab Ifthikar Ana Eliza Velez Nikki Duong Luis Antonio Diaz Juan Pablo Arab

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks.

Journal of Personalized Medicine doi: 10.3390/jpm16040227

Authors: Journal of Personalized Medicine Editorial Office Journal of Personalized Medicine Editorial Office

With this notice, the Journal of Personalized Medicine Editorial Office and Editorial Board wishes to alert readers to concerns related to this article [...]

Journal of Personalized Medicine doi: 10.3390/jpm16040226

Authors: Andreas Pfützner Julia Jantz

The diagnosis of type 2 diabetes using classical clinical and laboratory biomarkers (HbA1c, glucose, lipids, BMI, and blood pressure) is a classification by symptoms and does not provide insight into the underlying pathophysiological disorders (insulin resistance, β-cell dysfunction, visceral adipose tissue hormonal secretion, and chronic systemic inflammation). A better understanding of these disorders may help in the selection of appropriate and potentially more successful personalized therapeutic interventions. Based on extensive clinical trial experience, a method for individual phenotyping and consecutive personalized diabetes therapy has been developed in our practice, which we have been using for more than 15 years and would like to share for discussion and debate. In this Part 1, the pathophysiological background and diagnostic approach to phenotyping is described. A consecutive Part 2 will present the translation of the phenotyping result into a personalized diabetes therapy, and another consecutive Part 3 will provide more comprehensive real-world patient observations when practicing this concept. This article is intended as a discussion/concept paper and does not present unpublished patient-level outcome data or formal effectiveness analyses. Prospective validation studies are needed to evaluate the clinical utility of this phenotype-based framework.

Journal of Personalized Medicine doi: 10.3390/jpm16040225

Authors: Jack T. Peterson Jenny N. Guo Amir Patel Nabila Khondakar Perry Xu Amy E. Krambeck

Background/Objectives: Obesity has been associated with the development and severity of benign prostatic hyperplasia (BPH), yet its influence on outcomes following definitive surgical management, like holmium laser enucleation of the prostate (HoLEP), remains unclear. Furthermore, gradation of body mass index (BMI) severity has yet to discern personalized outcome stratification. We evaluated BMI’s influence on perioperative, immediate, short-term follow-up, and patient-reported outcomes for HoLEP patients. Methods: We performed a retrospective review of a prospectively maintained database of patients undergoing HoLEP for BPH at a single institution between January 2021 and August 2025. Outcomes included operative characteristics, post-operative complications, and validated symptom score changes. Analyses treated BMI as both a continuous and categorical variable. Multivariable linear and logistic regression models adjusted for common colinear confounders. Results: Among 1445 patients, BMI was not associated with most immediate, three-month, or patient-reported outcomes. Surgical complications were low across all BMI categories, and post-operative reported outcomes indicating high success rate for HoLEP. Higher BMI correlated with a modest increase in enucleation time (β = 0.197; p = 0.0132), increased odds of dysuria (OR = 1.084; p < 0.001), and change in American Urological Association Symptom Score (β = 0.211; p = 0.0334). All other operative metrics, complication rates, continence outcomes, and symptom scores (17 other total) were independent of BMI. Conclusions: After adjustment for relevant confounders, BMI does not meaningfully predict surgical safety, functional recovery, or patient-reported benefit following HoLEP. BMI alone should not influence candidacy or risk stratification for HoLEP in patients with BPH, instead favoring personalized, risk-stratified approaches.

Journal of Personalized Medicine doi: 10.3390/jpm16040224

Authors: Melania Bertolini Lorenzo Fucci Luca Guastini Carlo Conti Gregorio Santori Frank Rikki Mauritz Canevari

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns.

Journal of Personalized Medicine doi: 10.3390/jpm16040223

Authors: Tatsuya Tanaka Eiichi Suehiro Anh Tran Hue Ryosuke Doi Shunsuke Hatakenaka Junpei Kato Tomihiro Wakamiya Kimihiro Nakahara Takashi Agari Masahiro Indo Takashi Sugawara Hiroshi Itokawa Kazuaki Shimoji Keisuke Onoda Akira Matsuno

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding early complications, cerebrospinal fluid overdrainage, and discharge readiness in older adults. This study evaluated the feasibility and short-term safety of a perioperative optimization pathway for planned short-stay hospitalization after LP shunt surgery. Methods: This single-center retrospective before-and-after cohort study included 15 consecutive patients who underwent elective LP shunt surgery. Six patients were managed using a conventional hospitalization pathway, whereas nine patients were treated under a short-stay pathway targeting discharge after one postoperative night. Key perioperative modifications included a uniform higher initial programmable valve pressure (level 7), structured discharge education, scheduled postoperative analgesia, waterproof wound sealing permitting early showering, and early outpatient follow-up with head computed tomography for staged valve pressure adjustment. The primary outcome was 30-day safety, defined as readmission, reoperation, or major postoperative complications. Results: Baseline characteristics were generally comparable between groups, although the short-stay group was slightly older and had more frequent antithrombotic therapy. Mean hospital length of stay was shorter in the short-stay group than in the conventional group (3.7 ± 2.0 vs. 9.7 ± 0.8 days; median, 3 vs. 9.5 days). Orthostatic headache requiring valve adjustment occurred in three conventional cases but in none of the short-stay patients. No patients in the short-stay group required readmission or reoperation within 30 days. Conclusions: In this pilot before-and-after study, a short-stay LP shunt pathway incorporating perioperative optimization and individualized discharge decision-making was feasible and was not associated with an apparent increase in early adverse events. These findings should be interpreted as exploratory and may support further evaluation of short-stay management strategies for selected patients undergoing LP shunt surgery in Japan.

Journal of Personalized Medicine doi: 10.3390/jpm16040222

Authors: Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Octavio Gonzalez-Chon Rebeca Garazi Elguezabal Rodelo Carmelo Calvagna Daniele Paternò Luigi La Via Massimiliano Sorbello

Background: Artificial intelligence (AI) is progressively entering perioperative medicine; however, its role in preoperative anesthetic decision-making remains insufficiently characterized. We evaluated the concordance between anesthesiologist-selected anesthetic techniques and algorithm-generated recommendations in a cohort of adult patients undergoing non-cardiac surgery. Methods: This retrospective observational study included adult patients (≥18 years) undergoing elective non-cardiac surgery between January 2024 and January 2025 at two international centers (Mexico and Italy). Clinical, demographic, and surgical variables were extracted from electronic medical records. For each case, a structured anonymized vignette was submitted to ChatGPT (version 5.0, medical configuration) to obtain an independent recommendation regarding anesthetic technique. Concordance between AI-generated and clinician-selected techniques was assessed using agreement analysis and stratified by country and surgical specialty. Results: A total of 1965 patients were analyzed. Overall concordance between ChatGPT recommendations and anesthesiologist-selected techniques was 84.6%. Agreement remained stable across centers (Mexico 84.3%; Italy 88.7%). Disagreement rates varied by surgical specialty, with the highest values observed in vascular and proctologic surgery (28.6%), followed by urology (21.1%) and thoracic surgery (18.8%). Orthopedic procedures—particularly shoulder arthroscopy—accounted for a relevant proportion of divergences, where AI frequently favored regional techniques over general anesthesia. No specialty demonstrated discordance exceeding 30%. Conclusions: AI-generated anesthetic recommendations demonstrated substantial concordance with expert clinical decision-making across heterogeneous surgical settings. These findings support the potential integration of AI within a hybrid decision-making framework, complementing—rather than replacing—anesthesiologist expertise in contemporary perioperative care.

Journal of Personalized Medicine doi: 10.3390/jpm16040221

Authors: Su-Jun Lee

Inter-individual variability in drug efficacy and toxicity remains a major challenge in modern healthcare, particularly as aging populations are increasingly exposed to polypharmacy and complex treatment regimens [...]

Journal of Personalized Medicine doi: 10.3390/jpm16040220

Authors: Konstantinos Kapriniotis Ioannis Loufopoulos Mohammad U. Sharif Ioannis Manolitsis Lazaros Tzelves Amy Nagle James S. A. Green

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic biomarkers to overcome these limitations. Methods: We carried out a narrative review of the literature searching for research articles on diagnostic and prognostic biomarkers for upper tract urothelial carcinoma (UC) and underlined the limitations of current diagnostic modalities. Results: CT urogram (CTU) is the imaging modality of choice in suspected upper tract UC with sensitivity and specificity exceeding 90% but with limitations in smaller lesions. Urine cytology has an excellent specificity for high-grade UC but is limited by low sensitivity leading to a high number of diagnostic ureteroscopies with significant associated risks. Adjuncts such as Fluorescence In Situ Hybridization (FISH) technology and urine DNA methylation markers have shown promising results but need further validation in large cohorts of upper tract UC. Finally, circulation tumour DNA (ctDNA) is a novel approach with great potential in risk stratification and monitoring of minimal residual disease post radical surgery; however, larger prospective studies are required to validate its role similarly to the recent bladder UC trials. Conclusions: There is an urgent need for non-invasive biomarkers that can reliably replace diagnostic ureteroscopies, identify high-risk/invasive disease and select patients for radical surgery or kidney sparing procedures.

Journal of Personalized Medicine doi: 10.3390/jpm16040219

Authors: Maria Rogalidou Maria-Veatriki Christodoulou Alexandros Skamnelos Dimitrios K. Christodoulou

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD.

Journal of Personalized Medicine doi: 10.3390/jpm16040218

Authors: Mian Urfy Mariam Tariq Mir

Background/Objectives: Stroke generates 157 million disability-adjusted life-years (DALYs) annually, making it the leading neurological cause of global disease burden. Artificial intelligence (AI) and machine learning (ML) have emerged as transformative technologies across the stroke care continuum. This narrative review maps the trajectory of AI in stroke medicine over the decade from 2015 to 2025. Methods: We conducted a narrative review with a structured, pre-specified search strategy across eight pre-specified thematic clusters using PubMed/MEDLINE (January 2015–December 2025), identifying 8549 records and including 1335 studies after screening. Inclusion criteria encompassed primary research articles, systematic reviews, meta-analyses, and RCTs reporting quantitative performance metrics or clinical outcome data for AI/ML in stroke. Results: Stroke imaging AI is the most commercially mature domain, with over 30 FDA-cleared tools. Automated ASPECTS scoring reduced radiologist reading time by 74.8% (AUC 84.97%; 95% CI: 83.1–86.8%). The only triage AI RCT demonstrated an 11.2 min reduction in door-to-groin time without significant improvement in 90-day functional independence (OR 1.3, 95% CI 0.42–4.0). Brain–computer interface rehabilitation showed significant upper limb recovery in a 17-center RCT (FMA-UE mean difference +3.35 points, 95% CI 1.05–5.65; p = 0.0045). AF detection AI is FDA-cleared and RCT-validated. LLMs and federated learning are pre-regulatory but growing exponentially. Conclusions: AI in stroke has achieved diagnostic maturity but therapeutic immaturity. Bridging algorithmic performance to patient outcomes, addressing equity gaps, and building the economic evidence base for scalable deployment are the defining challenges of the next decade.

Journal of Personalized Medicine doi: 10.3390/jpm16040217

Authors: Kenneth P. H. Pritzker Arash Samari

Personalized Medicine has been a central aspiration of medical practice and has guided the direction of medical advances from ancient times to the present. This narrative review highlights some of the most significant past advances and present practices, discusses issues currently limiting Personalized Medicine and proposes activities necessary for Personalized Medicine to have a promising future. Throughout history, Personalized Medicine has developed along with the evolution of science and societal concepts. Notable advances paralleled the growth in what an individual person is and how experimental science can apply to medical practice. In the twentieth century, the study of inborn errors of metabolism and pharmacogenetics broadened the horizons of what Personalized Medicine could be. Presently, Personalized Medicine is challenged by different perspectives on its scope, by the various clinical scientific activities which can inadvertently or by misinterpretation serve to depersonalize medicine, and by the difficulties involved in integrating the massive amount of available scientific data to optimize medical practice centered on the individual. The conditions necessary for Personalized Medicine to have a promising future include developing broader, deeper, and more dynamic knowledge of disease processes, new methods to identify anomalous, singular disease-contributing characteristics in individuals, and improving data quality in research and medical practice. Advancing Personalized Medicine requires developing new perspectives for research, healthcare education, medical practice, and healthcare governance, as well as deploying medical advances at scale across populations.

Journal of Personalized Medicine doi: 10.3390/jpm16040216

Authors: Laura Ambrosi Giorgio Ammerata Maurizio Mastrapasqua Gianmarco Sirago Valentina Cianci Biagio Solarino Alessandro Dell’Erba Davide Ferorelli Michele Simone

Background: Postoperative complications after colorectal cancer surgery imply challenges to patient safety, recovery, and healthcare resources. Clinical Risk Management (CRM) is vital for reducing complications. This study aims to provide a comprehensive overview of short-term outcomes in a high-volume hospital over four years, evaluating the impact of complications through the lens of CRM. Methods: A retrospective cohort study was conducted on 483 patients (332 colon tumors, 151 rectal tumors) who underwent surgical resection. Data were extracted from the internal database, including demographic characteristics, diagnoses, surgical approaches, types of anastomoses, histological grades, and postoperative outcomes. Complications were categorized using the Clavien–Dindo system (grades I–V). Statistical analyses examined the link between clinical variables and complications. Results: Postoperative complications occurred in 44 (9.1%) patients in 483 cases. Among the 44 patients with postoperative complications, the most frequent events were anastomotic leakage (AL) (9/44, 20.5%; 9/483, 1.9% of the total cohort) and postoperative hemorrhage (POH) (8/44, 18.2%; 8/483, 1.7% of the total cohort). Moreover, complications were accompanied by an extended hospital stay and a higher in-hospital mortality (15.9% vs. 0%). The number of recorded postoperative follow-up visits differed significantly across complication severity categories. The overall in-hospital survival rate was 98.6%. Conclusions: The low rates of complications and in-hospital mortality observed in this cohort were documented within a hospital operating under a mandatory institutional CRM framework. However, due to the retrospective single-arm design, these findings should be interpreted as descriptive and hypothesis-generating rather than causal. The Clavien–Dindo system provided a useful tool for grading complication severity and supporting postoperative management. These findings support continued refinement of perioperative care pathways and further comparative studies on CRM implementation.

