Journal of Personalized Medicine doi: 10.3390/jpm16070348

Authors: Gorazd Kovac Ernst Josef Müller Martin Liebhauser Jochen Jung Haro Stettner Martin Halbherr

Background: Dislocations and fracture-dislocations of the lower cervical spine represent complex injuries with a high risk of neurological damage. Especially in the presence of a confirmed traumatic disc lesion, an anterior surgical approach is described as favoured in the literature. However, studies show that with sufficient reduction technique, even in the presence of a confirmed disc protrusion, posterior stabilization can be considered a safe therapeutic option. The aim of this study is to analyze anterior and posterior treatment of dislocations and fracture-dislocations of the subaxial cervical spine with regard to neurological and radiological outcomes. Methods: In our monocentric cohort study, we investigated the immediate postoperative radiological and neurological outcome depending on the chosen surgical approach and the presence of a disc protrusion. Patients treated at our centre between January 2005 and June 2025 were included. Patients with preoperative complete spinal cord injury were excluded. Neurological status was assessed using the ASIA score preoperatively at admission and postoperatively at discharge or prior to staged surgery. Results: A total of 92 patients were included in the study. Most patients showed an ASIA score C (33.7%). A total of 49 patients (53.3%) were operated anteriorly and 42 patients (45.6%) posteriorly. One patient was primarily stabilized bilaterally. Nine patients initially treated anteriorly had to be secondarily stabilized additionally from posterior. In both groups, neurological deterioration occurred in one case. All other patients remained stable on the ASIA score or improved by at least one point on the scale. Conclusions: The findings provide evidence in favour of a personalized, pathology-oriented approach to lower cervical spine fracture-dislocations rather than selecting the surgical approach based solely on the presence of traumatic disc protrusion. Further prospective studies are needed to validate these observations.

Journal of Personalized Medicine doi: 10.3390/jpm16070347

Authors: Adham M. Khalafallah Manav Daftari Tanuj Prajapati Sebastian Vargas-George Anurag Aka Christian K. Ramsoomair Malek Bashti Seth S. Tigchelaar Timur Urakov

Objectives: Tandem spinal stenosis (TSS) is often underdiagnosed and traditionally managed with multi-stage surgery (MSS). Single-stage surgery (SSS) is an alternative, but prior studies largely emphasize younger, healthier patients. This study evaluated perioperative and functional outcomes after SSS for TSS in a surgically diverse cohort. Methods: A retrospective chart review included 20 patients who underwent SSS for TSS at a single academic institution. Mean age was 63.75 years, and median modified frailty index was 2. Etiologies included degenerative, traumatic, and neoplastic disease across cervical, thoracic, and lumbar regions. Outcomes included operative characteristics, complications, readmissions, and functional recovery measured by Visual Analog Scale (VAS) pain and modified Japanese Orthopaedic Association (mJOA) scores. Results: The mean number of operated levels was 5.2, mean operative time was 232.4 min, total OR time was 355.1 min, and length of stay was 6.9 days. Surgical complications occurred in 15% of patients, medical complications in 25%, and 90-day readmission in 15%, with no 30-day mortality. Mean mJOA improved from 12.86 at baseline to 16.08 at first follow-up and 16.46 at 3 months; REML mixed-effects modeling showed a significant timepoint effect (F (4, 34.55) = 9.15, p < 0.001), with significant Sidak-adjusted improvement at both timepoints. VAS pain showed no significant longitudinal effect. Conclusions: SSS for TSS appears feasible in a real-world, surgically diverse cohort including older and moderately frail patients. These findings support individualized SSS candidacy assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16070346

Authors: Giuseppe Mazza Giuseppe Neri Helenia Mastrangelo Alessandro Russo Isabella Aquila Matteo Antonio Sacco Jessica Ielapi Corrado Pelaia Mario Cannataro Chiara Lupia Francesca Serapide Federico Longhini Vincenzo Bosco Zaninni Caroleo Andrea Bruni Eugenio Garofalo the SEPSIS-UMG Collaborative Group

Background/Objectives: Artificial intelligence (AI), machine-learning (ML), and deep-learning (DL) models are increasingly used for prognostic prediction in intensive care unit (ICU) sepsis, but their clinical readiness remains uncertain. This systematic review aimed to evaluate AI-, ML-, and DL-based models for mortality and clinically relevant outcome prediction in adult ICU patients with sepsis or septic shock. Methods: PubMed/MEDLINE, Scopus, and the Cochrane Library were searched up to April 2026. Eligible studies included adult ICU sepsis or septic shock cohorts evaluating AI/ML/DL-based prognostic models. Screening, full-text assessment, and data extraction were performed independently by two reviewers. Outcomes, model families, validation strategies, discrimination, calibration, clinical utility, explainability, comparative performance versus conventional severity scores, risk of bias, and reporting completeness were synthesized. Risk of bias was assessed using PROBAST domains supplemented by PROBAST + AI considerations, and reporting completeness was evaluated according to TRIPOD/TRIPOD + AI domains. Results: Seventy-five studies were included, comprising 50 PubMed-derived and 25 additional Scopus-derived studies. AUROC or C-statistic was extractable in 64 studies, external validation was reported in 27, prospective evaluation in three, calibration in 38, decision-curve analysis or clinical utility assessment in 37, and explainability in 64. Across 17 directly extractable within-study comparisons from nine studies, AI/ML models usually, but not uniformly, achieved higher discrimination than conventional severity scores, with a median paired ΔAUROC of +0.108 (IQR, +0.082 to +0.148; range, −0.013 to +0.203). Externally validated fixed-horizon models showed clinically relevant but heterogeneous discrimination across sepsis phenotypes, with stronger evidence in selected sepsis-induced coagulopathy cohorts and more variable transportability in respiratory and liver-injury subgroups. However, 45 studies were judged at high risk of bias, mainly because of limitations in the analysis domain. Conclusions: AI/ML models for adult ICU sepsis show a recurrent signal of prognostic discrimination and often perform comparably to or better than conventional severity scores in directly extractable within-study comparisons; however, this signal should be interpreted cautiously given clinical and methodological heterogeneity, limited prospective validation, incomplete calibration, and frequent high risk of bias. The strongest evidence comes from externally validated, phenotype-specific models, although routine clinical implementation remains limited by heterogeneous endpoints, incomplete calibration, insufficient prospective validation, and scarce workflow-level evaluation. Future studies should shift from retrospective AUROC optimization toward calibrated, externally validated, clinically actionable, and workflow-integrated decision-support tools tested in prospective ICU settings.

Journal of Personalized Medicine doi: 10.3390/jpm16070345

Authors: Fernando Diaz Dilernia Mutaz Tageldein Emad Anam Aaron Campbell Gavin Wood

Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without patellar resurfacing. Methods: We retrospectively reviewed a consecutive cohort of 39 patients (48 knees) who underwent PFJ replacement for isolated patellofemoral osteoarthritis between 2011 and 2021. Median age at surgery was 59 years, and median body mass index (BMI) was 31 kg/m2. Median follow-up for clinical and revision surveillance was 9 years (IQR 8–10). Functional outcomes were assessed using the Oxford Knee Score (OKS) and SF-12 Physical and Mental Component Scores (PCS and MCS). Implant survivorship was analyzed using Kaplan–Meier methodology, with conversion to total knee arthroplasty (TKA) as the endpoint. Statistical analyses were primarily descriptive and exploratory because only five TKA revisions occurred. Results: Median OKS improved from 19 (IQR 16–24) preoperatively to 36 (IQR 24–42) at the latest follow-up, with a median paired improvement of 17 points. SF-12 PCS improved from 25 to 47, and SF-12 MCS from 36 to 55. Eight knees (16.7%) underwent non-revision reoperation, and five knees (10.4%) underwent conversion to TKA. All TKA revisions were performed for the progression of tibiofemoral osteoarthritis. Kaplan–Meier survivorship free from TKA revision was 89.6% at 9 years (95% CI 76.8–95.5). No clear difference in TKA-free survivorship was detected between resurfaced and non-resurfaced knees. Conclusions: PFJ replacement demonstrated substantial functional improvement and mid- to long-term survivorship comparable to published registry ranges in a selected cohort with isolated patellofemoral osteoarthritis. TKA revision was uncommon and was attributable to the progression of tibiofemoral osteoarthritis. Because of the retrospective design, small cohort size, bilateral cases, and limited number of revision events, subgroup and risk-factor analyses should be interpreted as exploratory.

Journal of Personalized Medicine doi: 10.3390/jpm16070344

Authors: Nurlybek Mombekov Nigara Yerkhojayeva Aliya Ualiyeva Nazira Zharkinbekova Cigdem Ozkara Gulnaz Nuskabayeva Karlygash Sadykova Assylbek Mombek Bakhytkul Yernazarova Tangsholpan Zholdassova Rissalat Abdullayeva Aziz Nabiyev Nursultan Nurdinov

Background/Objectives: Adult epilepsy is clinically heterogeneous, and individual clinical predictors may not fully capture the multidimensional burden associated with drug-resistant epilepsy (DRE). This study aimed to identify latent clinical phenotypes in adults with epilepsy and examine their cross-sectional associations with DRE and broader disease burden. Methods: This regional observational cohort study used a source database of 1100 patients with epilepsy. After excluding two patients aged <18 years, the adult analytic cohort included 1098 patients. Complete-case latent class analysis (LCA) was performed in 1054 patients using age at onset, disease duration, seizure type, seizure frequency, serial seizures/status, postictal confusion, neurological status, neuroimaging category, and number of antiseizure medications. Model selection was based on statistical fit, class size, and clinical interpretability. Internal clinical validation outcomes included DRE, quality of life, cognitive screening, and stigma scores. Post hoc characterization described the classes by epilepsy etiology, derived epilepsy type, and seizure categories aligned with current terminology. Results: A three-class solution was selected, with class sizes of 314, 465, and 275. DRE prevalence increased stepwise across classes: 5.7%, 14.2%, and 33.1%, respectively (p < 0.001). In adjusted analysis, Class 2 had higher odds of DRE than Class 1 (odds ratio 2.70, 95% confidence interval 1.56–4.67), while Class 3 showed the strongest association (odds ratio 8.19, 95% confidence interval 4.15–16.16; both p < 0.001). Higher-burden classes showed lower quality-of-life and cognitive scores and higher stigma scores. Conclusions: LCA identified three clinically interpretable, burden-enriched phenotypic profiles associated with a stepwise gradient in DRE and broader multidimensional disease burden. These cross-sectional profiles may provide a useful framework for describing clinical heterogeneity in adult epilepsy and generating hypotheses for future validation studies.

Journal of Personalized Medicine doi: 10.3390/jpm16070343

Authors: Maysa Al-Hussaini Anas Al Okaily Osama Alsmadi

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has fundamentally transformed the treatment landscape for relapsed and refractory B-cell malignancies, yet antigen escape remains a persistent therapeutic challenge that limits long-term remission durability. While antigen loss is typically considered a somatic event acquired during tumor evolution under therapeutic selective pressure, germline CD19 polymorphisms could theoretically influence CAR-binding kinetics, alter epitope presentation, and modulate therapeutic outcomes in ways that remain largely not characterized. Unfortunately, Middle Eastern populations are underrepresented in pharmacogenomic databases and CAR-T clinical trials, creating a knowledge gap that may perpetuate global health disparities in access to precision immunotherapy. We analyzed publicly available whole-exome sequencing data from 1196 individuals of Arab origin to comprehensively characterize CD19 variants with potential relevance to CAR T-cell immunotherapy. The L174V (rs2904880) variant stood out, and showed the Valine/Valine (V/V) genotype frequency was 65.3%, corresponding to a V174 allelic frequency of 76.6%, while the minor allele, L174, has a frequency of 23.4%. The missense mutation (c.520C > G) responsible for this variant results in a leucine-to-valine (L174V) substitution at position 174 of the CD19 protein, relative to the reference genome. The cohort genotypes (CC, CG, and GG) exhibited a significant deviation from Hardy–Weinberg equilibrium (p < 0.00001). While this deviation is consistent with the high consanguinity rates (25–60%) amongst Arab populations, it remains not fully explained, and may be attributed to population structure, relatedness, or technical factors. We further emphasize that our computational analysis cannot establish any direct clinical or functional impact due to this variant, and therefore we refrain from suggesting any specific actions at the current time. In light of these findings, we hypothesize that the distinctive genetic architecture of consanguineous populations should not be viewed as a confounding variable. Instead, it presents a unique opportunity to investigate the clinical relevance of germline variation in the context of precision oncology, particularly at therapy-relevant loci, pending functional validation.

Journal of Personalized Medicine doi: 10.3390/jpm16070342

Authors: Filip Gajewski Grzegorz Kurec Aleksandra Litkowska Joanna Pec Jakub Kleinrok Weronika Pająk Oliwia Burdan Paweł Krawczyk Agnieszka Korolczuk

Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial–mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation.

Journal of Personalized Medicine doi: 10.3390/jpm16070341

Authors: Rui-Bin Huang Jia-Pang Jhang Bo-Da Huang Mansour Abtahi Albert K. Dadzie Behrouz Ebrahimi Xincheng Yao Yi-Ting Hsieh

Objective: This study aimed to evaluate the predictability of baseline optical coherence tomography angiography (OCTA) metrics utilizing a specialized capillary–large vessel segmentation analysis framework in patients with diabetic macular edema (DME) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Forty-two treatment-naïve eyes with DME receiving three monthly loading anti-VEGF injections were included. Superficial capillary plexus (SCP) images from 3 × 3 mm OCTA scans were processed to isolate the capillary network from the large vessels via image processing. Vessel density and skeleton density were extracted for the total, large-vessel, and capillary components. Multiple linear and logistic regression models were used to identify independent predictors of post-treatment best-corrected visual acuity (BCVA) and “good visual outcome” (≥3-line improvement or final BCVA of 20/40 or better). Results: Following three monthly anti-VEGF injections, the mean BCVA significantly improved from 0.57 ± 0.36 to 0.37 ± 0.30 LogMAR (p < 0.0001), and the mean central retinal thickness decreased from 424.3 ± 117.7 μm to 316.9 ± 84.7 μm (p < 0.0001). The proportion of patients who achieved a good visual outcome was 73.8%. Baseline central retinal thickness was associated with baseline BCVA (p = 0.049) but not predictive of post-treatment BCVA (p = 0.38) or good visual outcomes (p = 0.79). Baseline capillary vessel density was identified as a significant independent predictor of post-treatment BCVA (p = 0.024), whereas total and large-vessel metrics were not. Capillary vessel density was also the only significant predictor of good visual outcomes (p = 0.044). Conclusions: Baseline capillary vessel density is a robust predictor of visual prognosis after anti-VEGF therapy in patients with DME, underscoring the importance of capillary network integrity in functional recovery.

