Journal of Personalized Medicine doi: 10.3390/jpm16070390

Authors: Yee Ming Lee Elizabeth Kearney David F. Kisor Christopher L. Farrell

Background/Objectives: Germline pharmacogenomics (PGx) testing performed by clinical laboratories and companies can reveal secondary findings (SF) related to gene-disease risk that clinicians must appropriately manage. This study evaluated PGx panel content for potential SF using the Clinical Pharmacogenomics (ClinPGx) resource, the Clinical Genome Resource (ClinGen), and the American College of Medical Genetics and Genomics (ACMG). Methods: A cross-sectional review of PGx panels offered by laboratories and companies was assessed for ClinPGx PGx annotation, ClinGen’s gene-disease validity and clinical actionability classifications, Clinical Pharmacogenetics Implementation Consortium (CPIC) incidental finding (IF) comments, and ACMG SF v3.3 inclusion. Results/Discussion: Forty-four testing sites provided panel content, yielding 125 genes, alleles, and variants. Of these, 26.4% (33/125) had PGx annotations while 73.6% (92/125) did not. A small subset of genes—CACNA1S, CFTR, G6PD, LDLR, MT-RNR1, and RYR1—had actionable recommendations based on CPIC and ACMG. Additional genes such as ATM, F5, ITGB3, and SCN1A may require consultation with genetics professionals. These findings underscore the need for a centralized resource for identifying gene-specific SF from germline PGx testing and guidance on their clinical management. Conclusions: PGx panels often include genes with and without established PGx annotations, some of which have potential SF implications. ClinGen’s PGx Working Group, which aims to integrate PGx into the broader context of genomic medicine, may be well-positioned to facilitate the development of a standardized framework for managing potential SF from panel-based PGx testing as the field evolves.

Journal of Personalized Medicine doi: 10.3390/jpm16070389

Authors: Athanasios Saplaouras Panagiotis Mililis Stavroula Koskina Athanasios Makris Sokratis Oikonomou Vasileios Cheilas Theodoros Efremidis Athena Batsouli Ourania Kariki George Bazoukis Sotirios Xydonas Theodoros Karamitsos Christodoulos Papadopoulos Nikolaos Fragakis Michael Efremidis Konstantinos P. Letsas

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12–0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88–1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection.

Journal of Personalized Medicine doi: 10.3390/jpm16070388

Authors: Akira Sezai Masanori Abe Takashi Maruyama Makoto Taoka Hisakuni Sekino Masashi Tanaka

Background/Objectives: Esaxerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA) with potent cardiorenal protective effects. However, the clinical effects of switching from eplerenone to esaxerenone in patients with chronic heart failure complicated by hypertension remain unclear. This study investigated the effects of switching from eplerenone to esaxerenone on blood pressure, heart failure biomarkers, renal function, and the renin–angiotensin–aldosterone system (RAAS). Methods: A total of 156 patients with chronic heart failure and hypertension who had been receiving eplerenone for more than one year were prospectively enrolled. Eplerenone was switched to esaxerenone, and the patients were followed for 6 months. Blood pressure, heart rate, brain natriuretic peptide (BNP), renal function, urinary albumin-to-creatinine ratio (UACR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary osmolality (U-OSM) were evaluated. Results: Following the switch to esaxerenone, systolic and diastolic blood pressure significantly decreased (both p < 0.001), whereas heart rate remained unchanged. BNP levels significantly decreased at 3 and 6 months (p = 0.008 and p = 0.002, respectively). Serum creatinine decreased (p = 0.017), estimated glomerular filtration rate increased (p = 0.028), and UACR significantly decreased at both time points (both p < 0.001). PRA and PAC significantly increased after switching (both p < 0.05), whereas angiotensin II levels remained unchanged. U-OSM significantly decreased (p = 0.01 and p = 0.002 at 3 and 6 months, respectively). No major cardiovascular events or severe adverse events were observed. Conclusions: In patients with chronic heart failure and hypertension, switching from eplerenone to esaxerenone was associated with reductions in blood pressure, BNP, UACR, and urinary osmolality, together with improvements in renal function. These findings suggest favorable physiological changes following the switch from a steroidal to a non-steroidal mineralocorticoid receptor antagonist, although confirmation in randomized controlled studies with clinical outcome measures is warranted.