Journal of Personalized Medicine doi: 10.3390/jpm16040215

Authors: Evgenia Gkintoni Apostolos Vantarakis

Background: Psychoeducational interventions are increasingly implemented to promote psychological and physical health, yet evidence guiding personalized intervention selection remains limited. This systematic review and meta-analysis quantifies the effectiveness of psychoeducational interventions across five settings and identifies empirically derived moderator patterns to inform the selection of tailored interventions. Methods: Systematic searches of PubMed/MEDLINE, PsycINFO, Scopus, Web of Science, ERIC, the Cochrane Library, and Google Scholar were conducted to identify eligible studies published between January 2015 and December 2024. A two-tier analytical approach was employed: a random-effects meta-analysis of k = 53 studies reporting extractable effect-size data, and a direction-of-effect narrative synthesis of all 186 included studies (N = 50,328 verified from 124 studies reporting sample sizes), following SWiM guidelines. Results: The quantitative meta-analysis yielded a significant medium-to-large pooled effect (g = 0.66, 95% CI [0.50, 0.82], p < 0.001) with substantial heterogeneity (I2 = 96.1%). Effects varied across settings: clinical/vulnerable populations showed the largest effect (g = 0.91), followed by university programs (g = 0.62), school-based (g = 0.60), mindfulness/positive psychology (g = 0.55), and community-based (g = 0.49). The broader narrative synthesis confirmed near-universal effectiveness: 131 studies (70.4%) reported significant positive effects, 51 (27.4%) reported mixed results, and none reported null effects—yielding 97.8% favorable outcomes across the full evidence base. Direction-of-effect moderator patterns indicated a stepped severity gradient (indicated 100% favorable, selective 98.6%, universal 95.6%), and that programs exceeding 8 weeks (99.0% vs. 96.6%), theory-based interventions (98.2% vs. 95.2%), and guided digital delivery were consistently associated with the most favorable outcomes. Publication bias assessment confirmed robustness (fail-safe N = 22,942; leave-one-out range: 0.61–0.67). GRADE evidence quality was rated Moderate for four of five research questions. Conclusions: This systematic review and meta-analysis provide converging quantitative and direction-of-effect evidence supporting the effectiveness of psychoeducational interventions. The near-universal favorable direction across 186 studies, combined with a medium-to-large pooled effect in the quantitative subset, provides a preliminary empirical foundation for personalized intervention matching. A preliminary four-phase implementation framework is proposed as a hypothesis-generating heuristic; prospective validation through a meta-analysis of individual participant data is needed before prescriptive application.

Journal of Personalized Medicine doi: 10.3390/jpm16040214

Authors: Pasqualina Maria Picciotti Rolando Rolesi Giorgia Rossi Giuseppe Oliveto Jacopo Galli

Background: In the last few decades, a growing body of evidence has confirmed that vestibular rehabilitation (VR) can improve the symptoms of many unilateral and bilateral vestibular disorders, by facilitating vestibular compensation mechanisms, such as adaptation, substitution, and habituation. However, the usefulness of the vestibular rehabilitation approach in Persistent Postural–Perceptual Dizziness (PPPD) is currently highly debated and unclear. The aim of the present study was to evaluate the efficacy of VR using computerized dynamic posturography in PPPD patients as a single treatment and without other associated psychological or pharmacological therapies. Results were compared with patients with unilateral and bilateral vestibular disfunction, in order to define the role of our rehabilitation model within a framework of personalized therapy for different disorders. Methods: We evaluated 44 patients (23 F, 21 M; ranged from 28 to 82 years; mean age 63.72) affected by unilateral vestibular vestibulopathy (UVP) (n = 19), bilateral vestibular vestibulopathy (BVP) (n = 10) and PPPD (n = 15). For each patient, a comprehensive clinical bedside vestibular assessment was carefully performed by expert clinicians, as well as Bithermal caloric tests with videonystagmography (VNG), Video Head Impulse Test (vHIT) and Computed Dynamic Posturography (CDP). The impact of dizziness on quality of life (QoL) was assessed by the Italian Dizziness Handicap Inventory (DHI). All subjects evaluated in this study underwent five rehabilitative therapy sessions in our centre, once a week for 45 min and exercised daily for 30 min at home. All the exercises progressively became more difficult each week. Results: Our study showed that vestibular rehabilitation improved quality of life and reduced the level of self-perceived handicap in patients affected by unilateral and bilateral vestibular dysfunction, with significant improvement in DHI total score and posturographic parameters. In PPPD patients, rehabilitation did not significantly modify posturographic performances and the improvement in total DHI score did not reach statistical significance, although a significant change was observed in the functional sub-score. Conclusions: Vestibular rehabilitation confirmed its effectiveness in unilateral and bilateral peripheral vestibulopathies. In patients with PPPD, rehabilitation performed with computerized dynamic posturography may reduce subjective handicap and improve some aspects of daily functioning, although the small sample size and the absence of a control group do not allow definitive conclusions about its efficacy.

Journal of Personalized Medicine doi: 10.3390/jpm16040213

Authors: Alan Sinclair Mohammed Al-Banna Roxana Tutunariu Ahmed H. Abdelhafiz

The global population is ageing due to increased life expectancy, and the prevalence of diabetes is proportionally increasing. With advancing age, diabetes in older people is a complex condition due to associated morbidities and geriatric syndromes. As a result, the management of diabetes in old age is challenging. Due to the wide heterogeneity of older people, diabetes management in this age group should be personalised. While strict targets are accepted in fit individuals, relaxed targets should be considered in patients with multiple morbidities and a high risk of hypoglycaemia. The development of frailty changes the metabolic profile of older people, and their insulin resistance and diabetes trajectory, which will have an impact on the choice of glucose-lowering agents and the goals of therapy. For example, intensive therapy, the use of SGLT-2 inhibitors and GLP-1RA, and tight targets should be continued in frail, sarcopenic, obese individuals due to their increased insulin resistance and cardiovascular risk. On the other hand, relaxed targets and deintensification of therapy should be considered in anorexic, malnourished, frail individuals with significant weight loss due to their low insulin resistance, low prevalence of cardiovascular risk factors, and high risk of hypoglycaemia. Annual reviews of older people with diabetes should include screening for frailty, depression and dementia for early diagnosis, and appropriate interventions. The introduction of continuous glucose monitoring is increasingly used in older people with diabetes and has the potential to reduce the incidence of hypoglycaemia. With the expectation of a continued increase in the prevalence of older people with diabetes, the use of mobile health may allow care delivery on a wider scale without the need for face-to-face appointments. In addition, there is a promising scope for artificial intelligence to achieve better diabetes outcomes. Future research is still required to expand the use of these technologies in older age groups.

Journal of Personalized Medicine doi: 10.3390/jpm16040212

Authors: Ilias Chatziioannidis Angeliki Kontou Eleni Agakidou Theodora Stathopoulou Kostantia Tsoni Christos Paschaloudis William Chotas Kosmas Sarafidis

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO2) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO2 in the first 72 h were evaluated. Normocapnia was defined as PCO2 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO2 abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO2 values and greater PCO2 variability, although these were not independent predictors of SBI or death. Conclusions: PCO2 instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD.

Journal of Personalized Medicine doi: 10.3390/jpm16040211

Authors: Maurizio Martiradonna Rossella Mazzilli Virginia Zamponi Daniela Prosperi Massimiliano Mancini Antongiulio Faggiano

Background: Parathyroid lipoadenoma, oncocytic parathyroid adenoma, and water-clear cell parathyroid adenoma (WCCA) are exceptionally rare subtypes of parathyroid adenoma, whose real clinical impact remains unclear. Methods: We performed a literature review and comparison of these uncommon subtypes of parathyroid adenoma, as these lesions may be associated with distinct clinical, pathological and radiological phenotypes. Results: The three groups were comparable in terms of age and gender, mainly affecting middle-aged women. As for the biochemical findings, although PTH level did not show statistically significant differences among the three adenomas, in the two-tail comparison between WCCAs and lipoadenomas, there was a trend towards higher PTH values (p = 0.058). However, serum calcium levels differed significantly, with higher levels in WCCAs than in lipoadenomas (12.1 vs. 11.3 mg/dL; p = 0.002). From a preoperative point of view, ultrasound positivity was significantly higher in WCCAs than in lipoadenomas and oncocytic adenomas (97% vs. 50% vs. 55.3%, p < 0.001), compared to scintigraphy positivity, which was comparable between subtypes and relatively suboptimal (66.7% vs. 64.3% vs. 61.3%; p = 0.825); WCCAs also had an overall more voluminous morphological phenotype. Conclusions: This review, although limited by its reliance primarily on case reports and small case series, confirms that lipoadenoma, oxyphilic adenoma, and WCCAs are rare but clinically relevant subtypes of parathyroid adenoma. These entities may be associated with atypical presentations of primary hyperparathyroidism (including difficult preoperative localization and clinicopathological features raising suspicion of malignancy) and should be recognized as a potential source of diagnostic difficulty. A better understanding of these rare subtypes may improve clinicopathological interpretation, increase awareness of potential diagnostic pitfalls and support a more personalized diagnostic and surgical approach in the future.

Journal of Personalized Medicine doi: 10.3390/jpm16040210

Authors: Heydar Khadem Hoda Nemat Jackie Elliott Mohammed Benaissa

Background/Objectives: Blood glucose prediction (BGP) for individuals with type 1 diabetes (T1D) is a clinically essential yet highly challenging task in time series forecasting (TSF) and an important problem in personalised medicine. Accurate bespoke BGP is crucial for individualised T1D management, reducing complications, and supporting patient-specific glycaemic risk mitigation. However, the pronounced volatility of glycaemic fluctuations in T1D, combined with the need for mathematical rigor and clinical relevance, hampers reliable prediction. This complexity underscores the demand to explore and enhance more advanced techniques. While adversarial learning is adept at modelling intricate data variability, its potential for BGP remains largely untapped. Methods: This work presents a novel approach for BGP by addressing a key limitation in conventional adversarial learning when applied to this task. Typically, these methods optimise prediction accuracy within a set horizon by minimising adversarial loss. This focus overlooks how predictions align with longer-term patterns, which are critical for clinical relevance in BGP, thereby yielding suboptimal results. To overcome this limitation, we introduce collaborative augmented adversarial learning, designed to improve the model’s temporal awareness. Incorporating collaborative interaction optimisation, this approach enables the model to reflect extended time dependencies beyond the immediate horizon, thereby improving both the clinical reliability of predictions and overall predictive performance. We develop and evaluate four learning systems for BGP: independent learning, adversarial learning, collaborative learning, and adversarial collaborative learning. The proposed systems were evaluated for two clinically relevant prediction horizons, namely 30 min and 60 min ahead. Results: The interdependent collaboratively augmented learning frameworks, validated using the well-established Ohio T1D datasets, demonstrate statistically significant superior performance in both clinical and mathematical evaluations. Conclusions: Beyond advancing BGP accuracy and clinical reliability, the proposed approach supports personalised medicine by improving subject-specific glucose forecasting from CGM data, with potential relevance for more individualised diabetes monitoring and decision support. The proposed approach also opens new avenues for advancements in other complex TSF domains, as outlined in our future work.

Journal of Personalized Medicine doi: 10.3390/jpm16040209

Authors: Eleni Kolokotroni Paula Poikonen-Saksela Ruth Pat-Horenczyk Berta Sousa Albino J. Oliveira-Maia Ketti Mazzocco Haridimos Kondylakis Georgios S. Stamatakos

Background/Objectives: Patients with breast cancer show substantial heterogeneity in terms of psychological adjustment following diagnosis. We aimed to characterize longitudinal trajectories of quality of life (QoL) and depressive symptoms during the first 18 months post-diagnosis and to identify robust clinical, psychosocial, and behavioral predictors associated with distinct adjustment pathways. Methods: Women (N = 538; mean age 55.4 years; range 40–70) with operable breast cancer (stages I–III) were drawn from the multicenter BOUNCE cohort. QoL (Global Health Status/QoL scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) and depressive symptoms (depression subscale of the Hospital Anxiety and Depression Scale) were assessed at baseline and months 3, 6, 9, 12, 15 and 18. Latent class growth analysis and growth mixture modeling identified distinct trajectory classes. Associations between early predictors and trajectory membership were examined using logistic regression combined with elastic net regularization. Results: Depression trajectories demonstrated heterogeneity, with groups characterized by persistent resilience (59.7%), stable moderate/high (25.3%), delayed onset (5.0%), and recovery (10.0%). QoL trajectories ranged from stable excellent (13.2%) and stable high (40.7%) to moderate (31.4%) and persistent low/deteriorating (6.9%), as well as a distinct recovering trajectory (7.8%). Trajectory differentiation was primarily driven by psychological resources, symptom burden, functional status, and coping processes, alongside specific contributions from clinical factors. Conclusions: Distinct subgroups of women with breast cancer follow divergent adjustment pathways. These findings highlight the multidimensional nature of resilience and support the need for tailored interventions that promote long-term well-being beyond simple risk reduction.