Journal of Personalized Medicine doi: 10.3390/jpm16070340

Authors: Andrea Giovanni Parato Vincenzo Mirco La Fazia Marco Marino Marcello Marchetta Laura Colarocchio Giovanni Albano Francesco Pocelli Emanuele Chiarazzo Alessandro Di Francesco Lorenzo Gerardi Weili Marco Xu Valerio Marongiu Giuseppe Stifano Andrea Natale

Background: Venous closure devices (VCDs) are being increasingly used after femoral venous access to facilitate recovery, but their comparative efficacy and safety versus manual compression or figure-of-eight suture remain uncertain. Because femoral venous access management is influenced by patient-related and procedural factors, VCDs may contribute to a more personalized postprocedural recovery strategy. Objective: Evaluation of the impact of VCDs on procedural recovery and vascular complications in patients undergoing cardiac procedures via femoral venous access. Methods: We systematically searched PubMed, Embase, and CENTRAL through to April 2025 for randomized controlled trials (RCTs) comparing VCDs with manual compression and/or figure-of-eight suture. Primary efficacy outcomes were time to hemostasis (TTH), time to ambulation (TTA), time to discharge (TTD), and time to discharge eligibility (TTDe). Safety outcomes were major and minor vascular complications. Risk of bias was assessed with RoB 2, and certainty of evidence assessed with GRADE. Random-effects models were used to pool standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: Seven RCTs (n = 948) were included. VCDs use significantly reduced TTH (SMD: −1.00; 95% CI: −1.57 to −0.42) and TTA (SMD: −1.50; 95% CI: −2.42 to −0.58). TTD showed a non-significant trend favoring VCDs (SMD: −0.99; 95% CI: −2.13 to 0.15), while TTDe was consistently shorter with VCDs across three trials. Major vascular complications were rare and similar between groups (RR: 0.41; 95% CI: 0.09–1.89). Minor vascular complications were significantly reduced with VCDs (RR: 0.42; 95% CI: 0.22–0.79). Conclusions: In patients requiring femoral venous access for interventional cardiology procedures, VCDs improve time to hemostasis and ambulation and reduce minor vascular complications without increasing major events. These findings support VCDs as an effective and safe strategy for venous closure.

Journal of Personalized Medicine doi: 10.3390/jpm16070339

Authors: Cicerone Clelia Fabrizio Fanizzi Arianna Dal Buono Ilaria Faggiani Ferdinando D’Amico Alessandra Zilli Tommaso Lorenzo Parigi Virginia Solitano Federica Furfaro Sara Massironi Alessandro Armuzzi Silvio Danese Mariangela Allocca

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterized by marked heterogeneity, challenging disease monitoring and individualized treatment. Despite advances in treat-to-target strategies, unmet needs persist, particularly in assessing transmural healing and optimizing therapeutic decisions. This narrative review evaluates the role of intestinal ultrasound (IUS) as a key tool for precision medicine in IBD. IUS is a non-invasive, repeatable, and cost-effective imaging modality with diagnostic accuracy comparable to endoscopy and magnetic resonance enterography, with reported sensitivities and specificities frequently exceeding 80–90% for detecting active disease. It enables real-time assessment of transmural inflammation and complications, while parameters such as bowel wall thickness and Doppler vascularity support prognostic stratification. Early reductions in bowel wall thickness (≥25–30%) have been associated with improved treatment response, allowing identification of responders within weeks of therapy initiation. IUS informs therapeutic decision-making, including initiation, optimization, and de-escalation of advanced therapies, and may reduce reliance on invasive procedures. Integration into routine care has been associated with improved disease control and cost-effectiveness. Standardization of protocols, operator training, and prospective validation are required to establish IUS as a cornerstone of precision medicine in IBD.

Journal of Personalized Medicine doi: 10.3390/jpm16070338

Authors: Carlos Fonseca Pedro Ribeiro Karla de Carvalho Rodrigo Andraus Renata de Moura Andrei da Trindade Arislander Dumont Tiago Fernandes Daniel Marconi Hugo Pasin Neto Danilo Armbrust Claudia Oliveira

Background/Objectives: Chronic non-specific low back pain (CNLBP) is a leading cause of disability worldwide. Although several randomized trials have evaluated treatment effectiveness, less attention has been given to the responsiveness of outcome measures used to assess clinical change. This study aimed to evaluate the internal and external responsiveness of commonly used outcome measures in individuals with CNLBP. Methods: This study is a secondary analysis of a randomized controlled trial. Participants were analyzed as active and placebo groups and assessed at baseline, post-intervention, and follow-up. Internal responsiveness was evaluated using standardized mean differences (SMD) and standardized response means (SRM). External responsiveness was assessed using anchor-based approaches, including correlations with the Global Rating of Change Scale (GRCS) and receiver operating characteristic (ROC) curve analysis. Results: Outcome measures demonstrated moderate to high internal responsiveness, with large effect sizes observed for pain intensity (NRS) and quality of life (EQ-5D-3L). However, external responsiveness was limited, with all instruments presenting area under the curve (AUC) values below 0.70. The Bournemouth Questionnaire showed the highest discriminative performance among the instruments. Conclusions: The evaluated instruments were sensitive to detecting change at the group level but showed limited ability to discriminate clinically meaningful improvement at the individual level. These findings support the use of combined outcome measures to improve clinical interpretation and decision-making in CNLBP.

Journal of Personalized Medicine doi: 10.3390/jpm16070337

Authors: Christos Doukas Petros Galanis Athanasios Douzenis Panagiota Bali Marie Louise Psarra Ioannis Michopoulos Nikolaos Smyrnis Konstantinos Tasios

Precision psychiatry promises a more objective and effective approach to psychiatric care, yet its implementation raises growing ethical challenges as technology advances. This narrative review offers a qualitative synthesis of the ethical issues reported in 62 studies, with emphasis on the practical tensions that arise when core principles conflict. Rather than organising concerns around traditional ethical principles, the review maps them across the main modalities of precision psychiatry, namely genomics, neuroimaging, digital phenotyping, and AI-driven interventions. Four explicit positions are advanced. First, equity must be engineered from the outset rather than assumed. Second, interpretability should outweigh marginal gains in accuracy in a field built on subjective report. Third, stigma is bidirectional and contingent on framing and the availability of meaningful intervention. Fourth, individualised care must demonstrate clinical and economic superiority over standardised approaches. Precision psychiatry is likely to reshape psychiatric practice and the therapeutic relationship itself. Interdisciplinary collaboration, clear guidelines, and continuous ethical vigilance will be essential for responsible adoption and sustained public trust.

Journal of Personalized Medicine doi: 10.3390/jpm16060335

Authors: Victor A. Shahen Cheng-Hon Yap

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

Journal of Personalized Medicine doi: 10.3390/jpm16060336

Authors: Rauno Joks Tamar Smith-Norowitz Shawn Mathew Mansi R. Kothari Sairaman Nagarajan

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

Journal of Personalized Medicine doi: 10.3390/jpm16060334

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060333

Authors: Livio Vitiello

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

Journal of Personalized Medicine doi: 10.3390/jpm16060332

Authors: Heayyean Lee Khadijah Sajid Dayeon Lee

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

Journal of Personalized Medicine doi: 10.3390/jpm16060331

Authors: Joel Costoya Joaquin J. Jimenez

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

Journal of Personalized Medicine doi: 10.3390/jpm16060330

Authors: Joshua E. Chan Lisa C. Zaba

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

Journal of Personalized Medicine doi: 10.3390/jpm16060329

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060328

Authors: Aikaterini-Eleftheria Karanikola Agapi Ploussi Dimitrios Tsiachris Efstathios P. Efstathopoulos

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

Journal of Personalized Medicine doi: 10.3390/jpm16060327

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060326

Authors: Marco Agostini Pietro Traldi Mahmoud Hamdan

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

Journal of Personalized Medicine doi: 10.3390/jpm16060325

Authors: Evelina Maines Roberto Franceschi

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

Journal of Personalized Medicine doi: 10.3390/jpm16060324

Authors: Michael Igoumenidis Venetia-Sofia Velonaki

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

Journal of Personalized Medicine doi: 10.3390/jpm16060323

Authors: Emanuele Trovato Francesca La Marca Benedetta Simonini Martina Dragotto Enrico Calandra Francesca Lussana Alessandra Cartocci Pietro Rubegni

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

Journal of Personalized Medicine doi: 10.3390/jpm16060322

Authors: Camilla Calvieri Isabella Leo Jessica Ielapi Giulia Guglielmi Gian Luca Ragazzoni Vincenzo D’Ambrosio Leonie Luedke Sara Moscatelli

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

Journal of Personalized Medicine doi: 10.3390/jpm16060321

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060320

Authors: Chia-Yu Wang Chun-Yao Cheng Yi-Jie Peng

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

Journal of Personalized Medicine doi: 10.3390/jpm16060319

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060318

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060317

Authors: Sofia Bertona Javier Castillo Francisco Schlottmann

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

Journal of Personalized Medicine doi: 10.3390/jpm16060316

Authors: Filip Gajewski Joanna Pec Jakub Kleinrok Weronika Pająk Katarzyna Pacyna Agata Tokarzewska Paweł Krawczyk

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

Journal of Personalized Medicine doi: 10.3390/jpm16060315

Authors: Hee-Young Kim

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

Journal of Personalized Medicine doi: 10.3390/jpm16060314

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060313

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

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

Journal of Personalized Medicine doi: 10.3390/jpm16060312

Authors: Louiza Mpoumi Georgia Sarantos Vasiliki Bistola Sofia Bezati Christos Verras Ioanna Rita Sotirios Tsiodras John Parissis Effie Polyzogopoulou

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

Journal of Personalized Medicine doi: 10.3390/jpm16060311

Authors: Christina Koukouvitaki Sofia Flouda Theofanis Karageorgas Stelios Loukides Dimitrios T. Boumpas Antonis Fanouriakis Aggelos Banos Vasilios Tzilas

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

Journal of Personalized Medicine doi: 10.3390/jpm16060310

Authors: Alessia Pennacchi Basile N. Landis Michael B. Soyka Roberto Spasiano Matteo Trimarchi

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

Journal of Personalized Medicine doi: 10.3390/jpm16060309

Authors: Kashish K. Qureshi Andrea E. Cavanna

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

Journal of Personalized Medicine doi: 10.3390/jpm16060308

Authors: Nikolaos Veskoukis Nikos Stefanopoulos Panagiota Naoum Kostas Athanasakis

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

Journal of Personalized Medicine doi: 10.3390/jpm16060307

Authors: Nilton de Nadai Filho Claudio Peixoto Crispi Bruna Rafaela Santos de Oliveira Claudio Peixoto Crispi Marlon de Freitas Fonseca

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

Journal of Personalized Medicine doi: 10.3390/jpm16060306

Authors: Giuseppe Alberti Francesco Galletti Daniele Portelli Cosimo Galletti Sabrina Loteta Bruno Galletti Mario Lentini Salvatore Ronsivalle Salvatore Maira Jerome Rene Lechien Quentin Mat Antonino Maniaci

Background: Hearing loss is a widespread sensory disorder affecting over 1.5 billion people worldwide, with the number projected to exceed 700 million by 2050. It imposes social and economic burdens across all ages and regions. Approximately half of adult cases are preventable, but the underlying causes are complex, with 75–80% due to autosomal recessive genetic factors and key roles for mutations in genes such as GJB2. Advances in sequencing technologies have accelerated gene discovery, but challenges remain in interpreting variants. Epigenetic mechanisms such as DNA methylation and histone modifications are increasingly recognized as crucial in auditory biology and could offer new biomarkers and therapeutic targets. Integrating epidemiological, genetic, and epigenomic data is essential to developing targeted prevention and treatment strategies to reduce the global burden of hearing loss. Methods: This narrative review examines recent genomic and epigenomic advances in hearing loss, with particular emphasis on molecular mechanisms, emerging diagnostic applications, and translational therapeutic opportunities. A comprehensive review of current epidemiological data, genetic studies, and epigenomic research was conducted using the peer-reviewed literature from international databases. Key areas of interest include inheritance patterns, molecular pathways, and recent advances in omics technologies. Results: Epigenetic mechanisms, including DNA methylation and histone modifications, are increasingly recognized as important regulators of cochlear development and hair cell survival, although much of the current evidence remains preclinical. Studies suggest that peripheral epigenetic signatures may serve as biomarkers for early diagnosis and risk stratification. Conclusions: Integrating established screening pathways with epidemiological trends and molecular knowledge offers a promising path toward precision medicine in hearing care. Connecting these domains is essential to developing equitable and effective interventions and addressing persistent global disparities in hearing health. This review highlights the evolving landscape of auditory genetics and epigenetics and outlines future directions for translational research and personalized therapy.

Journal of Personalized Medicine doi: 10.3390/jpm16060305

Authors: Donato Casella Juste Kaciulyte Andrea Bartalini Cinughi de Pazzi Luca Sanvitale Alessia Pagnotta Pietro Maria Ferrando Alessandro Neri Marco Marcasciano Federico Lo Torto

Background: Thanks to its capacity to increase wound healing, NPWD (Negative-Pressure Wound Dressing) showed promising results in breast surgery. The authors developed the NDoCaSco system for select patients that may benefit the most from NPWD after breast oncologic surgery, aiming to improve outcomes in patients at risk for wound dehiscence and breast reconstruction failure. Methods: Patients scheduled for breast oncologic surgery were enrolled between 2022 and 2023. Surgical wound dressing was selected prior to assessing the risk for post-operative complications with the NDoCaSco. Low-risk patients (NDoCaSco score: 15–21) received traditional compressive dressing, while moderate- (NDoCaSco: 8–14) and high-risk (NDoCaSco: 0–7) patients received short-term or long-term NPWD, respectively. Results: Healing time and outcomes were compared to a retrospective control group that underwent the same surgeries between 2019 and 2021 and received traditional compressive wound dressing in all cases. The study population included 739 patients with an average age of 62.3 years (range, 29–95) and a mean BMI of 25.2 kg/m2 (range, 16–46). Breast-conserving surgery was performed in 437 cases, and 302 received mastectomy with implant-based reconstruction. A total of 152 patients scored medium (140 cases) or low (12 cases) NDoCaSco and received NPWD. Post-operative complications’ incidence, healing time, and drain removal time were lower in the study group, while scar quality was consistently improved with NPWD when comparing the two middle-risk groups. Conclusions: NDoCaSco helped in identifying patients who benefit the most from NPWD, achieving faster healing and reduction in outpatient visits and hospital admissions, leading to a lower expenditure of resources.