Journal of Personalized Medicine doi: 10.3390/jpm16070387

Authors: Thomas Repantis Ioanna Lianou Ioannis Papaioannou Maria Papathanasiou Lexi de Jager Andreas Filippopoulos Andreas Baikousis

Background/Objectives: Minimally invasive (percutaneous) pedicle screw fixation (PPSF) was initially introduced for the treatment of degenerative spinal deformities. Since then, its indications have progressively expanded to a broad spectrum of spinal pathologies. This method has gained increasing acceptance in spinal surgery due to lower morbidity when compared with conventional open procedures. This study presents a comprehensive review of the recent literature on hybrid minimally invasive spinal instrumentation techniques, focusing on the combined use of PPSF with open or mini-open approaches and their roles in personalized surgical management. Methods: A literature search was conducted in PubMed and Web of Science to identify studies reporting expanded indications of percutaneous pedicle screw fixation (combined with other approaches), novel surgical techniques, and their clinical outcomes. Results: Thirty-five studies met the inclusion criteria and were categorized according to pathology. Most included studies were retrospective observational investigations corresponding to Oxford CEBM Levels III–IV evidence, with a smaller number of prospective studies and systematic reviews. Conclusions: The findings from this review highlight the expanding role of hybrid methods in the management of complex spinal disorders. These approaches provide adequate stability and enable decompression or deformity correction, while minimizing tissue trauma, blood loss, and perioperative morbidity, thereby facilitating improved recovery and functional outcomes. The included literature predominantly represents moderate levels of evidence, supporting a patient-specific, pathology-driven surgical strategy that optimizes individualized outcomes in spinal surgery.

Journal of Personalized Medicine doi: 10.3390/jpm16070386

Authors: Dimitris Koukoulias Eustathios Kenanidis Michael Potoupnis Panagiotis V. Tsaklis Eleftherios Tsiridis

Background/objectives: Evidence on gait and postural recovery after robotically assisted total knee arthroplasty (raTKA), particularly with the ROSA system, remains limited. This study compared early gait, postural, functional, and patient-reported outcomes (PROMs) between ROSA raTKA and manual TKA (mTKA), with PROMs also assessed at final follow-up. Methods: This comparative cohort study included primary TKA patients treated by a single senior surgeon using the same implant and alignment strategy. Patients underwent either ROSA raTKA or mTKA. At three months, a senior physiotherapist assessed quadricep and tibialis anterior maximum voluntary isometric strength (MVIS), centre-of-mass (CoM) kinematics, lower-limb weight distribution, timed-up-and-go (TUG), range of motion (ROM), KOOS Pain, activities of daily living (ADL), and quality of life (QoL). The same KOOS domains were compared at final follow-up. Results: Seventy primary TKAs were included: 46 raTKAs and 24 mTKAs. No intraoperative complications occurred. Groups were comparable for age, BMI, sex, grip strength, and preoperative KOOS. At three months, no significant differences were found in quadricep MVIS (p = 0.257), tibialis anterior MVIS (p = 0.327), CoM kinematics (p = 0.066), weight distribution (p = 0.189), TUG (p = 0.599), ROM (p = 0.165), or KOOS domains. At final follow-up, KOOS-ADL (p = 0.041) and QoL (p = 0.032) were better in the raTKA group, but after Holm–Bonferroni correction, they were no longer significant (QoL, p = 0.384; ADL, p = 0.451). Conclusions: ROSA raTKA showed comparable early gait and postural recovery to mTKA. The marginal differences in KOOS domains are exploratory, as they were no longer significant after multiple-comparisons correction.

Journal of Personalized Medicine doi: 10.3390/jpm16070385

Authors: Carmine Iacovazzo Andrea Uriel de Siena Katarzyna Kotfis Pasquale Buonanno Serena Nappi Raffaele Merola Maria Vargas Giuseppe Servillo Pratik P. Pandharipande Annachiara Marra