Journal of Personalized Medicine doi: 10.3390/jpm16040208

Authors: Elvira Immacolata Parrotta Giorgia Lucia Benedetto Giovanni Cuda Umile Giuseppe Longo Arianna Carnevale Olimpio Galasso Giorgio Gasparini Michele Mercurio

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive condition characterized by bone necrosis, impaired vascularization, and immune dysregulation, often resulting in femoral head collapse. Effective strategies to halt disease progression are limited. Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication and influence osteogenesis, angiogenesis, and immune responses. This review summarizes current evidence on EVs in ONFH and their translational potential. Methods: A structured narrative review of PubMed, Scopus, Web of Science, and Cochrane Central databases was conducted, including in vitro, preclinical, and clinical studies on EVs in ONFH. Data on EV sources, molecular cargo, signaling pathways, functional effects, and translational implications were qualitatively synthesized. No pooled statistical analysis was performed because the extracted data were heterogeneous. Bioinformatic analyses such as Gene Ontology, KEGG enrichment, and protein–protein interaction networks were also summarized. Results: In vitro, EVs from bone marrow mesenchymal stem cells, endothelial cells, and M2 macrophages modulate osteogenic differentiation, angiogenesis, and inflammation. Preclinical studies demonstrate that EV administration reduces femoral head necrosis, improves trabecular structure, and enhances neovascularization. Clinical studies have identified EV-associated molecules (SAA1, C4A, RPS8) linked to disease stage and the risk of femoral head collapse. Bioinformatic analyses connect EV cargo to pathways regulating bone formation, vascularization, immunity, and metabolism. Conclusions: EVs appear to play key roles in ONFH pathogenesis and may represent promising candidates for diagnostic and therapeutic applications. However, current clinical evidence remains limited and requires validation in larger studies. Nonetheless, heterogeneity and limited clinical data require standardized, longitudinal studies to validate their translational relevance.

Journal of Personalized Medicine doi: 10.3390/jpm16040207

Authors: Muntaser Omari Mohamed Ali Luke Spray Adam McDiarmid Mohammad Alkhalil

Background: Current guidelines acknowledge that early discharge is not associated with late mortality and that in-hospital length of stay (LOS) of 48–72 h should be considered following successful primary percutaneous coronary intervention (PPCI) in low-risk patients. Recent studies have highlighted the safety of very early discharge after PPCI in highly selected low-risk patients; however, objective tools to guide discharge timing remain limited. The Index of Microcirculatory Resistance (IMR) offers a quantitative assessment of microvascular function and may help identify patients suitable for very early discharge. We aimed to evaluate the feasibility of using IMR to guide very early discharge in patients who underwent uncomplicated PPCI. Study design and objectives: The Safety of Early Discharge Using Index Microcirculatory Resistance in Patients with Acute Myocardial Infarction (SECURE) study is designed to assess the feasibility of using IMR, measured immediately following successful PPCI, to guide early discharge from hospital within 24 h. The SECURE study is a prospective, proof-of-concept, functional non-inferiority, single-centre, randomised, open-label trial to determine if patients with low IMR can be safely discharged when compared to standard discharge policy. The SECURE study will recruit 82 patients with low IMR following successful PPCI. Participants will be 1:1 randomised to either standard discharge timing or very early discharge (within 24 h). The left ventricle ejection fraction will be assessed using cardiac magnetic resonance imaging. A telephone follow-up at 3 months will be arranged. Clinical events are collected as secondary and exploratory safety endpoints. Conclusions: The SECURE study will provide proof-of-concept data about the feasibility of using IMR to guide very early discharge following PPCI. If successful, this study will provide data to plan for a larger study to determine the safety of this personalised approach.

Journal of Personalized Medicine doi: 10.3390/jpm16040206

Authors: Tu-Lan Vu-Han Enikö Regényi Vikram Sunkara Paul Köhli Friederike Schömig Alexander P. Hughes Michael Putzier Matthias Pumberger Thilo Khakzad

Background: ChatGPT is a large language model (LLM) online chatbot developed by OpenAI and launched in November 2022. Early adoption studies have shown high readiness to use this technology for health-related questions and self-diagnosis. However, the quality and clinical adequacy of health-related responses remain incompletely characterized. This study aimed to explore responses generated by ChatGPT-3.5 and ChatGPT-4.0 to common patient questions regarding scoliosis. Methods: Ten scoliosis-related frequently asked questions (FAQs) were selected from a larger pool of over 250 patient-facing questions compiled from 17 publicly available FAQ webpages and informed by a Google Trends analysis. Questions were harmonized, grouped by theme, and then reduced by rule-based expert review to a final set intended to represent common patient concerns. Results: The median ratings of ChatGPT-3.5 and ChatGPT-4.0 responses ranged from satisfactory, requiring minimal (2) to moderate clarification (3). Across the ten matched questions, no statistically detectable difference was found between models in this study setting (W = 8.0, p = 0.59; Cliff’s δ = −0.12 [95% CI −0.58, 0.40]); however, given the small question set, unblinded rating process, and poor inter-rater reliability, this should not be interpreted as evidence of equivalence, non-inferiority, or comparable model performance. The results apply only to the 10–15 April 2024, online snapshots of ChatGPT-3.5 and ChatGPT-4.0 and should not be generalized to later model iterations. Conclusions: This study should be interpreted as a clinically oriented observational report, intended to inform physician awareness and patient-physician communication rather than validate chatbot accuracy or safety. In this 10–15 April 2024, sample, both model outputs frequently required clinician clarification. Given the small FAQ set, low inter-rater reliability, unblinded design, and single-sample outputs, the findings do not establish equivalence or superiority and apply only to the specific 10–15 April 2024, model snapshots and evaluated questions.

Journal of Personalized Medicine doi: 10.3390/jpm16040205

Authors: Tomokazu Omori Akira Saito Yoshihisa Shimada Yujin Kudo Jun Matsubayashi Toshitaka Nagao Masahiko Kuroda Norihiko Ikeda

Background: This study employed artificial intelligence (AI) to analyze quantitative nuclear morphological features obtained from digital pathology images to predict postoperative recurrence in patients with lung squamous cell carcinoma (LSQCC). We aimed to develop a prediction model that contributes to the realization of ‘personalized postoperative management’ tailored to individual tumor biology by integrating AI-extracted morphological features with clinical information. Methods: A total of 185 of the 253 surgically resected LSQCC cases were included; 136 were randomly assigned to the training set and 49 to the test set. Nuclear features from manually selected regions of interest were extracted and used to build AI-based prediction models. Three recurrence models were developed: recurrence within 2 years, within 5 years, and a three-category model (≤2 years, 3–5 years, >5 years or no recurrence). Support vector machine (SVM) and random forest (RF) algorithms were applied to each, yielding six predictive models. An ensemble approach was used to calculate AI-based risk scores, and a “total risk score” was developed by integrating these with the pathologic stage. Results: All six AI models demonstrated stable predictive performance, with AUC values ranging from 0.76 to 0.91. Kaplan–Meier analysis showed that the total risk score provided the most precise risk stratification (p < 0.005), with clearer separation between risk groups than the AI-based risk score alone. Conclusions: The integration of AI-based nuclear morphology analysis and clinical data provides an objective and practical tool for personalized postoperative management in LSQCC. This approach enables tailored clinical decision-making by identifying patients at high risk for early recurrence and customizing postoperative treatment plans to meet the specific needs of each individual.

Journal of Personalized Medicine doi: 10.3390/jpm16040204

Authors: Adam E. Brown Chance W. Marostica Wayne A. Martini

Background/Objectives: Machine learning (ML) models can predict hospital admission from emergency department (ED) triage data with areas under the receiver operating characteristic curve (AUC) exceeding 0.85. Whether incorporating the assigned provider’s identity—as a proxy for unmeasured practice variation—improves prediction has not been systematically studied. We aimed to compare 10 supervised ML classifiers for predicting hospital admission at ED triage, with and without provider identity, and to characterize model reasoning using SHapley Additive exPlanations (SHAP). Methods: We conducted a retrospective cohort study of 186,094 ED visits (2020–2023, training) and 58,151 visits (2024, temporal holdout test) at one academic tertiary-care ED. Ten classifiers spanning linear, distance-based, tree-based, ensemble, probabilistic, and neural network families were each trained in two conditions: baseline (23 triage features) and with provider identity appended. SHAP TreeExplainer was applied to the top-performing models (CatBoost and XGBoost). Results: The admission rate was 31.3% (training) and 31.7% (test). CatBoost achieved the highest baseline AUC of 0.8906 (0.8878–0.8933). Adding provider identity produced negligible AUC changes across all models (ΔAUC range: −0.0029 to +0.0015; all DeLong p > 0.05). SHAP analysis identified ESI level, respiratory rate, temperature, complaint category, and age as the dominant predictors, with clinically intuitive directionality. Conclusions: Provider identity does not meaningfully improve ML prediction of hospital admission beyond standard triage variables. The observed 28-percentage-point variation in provider admission rates is explained by patient case-mix differences than with independent practice pattern effects on prediction. SHAP provides transparent, clinically interpretable explanations suitable for bedside decision support.

Journal of Personalized Medicine doi: 10.3390/jpm16040203

Authors: Konstantinos Vachlas Dimitra Grapsa Stylianos Gaitanakis Anna Papadopoulou Paraskevi Moutsatsou Nikolaos Syrigos Ioannis P. Trontzas

Background: Soluble immune checkpoint molecules, including soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), have emerged as potential minimally invasive biomarkers in non-small cell lung cancer (NSCLC). However, their diagnostic, kinetic, and prognostic significance across different disease settings remains unclear. This prospective study evaluated baseline levels, longitudinal fluctuations, and clinical associations of sPD-1 and sPD-L1 in early- and advanced-stage NSCLC. Methods: Three cohorts were prospectively enrolled: early-stage NSCLC patients undergoing curative surgery (n = 25), advanced-stage NSCLC patients receiving pembrolizumab-based immunotherapy (n = 55), and non-oncological controls (n = 16). Serum sPD-1 and sPD-L1 were measured by ELISA at baseline and at four months post-surgery (early stage) or six months post-treatment (advanced stage). Baseline comparisons, longitudinal changes, correlation with tumor PD-L1 expression (TPS), and associations with recurrence (early stage) or 6-month objective response (advanced stage) were assessed. Results: Baseline sPD-1 and sPD-L1 levels did not differ significantly among controls, early-stage, and advanced-stage cohorts. In early-stage patients, sPD-L1 increased post-operatively (p = 0.006) while sPD-1 decreased (p < 0.001). In advanced-stage disease, sPD-1 declined during immunotherapy (p < 0.001), whereas sPD-L1 remained unchanged (p = 0.37). Baseline levels and continuous percent changes were not predictive of most outcomes. However, a ≥20% postoperative increase in sPD-L1 was strongly associated with recurrence in early-stage NSCLC (OR = 10.29; 95% CI: 1.40–215.20; p = 0.019). No sPD-1/PD-L1 metric predicted response in advanced disease. Baseline sPD-L1 showed no correlation with tumor PD-L1 expression (ρ = −0.09, p = 0.53) in the advanced-stage cohort. Conclusions: sPD-1 and sPD-L1 demonstrate distinct kinetic patterns across NSCLC settings. A postoperative >20% surge in sPD-L1 may identify early-stage patients at elevated risk of recurrence, whereas soluble checkpoints were not predictive of treatment response in advanced disease. These findings support further investigation of soluble checkpoint dynamics as complementary biomarkers in NSCLC management in larger cohorts.

Journal of Personalized Medicine doi: 10.3390/jpm16040202

Authors: Parhesh Kumar Ingharan Siddarthan Catharine Kelsh Keim Daniel K. Cho John E. Rubin Robert S. White Rohan Jotwani

Background/Objectives: Simulation digital twins (DT) models that integrate patient-specific imaging with artificial intelligence (AI)-based segmentation and extended reality (XR) technologies are rapidly increasing in relevance in personalized medicine. While their clinical applications are expanding, their role as reusable educational tools and the technical pipeline utilized for their development remain incompletely characterized. This narrative review examines current approaches to digital twin creation and XR integration, illustrated by a scoliosis-specific proof-of-concept educational case study. Methods: A narrative technical review was conducted by identifying relevant search keywords within the fields of AI-based image segmentation, extended reality in medicine, and medical education based on the authors’ expertise and familiarity with the subject. PubMed, Google Scholar, and Scopus were searched for English-language studies published primarily between 2015 and 2025 addressing patient-specific three-dimensional modeling, AI-driven segmentation, and XR applications in spine, orthopedic, anesthesiology, and interventional care. A de-identified case of scoliosis is used to present a proof-of-concept example of this process of creating a simulated digital twin for the purpose of medical education in a recorded XR format. Results: Prior studies demonstrated benefits of patient-specific 3D models for anatomical understanding and procedural planning, while highlighting limitations in segmentation accuracy and workflow integration. Nevertheless, while DTs have traditionally served clinical roles in surgical planning or pre-procedural rehearsal, their pedagogical potential remains under-explored. In the proof-of-concept case study, AI-assisted segmentation enabled rapid creation of an anatomically detailed scoliosis digital twin that was incorporated into XR and used to produce a reusable, spatially anchored instructional experience focused on neuraxial access. Conclusions: AI-enabled digital twin models integrated with XR represent a promising approach for personalized, anatomy-driven medical education. Further evaluation is needed to assess educational outcomes, scalability, and integration into clinical training workflows.

Journal of Personalized Medicine doi: 10.3390/jpm16040201

Authors: Ricardo Carvalheiro Vera Vaz Ferreira Ana Raquel Santos Isabel Cardoso António Valentim Gonçalves Rita Ilhão Moreira Tiago Pereira da Silva Sílvia Aguiar Rosa Rui Cruz Ferreira

Background: Heart transplantation remains the definitive therapy for selected patients with end-stage heart failure, but outcomes are limited by acute rejection, chronic allograft injury, and cardiac allograft vasculopathy. Endomyocardial biopsy (EMB) remains the reference standard for rejection surveillance but is invasive and imperfectly captures diffuse myocardial injury. Cardiovascular magnetic resonance (CMR) offers noninvasive, multiparametric assessment of graft structure, function, tissue composition, and perfusion. We aimed to review current evidence supporting CMR in post-heart transplant surveillance and to evaluate the performance of serial CMR for acute cellular rejection in a prospective cohort. Methods: We performed a focused narrative review of the literature on CMR for detection of acute rejection, assessment of chronic allograft injury and prognosis, and evaluation of cardiac allograft vasculopathy and microvascular disease. In parallel, we conducted a prospective observational study of adult heart transplant recipients undergoing early post-transplant CMR (CMR1) and follow-up CMR (CMR2) with temporally matched EMB. Multiparametric CMR included cine imaging, native T1 and T2 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Clinically significant acute cellular rejection was defined as ISHLT grade ≥ 2R. Results: Eighteen recipients were included (median 53 days to CMR1 and 192 days to CMR2). Baseline CMR parameters correlated with invasive hemodynamic and biomarkers. Two patients had biopsy-proven ≥2R rejection at follow-up. T2 values at CMR2 were significantly higher in rejection versus non-rejection patients (59.0 ± 1.4 ms vs. 51.1 ± 1.9 ms; p = 0.015), with greater LGE burden in rejection (p = 0.029). In longitudinal analyses, rejection was associated with divergent patterns of cardiac remodelling and tissue characterization, including increases in indexed ventricular volumes and T2 over time, whereas non-rejection patients demonstrated stable ventricular volumes and a decline in T2. Conclusions: Multiparametric CMR, anchored by T2 mapping, provides clinically meaningful, non-invasive information for acute rejection surveillance after heart transplantation and complements EMB within a personalized, risk-adapted follow-up framework. Establishing individualized baseline CMR phenotypes and monitoring longitudinal changes may support more personalized, less invasive graft surveillance strategies. Larger multicentre prospective studies are needed to define standardized implementation pathways.