Journal of Personalized Medicine doi: 10.3390/jpm16060304

Authors: Alessia Pennacchi Elisa Raggini Roberto Spasiano Filippo Barucca Matteo Trimarchi

Background: Energy-based techniques for septal cartilage reshaping, including laser-mediated cartilage reshaping (LCR) and electromechanical reshaping (EMR), have been investigated for more than three decades as minimally invasive alternatives to conventional septoplasty. Despite encouraging preclinical findings, their clinical translation remains limited. Their relevance to personalized medicine lies in the possibility of tailoring septal correction to individual anatomy, cartilage-dominant deformity patterns, and patient-specific functional needs. Objective: To systematically review the experimental and clinical evidence on LCR and EMR for nasal septal cartilage reshaping and to evaluate their potential role within a personalized, function-oriented treatment framework. Methods: A PRISMA 2020-compliant systematic search of PubMed, Scopus, and Web of Science was performed for English-language studies published up to June 2025. Original experimental or clinical studies investigating LCR or EMR applied to human or animal septal cartilage were included. Because of heterogeneity in models, dosimetry, and outcome reporting, a qualitative synthesis was undertaken. A design-specific critical appraisal was also performed. Results: Eighteen studies met the inclusion criteria (LCR: n = 9; EMR: n = 9). LCR consistently induced shape change within a narrow thermo-mechanical relaxation range (55–75 °C), but showed dose-dependent risks of chondrocyte injury and matrix degeneration, with limited applicability to complex osseocartilaginous deviations. Only three human LCR studies were identified, all short-term and limited to mild cartilaginous deformities. EMR produced reproducible, charge-dependent reshaping at near-physiological temperatures, but human studies were lacking. Neither technique addressed bony deviations, and none assessed functional benefit using computational fluid dynamics. Conclusions: Both techniques remain predominantly preclinical and may currently serve only as adjunctive options for selected anterior, cartilage-dominant deformities. Future translation will require validated dosimetry, long-term human data, and patient-specific functional assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16060303

Authors: Avram R. Shack Tapas Kulkarni Alyssa Hawley Jessy Jagpal Maninder Janda Stephanie Glegg Uthaya Kumaran Kanagaraj Michael Castaldo Julia K. Charlton Jessie van Dyk Emily Kieran Souvik Mitra Horacio Osiovich Deepak Manhas Kanekal S. Gautham Sandesh Shivananda

Background/Objectives: Bronchopulmonary dysplasia (BPD) remains a major morbidity among extremely premature infants, with variability in the application of evidence-based interventions between and within neonatal intensive care units (NICUs). We evaluated a multi-component, risk-guided personalized implementation strategy for BPD prevention in a real-world setting. Methods: We conducted a prospective observational study of infants <29 weeks’ gestation at birth admitted to a quaternary NICU. The intervention combined risk stratification and structured longitudinal care planning rounds (LCPRs) that included standardized documentation, multidisciplinary facilitation, and associated continuous quality improvement strategies. Implementation outcomes were assessed using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Secondary outcomes included care processes, provider-reported measures, and exploratory clinical outcomes. Results: Over six months, 41 infants were included. Risk stratification was consistently applied and all fifteen high-risk infants received LCPR, demonstrating targeted reach. Multidisciplinary participation was broad, with implementation fidelity reflected by consistent screening, structured documentation, and timely care plan execution. Practice standardization was observed, including consistent corticosteroid use (100%), earlier initiation of systemic postnatal steroids (median 16 days), and selective adjunctive therapy use. Providers reported improved teamwork, care coordination, and confidence. Rates of BPD or mortality were comparable between higher-risk infants receiving LCPR and lower-risk infants, despite greater illness severity in the LCPR group. Respiratory severity scores showed a downward trend after implementation, though this did not reach statistical significance (p = 0.07). Strategy use continued beyond the study period indicating early sustainability. Conclusions: A multi-component, risk-guided implementation strategy can be effectively integrated into routine NICU practice, improving care processes while maintaining clinical outcomes in high-risk infants compared with lower-risk infants.

Journal of Personalized Medicine doi: 10.3390/jpm16060302

Authors: Elisabeth M. Mandler Zehra Düzgün Johannes M. Mittendorfer Jakob R. Altmann Lena Hirtler

Background: The superficial plantar-medial release (S-PMR) refers to a group of surgical procedures involving the release of the plantar aponeurosis and adjacent medial plantar soft tissues that are used in selected cases of plantar fasciitis and cavovarus foot deformity. The procedure aims to address pain and contracture of the plantar aponeurosis and intrinsic foot muscles, which may contribute to pathological foot alignment and gait instability. Due to the close proximity of highly variable neurovascular structures in the plantar region, precise anatomical knowledge and a patient-specific, personalized approach are essential to reduce the risk of iatrogenic injury during surgery. This study defined procedure-specific anatomical “low-risk” and “high-risk” zones. Methods: From the initial forty-two included feet, one specimen was excluded due to insufficient tissue quality, leaving forty-one specimens for analysis. The plantar aponeurosis, origins of the abductor hallucis muscle and regional neurovascular structures were analyzed. Distances between key landmarks were measured. Results: Abductor hallucis origins I and IV were present in all specimens, while origins II and III showed variable presence. Subdivision of muscle origin I was observed and was associated with the course of the medial calcaneal nerve. The medial calcaneal nerve demonstrated the closest proximity to origin I (3.2 mm) whereas both the medial and lateral plantar nerves showed close proximity to origin II (3 mm and 5.3 mm). Conclusion: Significant interindividual variability exists in the plantar region, highlighting the need for a personalized, anatomy-based approach for patients considered for surgical intervention. Anatomical “high-risk” zones were identified between origin I and the medial calcaneal nerve and near origin II by the bifurcation of the tibial nerve and posterior tibial artery. Anatomical “low-risk” zones were defined as dorsal regions at the calcaneus between origin I and the tibial neurovascular bundle, as well as medial areas near the malleolus.

Journal of Personalized Medicine doi: 10.3390/jpm16060301

Authors: Samantha Mairesse Antonino Maniaci Giovanni Briganti Jerome R. Lechien

Background/Objectives: Laryngeal disorders are among the most prevalent conditions in otolaryngology, yet they remain challenging to diagnose without specialized expertise. Artificial intelligence (AI) systems leveraging machine learning (ML) and deep learning (DL) have demonstrated promising performance for the automatic detection and classification of voice disorders and laryngeal lesions. Methods: This review synthesizes findings from 88 studies published between 2015 and 2025 on AI-based laryngeal disorder detection, considering physioacoustic mechanisms, databases and acquisition protocols, AI architectures and validation strategies, and diagnostic performance. Results: The current literature supports high internal accuracies for binary healthy versus pathological detection (88–99%); meanwhile, performance decreases for higher-level tasks such as pathophysiological category classification and identification, particularly under external validation. From a clinical perspective, clinicians do not infer specific diagnoses from isolated acoustic parameters such as percent jitter or shimmer. Instead, they rely on how these perturbation patterns dynamically evolve during connected speech, where alterations guide perceptual differentiation between underlying disorders. Recurrent sources of bias include dependence on a limited number of historical vowel-based databases, class and demographic imbalance, and limited ecological validity of recording protocols. Additional concerns involve the predominant use of internal cross-validation and insufficient reproducibility or code sharing. Conclusions: Drawing on the literature, an integrative three-level clinical recognition framework is proposed, delineating realistic use cases for AI as a decision-support tool rather than an autonomous diagnostic system. Key priorities for future personalized medicine and research are also identified, including diversified multi-center datasets, standardized methodological reporting, rigorous external validation, and compliance with regulatory and ethical requirements for medical AI deployment.

Journal of Personalized Medicine doi: 10.3390/jpm16060300

Authors: Areti Kourti Eirini Keskilidou Alexandra Skoura Paraskevi Karalazou Katerina Thisiadou Kali Makedou

Background/Objectives: Growth differentiation factor-15 (GDF-15) is a protein that belongs to the transforming growth factor beta superfamily and has been found elevated in cases of organ injury such as liver, kidney, heart, and lung, as well as cardiovascular diseases and cancer. Soluble urokinase plasminogen activator receptor (suPAR) is a protein which is expressed mainly on immune cells and endothelial and smooth muscle cells, and is a marker of severity and intensity of inflammation in acute and chronic diseases. The aim of the present study was to compare GDF-15 serum levels between patients with acute cerebrovascular incidents and healthy controls and to investigate the possible correlation of GDF-15 serum levels and inflammatory markers, such as serum C-reactive protein (CRP) and plasma suPAR, in the above-mentioned groups. Methods: This is a retrospective study. Thirty-one patients were included in the study, with a mean age ± SD of 67 ± 13 years, compared to 18 age-matched healthy controls. Results: In the patient group a statistically significant positive correlation of serum levels of GDF15 values with suPAR and CRP emerged (rs = 0.516, p = 0.003) and (rs = 0.409, p = 0.022), respectively, and no significant correlation was found in the group of controls (rs = 0.271, p = 0.277) and (rs = 0.423, p = 0.080), respectively. Conclusions: These findings support the role of inflammation as a key underlying mechanism in acute cerebrovascular injury and suggest that GDF-15 may serve as a valuable adjunct biomarker for assessing disease severity and inflammatory burden.

Journal of Personalized Medicine doi: 10.3390/jpm16060299

Authors: Nektaria Zagorianakou Stylianos Makrydimas Efthalia Moustakli Emmanouil D. Oikonomou Ioannis Mitrogiannis Eleni Sintou George Makrydimas

Endometriosis (EM) is a chronic, estrogen-dependent inflammatory disorder affecting approximately 6–10% of women of reproductive age in the general population and remains a major cause of chronic pelvic pain and infertility. High recurrence rates and enduring symptoms despite current treatments underscore the need for a more thorough understanding of its intricate biology. There is growing evidence that the interaction among oxidative stress (OS), microbiome dysbiosis, and epigenetic dysregulation contributes to immunological activation, hormonal imbalance, and the persistence of ectopic lesions. Important disease mechanisms, such as progesterone resistance, inflammatory signaling, and aberrant cellular proliferation, are influenced by epigenetic changes, which include aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs. Simultaneously, high levels of reactive oxygen species (ROS) reinforce lesion survival and chronic inflammation by promoting angiogenesis, fibrosis, and tissue damage. Changes in the microbiome also affect immunological responses, oxidative balance, estrogen metabolism, and epigenetic control, indicating the existence of interrelated pathogenic loops. This narrative review presents an integrated mechanistic framework for endometriosis, summarizing the available data that connect these pathways. Furthermore, the growing implications of non-invasive biomarkers and precision medicine techniques highlight the potential for improved diagnosis, disease classification, and targeted treatment approaches.

Journal of Personalized Medicine doi: 10.3390/jpm16060298

Authors: Vered Bar Adi Zundelevich Nancy Gavert Sara Aharon Bassima Ibrahim Anna Kosenko Guy Neev Ronen Viner Ravid Straussman Raanan Berger Seth J. Salpeter

Background/Objectives: Providing optimized and accurate treatment to cancer patients remains a major challenge in oncology care. The emergence of precision medicine tools to match the correct therapy to the patient has significantly advanced treatment modalities in the last few years. While genomics has been shown to be critical in selecting targeted therapies for a specific somatic mutation, the overall clinical benefit of broad genomic sequencing has been found lacking. Here, we evaluate the utility of our previously clinically validated ex vivo functional assay across different treatment scenarios, demonstrating its ability to transform predicted non-responders into predicted responders, rule out ineffective treatments, provide multiple treatment options, and validate physician choices. Methods: The evaluation was performed on a post-market surveillance study analyzing 312 patients, from which 278 patients had successful test reports (an 89.1% test success rate), with clinical outcomes available from 45 of those patients. Results: We show that in the group of patients with clinical response data, the tests yield a PPV of 91.18% and NPV of 90.91% with clinical utility impacting physician decision in 51.1% of cases. Further analysis of the entire cohort showed the potential of clinical utility to reach up to 59.3% on a large group of patients. Conclusions: The accurate prediction of patient response using the test suggests the potential for the platform to improve patient treatment in clinical practice by reducing ineffective drug use and optimizing personalized patient drug regiments.

Journal of Personalized Medicine doi: 10.3390/jpm16060296

Authors: Stefania Chiappinotto Chiara Moreal Aysun Bayram Nevenka Kregar Velikonja Aysel Özsaban Montserrat Solà-Pola Alba Roselló-Novella Kinga Zdunek Beata Dobrowolska Alvisa Palese

Background: The involvement of people living in situations of vulnerability has long been a central ethical issue in research, particularly in contexts marked by power asymmetries, limited access to resources, or restricted decisional autonomy. Although international ethical frameworks offer increasing guidance on protecting vulnerable participants, applying these principles in everyday research practice remains challenging, especially in qualitative and multi-country studies. This communication draws on the experience of the European Protecting You & Others project, an Erasmus+ initiative conducted across five countries. Methods: During the project design and implementation, the research team engaged in ongoing reflexive work to examine the ethical, methodological, and practical challenges encountered when defining vulnerability, involving participants living in situations of vulnerability, and adapting research activities and educational interventions to different specific needs. Reflexive notes and collective team discussions were used to identify recurrent challenges and the strategies adopted to address them. Results: Key challenges included (a) the difficulty of choosing an inclusive yet operational definition of vulnerability; (b) participants’ self-perceptions and tensions between externally assigned vulnerability; (c) risks of stigmatization associated with categorization; the use of respectful and context-appropriate language; and (d) the adoption of a shared international framework adapted to educational content across countries. Overall, vulnerability emerged as a dynamic and context-dependent condition that requires research designs, methodologies and interventions to remain open, flexible, and responsive throughout the study process. Conclusions: Studies involving people living in situations of vulnerability, particularly in international and multi-country contexts, should not rely solely on predefined classifications or standardized safeguards. Instead, adaptive procedures are needed to recognize how needs, barriers, resources, and forms of participation vary across individuals and contexts. Such openness may support more person-centered approaches to engagement, communication, and intervention adaptation, while preserving ethical consistency and methodological rigor across countries.