Background: Non-invasive ventilation (NIV) is a well-established approach for preventing endotracheal intubation (ETI) in critically ill patients with acute respiratory failure (ARF). Sedation is frequently used to improve comfort. This study aimed to analyze the impact of sedation during NIV on ETI rates and NIV success in critically ill patients. Methods: We systematically searched in PubMed, EMBASE, MEDLINE, Web of Science, and CENTRAL up to September 2023, including prospective observational studies, retrospective cohort studies (nRCTs), and randomized controlled trials (RCTs). Primary outcomes were NIV success and ETI rates; secondary outcomes were hypotension, bradycardia, 28-day mortality, delirium, and oversedation. Proportions were used for observational studies, odds ratios (OR) for retrospective studies, and risk ratios (RR) for RCTs. Retrospective studies compared intermittent and continuous analgosedation, while RCTs evaluated dexmedetomidine versus other sedatives, including direct comparisons. Results: Four observational studies, 2 retrospective studies, and 7 RCTs (738 patients) were selected. Dexmedetomidine showed increased NIV success (RR = 1.167, 95%C.I. 1.014–1.343, p = 0.032) and reduced ETI rate (RR = 0.553, 95%C.I. 0.405–0.755, p < 0.001), but higher rate of bradycardia (RR = 2.172, 95%C.I. 1.819–4.042, p < 0.001) and hypotension (RR = 2.441, 95%C.I. 1.608–3.706, p < 0.001). nRCTs revealed higher NIV success (Proportion = 0.694, 95%C.I. 0.528–0.912, p = 0.009), moderate ETI rates (Proportion = 0.379, 95%C.I. 0.282–0.511, p < 0.001), and low bradycardia and hypotension rates. Conclusions: Our findings suggest that sedation, particularly dexmedetomidine-based strategies, may enhance NIV success and lower ETI rates. However, dexmedetomidine was also associated with higher rates of bradycardia and hypotension, especially compared with midazolam. To establish the correct sedation strategy, it is important to tailor the drug to the patient, considering its hemodynamic instability, delirium risk, and mortality risk.

Journal of Personalized Medicine doi: 10.3390/jpm16070384

Authors: Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Diana Chavez-Muñoz Rebeca Garazi Elguezabal Rodelo Octavio Gonzalez-Chon Luigi La Via

Background/Objectives: Intraoperative hypotension (IOHs) affects up to 87% of patients under general anesthesia and is consistently associated with acute kidney injury, myocardial damage, stroke, and mortality. The intermittent unavailability of ephedrine across healthcare systems underscores the need for evidence-based alternatives. This review critically evaluates pharmacological options for IOH when ephedrine is unavailable, focusing on receptor pharmacodynamics, population-specific evidence, and clinical consequences of inadequately managed hypotension. Methods: A narrative, evidence-based review was conducted examining mechanisms of action, dosing strategies, adverse effect profiles, and clinical applicability of key vasoactive agents: ephedrine, phenylephrine, norepinephrine, and epinephrine. Population-specific evidence across obstetric, pediatric, and elderly cohorts was synthesized from randomized controlled trials, meta-analyses, and observational studies. The clinical impact of IOH on neurological, cardiovascular, and renal outcomes was reviewed. Results: Each vasopressor exhibits a distinct receptor-selectivity profile that determines its hemodynamic effect and optimal clinical context. Norepinephrine’s favorable α1/β1 balance tends to preserve cardiac output better than pure α1-agonists and has emerged as a promising alternative in obstetric and elderly populations, although the optimal agent ultimately depends on the underlying mechanism of hypotension and individual patient characteristics. Epinephrine provides combined vasopressor and inotropic support for hypotension with myocardial depression. IOH is associated with a greater than twofold increase in postoperative AKI and significantly elevated risks of myocardial infarction and stroke, with outcomes driven by cumulative hypotensive exposure rather than isolated pressure nadirs. Conclusions: Effective management of IOH requires individualized vasopressor selection guided by underlying pathophysiology, cardiovascular profile, and surgical context. A physiology-based strategy—rather than protocol-driven drug substitution—enables anesthesiologists to achieve precise hemodynamic control and preserve end-organ perfusion even when ephedrine is unavailable.

Journal of Personalized Medicine doi: 10.3390/jpm16070383

Authors: Petra Valković Zujić Nina Bartolović Manuela Avirović Emina Babarović Lucija Požgaj Maja Prutki Emina Grgurević Dujmić Ana Car Peterko