Journal of Personalized Medicine doi: 10.3390/jpm16040200

Authors: Serena Luponio Bianca Serio Idalucia Ferrara Andrea Gigantiello Anna Maria Della Corte Denise Morini Italia Conversano Francesco Verdesca Francesca Velino Anna Maria Sessa Simona Caruso Rossella Marcucci Martina De Leucio Valentina Giudice Maddalena Langella Carmine Selleri

Background/Objectives: Minimal residual disease (MRD) negativity is associated with improved outcomes in acute myeloid leukemia (AML) patients. In this retrospective observational real-life case series study, we investigated the efficacy and safety of venetoclax dose adjustment in unfit AML patients and the role of WT1 expression levels as a surrogate marker of MRD monitoring. Methods: A total of 24 consecutive unfit AML patients treated with azacytidine and venetoclax were enrolled in this study, and MRD monitoring was performed by flow cytometry as per international guidelines and by WT1 expression levels assessed by RT-qPCR. Dose adjustment of venetoclax was decided based on MRD status and the onset of grade > 2 neutropenia. Results: The overall response rate was 87.5%, and 16 patients achieved a response already at the first re-evaluation (66.7%). No statistically significant differences were observed between patients who received the standard dose and those with venetoclax dose adjustment in terms of overall survival (19.6 months vs. 30.1 months, respectively; p = 0.9428) and progression-free survival (not reached vs. 22.1 months, respectively; p = 0.3865), although a numerical trend toward lower relapse rates was observed in subjects with late (33.3%) or early and late dose reduction (37.5%) compared to those who had dose adjustment only at the first re-evaluation (75%) (p = 0.3014). The toxicity rate was 33.3% in patients who had early and late dose adjustments, which was lower than that observed with early adjustment (58.3%) and than that reported in the VIALE-A study (84%). Conclusions: Reduced-dose venetoclax regimens (from 28 to 21 days per cycle) in unfit AML patients do not affect response rates or survival and are associated with comparable rates of neutropenia and infectious events, supporting flexible dosing strategies based on patient response and side effects. In addition, WT1 expression could serve as a reliable marker for MRD monitoring.

Journal of Personalized Medicine doi: 10.3390/jpm16040199

Authors: Cristina Lanzotti Mariangela Allocca Alessandra Zilli Ferdinando D’Amico Virginia Solitano Sara Massironi Silvio Danese Federica Furfaro

Personalized medicine is increasingly shaping the management of inflammatory bowel disease (IBD), with the goal of tailoring diagnostic and therapeutic strategies to individual patients. Intestinal ultrasound (IUS) has emerged as a pivotal, non-invasive, and repeatable tool for assessing disease activity, treatment response, and complications in both Crohn’s disease and ulcerative colitis. Beyond its role in routine monitoring, IUS enables real-time decision-making and facilitates tight control strategies, aligning with the principles of precision medicine. By combining morphological assessment with advanced techniques, such as contrast-enhanced ultrasound and elastography, IUS offers unique opportunities for risk stratification and individualized treatment planning. Moreover, its accessibility, safety, and patient acceptability make IUS particularly suited for longitudinal follow-up and early detection of therapeutic failure, thereby reducing the need for invasive procedures. This review discusses the integration of IUS into personalized IBD care pathways, highlighting current evidence, clinical applications, and future perspectives.

Journal of Personalized Medicine doi: 10.3390/jpm16040198

Authors: Stavros P. Papadakos Ioannis Katsaros Stamatina Vogli Alexandra Argyrou Ioannis Karniadakis Ioannis A. Ziogas Paraskevas Gkolfakis Stamatios Theocharis Dimitrios Schizas

Backgrounds: Gastric malignancies are exceptionally rare among children and young adults, and their clinicopathological characteristics and outcomes remain poorly defined. This study aimed to evaluate the demographic, clinical, and survival features of gastric cancer in patients aged ≤24 years using population-based data. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016) for individuals ≤ 24 years with primary gastric malignancies. Cox proportional hazards models were used to identify predictors of overall survival (OS). Results: A total of 324 patients were included (mean age: 20 years; 50% female). Adenocarcinoma was the most common histologic subtype (52%), nearly half of which were signet ring cell carcinomas (46%). The majority of patients (59%) were diagnosed at stage IV. Median OS was 18 months, and 5-year OS was 49%. Children and adolescents (≤18 years) had significantly better survival than young adults (median OS: 34 vs. 15 months, p < 0.01). In multivariable analysis, advanced AJCC stage and higher lymph node ratio were independently associated with worse overall survival, while lymphoma histology and radiotherapy were linked to more favourable outcomes. Conclusions: Gastric cancers in patients ≤ 24 years often present at advanced stages and are dominated by aggressive histology. Prognosis is primarily determined by tumour stage, histological subtype, and lymph nodal burden. These population-based risk estimates support risk stratification and prognostic assessment in young patients by highlighting histology- and nodal-burden-driven prognostic strata.

Journal of Personalized Medicine doi: 10.3390/jpm16040197

Authors: Thomas J. Sorenson Carter J. Boyd Rebecca Lisk Nolan S. Karp

Breast-conserving therapy (BCT), consisting of lumpectomy followed by adjuvant radiation, provides oncologic outcomes equivalent to mastectomy for many patients with breast cancer. As survivorship increases, the demand for aesthetic restoration after BCT has grown; however, reconstructive strategies in this setting remain less standardized than those following mastectomy. Reconstruction after BCT presents distinct challenges due to partial tissue loss, nonuniform radiation injury, progressive fibrosis, and wide variability in patient expectations and tolerance for revision surgery. Consequently, mastectomy-based reconstructive algorithms are often insufficient for guiding care in this population. This review synthesizes contemporary reconstructive options following BCT through a personalized medicine framework, emphasizing patient-specific risk factors that influence technique selection, timing, and long-term outcomes. Key determinants include radiation exposure, breast morphology, comorbid conditions, prior breast surgery, and psychosocial preferences. Oncoplastic volume displacement, implant-based augmentation, fat grafting, and autologous reconstruction each demonstrate distinct risk profiles in the post-BCT tissue environment and require individualized application. Timing of reconstruction and willingness to undergo staged procedures play a central role in outcome durability and patient satisfaction. Across reconstructive strategies, revision burden emerges as a clinically meaningful, patient-centered outcome that is not adequately captured by traditional short-term complication metrics. A risk-informed approach that integrates individualized risk assessment with transparent counseling and shared decision-making may improve alignment between reconstructive planning and patient goals. Personalized reconstruction after BCT requires moving beyond technique-driven paradigms toward flexible, longitudinal care pathways. Future efforts should focus on developing BCT-specific predictive models and incorporating patient-reported outcomes to advance personalized reconstructive care.

Journal of Personalized Medicine doi: 10.3390/jpm16040196

Authors: Fotios Koliofotis Natalia Katrachoura Niki Papapostolou Styliani Taka Maria Martinou Anthi Bouchla Sotirios G. Papageorgiou Michael Makris

Background/Objectives: Hereditary alpha-tryptasemia (HαT) is increasingly recognized as a genetic modifier of mast cell-mediated disease severity and has been associated with heightened mediator-related symptoms and an elevated risk of anaphylaxis. This study aimed to describe the clinical characteristics, multisystem manifestations, and treatment responses of eight patients with HαT and concomitant mast cell disorders. Methods: In this single-center retrospective study, eight adults with confirmed TPSAB1 copy number gain and a diagnosis of systemic mastocytosis (SM), cutaneous mastocytosis (CM), or mast cell activation syndrome (MCAS) were evaluated. Baseline assessments included demographics, clinical history, basal serum tryptase (BST), TPSAB1 genotyping, KIT D816V testing, and bone marrow examination when indicated. Symptom burden was quantified at baseline and week 8 using the Mastocytosis Activity Score (MAS). All patients received mediator-targeted therapy; omalizumab was administered in selected high-risk cases. Results: Eight patients (62.5% male, mean age 53.9 ± 12.0 years) carried TPSAB1 duplication. The median BST was 16.2 ng/mL (range, 14.3–51.2). Severe anaphylaxis occurred in 75% of patients, predominantly drug-induced, while Hymenoptera venom triggered the remaining cases. Gastroesophageal reflux (87.5%), cutaneous symptoms (62.5%), neuropsychiatric features (62.5%), and autonomic dysfunction (37.5%) were common. The mean MAS decreased significantly from 27.25 ± 7.40 to 18.25 ± 6.48 after 8 weeks of high-dose antihistamines, with omalizumab providing marked additional benefit in selected patients. Conclusions: In this cohort, patients with HαT and coexisting mast cell disorders exhibited a high burden of mediator-related symptoms and a notable frequency of anaphylaxis. TPSAB1 genotyping may provide additional genetic information that aids in contextualizing clinical heterogeneity and mediator-related symptom burden in patients with mast cell disorders. Incorporation of HαT testing into routine evaluation may optimize individualized management.

Journal of Personalized Medicine doi: 10.3390/jpm16040195

Authors: Ashish Sharma Harendra Kumar Ruchir Paladiya Rajvardhan Sisodia Hareesha Rishab Bharadwaj Islam Mohamed Saqr Alsakarneh Umar Hayat Sneh Sonaiya Hema Sameera Pinnam Hassam Ali Dushyant Singh Dahiya

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring.

Journal of Personalized Medicine doi: 10.3390/jpm16040190

Authors: Pier Alberto Testoni Sabrina Gloria Giulia Testoni

Transoral endoscopic therapies in gastro-esophageal reflux disease (GERD) are increasingly performed in patients who do not respond to medical therapy or are not suitable for or willing to undergo long-term PPI therapy or surgery. Currently available effective techniques include reconstruction of the gastro-esophageal valve by transoral incisionless fundoplication (TIF) and tightening of the gastro-esophageal junction through scarring, obtained by mucosal resection or ablation. TIF may be accomplished by an EsophyX 2.0/Z, MUSE, or GERD-X device. An iatrogenic stricture of the cardia may be obtained using a procedure called anti-reflux mucosectomy (ARMS), which includes several technical variants, or through mucosal ablation (ARMA). TIF using EsophyX 2.0 has strong evidence of efficacy in patients with small hiatal hernias, irrespective of hernia reducibility, who experience high-volume reflux episodes and troublesome regurgitation despite PPI therapy. MUSE can be performed only in the presence of a spontaneously reducing hiatal hernia and is probably more effective than EsophyX in maintaining the reduced hernia over time. However, MUSE is no longer available in Western countries. GERD-X shows promising results but needs further confirmation of its efficacy over the long term. ARMS and ARMA are not indicated in the presence of hiatal hernias but have shown promising results in the short term and are less expensive than TIF. Appropriate patient selection and the possibility of proposing a tailored approach to different types of patients and clinical/anatomical conditions result in favorable outcomes in most GERD patients, especially considering their quality of life and independence from PPIs. In the last several years, transoral endoscopic therapies have been proposed, along with concomitant laparoscopic repair for large hiatal hernias (cTIF), for GERD occurring after esophageal peroral endoscopic myotomy (E-POEM), in obese patients before or after bariatric surgery, and in patients with Barrett’s esophagus.

Journal of Personalized Medicine doi: 10.3390/jpm16040194

Authors: Zade Pederson Hugo Giambini

Background/Objectives: Type II superior labrum anterior–posterior (SLAP) lesions of the long head of the biceps (LHB) tendon are associated with excessive tendon loading and are commonly treated surgically using SLAP repair, tenotomy, or tenodesis. These procedures alter musculotendinous length and loading and may affect functional outcomes, including forearm supination strength. Appropriate restoration of tendon tension is critical for favorable muscle adaptation and recovery. Shear wave elastography (SWE) is a non-invasive imaging technique capable of quantifying tissue stiffness as a surrogate for in vivo musculotendinous tension. This study aimed to characterize LHB tendon tension across forearm positions and loading conditions to improve the understanding of functional tendon loading relevant to postoperative activation and rehabilitation. Methods: In this controlled laboratory study, thirteen healthy female volunteers without shoulder pathology were assessed using SWE with the elbow positioned at 90° flexion. LHB tendon tension was measured in forearm pronation and supination under passive, active (unresisted), and weighted conditions. Paired t-tests were used to compare forearm positions within each loading condition. Results: LHB tendon tension was significantly greater during active and weighted conditions compared with passive loading in the pronated position (p < 0.05). During active contraction, tendon tension was significantly lower in supination than pronation (p < 0.05), whereas no positional differences were observed under passive or weighted conditions. Relative to passive loading, tendon tension increased by approximately 18.2% and 89.2% in supination, and 67.0% and 97.9% in pronation during active and weighted conditions, respectively. Conclusions: Forearm position selectively influences LHB tendon tension during active, unresisted contraction. Forearm orientation affected LHB tendon stiffness primarily during active, unweighted contraction, where pronation resulted in higher stiffness than supination. On the other hand, stiffness outcomes measured during passive and weighted positions were comparable between forearm orientations, indicating that positional effects are most evident when tendon loading is primarily muscle-driven. These findings highlight the relevance of forearm positioning during early postoperative activation and provide normative in vivo reference data to inform personalized rehabilitation strategies and future investigations of postoperative tendon loading following SLAP lesion treatment.