Journal of Personalized Medicine doi: 10.3390/jpm16060297

Authors: Giorgia Citriniti Filippo Crescentini Niccolò Possemato Nicolo Girolimetto Alessandra Rai Elena Bolletta Pietro Gentile Luca De Simone Fabrizio Gozzi Chantal Adani Maria Grazia Orlando Luca Cimino Carlo Salvarani Pierluigi Macchioni

Background/Objectives: Patients with acute anterior uveitis (AAU) have a high prevalence of occult spondyloarthropathy (SpA). Only one previous study investigated ultrasonographic (US) changes at peripheral entheses and joints in patients with acute anterior uveitis (AAU) and no study has used these data in recognizing unknown SpA as defined by ASAS criteria. No previous study compared non-granulomatous (NGAU) with granulomatous uveitis (GAU) for these US features. The objective of this study was to investigate the prevalence of US enthesis and joint abnormalities in a consecutive series of GAU and NGAU patients and to use these data in recognizing unknown SpA as defined by ASAS criteria. Methods: A total of 152 consecutive patients diagnosed with AAU [103 NGAU (42 B27−, 61 B27+) and 49 GAU] from the Immunology Eye Unit (AUSL-IRCCS Reggio Emilia, Italy) were enrolled in this study. Six peripheral entheses as well as knee and ankle joints were bilaterally evaluated by US according to standard methods. The presence of any elementary lesion, structural damage and active enthesitis, according to OMERACT definitions, was recorded. ASAS classification criteria of SpA were integrated with the US data of active enthesitis and joint synovitis in defining the presence of enthesitis and arthritis. Results: NGAU patients had a higher prevalence of entheseal erosions (11.9% vs. 9%, P0 0.009), of enthesis exhibiting a PD signal (29.7% vs. 12.2%, p = 0.025) and of active enthesitis (23% vs. 8.2%, p = 0.026) compared with GAU group. Unknown SpA as defined by ASAS criteria was recognized in 29 patients by clinical and MR/Rx examination of sacroiliac joints and in 13 additional patients with the use of US data. Conclusions: Acute entheseal lesions and erosions are associated with NGAU, without apparent influence of HLA-B27 positivity. US examination helps to recognize previously unknown SpA and to define the disease phenotype of patients, moving toward more personalized treatment.

Journal of Personalized Medicine doi: 10.3390/jpm16060295

Authors: Raquel Diaz Federica Murelli Franco Alessandri Maria Grazia Centurioni Fabio Barra Letizia Cuniolo Rebecca Allievi Abdallah Saad Chiara Cornacchia Francesca Depaoli Cecilia Margarino Ludovico Ponzielli Elisa Bertulla Chiara Boccardo Ilaria Baldelli Maria Stella Leone Michaela Adami Simonetta Franchelli Marianna Pesce Lucia Trevisan Piero Fregatti

Background: Women carrying BRCA1 and BRCA2 pathogenic variants face a substantially increased lifetime risk of breast and ovarian cancer. Risk-reducing bilateral mastectomy and salpingo-oophorectomy are well-established strategies to lower this risk. Traditionally, these procedures are performed in separate surgical sessions; however, a simultaneous approach may reduce the overall treatment burden. Evidence regarding the safety and feasibility of combined procedures remains limited. Methods: We conducted a retrospective observational study of BRCA1 and BRCA2 pathogenic variant carriers who underwent risk-reducing or therapeutic breast surgery at the Breast Unit of Policlinico San Martino Hospital (Genova, Italy) between January 2013 and March 2025. Patients were divided into two groups according to surgical strategy: a simultaneous procedure group undergoing risk-reducing mastectomy with immediate breast reconstruction and concurrent salpingo-oophorectomy in a single operative session, and a staged procedure group undergoing the same interventions in separate surgeries. Demographic, surgical, and postoperative variables were collected and analyzed descriptively. Results: A total of 124 BRCA1 and BRCA2 pathogenic variant carriers were included, with 73 patients undergoing the simultaneous approach and 51 undergoing staged procedures. The mean age was similar between the Simultaneous and Staged Procedure Groups Descriptively, similar patterns were observed across the two groups in terms of age distribution, postoperative outcomes, and length of hospital stay (mean 4.56 days). Minor complications such as seroma or delayed wound healing showed similar patterns across both groups, with no apparent increase in major complications in the simultaneous surgery group. Patients undergoing the simultaneous approach required fewer surgical sessions and were exposed to general anesthesia only once. Conclusions: Simultaneous risk-reducing mastectomy with immediate reconstruction and salpingo-oophorectomy appears to be a safe and feasible strategy for selected BRCA1 and BRCA2 pathogenic variant carriers. This integrated surgical approach may reduce the overall surgical burden, with descriptively similar perioperative outcome patterns.

Journal of Personalized Medicine doi: 10.3390/jpm16060294

Authors: Mar Gimeno-Coret Natsuki Oishi Rosa Hernández-Sandemetrio Enrique Zapater

Aim: The aim of this study was to analyze anterior and posterior thickness measurements of the thyroid cartilage lamina and to assess their association with age and sex, with a focus on interindividual anatomical variability relevant to personalized medialization thyroplasty. Methods: A retrospective observational study was conducted on 47 patients with unilateral vocal cord paralysis who were candidates for medialization thyroplasty. The thickness of the thyroid cartilage was measured at its anterior and posterior aspects on an axial CT scan at the level of the glottic plane. The Wilcoxon signed-rank test was used to compare anterior and posterior thickness measurements, and a generalized linear mixed model (was fitted to assess the influence of anatomical region, age, and sex on cartilage thickness, with patient as a random effect. Results: The posterior thickness was significantly greater than the anterior thickness (median difference = 1 mm; p < 0.001). No significant differences were found in the magnitude of this difference by gender (p = 0.37) or a significant correlation with age (r = 0.16; p = 0.28). The mixed model confirmed that anatomical region was the only statistically significant fixed effect: the posterior region showed a Risk Ratio of 1.71 (95% CI: 1.26–2.32; p < 0.001) relative to the anterior region, indicating that the posterior thickness was approximately 71% greater than that of the anterior region. The interaction between cartilage thickness, age and gender was not statistically relevant. Discussion: In our sample, the thyroid cartilage had a thicker posterior width in both sexes. These findings underscore the importance of individualized radiological assessment in laryngeal framework surgery and support a personalized approach to implant selection and surgical planning in medialization thyroplasty.

Journal of Personalized Medicine doi: 10.3390/jpm16060293

Authors: Apoenna Marina Noronha Brito Enilson Carmo Barbosa Dos Santos Andre Rodrigues Duraes Carla Daltro

Background: Resistant arterial hypertension (RAH) is a heterogeneous cardiovascular condition influenced by biological, behavioral, psychosocial, and neuroendocrine mechanisms. Within emerging precision medicine frameworks, psychobehavioral assessment may contribute to a more individualized characterization of patients with RAH and help identify modifiable dimensions associated with therapeutic resistance. This study evaluated the feasibility and preliminary outcomes of a brief psychobehavioral intervention in patients with RAH. Methods: This feasibility-oriented exploratory pre–post pilot study included 20 adults with RAH recruited from a tertiary outpatient clinic specialized in resistant hypertension. Participants underwent psychobehavioral assessment using the Hospital Anxiety and Depression Scale (HADS). Individuals presenting clinically significant anxiety and/or depressive symptoms (scores ≥ 8) received an individualized semi-structured brief cognitive–behavioral therapy (CBT) intervention consisting of 8–9 weekly sessions. Feasibility indicators included intervention adherence, completion of the protocol, operational flexibility, and absence of symptom worsening. Pre- and post-intervention emotional symptoms were compared using nonparametric analyses. Results: High baseline emotional burden was observed, with 90% of participants presenting anxiety symptoms and 60% depressive symptoms. Following the intervention, reductions in anxiety [median 11 (IQR 8–13) vs. 6 (4–8); p < 0.001] and depressive symptoms [10 (8–11) vs. 5 (3–8); p < 0.001] were identified. No worsening of symptoms occurred. The intervention demonstrated satisfactory feasibility and acceptability, including flexibility for remote and in-person delivery. Conclusions: These preliminary findings suggest that psychobehavioral phenotyping combined with individualized brief CBT may represent a feasible complementary strategy within precision-oriented cardiovascular care for resistant hypertension. Although causal inference cannot be established due to the pilot design and absence of a control group, the findings support further investigation of psychobehavioral dimensions as potentially relevant components of personalized hypertension management.

Journal of Personalized Medicine doi: 10.3390/jpm16060292

Authors: Thanansayan Dhivagaran Fahad R. Butt Krystal Grover Krish Devgan Kyran Sachdeva Varounan Dhivagaran Fatima Abid Brendan K. Tao Michael Balas Ioannis Dimopoulos Adil Bhatti

Background/Objectives: Inherited retinal diseases (IRDs) represent a group of rare conditions characterized by significant clinical and genetic heterogeneity. Historically, the diagnosis of these conditions relied primarily on clinical presentation and imaging techniques. This literature review aims to discuss the current state of progress and ongoing challenges in applying precision medicine approaches to IRDs and to examine how advances in genetic testing have transformed diagnostics and opened new therapeutic avenues. Methods: This review examines the application of genetic testing methods to IRDs, with particular focus on next-generation sequencing (NGS) technologies. The review also evaluates current patient selection protocols that combine genetic confirmation, retinal structural evaluation, and detailed genetic counselling to achieve optimal therapeutic outcomes. Results: The implementation of NGS has significantly enhanced diagnostic capabilities for IRDs by enabling precise identification of specific genetic mutations. This advancement has paved the way for targeted therapeutic strategies, exemplified by Luxturna for RPE65-related IRDs. However, several barriers to broader adoption of precision medicine persist, including high costs, varied access to services, and complexities in interpreting genetic variants. Conclusions: While the continued development of innovative therapeutic modalities offers promise for expanding treatment options for IRDs, fully harnessing the potential of current and emerging therapeutic technologies requires addressing existing economic, technological, educational, and infrastructural challenges.

Journal of Personalized Medicine doi: 10.3390/jpm16060291

Authors: George Triantafyllou Adam Mylonakis Nikoletta Dimitriou Chrysovalantis Vergadis Orestis Lyros George Tsakotos Maria Piagkou Dimitrios Schizas

Esophageal cancer remains a global challenge, with poor overall survival despite advances in multimodal therapy. Surgical resection continues to be the main curative treatment, yet esophagectomy is among the most technically challenging oncological procedures due to the esophagus’s location within the densely packed mediastinal corridor. Critical vascular, neural, and lymphatic structures surround the esophagus, and their frequent anatomical variations pose significant risks during mobilization, lymphadenectomy, and reconstruction. This review synthesizes current evidence on the anatomical variability in the vessels, nerves, lymphatics, and fascial compartments relevant to esophageal surgery. Particular emphasis is placed on aberrant arterial and venous patterns, recurrent and non-recurrent laryngeal nerve pathways, thoracic duct variants and atypical courses, and the fascial planes that are used to define surgical boundaries. By shifting the surgical paradigm from standardized anatomical assumptions to patient-specific structural mapping, we highlight how understanding these variations is driving the field of personalized surgical medicine. By integrating these anatomical insights with surgical approaches—including right and left transthoracic, transhiatal, and transcervical techniques—we highlight the implications of variations for intraoperative safety and postoperative outcomes. A thorough understanding of these relationships is essential for surgical planning, minimizing morbidity, and achieving oncological outcomes. Ultimately, a thorough understanding of these relationships is essential for patient-tailored surgical planning.

Journal of Personalized Medicine doi: 10.3390/jpm16060290

Authors: Georgios S. Chatzopoulos Larry F. Wolff

Background/Objectives: The aim of this retrospective cohort study was to identify and analyze the demographic, systemic, and clinical factors associated with the type of periodontal therapy (surgical vs. non-surgical re-treatment) to better inform multifactorial approaches in periodontal treatment planning. Methods: Electronic health records were analyzed to identify two distinct patient cohorts. The surgical cohort included patients who received one or more surgical procedures (i.e., gingival flap, osseous surgery). The non-surgical re-treatment cohort included patients who received scaling and root planing on more than one occasion and had no history of surgical treatment. Bivariate analyses (t-tests and Chi-square tests) were used to compare cohort characteristics, and a multivariable binary logistic regression model was developed to identify independent predictors of receiving surgical treatment. Results: A total of 3794 patients were included in the final analysis. The non-surgical re-treatment cohort presented with significantly more severe periodontal disease at baseline, including a higher number of bleeding sites and deep pockets (p < 0.001). The logistic regression analysis revealed that a higher number of bleeding sites (OR = 0.984) and deep pockets (OR = 0.987) were significantly associated with a decreased likelihood of receiving surgical treatment. Patients with high blood pressure (OR = 0.620) or arthritis (OR = 0.611) also had significantly lower odds of receiving surgery. Conversely, White patients had significantly higher odds (OR = 1.366) of receiving surgical therapy compared to non-White patients. Conclusions: Within the limitations of this study, the selection between surgical and non-surgical periodontal therapy is a multifactorial decision. Initial disease severity, specific systemic conditions, and patient race were significant predictors of the treatment provided. These findings highlight the necessity of adopting a multifactorial risk assessment framework in periodontology—one that integrates systemic and demographic risk factors alongside clinical parameters to tailor equitable, patient-specific care.