Background: Accurate delineation of ductal carcinoma in situ (DCIS) remains a key challenge in surgical planning. Although contrast-enhanced mammography (CEM) improves lesion detection, its clinical role in informing individualized surgical strategies remains unclear. This study evaluated the impact of CEM on preoperative assessment and surgical planning, with particular emphasis on whether its effect varies across patient subgroups. Methods: This multicentre pilot observational cohort study included 102 patients: 51 prospective patients undergoing preoperative CEM and mammography (MMG) and 51 retrospective controls assessed with MMG alone. Imaging-derived lesion size and planned resection volume were compared with pathological size using correlation analysis, intraclass correlation coefficient (ICC), and Bland–Altman methods. Surgical outcomes were assessed, and subgroup analyses explored differences according to CEM enhancement status. Results: CEM showed improved correlation with pathological DCIS size compared with MMG (ρ = 0.54 vs. 0.37), with the strongest agreement in CEM-positive lesions (ρ = 0.67; ICC 0.745). However, its clinical impact was not uniform. At the population level, CEM did not significantly change planned resection volume or surgical thresholds. In contrast, in CEM-positive patients, CEM was associated with larger planned resections, proportional to pathological tumor burden. Reoperation rates were lower in the CEM cohort (5.9% vs. 17.6%), without statistical significance, and margin status was comparable. Conclusions: The impact of CEM on surgical planning in DCIS is heterogeneous and largely confined to patients with enhancing lesions. These findings suggest that the value of CEM may lie in its selective use, where it can refine assessment of disease extent in specific subgroups rather than in routine application. Further studies incorporating predictive approaches are needed to support risk-adapted imaging strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16070382

Authors: Xue-Qing Li Roslyn Stella Thelingwani Leif Bertilsson Ulf Diczfalusy Tommy B. Andersson Collen Masimirembwa

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Journal of Personalized Medicine doi: 10.3390/jpm16070381

Authors: Shilpa Bhandi Ahmed Al Kahtani Mohammed Mashyakhy Loai Alsofi Prabhadevi C. Maganur Satish Vishwanathaiah Luca Testarelli Andrea Del Giudice Deepak Mehta Nishant Vyas Vikrant R. Patil A. Thirumal Raj Shankargouda Patil

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Journal of Personalized Medicine doi: 10.3390/jpm16070380

Authors: Tímea Szigethi Dorottya Olajos Levente Molnár István Ferenc Édes György Bárczi Dávid Becker László Gellér Béla Merkely Zoltán Ruzsa

Background: Transradial access has become a preferred strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) because of lower access site complication rates and increasing feasibility for complex CTO techniques using large-bore slender or sheathless systems. However, long-term outcomes after successful transradial CTO recanalization and their predictors remain incompletely defined. We aimed to identify long-term clinical and procedural predictors of major adverse cerebrovascular and cardiac events (MACCEs) after successful transradial CTO PCI. Methods: We performed a prospective dual-center cohort study including 227 consecutive patients who underwent successful transradial CTO PCI at two high-volume catheterization laboratories with dedicated CTO programs. A total of 405 CTO PCI procedures were screened; all femoral access cases were excluded and only transradial cases were eligible. Baseline clinical characteristics, left ventricular ejection fraction (LVEF), lesion complexity including J-CTO score, coronary disease extent, and procedural variables were prospectively collected and/or verified from institutional databases. The primary endpoint was MACCEs, defined as a composite of all-cause death, non-fatal myocardial infarction, target vessel revascularization, and stroke/transient ischemic attack. Event rates were estimated using Kaplan–Meier methods. Predictors were explored using Cox proportional hazards regression with clinically relevant covariates and procedural characteristics entered into multivariable models. Results: Among 227 patients with successful transradial CTO recanalization and complete 5-year follow-up among survivors, cumulative MACCEs and all-cause mortality were 44.0% and 21.5%, respectively. In multivariable Cox analysis, prior myocardial infarction, right coronary artery target vessel, and a higher number of implanted stents were independently associated with increased MACCE risk, whereas previous PCI and preserved LVEF (≥40%) were associated with lower MACCE risk. For all-cause mortality, preserved LVEF was independently protective, while right coronary artery target vessel intervention was associated with increased mortality risk; severe chronic kidney disease showed a significant univariable association and remained a strong signal after multivariable adjustment. Conclusions: After successful transradial CTO PCI, long-term MACCEs appear to be driven primarily by baseline comorbidity and coronary disease burden. No deaths were related to access site bleeding, and vascular access was not associated with fatal complications. These findings contribute to personalized cardiovascular medicine by identifying readily available clinical, anatomical, and procedural factors that enable individualized long-term risk stratification following successful transradial CTO recanalization. Integrating these predictors into post-procedural assessment may support tailored secondary prevention, follow-up strategies, and patient management according to individual risk profiles.