Journal of Personalized Medicine doi: 10.3390/jpm16040193

Authors: Yan Sun Donovan Veccia Gengqing Song Nisheet Waghray

Background/Objectives: Proton pump inhibitors (PPIs) are known to alter gut microbiota composition; however, their association with disease courses and outcomes in patients with inflammatory bowel disease (IBD) remains uncertain. Our aims were to evaluate the association between PPI use and treatment escalation, Clostridioides difficile infection, and healthcare utilization in IBD. Methods: We conducted a retrospective cohort study on the TriNetX platform. IBD patients with PPIs or histamine-2 receptor antagonists (H2RAs) were matched one-to-one using propensity scores. Outcomes included initiation of corticosteroids, biologic therapy, Clostridioides difficile (C. difficile) infection, and healthcare utilization. Outcomes were assessed during the 0–12-month and 3–12-month follow-up windows. Associations were estimated using odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals. Results: After matching, 12,808 patients were included in each group. During 0–12 months of follow-up, PPI use was associated with higher odds of systemic corticosteroid exposure (OR 1.56, 1.35–1.79), biologic therapy initiation (OR 1.99, 1.72–2.29), C difficile infection (OR 1.42, 1.18–1.70), and healthcare utilization (OR 1.18, 1.03–1.36) compared with H2RA use. Time-to-event analyses showed persistent associations with systemic corticosteroid exposure (HR 1.50, 1.31–1.72) and biologic therapy initiation (HR 1.91, 1.66–2.19), with attenuation of associations for infection and healthcare utilization in 3–12-month lag-time analyses. Similar patterns were observed in ulcerative colitis and Crohn’s disease subgroups. Conclusions: PPI was associated with higher risks of treatment escalation and C. difficile compared with H2RA in IBD. These findings highlight the importance of individualized selection and periodic reassessment of acid suppression therapy as part of personalized management strategies in IBD.

Journal of Personalized Medicine doi: 10.3390/jpm16040192

Authors: Stanislovas S. Jankauskas Fahimeh Varzideh Urna Kansakar Gaetano Santulli

Artificial intelligence (AI) is rapidly reshaping cardiovascular (CV) medicine, driving a paradigm shift toward truly personalized and data-driven care. This comprehensive review examines the conceptual foundations, clinical applications, and future implications of AI across the CV continuum, spanning prevention, diagnosis, risk stratification, and therapy. Core AI methodologies (including machine learning, deep learning, natural language processing, and computer vision) are discussed in the context of cardiology’s uniquely data-rich environment, encompassing imaging, electrocardiography, electronic health records, wearable devices, and multi-omics data. This systematic review highlights major clinical domains where AI has demonstrated a substantial impact, including CV imaging, ECG interpretation, hypertension and heart failure management, coronary artery disease, acute coronary syndromes, interventional cardiology, and cardiac surgery. AI-driven predictive analytics enable early detection of subclinical disease, improved prognostication, and individualized prevention strategies, while wearable technologies and remote monitoring platforms facilitate continuous, real-world patient surveillance. Emerging applications in pharmacotherapy, drug repurposing, and genomics further reinforce AI’s role in advancing precision cardiology. Equally emphasized are the ethical, legal, and social challenges accompanying AI adoption, such as algorithmic bias, data privacy, cybersecurity, interpretability, and regulatory oversight. Our review underscores the necessity of rigorous clinical validation, transparent model design, and seamless integration into clinical workflows to ensure safety, equity, and physician trust. Ultimately, AI is best positioned as an augmentative tool that complements (but does not replace!) clinical expertise. By fostering hybrid intelligence that integrates human judgment with computational power, AI has the potential to redefine CV care delivery, improve outcomes, and support a more proactive, patient-centered healthcare model.

Journal of Personalized Medicine doi: 10.3390/jpm16040191

Authors: Krister Mogianos Anna K. M. Persson

Acute postoperative pain remains a major clinical challenge, affecting both recovery and resource utilisation. Beyond nociceptive input, pain is shaped by cognitive and emotional factors, including patient expectations. This narrative review examines the role of expectations in perioperative pain modulation, framed within predictive coding and Bayesian inference models. These models conceptualise pain as a probabilistic process that integrates sensory input with prior expectations, weighted by precision. In theory, positive expectations may enhance analgesic efficacy, whereas negative expectations may amplify pain via nocebo mechanisms. Control modifies expectations and may reduce perceived pain, while uncertainty diminishes these benefits. Evidence from observational studies links preoperative pain self-efficacy and anticipated pain scores to postoperative outcomes, yet interventional trials remain scarce. In this narrative review, we propose that expectation-sensitive strategies, including structured communication and computational modelling, may inform individualised anaesthesia and analgesia. Future research should validate these frameworks in clinical trials, optimise preoperative expectation management, and explore synergistic approaches that combine pharmacology with cognitive modulation. Understanding and leveraging expectations may offer a promising conceptual direction for more individualised perioperative care, although this approach remains hypothesis-generating at present.

Journal of Personalized Medicine doi: 10.3390/jpm16040189

Authors: Maria Puntarello Giuseppe Davide Albano Stefania Zerbo Ginevra Malta Antonina Argo

Background: Biological sex contributes to variability in drug metabolism, receptor sensitivity, and susceptibility to adverse drug reactions (ADRs). Despite this, dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) are still largely sex-neutral. This systematic review examines sex-related differences in pharmacokinetics (PK), pharmacodynamics (PD), and safety outcomes, with the aim of clarifying their potential implications for personalized psychopharmacology. Methods: A systematic search of PubMed was conducted for studies published between January 2010 and March 2026. The strategy combined MeSH terms and free-text keywords related to SSRIs, SGAs, sex differences, pharmacokinetics, pharmacodynamics, and ADRs. Two independent reviewers performed study selection and data extraction. Studies reporting sex-stratified PK, PD, or safety outcomes in humans were included. Owing to methodological heterogeneity, results were synthesized narratively. Results: Twenty-seven studies met the inclusion criteria. Overall, the evidence indicates clinically meaningful sex-related differences in psychotropic drug exposure and response. Women more frequently exhibited higher dose-adjusted serum concentrations, particularly for risperidone and some SSRIs, with age-related increases more evident in females. Pharmacodynamic findings suggest that women may reach comparable dopamine D2 receptor occupancy at lower olanzapine doses. Pharmacovigilance analyses revealed sex-specific adverse event patterns, including greater reporting of endocrine-related effects and QT prolongation in women. Conclusions: Sex influences psychotropic drug exposure, pharmacodynamic sensitivity, and safety profiles in ways that may be clinically relevant. Integrating sex-aware considerations into dosing strategies could improve therapeutic precision and reduce adverse outcomes, reinforcing the importance of sex as a key variable in personalized psychiatric care.

Journal of Personalized Medicine doi: 10.3390/jpm16040188

Authors: Bianca Kruger Emile R. Chimusa Aron B. Abera Jesmika Singh Delva Shamley Collet Dandara

Background: Tamoxifen is widely used in the treatment of hormone receptor-positive breast cancer and has been shown to successfully reduce recurrence and mortality rates. Nonetheless, variability in patient response to tamoxifen treatment is observed with up to 40% of patients experiencing recurrence. Genetic polymorphisms in pharmacogenes encoding enzymes involved in tamoxifen metabolism have been linked to some of this observed interindividual variability. The pharmacogenetics of tamoxifen in populations of African descent remain understudied, creating difficulties in pinpointing the primary factors behind the observed variable response. To address this gap, this study aimed to investigate the role of genetic variation in tamoxifen treatment outcomes in a South African cohort. Methods: Participants included 166 Mixed and African Ancestry breast cancer patients who had received tamoxifen treatment. Genetic characterization was performed for 53 single nucleotide polymorphisms (SNPs) and two copy number variations across eight drug-metabolizing enzymes, including cytochrome P450s (CYP2D6, CYP3A4, CYP3A5, CYP2B6), UDP-glucuronosyltransferases (UGT1A4), and sulfotransferases (SULT1A1, SULT1E1, SULT2A1). The association between genotypes and disease-free survival (DFS) was evaluated using Cox proportional hazards regression models. Results: The CYP2B6*1/*6 or *4/*9 genotype showed a nominal association with improved DFS (p = 0.049), with a similar trend observed for UGT1A4 rs11888492. In contrast, SULT1E1 rs3775779 heterozygosity showed a nominal association with reduced DFS (p = 0.044). SULT1A1 SNPs (rs4149393, rs4149394, rs1042157) demonstrated trends toward reduced DFS. Conclusions: These exploratory findings highlight the need for more inclusive pharmacogenomic research and point to potential biomarkers for optimizing tamoxifen therapy in African populations.

Journal of Personalized Medicine doi: 10.3390/jpm16040187

Authors: Danijel Jurković Stjepan Ivandić Tomislav Čengić Stipe Ćorluka

Osteochondral allograft transplantation is a safe and effective surgical option for the treatment of large, focal, full-thickness chondral and osteochondral defects, particularly in young patients. We describe a low-cost new hybrid workstation for osteochondral allograft transplantation based on modified Ilizarov components and its clinical application in a patient with a large osteochondral femoral defect. The technique was applied in a 28-year-old male with chronic knee pain following two prior failed arthroscopic surgeries. Osteochondral allograft transplantation was performed using our modified workstation instrumentation. At the 8-month follow-up, MRI revealed excellent incorporation of the graft, and the patient reported ambulation without pain with return to physical activity. Our hybrid workstation presents a cost-effective alternative for graft preparation while maintaining a high standard of surgical care.

Journal of Personalized Medicine doi: 10.3390/jpm16040186

Authors: Silvia Cavalli Maria Rosa Pellico Giorgia Trignani Manuel Sette Claudia Iannone Roberto Caporali Nicoletta Del Papa

Objectives: To describe the efficacy and safety of tocilizumab (TCZ) and rituximab (RTX) in real-world patients with systemic sclerosis (SSc), across different clinical phenotypes and lines of therapy, evaluating both global clinical outcomes and lung function. Methods: SSc patients treated with TCZ (n = 27) or RTX (n = 23) were retrospectively followed for 12–24 months. Clinical measures, including modified Rodnan Skin Score (mRSS), C-reactive protein (CRP), and revised EUSTAR activity index 2017 (RAI), as well as spirometric parameters, were recorded at baseline and 6, 12, and 24 months. Statistical methods for repeated measures were applied to investigate outcome trends. Given the baseline differences, between-group comparisons were considered exploratory. Results: RTX was used earlier in disease course, while TCZ was mainly used as a rescue therapy. In both groups, mRSS, CRP levels and RAI significantly decreased over time. RTX-treated patients showed a greater absolute mRSS improvement, in line with higher baseline skin scores. No treatment discontinuations due to adverse events occurred in either group; one death and one discontinuation due to inefficacy were observed in the TCZ group. Among SSc-ILD patients, FVC% showed a modest decline in both groups, while DLCO% remained overall stable, and only a few patients met the OMERACT criteria for functional progression. Conclusions: In this real-world, single-center cohort of SSc patients, both agents were associated with a positive impact on disease activity, with a low rate of lung progression and with favorable safety profiles. Owing to substantial baseline imbalances and confounding by indication, between-group comparisons do not allow firm conclusions on comparative effectiveness. Overall, these data support the use of both agents in different clinical scenarios.

Journal of Personalized Medicine doi: 10.3390/jpm16040185

Authors: Ángel Pérez-Sempere Elena García-Arcelay Jacobo Caruncho Pérez Antonio Candeliere-Merlicco Aida Orviz Jesús Martín-Martínez Raquel Piñar-Morales Elena Álvarez-Rodríguez Eva M. Pacheco-Cortegana Laura Borrega Ignacio Casanova Ana Belén Caminero José Luis Sánchez-Menoyo Montserrat Gómez-Gutiérrez Olga Carmona Carmen Calles Miguel Ángel Hernández Pablo López-Muñoz Fabien Bakdache Enric Monreal Inés González-Suárez Jorge Maurino

Background: Serum neurofilament light chain (sNfL) is an established biomarker of neuroaxonal damage in multiple sclerosis (MS). Despite its prognostic utility, patient awareness of its clinical application remains poorly characterized. The objective of this study was to assess the acceptance of sNfL monitoring among patients with early-stage relapsing–remitting MS (RRMS) and identify factors predicting their willingness to adopt this tool. Methods: This non-interventional, cross-sectional study was conducted across 16 neuroimmunology clinics. We included RRMS patients with a disease duration of ≤3 years receiving disease-modifying therapy. Acceptance was assessed following a standardized educational tutorial. Multivariable logistic regression was employed to identify predictors of patient acceptance. Results: The study included 144 patients (mean age 37.6 [SD 10.3] years, 69.4% female). Only 19.4% (n = 28) had prior awareness of sNfL. However, after the tutorial, 84.0% (n = 121) expressed willingness to adopt sNfL testing. Furthermore, 62.5% (n = 90) indicated that normal sNfL levels would provide emotional reassurance between clinical visits. Patients willing to undergo testing showed higher disease knowledge, less treatment regret, and better physical quality of life and cognitive performance. In the multivariable analysis, higher disease knowledge (OR = 1.52, 95%CI 1.16–1.99; p = 0.002) and lower symptom burden (OR = 0.96, 95%CI 0.93–0.99; p = 0.038) were associated with greater acceptance. Conclusions: Patients demonstrate high receptivity to sNfL monitoring when provided with adequate clinical context. Because disease knowledge is a primary driver of acceptance, personalized educational initiatives may be a complementary strategy to facilitate the integration of precision biomarkers into MS management.