Journal of Personalized Medicine doi: 10.3390/jpm16060289

Authors: Giulia Colombo Marco Longhi Matteo Capuzzo Pietro Bisagni

Background: Gastrointestinal perforation is a life-threatening surgical emergency associated with high morbidity and mortality despite advances in imaging, perioperative care, and emergency surgical management. Early identification of patients at increased risk of death may improve perioperative risk stratification and support personalized clinical decision-making in emergency settings. Methods: We conducted a retrospective observational cohort study including 166 consecutive adult patients undergoing emergency surgery for gastric, duodenal, ileal, colonic, or intraperitoneal rectal perforation between January 2021 and December 2025. Appendiceal perforations, iatrogenic perforations, and anastomotic leaks were excluded. Univariate analysis was performed using appropriate non-parametric and categorical statistical tests. Variables with p < 0.05 were considered for multivariable logistic regression analysis. Postoperative variables potentially influenced by the outcome were excluded to reduce reverse causation and overadjustment bias. Age was analyzed as a continuous variable in regression analysis and subsequently dichotomized at 75 years for development of a simplified bedside score. Results: Overall in-hospital mortality was 22.3% (37/166). Increasing age (OR 1.08 per year increase, 95% CI 1.04–1.12; p < 0.001), septic shock at emergency department admission (OR 7.06, 95% CI 1.29–38.65; p = 0.024), and intraoperative vasopressor requirement (OR 6.45, 95% CI 1.34–31.10; p = 0.020) were independently associated with mortality. A simplified predictive score based on these variables demonstrated good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.83. Conclusions: Mortality following gastrointestinal perforation was associated primarily with early physiological derangement and patient frailty rather than anatomical or technical surgical factors alone. Early identification of high-risk patients may support perioperative risk stratification and patient-centered emergency surgical decision-making. The proposed predictive score should be considered preliminary and hypothesis-generating, as neither internal nor external validation was performed.

Journal of Personalized Medicine doi: 10.3390/jpm16060288

Authors: Sujin Kang Byron L. Lam Winston Lee Audina M. Berrocal Ninel Z. Gregori Carlos E. Mendoza-Santiesteban Jesse D. Sengillo

Inherited retinal diseases (IRDs) are a major cause of visual impairment worldwide, marked by extensive genetic and phenotypic heterogeneity. Recent estimates from the U.S. suggest a prevalence of nearly 1 in 1000 individuals, reflecting both disease burden and improved diagnostic recognition. This review traces the shift from linkage analysis and Sanger sequencing to high-throughput next-generation sequencing, including panel-based, whole-exome, and whole-genome sequencing. Phenotype-driven testing strategies and standardized variant interpretation frameworks, such as the American College of Medical Genetics and Genomics guidelines, have substantially increased diagnostic yield. Copy number and structural variant detection, transcriptomics, and functional assays further help address unresolved cases. Nonetheless, barriers remain regarding cost, access, and the interpretation of variants of uncertain significance. Molecular confirmation has become essential for access to novel gene-directed therapies, exemplified by voretigene neparvovec for biallelic RPE65 variants, and is often a prerequisite for clinical trial participation. The growing role of genetic testing highlights the need for multidisciplinary evaluation and standardized outcome measures. Emerging tools, including artificial intelligence-assisted variant prioritization, image-to-genotype modeling, and multi-omics analyses, bridge molecular diagnoses with clinical phenotypes, accelerating the transition to targeted therapies. Continued progress will depend on increased access, standardized analytical regulations, and the integration of emerging technologies into routine clinical care.

Journal of Personalized Medicine doi: 10.3390/jpm16060287

Authors: Jacopo Costantino Federico Ballatore Daniele Porcelli Barbara Romani Massimiliano Campoli Lorenzo Maria Zuccaro Giulia Marchionni Maria Alfarano Samuel Costantino Cristina Chimenti

Hypertrophic Cardiomyopathy (HCM) is one of the most common inherited cardiomyopathies and remains an important cause of ventricular arrhythmias and sudden cardiac death (SCD), particularly in younger individuals. Although the annual incidence of arrhythmic death is relatively low in contemporary cohorts, identifying those patients who may benefit from primary prevention with an implantable cardioverter-defibrillator (ICD) remains a major clinical challenge. Current risk stratification strategies rely on two principal paradigms. The European approach is centered on the HCM Risk-SCD score, whereas the American approach is mainly based on major clinical risk markers. Both strategies have important strengths and limitations, reflecting the persistent difficulty of accurately predicting arrhythmic events in such a heterogeneous disease. The HCM Risk-SCD score has demonstrated robust external validation and high specificity for identifying patients at higher risk, but it may fail to recognize some vulnerable individuals who remain below conventional treatment thresholds. For this reason, several additional risk modifiers have gained increasing relevance in contemporary practice. Among them, extensive late gadolinium enhancement, left ventricular systolic dysfunction, apical aneurysm, and clinically meaningful genetic findings may provide important incremental prognostic information beyond traditional models. Emerging disease-modifying therapies, in particular Mavacamten, may also influence future risk assessment. However, whether these improvements translate into a true reduction in SCD risk remains uncertain. Importantly, the decision to implant an ICD should not depend on numerical risk alone. It should arise from a process of shared decision-making integrating estimated risk, treatment burden, competing comorbidities, age, lifestyle, and patient values. In this context, the concept of an individualized threshold of “acceptable risk” becomes central. In conclusion, prevention of SCD in HCM is moving beyond conventional scores toward a personalized and dynamic framework in which predictive tools, advanced phenotyping, evolving therapies, clinical expertise, and patient preferences are combined to guide individualized care.

Journal of Personalized Medicine doi: 10.3390/jpm16060286

Authors: Abu Taha Yi Stephanie Zhang Chu Jian Ma Jay M. Stewart

Purpose: We investigated the association between age and retinal microvasculature parameters as measured by optical coherence tomography angiography (OCTA) and the modifying effect of diabetes status on this association. Methods: In this serial, cross-sectional study, 3 × 3 mm2 macular OCTA images were obtained from healthy adults and adults with diabetes mellitus (DM) with no diabetic retinopathy (DR) or with mild non-proliferative DR (NPDR). The parameters analyzed included foveal avascular zone (FAZ) area and perimeter, vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The associations between OCTA parameters and age were explored using multivariable linear regression models. Results: For the included 1855 patients (1855 eyes) (49% male; mean age: 55 years), the results were as follows: no diabetes (N = 217), DM no DR (N = 1352), and mild NPDR (N = 286). Increasing age was significantly associated with decreased SCP and DCP VD and VLD in the diabetic and non-diabetic groups. The slope of association between SCP and DCP FI and age in the diabetic patients was significantly different than that in the control patients. Conclusions: The strength of the association between aging and OCTA parameters differed significantly between the controls and those with early retinopathy, pointing to a potentially altered retinal vascular homeostasis secondary to diabetic pathophysiology. This finding offers insight into the early pathological biomarkers of DR and may guide early DR management for patients based on personalized risk scores.

Journal of Personalized Medicine doi: 10.3390/jpm16060285

Authors: Cosimo Aliani Piergiorgio Francia Cosimo Nardi Alessandra De Bellis Roberto Anichini Leonardo Bocchi

Emerging optical technologies may offer new opportunities for the non-invasive assessment of diabetic foot ulcers (DFUs), but the role of artificial intelligence (AI)-assisted autofluorescence-based approaches remains unclear. This scoping review aimed to map and summarise the published evidence on AI-assisted analysis of autofluorescence/fluorescence-based signals for DFU assessment and management. We searched Scopus, Web of Science, Embase, PubMed, CINAHL, Google Scholar, and the SPIE Digital Library, and also considered conference proceedings. We included English-language studies published between 2010 and October 2025. Of 197 records identified through database searching, 22 full-text articles were assessed for eligibility, and 5 studies met the inclusion criteria. Four studies focused on infection-related applications, specifically bacterial burden detection and Gram-type classification, whereas one study investigated tissue oxygenation estimation using a related optical imaging approach. All included studies were published between 2022 and 2025, were conducted in India, and four of the five evaluated the same device family or related variants. Overall, the evidence base was limited, geographically restricted, and technologically narrow. In addition, reporting of participant characteristics and AI methodology was often incomplete, with several studies relying on embedded proprietary or insufficiently described algorithmic components. Taken together, the available literature supports early proof-of-feasibility in restricted and largely device-specific evaluation settings rather than robust evidence of broad clinical validity, implementation readiness, or routine-care utility. Larger, more diverse, and independently validated studies with standardised acquisition procedures and more transparent AI reporting are needed before these approaches can be meaningfully evaluated for routine DFU care.

Journal of Personalized Medicine doi: 10.3390/jpm16060284

Authors: Simona Buonanno Carla Gaggiano Caterina Baldi Luca Cantarini Bruno Frediani Stefano Gentileschi

Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with a substantially increased risk of cardiovascular (CV) disease, driven by both persistent systemic inflammation and a high burden of traditional cardiometabolic risk factors. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs), licensed for type 2 diabetes mellitus and obesity, have attracted attention for their broader metabolic and cardiovascular benefits, raising the question of their potential role in RA. This scoping review summarizes current evidence on the impact of GLP-1RAs on RA disease activity, CV comorbidities, and the underlying immuno-metabolic mechanisms. Experimental studies suggest that GLP-1RAs could modulate key inflammatory pathways in synovial cells, reducing pro-inflammatory cytokine production, oxidative stress, and tissue-degrading enzymes, while improving mitochondrial function. Although clinical data remains limited, observational studies report improvements in disease activity, inflammatory markers, and pain in patients with RA treated with GLP-1RAs in addition to immunosuppressive treatment. Extensive evidence from randomized trials in metabolic populations demonstrates that GLP-1RAs improve glycemic control, induce significant weight loss, and reduce modestly but consistently blood pressure and atherogenic lipids, ultimately lowering major CV events and mortality. Although this evidence cannot be directly translated to RA populations, early real-world data specific to the disease suggest similar favorable trends, including reductions in cardiometabolic risk factors and thromboembolic events. Taken together, these findings suggest that GLP-1RAs may offer dual benefits in RA by addressing both metabolic dysfunction and inflammation. However, the current evidence base is heterogeneous and largely non-randomized, underscoring the need for dedicated trials.

Journal of Personalized Medicine doi: 10.3390/jpm16060283

Authors: Batya Davidovici Yarden Drutin Amir Ben-Tov Daniel Mimouni Yonit Wohl

Background: Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss and commonly coexists with other autoimmune diseases, suggesting systemic immune dysregulation. An association between AA and iron deficiency anemia (IDA) has been proposed, though prior studies have yielded conflicting results. Objective: Our aim was to examine the association between AA and IDA in a large, population-based cohort. Methods: We conducted a retrospective case–control study using data from a health maintenance organization (HMO) serving approximately 2.35 million individuals. We included 33,401 AA patients diagnosed between 2005 and 2019, matched 1:2 by age and sex with 66,802 controls without AA. Diagnoses of AA and IDA were confirmed through clinical coding by board-certified dermatologists and primary care physicians. Statistical analyses employed Kruskal–Wallis, Pearson’s χ2, and Fisher’s exact tests. Results: IDA prevalence was significantly higher in AA patients than in controls (15% vs. 10%; OR 1.61, 95% CI: 1.55–1.67; p < 0.01). IDA preceded AA in 40% of cases, followed AA in 58%, and occurred concurrently in 2%. Limitations: The retrospective design limits causal inference. Conclusion: This study reinforces an association between AA and IDA, highlighting the need to assess and manage IDA as a potential treatable comorbidity in AA patients.

Journal of Personalized Medicine doi: 10.3390/jpm16060282

Authors: Ilaria Ambrosini Roberto Francischello Salvatore Claudio Fanni Lorenzo Faggioni Francesca Pia Caputo Karolina Cwiklinska Gayane Aghakhanyan Emanuele Neri Riccardo Lencioni Dania Cioni

Background: Response to neoadjuvant therapy in locally advanced rectal cancer (LARC) is heterogeneous, and early identification of non-responders may help optimize treatment strategies and reduce unnecessary toxicity. This study aimed to develop and internally validate a machine learning model based on radiomic features extracted from baseline magnetic resonance imaging (MRI) to predict treatment response defined according to MRI tumor regression grade (mrTRG) at restaging MRI. Methods: In this retrospective single-center study, 86 patients with histologically confirmed LARC who underwent baseline and restaging MRI, neoadjuvant therapy, and surgery were included. Primary tumors were manually segmented on oblique axial T2-weighted images. A total of 107 radiomic features were extracted using PyRadiomics (vrs 3.0.1), with and without N4 bias field correction. Feature selection was performed using LASSO, followed by elastic net–regularized logistic regression. Model performance was evaluated using repeated stratified 5-fold cross-validation (20 repetitions). Treatment response was defined according to MRI tumor regression grade (mrTRG) at restaging, dichotomized into responders (mrTRG ≤ 2) and non-responders (mrTRG ≥ 3). Results: The model achieved a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73, with an accuracy of 72.5%, sensitivity of 79.2%, and specificity of 50%. Conclusions: Baseline MRI-based radiomics shows potential for identifying patients at higher risk of non-response to neoadjuvant therapy in LARC. However, limited specificity and the absence of external validation restrict immediate clinical applicability. Further validation in larger multicenter cohorts and integration with clinical variables are warranted to improve model robustness and generalizability.

Journal of Personalized Medicine doi: 10.3390/jpm16060281

Authors: Maria Concetta Torrione Andrea Gaia Azzarito Vanessa Marisi Maria Francesca Savina Angela Di Credico Riccardo Luberti Marzia Muzi Claudia D'Eramo Massimo Caulo Andrea Delli Pizzi

Background/Objectives: The clinical management of ductal carcinoma in situ (DCIS) remains controversial due to its heterogeneous biological behavior and uncertain risk of progression. Standard treatment often includes surgery and radiotherapy, although the actual recurrence risk varies considerably among patients. This study aimed to evaluate recurrence patterns and associated clinicopathological factors in a large single-center cohort of patients with pure DCIS. Methods: We retrospectively analyzed 403 patients with histologically confirmed pure DCIS treated with breast-conserving surgery or mastectomy between 2016 and 2023. Clinical, imaging, pathological, and treatment-related variables were assessed. Descriptive and exploratory comparative analyses were performed between patients with and without ipsilateral recurrence. Results: A total of 417 lesions were analyzed, with 21 ipsilateral recurrences (5%) observed during follow-up. Among recurrent cases, 57% were non-invasive recurrent DCIS and 38% were invasive carcinomas. Most recurrences occurred in patients treated with breast-conserving surgery, and 52% of recurrent patients had not received adjuvant radiotherapy. All recurrent cases were estrogen receptor–positive at initial diagnosis, whereas none had received endocrine therapy. No clear association between recurrence patterns and tumor grade or tumor size emerged in this exploratory analysis. No distant metastases or disease-related deaths were observed during follow-up. Conclusions: Recurrence after treatment for pure DCIS was relatively uncommon and frequently non-invasive. Traditional clinicopathological variables alone appeared insufficient to consistently identify recurrence patterns in this cohort. These findings support the need for more individualized risk stratification approaches integrating clinical, imaging, and molecular factors in order to reduce potential overtreatment in selected patients with DCIS.