Journal of Personalized Medicine doi: 10.3390/jpm16070379

Authors: Paul Whiteley Kevin Carr Paul Shattock Malcolm Hooper Carol Stott Karl Hardy Ben Marlow Chandoshi Rhea Mukherjee Athena Whiteley

Plural autisms offer one important way of organising the massive heterogeneity that is currently included under the singular diagnostic label of autism spectrum disorder (ASD). Characterised exclusively by behavioural criteria related to social communication skills and restricted or repetitive patterns of symptoms, the observable diversity in presentations and developmental trajectories partially explains the lack of universally applicable biomarkers and answers about underlying biology. One particularly important area potentially pertinent to several manifestations of the plural autisms is a connection to the immune system, whether noted across differing patterns of immune functions or following immune challenge in the context of inflammatory processes exerting an effect on developmental processes and behaviour. Utilising a narrative review, we highlight various research analysing a role for immune functions in the context of the heterogeneous autisms stretching across under-, over- and autoimmune processes. Current evidence for immune system involvement in various autisms carries considerable limitations, and studies are often based on small sample sizes, focusing on selective clinical subgroups, and using case-based observations. Notwithstanding the available evidence, substantial and more detailed further studies are required in relation to immune-related screening, building also on the currently limited evidence on the potential usefulness of personalised immune-affecting interventions following appropriate screening and identification of pertinent immune-related issues.

Journal of Personalized Medicine doi: 10.3390/jpm16070378

Authors: Rocío Martín-Valero Antonia M. Ruiz-Moreno Pablo J. Gallardo-García María Dolores Martínez Colmena Catalina Muñoz Pagan Pedro González-Rojas Paloma Ortega Quiñonero

Background/Objectives: Genitourinary Syndrome of Menopause (GSM) negatively affects quality of life in postmenopausal women, causing sexual dysfunction, vaginal atrophy, and pelvic discomfort. Personalized medicine highlights the need for individualized, non-hormonal therapeutic options for women with contraindications to or preferences against hormonal treatment. Non-hormonal therapies, such as laser treatments, have emerged as potential alternatives, but evidence comparing intravaginal and extravaginal K-Laser therapy remains limited. This study aimed to evaluate the efficacy of intravaginal and extravaginal K-Laser therapy on the symptoms of Genitourinary Syndrome of Menopause (GSM) in postmenopausal women. Methods: In this single-center, randomized, single-blind, placebo-controlled trial, 57 postmenopausal women were randomly assigned to receive either intravaginal and extravaginal K-Laser Cube Plus 30 therapy (n = 36) or a simulated control treatment (n = 21). The primary outcome was sexual function, measured by the Female Sexual Function Index (FSFI). Secondary outcomes included vaginal pH and pelvic floor muscle function assessed via the PERFECT protocol. Outcomes were assessed at baseline and after 6 weeks. Results: Sixty-seven women were enrolled, and ten were lost to follow-up. The treatment group showed significant improvements over the control group in FSFI (mean difference = 6.38; p < 0.001), PERFECT protocol scores (mean difference = 0.78; p = 0.004), CPPQ-Mohedo (mean difference = 5.44; p < 0.001), and Menopause Rating Scale (mean difference = 6.50; p = 0.017). Significant reductions were also observed in vaginal dryness, vulvar dystrophy, and atrophy (p < 0.001). Conclusions: Intravaginal and extravaginal K-Laser therapy appears to be a safe and effective non-hormonal treatment for GSM and may support personalized management strategies. However, further well-designed randomized clinical trials with larger samples, longer follow-up of both laser-treated and control groups, and objective outcome measures are needed to provide higher-quality evidence regarding efficacy and identify the patients most likely to benefit.

Journal of Personalized Medicine doi: 10.3390/jpm16070377

Authors: Ayokunle Osonuga Madhavi Dave Ikponmwosa Jude Ogieuhi David B. Olawade Stergios Boussios