Journal of Personalized Medicine doi: 10.3390/jpm16040184

Authors: Tatiana Chavez-Arias Cecilia Manrique-Sam Yuma Ita-Balta Edgar Montánchez-Carazas Alexis Germán Murillo Carrasco Miguel Farfán-Delgado

Tuberculosis (TB) remains a major public health challenge in Peru, where interindividual variability in treatment response and drug-induced hepatotoxicity may be influenced by host genetic background. This study aimed to characterize clinically relevant polymorphisms in NAT2, CYP2E1, and SLCO1B1 in a cohort of TB patients from Southern Peru, a genetically underrepresented Andean population. Thirty-five adults receiving first-line therapy (isoniazid and rifampicin) underwent targeted Sanger sequencing of key functional variants among these three genes. NAT2 acetylator phenotypes were predominantly intermediate (68.6%), followed by rapid (20%) and slow (11.4%) profiles, with high minor allele frequencies for rs1041983 and rs1801280. CYP2E1 functional promoter variants were infrequent, whereas SLCO1B1 exhibited notable allelic heterogeneity, suggesting potential variability in rifampicin transport. Comparative analysis with previously reported Peruvian data revealed regional differences in acetylator distribution, supporting population-specific pharmacogenomic stratification. Although clinical toxicity outcomes were not evaluated, the high prevalence of reduced acetylation genotypes suggests a substantial proportion of patients may benefit from genotype-informed isoniazid dosing strategies. These findings provide foundational data for implementing precision medicine approaches using affordable and targeted technologies in TB management within Andean populations and support the integration of pharmacogenomics into national TB control programs.

Journal of Personalized Medicine doi: 10.3390/jpm16040183

Authors: Pálma Porrogi

Traditional one size fits all pharmacotherapy often yields suboptimal clinical outcomes, preventable adverse drug reactions (ADRs), and significant drug waste, imposing substantial economic and ecological burdens on healthcare systems. This review evaluates the transformative potential of pharmacogenomics (PGx) testing, particularly cytochrome P450 (CYP) gene variants, as a foundation for an ecosystem-centric accountability framework for green pharmacy and links human metabolic variability to specific environmental outcomes. Personalized CYP profiling is shown to minimize the environmental release of unused drugs and potentially ecotoxic metabolites into aquatic ecosystems, in contrast to standard uniform drug use approaches. The limitations of ethnicity-based dosing models, which rely on population genetic variation, are examined in the context of increasing global genetic admixture. It is argued that individual genetic profiling, conceptualized as a PGx-Green Passport, provides a reliable safety standard that accounts for individual differences, thereby enhancing efficiency and well-being in a globalized society. By integrating clinical data, including real-world evidence on hospital utilization, with sustainability frameworks, this review demonstrates that PGx-guided therapy is not only a tool for clinical efficiency but also a fundamental requirement for systematically achieving environmentally sustainable healthcare.

Journal of Personalized Medicine doi: 10.3390/jpm16040182

Authors: Kannayiram Alagiakrishnan Tyler Halverson Desiree Virginia Fermin Olivares Cheryl A. Sadowski

When using traditional approaches, such as pharmacokinetics and pharmacodynamics, the entire cellular or molecular response to drugs in the body cannot be fully ascertained or established. The oral medication process involves pharmacokinetics, followed by oral microbiomics and then gut microbiomics and pharmacodynamics. Recently, there has been increasing interest in the role of genetics (pharmacogenetics and pharmacogenomics) in both humans and microbiomes, as well as omics alterations (e.g., epigenetic, transcriptomic, proteomic, and metabolomic alterations as a consequence of drug exposure), which can help to ascertain the cellular responses to medications. Both the efficacy and toxicity of a drug are influenced by these factors. To assess these at an individual level, an integrative Personalized Medicine Model may be needed to help with medication management. Two example application cases for SSRIs and statins demonstrate the clinical usefulness of such a model, which can guide clinicians during drug selection and dosing to reduce reliance on trial-and-error, thus potentially improving patient outcomes and safety. Integrating this framework into practical clinical workflows requires the capture, analysis, and translation of multi-omics data in order to realize decision support protocols and actionable drug recommendations. This review also discusses IT requirements and different stakeholder roles. Although the proposed model can guide the treatment of diseases at the individual patient level, further research is still needed before it can be implemented as part of drug development research, clinical care, and healthcare delivery systems.

Journal of Personalized Medicine doi: 10.3390/jpm16040181

Authors: Giulia Gentile Giovanna Morello Valentina La Cognata Maria Guarnaccia Sebastiano Cavallaro

To better understand the complexity of biological systems, research has shifted from a reductionist to a holistic approach, expanding the focus from single genes to a genome-scale view of gene activity and regulation. This is known as transcriptomics, a continuously growing field generating gene expression signatures from different technologies. A comparable paradigm shift has occurred in computational systems biology with the implementation of Artificial Intelligence (AI) learning models for gene expression analysis and integration. These models enable transcriptome-based profiling to address challenges of data heterogeneity, integration, and updating, assisting human intelligence and enhancing their ability to retrieve, analyze, integrate, and generate data recursively, thanks to their intrinsic predictive, inferential, reinforcement, and generative capabilities. Additionally, while scientists worldwide are still learning how to leverage AI methods that can maintain the human-in-the-loop, a new fundamental change is emerging: agentic AI, which can autonomously act and employ other AI methods to pursue its objectives. As a futuristic perspective, the proposed data analysis pipeline imagines agentic AI systems allowing the automated retrieval and pre-processing of heterogeneous transcriptomics data, analysis and integration with other omics datasets, performed with an incremental updating and recurrent analysis (IURA) model that could allow the detection of guideline updates (e.g., disease reclassification) and the generation of new hypotheses, such as candidate biomarkers or transcriptome–phenotype correlations. Since personalized medicine could derive profound benefits from its use, this scenario also raises important considerations regarding the advantages and concerns associated with the use of scientific AI agents in research and clinical practice.

Journal of Personalized Medicine doi: 10.3390/jpm16040180

Authors: Angela Bertolini Marisa Gorrese Serena Luponio Francesca Picone Annapaola Campana Francesco Verdesca Francesca Velino Anna Maria Sessa Simona Caruso Martina De Leucio Rossella Marcucci Anna Maria Della Corte Pasqualina Scala Maddalena Langella Bianca Serio Carmine Selleri Valentina Giudice

Background/Objectives: Clonal evolution is mainly defined based on the appearance or expansion of clones harboring specific somatic mutations and/or cytogenetic abnormalities, whereas few studies have investigated immunophenotypic heterogeneity assessed by flow cytometry and its relationship with disease progression. In this study, flow cytometry immunophenotyping of acute myeloid leukemia (AML) was carried out to identify phenotypic subclones based on antigen expression and to investigate clonal sweep. Methods: A total of 24 patients diagnosed with AML followed at the Hematology and Transplant Center of Salerno were included. Bone marrow or peripheral blood specimens were subjected to flow cytometry immunophenotyping and leukemic cell characterization. Phenotypic profiles were also compared to molecular alterations detected by next-generation sequencing. Results: We found that flow cytometry-defined clonal heterogeneity was more complex than molecular heterogeneity at diagnosis and disease relapse. Flow cytometry enabled the identification of small phenotypic subclones that were not detected by molecular profiling and that, in several cases, expanded over time, consistent with a phenotypic clonal sweep. The presence of small clones was associated with shorter progression-free survival and overall survival. Conclusions: Flow cytometric clonal heterogeneity, especially the presence of small clones (defined by antigen expression from 2 to 30%), may serve as an additional prognostic factor in AML. Immunophenotyping integrated with molecular data may improve risk stratification, enhance measurable residual disease assessment, and contribute to a more personalized disease monitoring strategy.

Journal of Personalized Medicine doi: 10.3390/jpm16040179

Authors: Ahmed I. Alrefaey Elena V. Vorobeva Jamil Jubrail Ibemusu Michael Otele Mikaela Lee Tilman Sanchez-Elsner Syed Hasan Arshad Ramesh J. Kurukulaaratchy Mohammed Aref Kyyaly

Background: MicroRNAs (miRNAs) are stable, small non-coding RNAs involved in asthma-related pathways and are promising diagnostic biomarkers and therapeutic targets in childhood asthma. Objective: To identify miRNAs differentially expressed in preschool wheezing and childhood asthma, evaluate their association with asthma diagnosis and severity-related phenotypes, and explore their potential translational relevance through exploratory bioinformatic analyses. Methods: A systematic search of Medline, Embase, SCOPUS, PubMed, CINAHL, and Web of Science was conducted for English-language articles published up to March 19, 2025. Eligible human studies reported that miRNAs were differentially expressed in children with wheeze or asthma versus healthy controls (p < 0.05, fold change ≥ 1.5). Bioinformatic analysis identified hub genes, constructed protein–protein interaction networks, and predicted drug–gene interactions. Results: Forty-seven studies met the inclusion criteria, yielding 58 differentially expressed miRNAs (31 up, 27 down). Recurrently reported miRNAs included miR-497, let-7e, miR-98, miR-21, miR-126a, miR-196a2, miR-1, miR-146a-5p, miR-210-3p, miR-145-5p, and miR-200c-3p across blood, nasal swabs, BALF, and exhaled breath condensate. miR-26a showed strong diagnostic performance (sensitivity 83%, specificity 93%; p < 0.002, 95% CI 0.831–0.987). Functional enrichment implicated 56 differentially expressed genes in metabolic and immune processes. Ten hub genes (including TNF, IL5, IL13, TLR4) were linked to 339 potential therapeutic agents; the exploratory network analysis highlighted overlap between predicted miRNA-regulated hub genes and existing asthma-relevant drug targets, including approved biologics. Conclusions: Our review findings suggest that several miRNAs are promising candidate biomarkers for childhood asthma phenotyping and severity assessment; however, their diagnostic utility remains exploratory and requires rigorous external validation and standardisation before clinical application.

Journal of Personalized Medicine doi: 10.3390/jpm16040178

Authors: Giovanni Camardese Marco Maria Pascale Antonio Maria D’Onofrio Rosaria Calia Michele Ribolsi Alexia Koukopoulos Federico Fiori Nastro Gaspare Filippo Ferrajoli Elisa Schirra Eleonora Maggio Gabriele Sani Gianluca Costa

Background and Objectives: Psychological resilience is increasingly recognized as a determinant of how patients respond to surgical stress, yet its role in perioperative medicine remains poorly defined. This narrative review aims to synthesize current evidence on resilience in surgical populations from a psychobiological perspective, spanning conceptual models, measurement approaches, clinical correlates, biological mechanisms, and intervention strategies. Materials and Methods: This narrative review was conducted to examine psychological resilience in adult surgical populations from an integrated psychobiological and perioperative perspective. A structured literature search was performed in December 2026 using PubMed, Scopus, and PsycInfo, combining resilience-related constructs with surgical, perioperative, biological, and clinical outcome keywords. Eligible publications included observational, longitudinal, interventional, translational, and conceptually relevant studies addressing resilience in adult surgical settings. Evidence was synthesized qualitatively across predefined domains, including conceptualization and measurement of resilience, associations with perioperative outcomes, neuroendocrine and inflammatory mechanisms, and resilience-modulating interventions within perioperative and Enhanced Recovery After Surgery (ERAS) frameworks. Results: Contemporary models conceptualize resilience as a dynamic, context-dependent process supported by interacting psychological, biological, and social factors. In surgical cohorts, higher resilience is consistently associated with better patient-reported outcomes, including quality of life, pain control, and emotional adjustment, and in some studies with survival and functional recovery. Preoperative depression, anxiety, maladaptive coping, and low social support converge as components of a broader “resilience profile” linked to poorer postoperative trajectories. Biologically, resilient phenotypes are characterized by more regulated hypothalamic–pituitary–adrenal and autonomic responses and reduced inflammatory activation. Psychological therapies, prehabilitation programs, and selected pharmacological strategies show convergent, though heterogeneous, signals of benefit and can be interpreted as indirect resilience-enhancing interventions. Conclusions: Resilience appears to be a clinically meaningful, potentially modifiable construct that links psychosocial functioning, biological vulnerability, and postoperative outcomes. Incorporating resilience assessment into preoperative risk stratification and systematically embedding resilience-building strategies within perioperative and ERAS pathways may support more personalized, psychologically informed surgical care. Prospective, multidomain studies are needed to validate measurement tools, clarify mechanisms, and test resilience-targeted interventions in surgical populations.

Journal of Personalized Medicine doi: 10.3390/jpm16040177

Authors: Emanuele Chioccola Mara Caroprese Christina Amanda Goodyear Angela Barillaro Gianluca Valerio Caterina Oliviero Mauro Buono Stefania Clemente Antonio Farella Manuel Conson Roberto Pacelli

Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials.

Journal of Personalized Medicine doi: 10.3390/jpm16040176

Authors: Dario Rusciano

Background: Precision oncology has traditionally relied on genomic biomarkers to guide therapy selection; however, static molecular profiling often fails to predict real-world responses to cytotoxic chemotherapy. Increasing evidence suggests that treatment outcomes are determined by the interaction between tumor-intrinsic biology and host-specific pharmacology. Functional ex vivo platforms, including patient-derived organoids and tumor slice cultures, provide a complementary phenotypic readout of drug sensitivity that reflects tumor architecture and microenvironmental interactions. Methods: This narrative review integrates recent experimental, translational, and clinical evidence on molecular oncodiagnostics combining tumor transcriptomics, germline pharmacogenetics, and ex vivo drug sensitivity testing. Relevant literature was identified through targeted searches of major biomedical databases, focusing on studies describing multi-omic predictive models, functional precision oncology platforms, and patient-derived tumor models. Results: Converging data indicate that integrated oncodiagnostic strategies can improve prediction of chemotherapy response beyond genomics-only approaches. Transcriptomic profiling captures dynamic pathway activity and resistance programs, pharmacogenetic testing informs host-specific toxicity and dosing constraints, and ex vivo assays enable direct phenotypic validation of drug efficacy. Together, these complementary approaches provide a biologically grounded framework for individualized therapy selection. Conclusions: The convergence of molecular profiling and functional phenotyping represents an emerging paradigm in precision oncology. Integrating multi-omic and functional data may enhance treatment prediction and reduce ineffective therapy, although prospective validation and standardization remain necessary for routine clinical implementation.