Journal of Personalized Medicine doi: 10.3390/jpm16060280

Authors: Alishah Ahmadi Anthony J. Kaywood Areeb Ansari Alejandra Chavarria Oserekpamen Favour Omobhude Adam Kiss Mateusz Faltyn Jason S. Hoellwarth

Background/Objective: Osteoarthritis (OA) is the most common indication for total hip arthroplasty (THA), yet postoperative utilization and discharge outcomes vary substantially due to heterogeneous comorbidity burdens. This study applied unsupervised machine learning clustering to identify distinct comorbidity profiles among OA patients undergoing THA and to evaluate their association with non-routine discharge (NRD) and length of stay (LOS). Methods: The 2015–2021 National Inpatient Sample was queried using ICD-10 CM/PCS codes to identify patients with OA undergoing THA. Forty-nine comorbidities, complications, and in-hospital clinical covariates were incorporated into a k-modes clustering analysis. The Davies–Bouldin and Calinski–Harabasz indices were used to determine the optimal number of clusters. Multivariable logistic regression assessed adjusted odds of NRD across clusters, and Kruskal–Wallis H testing evaluated differences in LOS. Results: A total of 401,846 patients were included, and five distinct clusters were identified, ranging from 777 to 331,755 patients. Clusters with higher prevalence of renal dysfunction, cardiovascular disease, anemia, and heart failure demonstrated significantly increased risk of NRD (adjusted odds ratios up to 3.01, p < 0.001) and prolonged hospitalization, with median LOS up to 4 days. Lower-risk clusters exhibited shorter hospitalizations with median LOS of 2 days and higher rates of routine discharge. Kruskal–Wallis testing confirmed significant LOS differences across all clusters (p < 0.001). Conclusions: Machine learning clustering of OA patients undergoing THA identified clinically distinct subgroups with graded differences in postoperative hospital utilization. Patients with greater comorbidity burden experienced disproportionately higher risk of NRD and prolonged LOS. This data-driven framework highlights heterogeneity within the OA population and may inform future strategies for perioperative risk stratification and resource planning.

Journal of Personalized Medicine doi: 10.3390/jpm16060279

Authors: Lara Smoljo Tonka Mateljak Anita Racetin Petar Todorović Jelena Komić Luka Komić Petar Đolonga Danijel Antonio Grubišić Sandra Kostić Katarina Vukojević Nela Kelam

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cancer, characterized by frequent metastasis and poor prognosis. Epithelial–mesenchymal transition (EMT) plays a pivotal role in tumor progression. Protocadherin 9 (PCDH9) has emerged as a potential tumor suppressor, but its relationship with EMT markers in ccRCC remains unclear. This study aimed to investigate the expression patterns and prognostic significance of PCDH9, β-catenin (CTNNB1), Snail (SNAI1), and Vimentin (VIM) in ccRCC. Methods: Immunofluorescence analysis was performed on formalin-fixed paraffin-embedded tissue sections from 48 ccRCC patients (31 low-grade, 17 high-grade) and adjacent normal renal cortex. Findings were validated using The Cancer Genome Atlas (TCGA-KIRC) dataset via GEPIA2/GEPIA3 platforms, including differential expression, correlation, and survival analyses. Results:PCDH9 mRNA was significantly downregulated in ccRCC tumors (TCGA-KIRC), while VIM was upregulated at the transcriptomic level. Tissue-level immunofluorescence quantification revealed discordant patterns, highlighting the influence of cellular heterogeneity on bulk protein assessment. The strong positive correlation between PCDH9 and CDH1 observed in normal kidney was completely lost in tumor tissue. Unexpectedly, PCDH9 showed positive correlations with EMT transcription factors (ZEB1, SNAI1) in tumors. In univariate survival analysis, high PCDH9 and CTNNB1 expression were associated with improved overall survival. Multivariate Cox regression revealed endpoint-specific prognostic signatures: VIM independently predicted disease progression, while SNAI1 predicted overall mortality. CTNNB1 was consistently protective across both endpoints. Conclusions: Our findings support a tumor-suppressive role for PCDH9 in ccRCC and reveal disruption of epithelial adhesion molecule co-regulation during tumorigenesis. The identification of endpoint-specific prognostic signatures has implications for patient stratification and suggests that ccRCC exhibits a partial EMT phenotype rather than classical EMT.

Journal of Personalized Medicine doi: 10.3390/jpm16060278

Authors: Alesya S. Gracheva Darya A. Kashatnikova Maryam B. Khadzhieva Vladislav E. Zakharchenko Tatyana N. Krylova Artem N. Kuzovlev Lyubov E. Salnikova

Background: Chronic critical illness (CCI) following acute brain injury involves persistent immune dysfunction, yet its genetic determinants remain unclear. We investigated whether the rate of T-cell receptor excision circle (TREC) depletion—a proposed marker of adaptive homeostatic resilience—is associated with the burden of rare damaging genetic variants. Methods: Whole-exome sequencing (WES) was performed on a cohort of 84 patients (64 with traumatic brain injury, 20 with stroke). In a longitudinal sub-cohort (n = 27), patients were stratified into quartiles (Q1–Q4) based on the slope of their TREC trajectories. “Qualifying variants” (QVs) were defined using strict rarity (gnomAD allele frequency ≤ 0.001) and pathogenicity criteria. Gene-level burden (collapsing) analysis and permutation-based statistical testing (10,000 iterations) were employed to evaluate genetic enrichment in the extreme quartiles. Results: While baseline TREC levels were strictly age dependent (p < 0.0001), the rate of change (TREC slope) was age independent. Rapid TREC decline (Q1) correlated with significantly higher final SOFA scores (p = 0.001) and neutrophil-to-lymphocyte ratios (p = 0.020). Rare variant burden analysis revealed that Q1 patients were significantly more likely to harbor QVs in immune-related genes compared to the Q4 recovery group (odds ratio = 8.25; permutation p = 0.016). Patients with rapid decline were enriched for QVs in putative core “housekeeping” pathways essential for T-cell maintenance and DNA repair (e.g., ERCC3, FANCM), whereas variants in recovering patients were restricted to peripheral effector or structural pathways. Conclusions: Our findings suggest, as a conceptual framework, that an individual’s ability to maintain T-cell homeostasis during critical illness is influenced by their underlying genetic buffering capacity. We propose a hypothetical “two-hit” framework where physiological stress unmasks pre-existing fragilities in core homeostatic pathways—potentially reflecting a state of functional haploinsufficiency under extreme proliferative demand—leading to accelerated immune exhaustion. These results position the TREC slope as a dynamic, age-independent biomarker of genomic resilience in the ICU. All findings are exploratory and hypothesis generating.

Journal of Personalized Medicine doi: 10.3390/jpm16060277

Authors: Ahmed Abo Kalam Jameela Roshanuddin BalaSubramani Gattu Linga Faisal E. Ibrahim Rand Hamdan Thomas Farrell Zeena Saeed BU Shurbak Wael M. Y. Mohamed Nader Al-Dewik

Background: Vitamin D receptor (VDR) polymorphisms have been widely investigated as genetic determinants of neurodegenerative diseases, yet findings remain inconsistent and population-dependent. Evidence from the Middle East, North Africa, and Türkiye (MENA&T) regions, which is characterized by widespread vitamin D deficiency and distinct genetic backgrounds, has not been comprehensively synthesized. Methods: We conducted a systematic review and meta-analysis evaluating associations between four common VDR polymorphisms (ApaI rs7975232, FokI rs2228570, TaqI rs731236, and BsmI rs1544410) and the risk of multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD) in MENA&T populations. Six databases were searched from inception to November 2025. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using fixed- and random-effects models across multiple genetic contrasts. Subgroup analyses by ethnicity were conducted for MS. Study quality was assessed using the Newcastle–Ottawa Scale (NOS), and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Nineteen unique case–control studies (20 reports), including 4744 participants, were included. For MS, the ApaI polymorphism showed consistent associations with increased risk across genetic models (random-effects ORs = 1.4–1.9), with stronger effects in Arab and Iranian populations and no association in Turkish cohorts. FokI showed associations with MS under selected genetic models, particularly recessive and homozygous contrasts, although findings were not consistent across all analytical approaches. TaqI showed model-dependent associations with substantial heterogeneity, while BsmI showed no significant association. For AD, a meta-analysis of two studies showed no significant associations. For PD, ApaI showed associations with increased risk across several models without heterogeneity; however, these findings were based on a limited number of studies. Overall certainty of evidence ranged from very low to moderate. Conclusions: In MENA&T populations, VDR ApaI polymorphism shows consistent evidence of association with MS susceptibility, while FokI may be associated under specific genetic models; evidence for AD and PD remains limited and should be considered exploratory. These findings highlight population-specific genetic heterogeneity and underscore the need for further large-scale studies to confirm these associations. These population-specific genetic associations underscore the importance of incorporating VDR genotyping into precision medicine frameworks for neurodegenerative disease risk stratification in MENA&T populations, where vitamin D deficiency is highly prevalent.

Journal of Personalized Medicine doi: 10.3390/jpm16060276

Authors: Pratik Vijay Shah Anita Ng Andrew Shih Tony Pham Justin Wang Houman Khalili Cho Han Chiang Adit Singhal Alix Rosenberg Sally Ko Monica Wallin Douglas E. Gladstone

Classic Hairy Cell Leukemia (cHCL) and related conditions are rare, indolent B-cell malignancies characterized by distinctive morphological, immunophenotypic, and molecular features. Over the past decade, major advances in understanding the pathophysiology and molecular underpinnings have reshaped diagnostic and therapeutic approaches. This review synthesizes current knowledge on the cellular origins and signaling pathways that drive cHCL and Hairy Cell Variant (HCL-v)/splenic B-cell lymphoma/leukemia (SBLPN) and other molecular aberrations in disease pathogenesis. We discuss evolving diagnostic modalities, including flow cytometry, immunohistochemistry, and next-generation sequencing, that enhance diagnostic precision and disease monitoring. Additionally, we examine established and emerging therapeutic strategies—from purine nucleoside analogs (PNA) to targeted inhibitors and immunotherapies—that have significantly improved patient outcomes while highlighting challenges such as relapse and treatment resistance. By integrating insights from molecular biology and clinical practice, this review aims to provide a comprehensive understanding of cHCL and related disorders.

Journal of Personalized Medicine doi: 10.3390/jpm16050275

Authors: Nikolaos Martinos Christos Kroupis Marilena Stamouli Andreas C. Lazaris Georgia-Eleni Thomopoulou

Background: Persistent histologic inflammation may remain present in patients with inflammatory bowel disease (IBD) despite endoscopic remission. This study evaluated a clinically interpretable cytokine-based framework for risk stratification of residual histologic activity. Methods: In this prospective cohort study, 59 patients with IBD undergoing colonoscopy were included. Primary analyses were restricted to patients with ulcerative colitis (UC) in endoscopic remission (n = 31). Histologic activity was assessed using the Geboes score. Serum interleukin-10 (IL-10), interleukin-23 (IL-23), and C-reactive protein (CRP) were measured prior to endoscopy. Receiver operating characteristic (ROC) analysis and ROC-derived thresholds were used to evaluate biomarker performance and construct a cytokine-based risk stratification framework. Results: Among patients with UC in endoscopic remission, 14/31 (45.2%) demonstrated persistent histologic activity. IL-10 showed the strongest discriminatory performance for histologic activity (AUC 0.850), with a threshold < 3.9 pg/mL associated with sensitivity of 84.6% and specificity of 77.8%. Similar performance was observed using raw assay-reported IL-10 values (AUC 0.906). IL-23 showed limited overall discrimination (AUC 0.615). A combined IL-10/IL-23 framework stratified patients into progressively higher-risk subgroups, with histologic activity observed in 1/14 patients (7.1%) in the low-risk subgroup, 1/2 patients (50.0%) in the Intermediate A subgroup, 9/12 patients (75.0%) in the Intermediate B subgroup, and 3/3 patients (100%) in the high-risk subgroup (p < 0.001), although estimates for smaller subgroups should be interpreted cautiously. Reduced IL-10 levels were independently associated with histologic activity, whereas IL-23 primarily refined subgroup classification without substantially improving discrimination. Conclusions: An exploratory cytokine-based framework incorporating IL-10 and IL-23 may support risk stratification of residual histologic activity in UC during endoscopic remission. Larger multicenter studies are required to validate these findings and define their clinical utility.

Journal of Personalized Medicine doi: 10.3390/jpm16050274

Authors: Roberto Fabiani Valentina Squadroni Patrizia Rosignoli

Background/Objectives: The triglyceride–glucose (TyG) index, a reliable marker for insulin resistance, is strongly associated with T2DM, hypertension, and cardiovascular disease. Less well known is its relationship with cancer risk. The aim of this study was to quantify the association between the TyG index and risk of different types of cancer. Methods: Publications were searched in the PubMed, Web of Science, and Scopus databases using appropriate keywords. The PICOS framework was used to select the studies, and their quality was evaluated according to the “Newcastle–Ottawa Scale” (NOS). Meta-analysis was performed through a random-effects model using cancer risk parameters (RR: relative risk, OR: odds ratio and HR: hazard ratio) extracted from 26 selected studies associated with TyG index values. The weighted mean difference (WMD) was used to compare the mean of the TyG index in cancer patients to that of the control group. Heterogeneity was assessed by Cochran’s Q and I2 statistics, while publication bias was evidenced using the Egger test and the Begg test, and funnel plot asymmetry. Results: A higher TyG index value was observed in cancer subjects (9483) compared to healthy controls (978,675) (WMD: 0.23, 95% CI: 0.16–0.31, p < 0.0001, n = 15). A statistically significant increase in cancer risk was associated with the TyG index level, expressed as both a categorical (OR 1.33, 95% CI 1.22–1.45, p < 0.0001, n = 29) and continuous (OR 1.14, 95% CI 1.10–1.19, p < 0.0001, n = 27) variable. The effect was more evident in case–control/cross-sectional studies compared to cohort studies (OR 1.78, 95% CI 1.51–2.09 vs. OR 1.19, 95% CI 1.10–1.29 TyG categorical; OR 1.46, 95% CI 1.21–1.76 vs. OR 1.09, 95% CI 1.05–1.12 TyG continuous). Stratified analysis showed an increased risk of cancer occurrence for gastrointestinal, gynecological, colorectal, breast, and gastric sites, while no association was observed for endometrial, ovarian, prostate, lung or esophageal cancers. Conclusions: Our results evidence an increase in cancer risk associated with higher TyG index values. However, due to the low number of studies, the effect on specific tumor sites was not statistically significant. Additional epidemiological studies with a cohort design are necessary to confirm these associations.

Journal of Personalized Medicine doi: 10.3390/jpm16050273

Authors: Maria Perifanou-Sotiri Evaggelia Anyfanti Eleftherios Meletis Olympia Lioupi Chaido Pastaka Polychronis Kostoulas Konstantinos I. Gourgoulianis Garyfallia Perlepe

Background/Objectives: Two diagnostic approaches for sleep studies are commonly used worldwide: in-laboratory polysomnography [PSG] and home sleep apnea testing [HSAT]. Although HSAT has gained increasing acceptance due to its convenience and lower cost, clinical criteria for HSAT use remain complex and cannot be inferred directly from AHI/ODI severity indices alone. The aim of the present exploratory study was to examine associations between routinely collected demographic, clinical, and symptom-related variables and objective indices of disease severity, namely the apnea–hypopnea index [AHI] and oxygen desaturation index [ODI] as an initial, hypothesis-generating step toward future patient-level model development and validation. Methods: A retrospective observational analysis was conducted in 1100 individuals who previously underwent in lab-polysomnography [PSG] at the University Hospital of Thessaly, Greece, between 2006 and 2023. Specific demographic, clinical and symptom-related variables were included in this study [six continuous and fifteen categorical], which were analyzed in relation to AHI and ODI values. A three-step process was carried out: variable selection followed a screening and backward elimination process. Multivariable linear regression models were subsequently estimated within a Bayesian framework using Hamiltonian Monte Carlo methods. Results: Out of 1100 individuals, the mean age was 51.9 years with the predominant gender being male [76%]. Obesity [65.6%] and hypertension [40.5%] were the most common comorbidities. For AHI, male gender, body mass index [BMI], Epworth Sleepiness Scale [ESS] score, reported breathing interruptions during sleep, and chronic obstructive pulmonary disease [COPD] were significant predictors. For ODI, significant predictors included male gender, BMI, ESS score, breathing interruptions during sleep, daytime sleepiness, obesity, and COPD. COPD showed an inverse association with both indices. Conclusions: These findings support the feasibility of integrating routinely available clinical variables within a Bayesian probabilistic framework to estimate disease severity pre-test probability. The current analysis may not constitute a validated tool for HSAT versus PSG selection; however, it is an initial, hypothesis-generating step toward future model development.

Journal of Personalized Medicine doi: 10.3390/jpm16050272

Authors: Mattia Alexis Amico Andrea Taddei Matteo Casini Carlo Fumagalli Manlio Acquafresca Mario Moroni Angela Migliorini Francesco Meucci Carlo Di Mario Niccolò Marchionni Renato Valenti Nazario Carrabba

Background: Coronary computed tomography angiography (cCTA) is now indicated as a non-invasive tool for ruling out obstructive coronary artery disease (O-CAD) in patients who are candidates for transcatheter aortic valve implantation (TAVI) showing low-intermediate pre-test probability of O-CAD. In elderly and comorbid TAVI candidates, the safety and accuracy of cCTA as an alternative to invasive coronary angiography (ICA) for ruling out O-CAD remain to be established. Aim: To assess the feasibility, diagnostic accuracy, and clinical safety of cCTA for ruling out proximal O-CAD in elderly, comorbid, high-risk patients undergoing TAVI. Methods: We conducted a retrospective, single-center study including all consecutive patients with severe symptomatic aortic stenosis who underwent TAVI between January 2019 and December 2020. All patients underwent pre-TAVI cCTA. Patients with positive or non-diagnostic cCTA underwent ICA selectively (ICA group). In patients with no-O-CAD, ICA was omitted and proceeded directly to TAVI (no-ICA group). Accordingly, patients were divided into two groups: no-ICA and ICA group. Clinical follow-up was extended up to 5 years, with assessment of major adverse cardiovascular events (MACEs), mortality, heart failure hospitalizations, and unplanned revascularization. Results: Among 355 patients enrolled, 210 were included in the study. Among them, 140 (66.7%) had negative cCTA for O-CAD, and ICA was safely omitted in 132 patients (62.8%). cCTA was inconclusive in 43 patients (20.5%) and positive in 27 (12.9%). ICA confirmed O-CAD in 53 of 78 patients (67.9%) and PCI was performed in 35 of 53 (66.0%). The accuracy of cCTA for ruling in O-CAD was low (66.28%). During the follow-up period (1513 ± 508 days), the no-ICA group showed comparable outcomes to the ICA group in terms of periprocedural complications and long-term results—at both 1 and 5 years—for MACEs, heart failure hospitalizations, mortality and unplanned revascularization. Outcomes remain comparable between the two groups after performing matched-pair analyses. Conclusions: Our data show that cCTA may provide a reliable, safe, and effective alternative to ICA for ruling out obstructive CAD in elderly patients undergoing TAVI when image quality is diagnostic. A cCTA-based strategy allows deferral of ICA in most cases without compromising procedural safety or long-term clinical outcomes, enabling a personalized and tailored clinical pathway. Whether advanced CT techniques, such as CT-FFR and photon-counting CT, may help refine patient selection for invasive coronary assessment remains to be demonstrated.

Journal of Personalized Medicine doi: 10.3390/jpm16050271

Authors: Theoklitos Tsaprazlis Konstantinos Lappas Miltiadis A. Makrygiannakis Heleni Vastardis Eleftherios G. Kaklamanos

Background: Body Dysmorphic Disorder (BDD) is characterized by an intense preoccupation with perceived flaws in physical appearance, which can influence choices related to aesthetically driven healthcare. In orthodontics, this may cause a mismatch between a person’s subjective concern about their appearance and the treatment need determined by established indices. Therefore, orthodontic treatment indices are crucial to ensure that interventions are clinically justified rather than primarily motivated by disproportionate appearance-related distress. Objective: To systematically review and appraise the existing evidence on the connection between BDD and orthodontic treatment need as assessed by established indices. Materials and Methods: A systematic search of five electronic databases was conducted for studies published up to March 2026 that examined the association between BDD and orthodontic treatment need. Eligible studies included individuals undergoing orthodontic treatment or seeking orthodontic care, in whom BDD was evaluated using validated instruments and treatment need was assessed using established orthodontic indices. Risk of bias was assessed using the ROBINS-E tool. Results: A total of 2743 records were identified, and four observational studies met the inclusion criteria. Due to heterogeneity in study design, assessment methods and outcomes, findings were synthesized narratively. Orthodontic treatment need was assessed using the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN-DHC), the Aesthetic Component of the Index of Orthodontic Treatment Need (IOTN-AC), and the Index of Complexity, Outcome and Need (ICON). Two studies using IOTN-DHC reported a negative association between BDD and orthodontic treatment need, whereas studies using IOTN-AC and ICON found no significant relationship. Associations with sex, age, education, depression, and anxiety were inconsistent across studies. Conclusions: Current evidence suggests an inconsistent relationship between Body Dysmorphic Disorder and orthodontic treatment need, highlighting the relevance of personalized assessment in orthodontic decision-making. Given the limited number of studies and the high risk of bias, the findings should be considered preliminary, and further standardized studies are needed to clarify this association.

Journal of Personalized Medicine doi: 10.3390/jpm16050270

Authors: Beatriz Lechuga Carrasco Beatriz Piqueras-Sola Nicolás Cordero Tous Jonathan Cortés-Martín Juan Carlos Sánchez-García Raquel Rodríguez-Blanque Rafael Gálvez Mateos

Background: Traditional refills of intrathecal infusion pumps rely on manual palpation and the use of external templates, a method that can be challenging in patients with anatomical variations or a high body mass index. Ultrasound guidance has emerged as a precision-based alternative. This study aimed to evaluate the impact of the ultrasound-guided technique versus the conventional template-based technique on patient satisfaction. Methods: A quasi-experimental before-and-after study was conducted on a cohort of 45 chronic pain patients. Immediate satisfaction with procedure duration (IPP-SQ), overall treatment efficacy (CRES-4), and pain interference via the Brief Pain Inventory (BPI) were assessed. Results: The use of ultrasound was associated with significantly higher satisfaction regarding procedure duration, with a mean score of 5.00 (95% CI: 4.35–5.65) compared to 3.22 (95% CI: 2.70–3.75) with the traditional method (p < 0.001). Overall satisfaction (CRES-4) also improved significantly (12.4 vs. 11.3; p = 0.001). Regarding patient-reported outcome measures (PROMs), the mean pain intensity in the subsequent week was lower following the ultrasound technique (mean difference −0.48; p = 0.040). Technically, no first-attempt failures were recorded under ultrasound guidance in this sample, compared to a 20% re-attempt rate observed with the manual method. Conclusions: The transition from the traditional method to ultrasound-guided refill optimizes technical precision and substantially enhances the patient experience. By reducing pain and increasing satisfaction, ultrasound guidance proves to be a valuable resource for improving procedural precision, representing an advancement toward a more personalized medicine approach.

Journal of Personalized Medicine doi: 10.3390/jpm16050269

Authors: Almudena Aguilera-Diaz Philip B. Feinberg Jianmin Huang Eugene Spier Francis Barany Manny D. Bacolod

Background/Objectives: Bisulfite-based cell-free DNA (cfDNA) methylation assays enable the detection of clinically valuable epigenetic biomarkers but often cause DNA degradation and inconsistent conversion efficiency, limiting performance in low-input liquid biopsy samples. We aimed to develop and evaluate a fully enzymatic cfDNA methylation workflow that preserves DNA integrity and supports quantitative clinical detection. Methods: The assay integrates TET2-mediated oxidation and APOBEC3A deamination with RNase H2-guided primer design, uracil-DNA glycosylase error suppression, and dual-probe detection compatible with quantitative PCR (qPCR) and digital PCR (dPCR). Performance was assessed using serial dilutions of methylated HT29 DNA, unmethylated controls, and plasma cfDNA from colorectal cancer (CRC) patients and healthy donors. Analytical sensitivity, linearity, and concordance between platforms were evaluated. Results: The 40-marker panel demonstrated higher cumulative methylation scores and more frequent methylation-positive signals in CRC cfDNA compared to controls. dPCR confirmed single-molecule resolution and clear discrimination between methylated and unmethylated templates, with occasional double-positive partitions consistent with mixed allelic methylation. Signal intensity across the dilution series followed a four-parameter logistic model, achieving detection sensitivity below 0.2% methylated DNA. qPCR and dPCR results showed strong correlation across the HT29 dilution series (R2 = 0.80) and high concordance in classifying CRC and healthy samples. Conclusions: This TET2–APOBEC-based enzymatic cfDNA assay enables sensitive, quantitative, sequencing-free methylation detection under gentle conditions, supporting its application in early colorectal cancer screening and routine clinical liquid biopsy workflows.

Journal of Personalized Medicine doi: 10.3390/jpm16050268

Authors: Milica Markovic Gemma Lepri Marco Matucci Cerinic Serena Guiducci

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major extra-articular manifestation of rheumatoid arthritis (RA), contributing substantially to morbidity, mortality, and patient burden. Its diagnosis and management require integration of rheumatologic, pulmonary, and radiologic perspectives. Multidisciplinary approaches may provide a practical framework for implementing personalized medicine by integrating clinical and immunologic heterogeneity into individualized care strategies, although real-world data remain limited. Objectives: To synthesize primary studies published between 2015 and 2025 examining diagnostic, organizational, educational, and clinical aspects of RA-ILD within a multidisciplinary care framework. Methods: A narrative review of original research was conducted using PubMed and major publisher platforms from 1 January 2015 to 30 November 2025. Search terms included “rheumatoid arthritis,” “interstitial lung disease,” “RA-ILD,” “connective-tissue disease ILD,” “multidisciplinary,” “diagnosis,” “management,” and “patient experience.” Reviews and consensus statements were excluded. Results: Fifteen articles underwent full-text review, and five primary studies met all inclusion criteria and were incorporated into the final synthesis. RA-ILD emerged as a condition requiring coordinated interpretation of imaging, pulmonary physiology, and rheumatologic features. Multidisciplinary evaluation may improve diagnostic accuracy, reduce unclassifiable ILD, and support differentiation of autoimmune-related from idiopathic disease. A global assessment of ILD multidisciplinary team practices revealed substantial variability in structures and processes. Patient-reported data demonstrated significant emotional distress and a need for clearer communication and coordinated educational support. Conclusions: Effective RA-ILD management depends on collaborative assessment across specialties. Multidisciplinary care may support diagnostic precision and provide a practical framework for personalized medicine by integrating clinical, radiologic, and immunologic heterogeneity into tailored diagnostic and therapeutic strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16050267

Authors: Walaa Bakhamees Hend Alsafran Hani Basher ALBalawi Naif M. Alali Yousef A. Alotaibi Moustafa S. Magliyah

Background/Objectives: To assess the knowledge, attitudes, and practices of ophthalmologists in Saudi Arabia towards genomic medicine and genetic testing, in light of the growing significance of genomics in ophthalmology and the national transition towards precision medicine. Methods: A cross-sectional, questionnaire-based survey was conducted among ophthalmologists, including consultants, specialists, fellows, and residents, across Saudi Arabia. The questionnaire included four domains: demographics, knowledge of genomic principles and gene therapy, self-rated confidence in genetic tasks (scored 1–10), and attitudes toward genetic testing. Data were analyzed using descriptive and inferential statistics, with subgroup comparisons performed using chi-square tests and t-tests/ANOVA. Results: A total of 115 ophthalmologists participated (46% male, 54% female; mean age 34 years; mean post-board experience 4 years). Most were consultants (40%) and practiced in Riyadh (52%). Knowledge was variable: 92% correctly identified human chromosome count, and 99% recognized autosomal recessive inheritance, but only 9% answered DNA base-pairing correctly, and 54% recognized mitochondrial inheritance. Confidence was highest for referral to specialists (mean 7.3/10) and lowest for test selection and counseling (4.7/10). The internet was the primary knowledge source among our sample (65%). The majority of individuals had positive attitudes towards genomic medicine: 90% believed testing was beneficial, 89% considered it enhanced health outcomes, and 89% indicated they would undergo testing themselves. On the other hand, 77% indicated difficulty in access, 91% strongly concurred on the significance of privacy and confidentiality, and more than half expressed concerns regarding misuse and bias. Conclusions: Ophthalmologists in Saudi Arabia acknowledge the importance of genetics. Yet, there are substantial gaps in knowledge and familiarity with genomic medicine and genetic testing. To overcome these challenges, it is essential to integrate genetics into ophthalmology curricula.