Journal of Personalized Medicine doi: 10.3390/jpm16040175

Authors: Patrick Sterner Sanna Gimbergsson Markus Johansson Farhood Alamdari Amir Sherif Abbas Chabok Johan Styrke

Background: High recurrence rates for non-muscle-invasive bladder cancer (NMIBC) remain a clinical challenge. Recommended post-operative treatments are underutilized, highlighting the need for alternative strategies. Given the variability in bladder cancer prognosis, personalized treatment approaches are highly relevant. In this study, we evaluated post-operative two-hour continuous sterile water bladder irrigation (CSWBI) regarding recurrence and safety, as a potential addition to the treatment arsenal for bladder cancer. Method: In 2018, two-hour CSWBI was implemented as routine treatment after all transurethral resection procedures of the bladder (TURB), at the urology department of Sundsvall Hospital. All patients who underwent TURBs four years prior (control group) and four years after the implementation of CSWBI (intervention group) were analyzed. Primary NMIBC were included, MIBC and CIS were excluded. Data were collected retrospectively from patient records, including baseline characteristics, adverse events, and recurrence rates within 12 months follow-up. Statistical analyses included Chi-squared test, Wilcoxon rank-sum test, univariate and multivariate logistic regression analyses, Kaplan–Meier curves and log-rank test. Results: A total of 168 patients were included (control group n = 90, irrigation group n = 78). Median age was 73 years, 23% were female, 77% were male, and 74% were active or previous smokers. The recurrence rate within twelve months for the intervention group vs. the control group was: 27% vs. 21% (p = 0.4) respectively. CSWBI had no statistically significant impact on recurrence (OR 1.25, 95% CI 0.58–2.68, p = 0.6). Adverse effects were limited and equal between groups. Conclusions: Post-operative two-hour CSWBI did not significantly reduce NMIBC recurrence within twelve months in this cohort.

Journal of Personalized Medicine doi: 10.3390/jpm16040174

Authors: Mark B. Hellerman Cassie Wang David T. Zhang Andreas P. Kalogeropoulos Hal A. Skopicki

Background: Patients with NSTEMI who are found with a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Artificial intelligence (AI) models can help identify this subgroup of NSTEMIs. Objectives: The purpose of this study was to examine the performance of an AI model in identifying patients with total thrombotic coronary artery occlusion myocardial infarctions (OMIs) using a single 12-lead ECG as input. Methods: In this retrospective cohort study, 12-lead ECGs corresponding to patients with suspected OMI were analyzed by an AI model. Confirmation of OMI was based on angiographic evidence of acute culprit coronary artery stenosis. Results: Over a one-year period, emergency physicians at our hospital identified 474 patients with suspected OMI, of whom 88 met STEMI criteria. Out of the 142 angiographically confirmed OMIs, the AI model correctly identified 115 (81%) with high confidence, corresponding to an accuracy of 89.4%, sensitivity of 90.0%, specificity of 93.2%, positive predictive value (PPV) of 84.6%, and negative predictive value (NPV) of 91.4%. Out of the 74 angiographically confirmed OMIs that did not meet STEMI criteria, the AI model correctly identified 49 (66%) with high confidence, corresponding to an accuracy of 87.9%, sensitivity of 66.2%, specificity of 93.4%, PPV of 72.1%, and NPV of 91.5%. Out of the 68 angiographically confirmed OMIs that met STEMI criteria, the AI model correctly identified 66 (97%) with high confidence, corresponding to an accuracy of 95.5%, sensitivity of 97.1%, specificity of 90.0%, PPV of 97.1%, and NPV of 90.0%. Conclusions: The AI model examined in this study outperformed the STEMI criteria for the identification of OMI with respect to accuracy, sensitivity, specificity, PPV, and NPV and accurately identified a significant portion of NSTEMIs found to have total thrombotic coronary artery occlusion.

Journal of Personalized Medicine doi: 10.3390/jpm16030173

Authors: Jonas Krueckel Dominik Szymski Nura Ahmad David Schiffelholz Johannes Weber Siska Buchhorn Tomas Buchhorn Kai Fehske Siegmund Lang Volker Alt Franz Hilber

Background: Platelet-rich plasma (PRP) therapy is increasingly used for musculoskeletal conditions, yet patients seeking supplementary information online encounter resources of variable quality. Large language models (LLMs) such as ChatGPT and Google Gemini may support patient education, but their performance in answering common patient questions about PRP therapy has not been well characterized. Methods: This study compared the quality of responses generated by ChatGPT-4, ChatGPT-3.5, and Google Gemini to common PRP-related patient questions. Ten frequently asked PRP-related questions were identified through a structured search of online sources, PubMed, Google Trends, and AI-assisted query generation. Each question was submitted to the three LLMs using a standardized prompt designed to elicit clear and empathetic responses. Five orthopedic surgeons, blinded to model identity, assessed each answer using a previously published four-tier rating framework. Secondary metrics included exhaustiveness, clarity, empathy, and response length. Results: All models produced mostly satisfactory answers. ChatGPT-3.5 received the highest proportion of excellent ratings (70%), compared with 40% for ChatGPT-4 and 22% for Gemini, and outperformed both models in overall quality. The most common limitation across models was insufficient detail. ChatGPT-4 and Gemini performed similarly in several categories, although Gemini was rated lower in empathy and comprehensiveness. Overall differences between models were statistically significant. Conclusions: Commonly available LLMs were able to provide mostly satisfactory responses to patient questions about PRP. However, important limitations remained, particularly with respect to detail and individualization. These tools may support initial patient information-seeking, but they should complement rather than replace expert medical counseling.

Journal of Personalized Medicine doi: 10.3390/jpm16030172

Authors: Ioannis Boutsikos Themis Gkraikou Richard Saad Alexandros Kasiakogias Ioannis Patrikios Argyrios Ntalianis Dimitrios Chatzis

Coronary atherosclerosis in master athletes represents a paradox: despite the well-established cardiovascular benefits of regular exercise, highly trained endurance athletes show a higher prevalence of coronary plaques than their non-athletic peers. The mechanisms behind this finding are multifactorial, involving sustained high shear stress on the vascular wall, exercise-induced inflammatory activation, altered calcium homeostasis, and interactions between genetic predisposition and sport-specific lifestyle factors. Although athletes tend to exhibit predominantly calcified—potentially more stable—plaques, recent studies highlight that mixed and non-calcified lesions are also present, particularly among lifelong endurance athletes, raising questions about their true long-term risk. Clinically, traditional risk scores often underestimate risk in this population, making multimodal assessment with tools such as coronary calcium scoring and coronary CT angiography essential. This review synthesizes the current knowledge on mechanisms, clinical implications, diagnostic strategies, and prevention of coronary atherosclerosis in athletes, while underscoring key gaps that future research must address.

Journal of Personalized Medicine doi: 10.3390/jpm16030171

Authors: Saif F. Dababneh Kevin Ong Darwin Yeung Nathaniel M. Hawkins Andrew Krahn Zachary Laksman Rafik Tadros Thomas M. Roston

Background: Hypertrophic cardiomyopathy (HCM) is a common inherited disease and a leading known cause of sudden cardiac arrest in young adults and athletes. While genetic testing has advanced rapidly in the past decade, the yield of genetic testing remains low. The Clinical Genome Resource (ClinGen) initiative has become a leading resource for defining the clinical relevance of genetic variants with expert groups focusing on evaluating the strength of evidence for each HCM implicated gene. With the rise of large biobanks and population databases, genetic discovery has been significantly advanced. However, whether these databases can be used to validate gene–disease associations curated by ClinGen and provide evidence for novel gene–disease associations remains unclear. Objectives: Here, we utilized a publicly available database containing 748,879 individuals across three large biobanks (All of Us, UK biobank, Mass General Brigham biobank). Methods: We tested the association of rare coding variants in each gene in the HCM ClinGen panel with HCM. In total, 38 genes were tested, and Bonferroni correction was applied accordingly. Results: Of the 12 genes with definitive evidence for HCM (e.g., MYBPC3, MYH7, TNNT2, ALPK3), 8 (67%) demonstrated nominally significant association with HCM on a population level, and 5 (42%) remained significant after Bonferroni correction, further supporting the validity of these genes in HCM panels. Several definitive genes which are much less commonly affected in HCM (CSRP3, MYL3, ACTC1, TPM1, FHOD3, MYL2, and TNNC1) did not pass our Bonferroni corrected-significance threshold, but all had positively associated effect sizes with HCM. No genes deemed to have moderate or limited evidence had any significant associations with HCM even before Bonferroni correction. Conclusions: Altogether, we show that large biobanks and population databases generally recapitulate established gene–disease associations for HCM and support the ClinGen group’s gene curations. The utilization of such publicly accessible databases represents an additional tool for assessing gene validity in monogenic cardiac disorders with an established phenotype, although it may have limited sensitivity and should not be solely relied on.

Journal of Personalized Medicine doi: 10.3390/jpm16030170

Authors: Polina Chliapnikov Mark Bernstein

Background: Difficult benign intracranial tumors (including meningiomas, schwannomas, neurofibromatosis-related tumors, and pituitary neuroendocrine tumors) have substantial morbidity in patients. Due to their limited treatment options, there is a need for individualized treatment beyond histological and surgical approaches. Objective: To summarize how novel treatment innovations have been implemented for these tumors, meningiomas and schwannomas are prioritized, followed by NF-associated neoplasms, and then pituitary neuroendocrine tumors in comparison to low-grade gliomas. Methods: We summarize the current knowledge relating to targeted therapies for gliomas, meningiomas, schwannomas, neurofibromatosis (NF) tumors, and pituitary neuroendocrine tumors to investigate an individual’s treatment options for difficult benign brain tumors. This review synthesizes evidence on tumor genomics and molecular markers, supported by methylation-based classification, immunohistochemistry, and functional assays, emphasizing current clinical applications. Evidence Synthesis: The recent data show that DNA methylation-based models can predict post-surgical outcomes and radiotherapy responses, enabling risk stratification and radiotherapy benefit prediction. Early signals support target-directed treatment, including cMET blockade that radiosensitizes NF2 schwannoma models, brigatinib-associated tumor shrinkage in NF2-deficient models, and PitNET organoid data. Conclusions: We support clinical decision-making that utilizes molecular profiling with functional testing to guide targeted treatment. We also identify evidence gaps such as biomarker-defined prospective trials that are needed for broader clinical implementation.

Journal of Personalized Medicine doi: 10.3390/jpm16030169

Authors: Kaitlyn H. Ko Rebecca Gelfer Justin C. Wheat Sheng F. Cai

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.

Journal of Personalized Medicine doi: 10.3390/jpm16030168

Authors: Krzysztof Nowak Wiktor Bek Maja Mrugała Zofia Borowiec Ewa Milnerowicz-Nabzdyk

Objectives: This study aimed to investigate the usefulness and safety of sentinel lymph node (SLN) mapping in comparison to other types of lymph node dissection in patients with uterine corpus cancers. Methods: Retrospective data from 161 patients subjected to uterine corpus cancer staging with SLN mapping with indocyanine green (ICG) dye were collected. Results: SLN procedure was associated with a complication rate of 0%, a median number of dissected lymph nodes of 2 (range 0–13), and a median hospitalization following surgery of 5 (range:2–23) days. Systemic lymphadenectomy and one-sided pelvic lymph node resection were associated with the highest percentage of complications (12% and 25%; p = 0.0030), while the post-surgery course was uneventful for the selective lymphadenectomy group and SLN. Complication rates were the highest in patients with obesity and severe obesity (5.1% and 9.1%, respectively). The number of lymph nodes resected dropped numerically with increasing BMI. Successful ICG injection and SLN mapping were significantly more frequent in SLN procedures. Conclusions: Our study showed that SLN mapping was characterized by a low complication rate and short hospitalization following surgery, and obesity appeared to be related to a higher complication rate. Tailored surgical strategies and individualized patient selection are crucial for the success of SLN mapping; therefore, factors associated with successful SLN mapping with ICG need further exploration.

Journal of Personalized Medicine doi: 10.3390/jpm16030167

Authors: Eusebi Chiner Ignacio Boira Mónica Antón María Ángeles Bernabeu Celia Cuevas Paula Fernández Violeta Esteban Mónica Llombart

Background: Tezepelumab has demonstrated efficacy in severe uncontrolled asthma (SUA), although real-world evidence remains limited. Methods: We included patients with SUA who completed at least 6 months of treatment. Lung function, eosinophil counts, IgE, FeNO, comorbidities, and changes in asthma control were assessed using ACT, ACQ, the VAS, and quality of life (AQLQ), as well as severe exacerbations (hospital admissions and emergency visits), oral corticosteroid (OCS) courses, OCS withdrawal/dose reduction, and reductions in maintenance and reliever medication. Response was evaluated using the FEOS and EXACTO scales. Baseline (T0) and 6-month (T6) outcomes were compared in the overall cohort and according to T2-high (eosinophilic/allergic) vs. T2-low phenotype. Results: A total of 33 patients were analyzed (58 ± 12 years; 94% women), with a high burden of comorbidities (88%), mainly rhinosinusitis (79%), obesity (41%), and smoking (37%). Of these, 45.5% had received prior biologic therapy. All patients were on high-dose ICS + LABA, frequently with LAMA and other controllers; 30% were on maintenance OCS. In the previous year, 49% had been hospitalized, 97% had attended the emergency department, and 100% required OCS courses. After 10 ± 3 months, the overall group showed significant improvement in VAS, ACT, ACQ, and AQLQ (p < 0.001), with a reduction in eosinophils, but no significant change in FEV1%. Severe exacerbations, emergency visits, hospitalizations, and OCS courses decreased markedly (p < 0.001). Among 10 patients on maintenance OCS, OCS were discontinued in 7 and reduced in 3; maintenance/reliever medication was also reduced. The T2-high phenotype showed a higher likelihood of “complete response” (52% vs. 17% in non-T2), although “good response” predominated in non-T2; this difference was significant (p = 0.04). Conclusions: Tezepelumab improved asthma control and reduced healthcare utilization and corticosteroid use in both T2 and non-T2 patients, achieving clinical remission in 40%, with better outcomes in T2.