Journal of Personalized Medicine doi: 10.3390/jpm16050266

Authors: Pasquale Niscola Valentina Gianfelici Marco Giovannini Carla Mazzone Maria Ilaria Del Principe

After many years of stagnation in the treatment of acute myeloid leukemia (AML), there is currently a rapid move towards personalized medicine. Improvements in molecular diagnostics, risk assessment tools, targeted therapies, overall patient fitness assessments, and quality-of-life assessments have significantly changed how patients are treated. Genetic and molecular analyses, risk and health assessments, and measurable residual disease (MRD) monitoring are now integral to the treatment plan for evaluating patient responses and recurrence. In this regard, lower-intensity treatments are provided to older or unfit individuals. On the other hand, younger patients are usually subjected to curative therapies such as intensive chemotherapy to induce remission. Depending on their fitness and disease risk, they can be considered for hematopoietic cell transplantation, which is done after close observation for MRD. In addition, newer therapeutic drugs and immunotherapy techniques are being applied for patient management. Tremendous strides have been made in improving the efficiency of treatment programs in the relatively new area of personalized AML therapy, with a focus on functionality.

Journal of Personalized Medicine doi: 10.3390/jpm16050265

Authors: Beani J. Forst Linda R. Chambliss David S. Majdalany

Preeclampsia (PE) is a multifactorial hypertensive disorder of pregnancy that significantly increases both short- and long-term cardiovascular risk for affected women. PE and cardiovascular disease (CVD) share common risk factors, including endothelial dysfunction, obesity, insulin resistance, and dyslipidemia. Women with a history of PE face a markedly elevated risk of chronic hypertension, heart failure, and adverse cardiac remodeling, with evidence suggestive of persistent vascular and myocardial changes after pregnancy. The complex pathophysiology of PE is multifactorial and is thought to involve a combination of abnormal placentation, immune dysregulation, and anti-angiogenic factors, which may induce permanent cardiovascular alterations. Genetic predispositions may further link PE with cardiomyopathies and peripartum cardiomyopathy. However, despite these well-established risks, standardized long-term surveillance and management strategies for women with prior PE remain lacking. Early identification and targeted intervention in women with a history of PE represent critical opportunities to mitigate future cardiovascular morbidity and mortality. This review highlights the urgent need for comprehensive, evidence-based strategies that incorporate personalized follow-up and risk stratification to improve cardiovascular outcomes in this high-risk population.

Journal of Personalized Medicine doi: 10.3390/jpm16050264

Authors: María Catalina Morón Barreto José-María Sánchez-González Diana Cristina Palencia Florez

Background/Objectives: This study aimed to evaluate the relationship between cumulative occupational exposure and ocular surface alterations in Colombian tomato farm workers, using data collected through a cross-sectional survey. In addition, the study sought to explore how occupational exposure duration may support risk stratification and targeted preventive strategies in this vulnerable population. Methods: A cross-sectional observational study was conducted involving 72 tomato farm workers in Colombia. Participants were grouped according to duration of agricultural work experience (<15 years vs. ≥15 years). Clinical assessments included slit lamp examination, tear film break-up time (BUT), Schirmer test, and fluorescein staining. Subjective symptoms were evaluated using the McMonnies Dry Eye Questionnaire. Ocular surface alterations, including conjunctival changes and Meibomian gland dysfunction, were documented and statistically analyzed between groups. Results: Workers with ≥15 years of experience reported significantly higher dry eye symptom scores (McMonnies mean = 8.19 ± 2.54) than those with <15 years (mean = 6.59 ± 2.61; p = 0.006). Schirmer test scores were lower in the experienced group (16.30 ± 11.48 mm vs. 22.71 ± 11.20 mm; p = 0.018), indicating reduced tear production. Bulbar conjunctival alterations and Meibomian gland obstruction were significantly more frequent in the experienced group (p = 0.002 and p = 0.013, respectively). No significant differences were found in BUT or eyelid findings. Conclusions: Long-term agricultural work was associated with increased dry eye-related symptoms and clinical signs of ocular surface compromise among Colombian tomato farm workers. From a personalized medicine perspective, occupational exposure duration may represent a useful risk-stratification factor to identify workers who could benefit from targeted screening, preventive counseling, protective interventions, and individualized follow-up. These findings support the implementation of tailored occupational eye health strategies to reduce cumulative ocular surface damage in vulnerable rural populations.

Journal of Personalized Medicine doi: 10.3390/jpm16050263

Authors: Federica Cariati Maria Grazia Orsi Anna Maione Francesca Bagnulo Raffaella Di Girolamo Luigi Carbone Alberto Servetto Fabrizio Farina Roberto Bianco Sandro Cassiano Esteves Carlo Alviggi Alessandro Conforti

Background/Objectives: Testicular cancer accounts for approximately 1% of all male malignancies, with an incidence ranging from 1 to 10 per 100,000 men and it predominantly affects young individuals, with nearly 60% of cases diagnosed between 15 and 35 years of age. In recent decades, the incidence of testicular cancer has markedly increased, paralleling a global rise in male infertility rates. Although chemotherapy is known to adversely affect fertility, the extent to which the tumor itself and its different histological subtypes impact semen quality remains incompletely understood. The aim of this study was to evaluate semen parameters in men diagnosed with testicular cancer prior to oncological treatment and to assess the possible association between tumor histology and semen quality. Methods: This retrospective study included data from 284 men diagnosed with testicular cancer who underwent semen cryopreservation prior to surgery, chemotherapy, or radiotherapy. Data were collected between January 2016 and June 2022 at the Maternal and Child Department of the University of Naples Federico II. Histopathological classification was available for 278 patients and revealed the following distribution: 59% (165/278) classic seminoma, 14.7% (41/278) seminomatous mixed germ cell tumors, 13.3% (37/278) non-seminomatous mixed germ cell tumors, and 12.6% (35/278) non-seminomatous germ cell tumors. Results: No significant association was observed between tumor histology and abnormal semen parameters. According to World Health Organization (WHO) reference values, semen parameters in patients with testicular cancer were predominantly distributed between the 5th and 25th percentiles. Microscopic semen analysis revealed significantly lower sperm concentration, total motility, and normal morphology in cancer patients (p < 0.001; p < 0.001; and p < 0.002, respectively). Logistic regression analysis showed a significant association between age and testicular cancer risk (p < 0.001), with a negative coefficient indicating that the likelihood of developing the disease decreases with increasing age. Additionally, patients with seminoma were significantly older than those with non-seminomatous tumors: on average, 4.07 years older than those with pure non-seminoma (p = 0.007) and 5.60 years older than those with mixed non-seminoma (p < 0.001). No statistically significant age differences were observed among non-seminomatous subtypes. Conclusions: These findings underscore the importance of systematic semen evaluation in young men diagnosed with testicular cancer and highlight the critical role of fertility preservation strategies in the comprehensive management of these patients.

Journal of Personalized Medicine doi: 10.3390/jpm16050262

Authors: Nicolò Girolimetto Francesco Caso Marianna Oliva Alessandra Rai Giorgia Citriniti Filippo Crescentini Luca Magnani Olga Addimanda Giulia Galletto Maria Grazia Orlando Pierluigi Macchioni Carlo Salvarani Francesco Ursini Niccolò Possemato

Background: In psoriatic arthritis (PsA), clinical tenderness and ultrasound (US) capture distinct yet related aspects of entheseal disease activity. However, their longitudinal relationship after initiation of biologic disease-modifying antirheumatic drugs (bDMARDs), and the clinical significance of early discordance during follow-up remain unclear. Methods: In this retrospective observational cohort study based on routinely collected medical records, patients with CASPAR-defined PsA and clinically and ultrasonographically active enthesitis at baseline (Clin+/US+) who initiated bDMARD therapy underwent paired, same-day, blinded clinical and US assessments at approximately 6 and 12 months. Agreement between clinical and US findings was quantified using Cohen’s kappa. Discordant states (Clin−/US+ and Clin+/US−) were prespecified, and predictors of Clin−/US+ status at 6 months were analyzed using models that accounted for within-patient clustering. Results: Thirty-nine patients contributed 82 entheses and were treated with either tumour necrosis factor inhibitors (53.8%) or interleukin-17 inhibitors (46.2%). At 6 months, agreement between clinical and US assessments was fair (κ = 0.286; 95% confidence interval [CI], 0.080 to 0.492), with 23.2% of entheses classified as Clin−/US+ and 52.4% as concordantly inactive. At 12 months, agreement improved to substantial-to-almost-perfect levels (κ = 0.779; 95% CI, 0.595 to 0.963), with only 1.2% of entheses remaining Clin−/US+ and 80.5% achieving concordant remission. NSAID exposure was the only significant predictor of Clin−/US+ status at 6 months in univariable analysis (odds ratio [OR], 3.82; 95% CI, 1.27 to 11.47; p = 0.017) and remained associated after multivariable adjustment (OR, 6.16; 95% CI, 1.14 to 33.2; p = 0.03). Conclusions: In PsA patients starting bDMARD therapy, clinical and US assessments of enthesitis showed partial discordance at 6 months, followed by greater convergence at 12 months. These findings suggest that clinical and imaging abnormalities may resolve asynchronously during follow-up and should therefore be interpreted in an integrated, time-aware manner. Residual US abnormalities in the setting of clinical improvement should be interpreted cautiously and within the broader clinical context.

Journal of Personalized Medicine doi: 10.3390/jpm16050261

Authors: Francesco Amico Scott Shannon Steve Rondeau

Background: Psychiatric assessments traditionally rely on the Diagnostic and Statistical Manual of Mental Disorders (DSM) for diagnostic guidance. This approach, however, is heavily based on the identification of cluster symptoms assessed through subjective interviews and questionnaires, without adequately controlling for overlapping symptoms or symptom specificity. This may lead to broad and often inaccurate diagnoses that overlook the patient’s unique experience and underlying neurobiological imbalances. As mental healthcare strives to move towards personalized medicine, incorporating more objective and precise measures of neuropsychological distress, it is essential to reduce the diagnostic and treatment inaccuracies that may stem from relying solely on empirical guidelines. This narrative review examines the limitations of the current approach and considers the potential role of quantitative electroencephalography (qEEG) as an adjunctive method that may enrich existing diagnostic processes. Methods: A structured literature search was conducted in Europe PMC on 31 January 2026. Original human studies and clinical trials in English with available abstracts were thematically selected. Results: The search yielded 1934 records, from which a focused subset of studies was selected based on direct relevance to the review themes. Conclusions: Integrating qEEG methods into traditional assessments could enhance diagnostic accuracy in psychiatric care and reduce patients’ exposure to inadequate treatments, ultimately leading to improved treatment outcomes and patient satisfaction.

Journal of Personalized Medicine doi: 10.3390/jpm16050260

Authors: Ömer Kokaçya Umut Dalgıç Abdullah Arslan İbrahim Tabakan Gazi Kutalmış Yaprak Ahmet Cemil Dalay Erol Kesiktaş

Background/Objectives: Reconstruction of complex soft-tissue defects of the arm and elbow remains challenging because of exposed neurovascular structures, wide joint mobility, and the need to preserve function. The pedicled latissimus dorsi (LD) flap remains a valuable option, particularly when recipient vessels are compromised or functional restoration is required. Given the heterogeneity of these injuries, treatment must be individualized according to each patient’s defect characteristics, functional demands, and rehabilitation goals, reflecting personalized medicine principles. This study evaluated the indications and outcomes of pedicled LD flap transfer in arm and elbow defects. Methods: All consecutive patients who underwent pedicled LD flap reconstruction for upper extremity soft-tissue defects at our institution (January 2015–January 2025) were retrospectively reviewed. Demographic data, defect etiology, flap type, reconstructive goals, complications, and functional outcomes were analyzed. Results: Twenty-six patients were included (mean age 28.5 ± 7.6 years; 84.6% male). Electrical burns were the predominant etiology (92.3%). A musculocutaneous flap was used in 22 patients (84.6%) and a muscle-only flap in 4 (15.4%); supplementary split-thickness skin grafting was required in 17 (65.4%). Reconstructive goals included elbow flexion restoration (±neurovascular repair and soft-tissue coverage) in 12 patients (46.2%) and humeral stump preservation for prosthetic use in 14 (53.8%). No total flap loss occurred. Complications included partial necrosis in 1 patient (3.8%), donor-site seroma in 3 (11.5%), wound dehiscence in 2 (7.7%), and recipient-site hematoma in 1 (3.8%). No patient required amputation or shoulder disarticulation. Conclusions: The pedicled LD flap is a reliable option for complex arm and elbow defects. By tailoring flap design, nerve management, and rehabilitation to individual patient needs, this approach exemplifies personalized reconstructive planning in upper extremity trauma.

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.