Journal of Personalized Medicine doi: 10.3390/jpm16030166

Authors: Bruna Rafaela Oliveira Claudio Peixoto Crispi Jr. Fabio Bastos Russomano Fernando Maia Peixoto Filho Nilton de Nadai Filho Marlon de Freitas Fonseca

Background/Objectives: Deep endometriosis is a chronic inflammatory disease that significantly affects fertility. The objective was to evaluate the magnitude of the effect of minimally invasive nerve-sparing complete excision of endometriosis on natural conception rate in women with documented infertility. Methods: This pre-planned interdisciplinary retrospective observational study included 45 patients who wished to conceive naturally (spontaneous pregnancy) and were followed for 12 months after surgery. Results: The spontaneous conception rate was 33.3% (95% CI: 20.0–46.7) and the mean time to conception was 6.7 months. Age, body mass index, and history of infertility showed no significant differences between the success and failure spontaneous pregnancy groups, but annual income was positively associated with reproductive success (p = 0.022). None of the procedures needed to be converted to open surgery, required colostomy/ileostomy, blood transfusion or abdominal drains. No cases of urinary retention were observed across different levels of nerve preservation. In addition, the absence of serious surgical complications (Clavien–Dindo III/IV) supports the safety of this intervention for infertile patients. Conclusions: The absence of serious surgical complications in this cohort supports the concept that minimally invasive nerve-sparing complete excision of endometriosis is a safe intervention when performed by an experienced team. The results underscore the importance of exploring socioeconomic-related factors through an individualized assessment of patients who wish to conceive naturally after minimally invasive nerve-sparing surgery. Future studies focusing on personalized management of endometriosis should attempt to identify socioeconomic-related covariates that influence natural conception.

Journal of Personalized Medicine doi: 10.3390/jpm16030165

Authors: Ottavia Borghese Arisa Ibrahimi Antonio Luparelli Giulia Piermarini Yamume Tshomba

Background: Anatomical variations in visceral arteries are not so uncommon (up to 20% of cases in general population), with splenic and hepatic artery anomalies being the most frequently reported. Aberrant arteries may be affected with aneurysmal lesions that are rare but potentially fatal conditions. In their treatment, a comprehensive understanding and knowledge of the underlining anatomical variation are pivotal to prevent potential ischemic complications for the end organ. Methods: A comprehensive literature search on the PubMed, Cochrane and Scopus databases was done using the terms: “anomalous visceral artery aneurysm”, “Aberrant visceral arteries”, and “anomalous origin visceral vessels”. Eligible studies published from inception to 30 June 2024 were identified. Only those that had included the adopted treatment strategies (open, endovascular or hybrid repair) and the related outcomes (mortality, bleeding, end-organ ischemia, lesions of the surrounding organ, need for reintervention) were analyzed to evaluate the safety and efficacy of each approach. A narrative analysis of the indications informing the selection of each interventional treatment, based on individual procedural risks, was also presented. Results: A total of 30 publications describing 36 patients (mean age 48.9 ± 12.8 years, range 22–73 years) with aneurysms involving aberrant visceral arteries were included. Most patients were female (25/36, 69.4%). True aneurysms predominated (with a mean size of 30.5 ± 11.5 mm, range 6–60 mm), being reported in 33/36 (91.7%) patients. Most lesions involved a splenic artery arising from the superior mesenteric artery (27/36, 75.0%). Overall, 26/36 (72.2%) patients were symptomatic upon presentation, most commonly with abdominal or epigastric pain, often associated with nausea or vomiting, back pain or shortness of breath. All patients underwent preoperative Computed angiotomography or subtraction angiography to define the operative strategy. Most cases were managed electively (31/36, 86.1%), but 11.1% (4/36) of cases required urgent intervention (in one case the urgency status was not specified). Overall, 19/36 (52.8%) patients underwent purely endovascular repair, 15/36 (41.7%) were treated with open surgery, and 2/36 (5.6%) had hybrid procedures combining endovascular coiling with laparoscopic splenic artery ligation. Indication for treatment was based on vessel tortuosity, landing zones, and the presence of side branches supplying end organs. Early outcomes were favorable regardless of treatment strategies. A single organ-related complication was reported (1/36, 2.8%) following open/endovascular repair, consisting of mild pancreatitis, which resolved with conservative management. No perioperative or aneurysm-related deaths were reported in any of the included cases. No recurrent aneurysms or late aneurysm-related complications were described during the reported follow-up intervals (mean ≈ 10.5 months, range 1.5–42 months). Conclusions: Aneurysms arising from aberrant visceral arteries present unique challenges because their origin, course, and collateral networks deviate from standard anatomy. Patient selection and detailed anatomic mapping preoperatively are decisive as inadequate imaging or failure to recognize an aberrant origin can lead to the incomplete exclusion or inadvertent sacrifice of critical branches. Understanding the anatomy of visceral arteries and their variations is paramount in clinical practice, particularly when planning interventions for minimizing procedural risks, optimizing outcomes, and preventing potential complications. Contemporary practice favors endovascular repair due to lower perioperative morbidity, but success depends on vessel tortuosity, landing zones, and the presence of important side branches that supply end organs.

Journal of Personalized Medicine doi: 10.3390/jpm16030164

Authors: Giulia Iannaccone Alessandro Olimpieri Maria C. Meucci Rosa Lillo Maria Grandinetti Alessio Cianci Claudio Di Brango Angelica B. Delogu Massimo Massetti Gaetano A. Lanza Antonella Lombardo Francesca Graziani Francesco Burzotta

Background: Right-sided congenital heart diseases (R-CHDs) are frequently associated with right ventricular (RV) dysfunction and heterogeneous clinical trajectories, underscoring the need for individualized risk assessment. RV–pulmonary artery (RV–PA) coupling has emerged as an important prognostic marker in several cardiovascular conditions. However, its role in adults with R-CHD has not been well established. Methods: We retrospectively reviewed consecutive adults with R-CHD evaluated at our outpatient clinic between October 2013 and November 2023. RV–PA uncoupling was defined by echocardiography as a tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio ≤0.55. The primary composite endpoint included all-cause mortality, major supraventricular and ventricular arrhythmias, unplanned cardiac hospitalizations, and need for (re)-interventions. Results: A total of 132 patients (mean age 41.6 ± 15.7 years; 51.5% male) were included. RV–PA uncoupling was identified in 48 patients (36.4%). Over a median follow-up of 40.3 months, the primary composite endpoint occurred in 71 patients (53.8%). Patients experiencing adverse outcomes were older and showed lower TAPSE, higher PASP, larger RV and right atrial dimensions, and a significantly higher prevalence of RV–PA uncoupling (p < 0.001). Multivariable Cox regression analysis demonstrated that RV–PA uncoupling was a strong independent predictor of adverse outcomes (HR 4.478, p < 0.001), outperforming its individual components. In addition, RV–PA uncoupling and RV mid-diameter independently predicted the need for surgical or interventional procedures during follow-up. Conclusions: RV–PA uncoupling provides robust and independent prognostic information in adults with R-CHD and represents a practical tool for personalized risk stratification, potentially guiding tailored surveillance strategies and timing of therapeutic interventions.

Journal of Personalized Medicine doi: 10.3390/jpm16030163

Authors: Silvia Lai Alessandra Punzo Adolfo M. Perrotta Giuseppe Guaglianone Silverio Rotondi Paolo Menè Paolo Izzo Sara Izzo Andrea Polistena Lida Tartaglione Francesca Tinti Marta Barattini Andrea Botticelli Simone Scagnoli Daniele Santini Anna P. Mittherhofer Giovanni Pintus

Introduction: Oncological therapies have significantly improved patient outcomes but are increasingly associated with renal toxicity, which can markedly influence therapeutic decisions. Integrating early identification of kidney injury into clinical workflows is essential for personalized medicine, allowing treatment tailoring based on individual risk profiles. Aim: To evaluate the incidence of acute kidney injury (AKI) and chronic kidney Disease (CKD); assess indices of renal function recovery in patients who developed AKI; and investigate the incidence of renal immune-related adverse events (irAEs) in patients receiving immunotherapy. Materials: Renal function, serum electrolytes, inflammatory markers, blood gas analysis, and urinalysis were evaluated at baseline before oncological therapy (T0), after approximately 2 weeks (T1), and after 3 months (T2). Results: Seventy patients were analyzed (median age 71.5 years). AKI occurred in 43 patients (61.4%) and CKD in 18 (25.7%). Patients receiving immunotherapy displayed significantly higher blood urea nitrogen (p < 0.01) and creatinine (p < 0.01) levels compared to those undergoing traditional therapies (targeted therapy and chemotherapy). Treatment discontinuation was required in 14 (56%) immunotherapy patients versus 7 (19.4%) receiving traditional therapy (anti-VEGF and cisplatin) (p < 0.01). Among 25 immunotherapy-treated patients, 13 (52%) developed immune-related adverse events (irAEs). Patients with irAEs predominantly experienced AKI (92.3%), whereas those without irAEs showed both AKI and CKD (44.4%) (p < 0.01). Treatment discontinuation occurred in 84.6% of patients with irAEs compared to 11.1% without irAEs (p < 0.001). Conclusions: We showed a high incidence of AKI and CKD among cancer patients; in particular, the majority of patients receiving immunotherapy presented irAEs. CKD also occurs in association with comorbidities, such as previous use of NSAIDs, investigations with contrast agents and episodes of AKI on CKD determined by drugs. It seems necessary for there to be multidisciplinary collaboration between oncologists and nephrologists to individualize treatment plans; thus allowing the non-suspension of therapy, which positively influences the prognosis of patients.

Journal of Personalized Medicine doi: 10.3390/jpm16030162

Authors: Linda Carli Simone Barsotti Chiara Romei Andrea Delle Sedie Federico Fattorini Michele Diomedi Elisa Cioffi Elenia Laurino Chiara Cardelli Gaetano La Rocca Marta Mosca

Background: Interstitial lung disease (ILD) is the most frequent extra-muscular manifestation in patients with idiopathic inflammatory myopathies (IIMs). Although high-resolution chest tomography (HRCT) represents the gold standard for the evaluation of ILD, lung ultrasound (LUS) might be a useful tool for its assessment. The aim of our study was to evaluate the number and distribution of pleural irregularities (PIs) identified by lung US in a cohort of patients with IIMs and to find possible correlations with clinical, serological and HRCT data to verify the potential usefulness of lung US for the study of ILD in patients with IIM. Patients and methods: Fifty-three patients with IIM according to EULAR/ACR classification criteria were enrolled. All patients underwent a clinical evaluation with measurement of disease activity and myositis-specific autoantibodies, pulmonary function tests, HRCT evaluated with the Warrick score, and lung US for the measurement of PIs. Results: The number of PIs was higher in patients with myositis-specific autoantibodies, particularly those with anti-synthetase autoantibodies (p < 0.001) and in patients with high-grade dyspnea (p < 0.03). A negative correlation was identified between PIs and pulmonary function tests, particularly TLC (r = −0.74; p < 0.001) and DLCO (r = −0.56; p < 0.001). Interestingly, PI score was higher in patients with ILD identified with HRCT (p = 0.015) and a positive correlation between PIs and Warrick score (r = 0.542; p < 0.001) was also found. Conclusions: The study of PIs with lung US represents a promising diagnostic tool for the bedside evaluation of patients with IIMs. This can possibly allow for a reduction in unnecessary HRCTs, reducing the exposition of patients to ionizing radiations, optimizing resources and reducing the costs of patients’ management.

Journal of Personalized Medicine doi: 10.3390/jpm16030161

Authors: Alice O’Regan Johnny Thornton Elisha Clark Sam Kant

End-stage kidney disease (ESKD) is a global health challenge, with kidney transplant demand outstripping supply. Allotransplantation remains the gold standard for treatment but organ scarcity leads to prolonged waiting times and high mortality. Xenotransplantation, using genetically modified porcine kidneys, offers a novel and potentially sustainable solution. Genetic engineering and immunosuppression advances have enabled xenotransplantation to transition from a theoretical possibility to feasible solution. This review explores the evolution of xenotransplantation, the scientific advancements in overcoming immunological barriers, and emerging clinical data. Furthermore, we discuss emerging approaches such as central immune tolerance induction, the ongoing risks of cross-species infection, and the ethical and environmental considerations inherent to scaling up porcine organ donation. With the commencement of the first formal clinical trials, progress in the field could transform kidney transplantation, though questions remain regarding long-term outcomes and societal impact.

Journal of Personalized Medicine doi: 10.3390/jpm16030159

Authors: Josip Katic Tomislav Bulum Josip Anđelo Borovac

Background: Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of ventricular arrhythmias and sudden cardiac death (SCD) despite contemporary therapy. Cardiac myosin inhibitors directly target sarcomeric hypercontractility and have demonstrated consistent symptomatic, hemodynamic, and structural benefits in randomized controlled trials (RCTs). However, their effects on malignant ventricular arrhythmias and SCD remain uncertain. This meta-analysis aimed to evaluate the incidence of ventricular arrhythmias and SCD with cardiac myosin inhibitor therapy in HCM. Methods: We conducted a meta-analysis of RCTs evaluating mavacamten or aficamten in patients with HCM. PubMed was systematically searched through September 2025. Eligible trials randomized myosin inhibitors versus control and reported ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD. Results: Seven RCTs including 1519 patients (779 myosin inhibitor; 740 control) were analyzed. Eight composite VT/VF/SCD events (1.03%) occurred in the treatment group compared with twelve (1.62%) in controls. Time-standardized incidence rates were 1.48 versus 2.36 per 100 patient-years, respectively. The pooled RR was 0.69 (95% CI 0.27–1.74; I2 = 0%), indicating no statistically significant difference. Sensitivity analyses yielded concordant results despite low event counts. Conclusions: No statistically significant increase in ventricular arrhythmia or SCD risk was observed. However, limited events and short follow-up preclude firm conclusions regarding the arrhythmic safety of myosin inhibitors.