Cardiovascular disease remains the leading global health challenge, claiming approximately 19.8 million lives annually. The convergence of wearable technology and artificial intelligence represents a transformative shift in cardiovascular healthcare, enabling continuous real-time monitoring beyond conventional clinical settings. This narrative review synthesises current evidence on integrating consumer-grade and medical-grade wearable devices with AI algorithms for continuous cardiovascular monitoring applications, with particular attention to real-world translational applicability and global health equity. This review examined the technological landscape of wearable cardiovascular monitoring devices, including smartwatches with photoplethysmography and electrocardiogram capabilities, continuous cardiac monitoring patches, and emerging biosensor technologies. Also, the review explored AI methodologies, particularly machine learning and deep learning architectures, employed in processing complex physiological data streams from these devices. Clinical applications demonstrate impressive capabilities: arrhythmia detection with sensitivity rates exceeding 98%, continuous blood pressure monitoring through cuffless technologies, heart failure decompensation prediction, and cardiovascular risk stratification. However, substantial challenges persist, including data quality assurance, algorithm interpretability, regulatory compliance, and seamless clinical workflow integration. Privacy concerns, health disparities in algorithm performance, and the need for robust validation across diverse populations remain critical considerations. AI-enhanced wearable systems hold considerable potential for shifting cardiovascular care from reactive treatment paradigms towards predictive, preventive, and precision medicine approaches. Future directions include edge computing architectures, federated learning approaches, personalised AI models, enhanced interoperability with electronic health records, and expansion to resource-limited settings, ultimately improving patient outcomes whilst reducing healthcare costs.

Journal of Personalized Medicine doi: 10.3390/jpm16070376

Authors: Nick Weidner Christian von Löffelholz Robert Patejdl Jan Seyfferth Heinrich Volker Groesdonk

Gastrointestinal dysfunction is common in critically ill patients and frequently compromises the delivery and tolerance of enteral nutrition. Traditional bedside markers such as gastric residual volume or nonspecific abdominal symptoms provide only limited diagnostic accuracy and often fail to capture dynamic alterations in gastrointestinal function. Gastrointestinal ultrasound (GIUS) has emerged as a noninvasive, bedside-applicable method that enables structural and functional assessment of the gastrointestinal tract and may support more individualized nutritional management in intensive care. This narrative review summarizes the physiology and pathophysiology of gastric emptying and intestinal transit in critically ill patients, reviews established GIUS protocols, including Gastrointestinal and Urinary Tract Sonography (GUTS), Acute Gastrointestinal Injury Ultrasound Scoring (AGIUS), the Lai protocol, and the Ultrasound Meal Accommodation Test (UMAT), and proposes pragmatic GIUS-based algorithms for enteral feeding decisions. Three clinical use cases are addressed: 8 h monitoring during ongoing enteral nutrition, preprandial assessment of feeding readiness, and once-daily screening of gastrointestinal function. Current evidence supports the clinical relevance of key sonographic parameters such as gastric antral cross-sectional area and small-bowel diameter, whereas other measures, including mucosal thickness, colonic wall thickness, and Doppler-derived resistive indices, require further validation. UMAT adds a dynamic component to static sonographic assessment and may improve the evaluation of gastric accommodation and emptying in selected patients. Structured GIUS protocols offer a promising, evidence-informed extension of bedside assessment for enteral nutrition management in the intensive care unit. However, the available literature remains heterogeneous and is largely based on physiological studies, observational cohorts, and expert consensus. Prospective multicenter studies are needed to validate cutoff values, training standards, and outcome effects before GIUS-based algorithms can be adopted as stand-alone decision tools.

Journal of Personalized Medicine doi: 10.3390/jpm16070375

Authors: Dhirendra K. Singh Yukihiro Yamaguchi Lei Huang Chieko Saito Olivia G. Cassidy Keita Nishiyama

DNA methylation plays a fundamental role in maintaining intestinal homeostasis, immune tolerance, and inflammatory balance. Active DNA demethylation, mediated by the ten-eleven translocation family of dioxygenases (TET1, TET2, and TET3), has emerged as an important epigenetic mechanism linking environmental and metabolic cues to gene regulatory programs in the gut. In the intestinal epithelium, TET-dependent DNA hydroxymethylation contributes to intestinal stem cell maintenance, epithelial differentiation, regeneration, and barrier integrity. Perturbations in TET activity are associated with epithelial dysfunction, chronic inflammation, and increased susceptibility to colorectal tumorigenesis. Within the immune compartment, TET-mediated demethylation is required for the epigenetic stabilization of gut-associated immune cells. Altered TET function has been implicated in immune imbalance in inflammatory bowel disease, Hirschsprung’s disease, and colitis-associated colorectal cancer. Emerging evidence further indicates that intestinal microbiota-derived metabolites, including short-chain fatty acids and aryl hydrocarbon receptor ligands, modulate TET activity, positioning TET enzymes as epigenetic sensors of microbial and metabolic signals. In turn, TET-dependent programs shape immune responses to commensal microbes and pathogens, establishing a bidirectional microbiota–epigenetic axis that influences both intestinal and systemic immunity. In this review, we summarize and critically evaluate current evidence on the roles of TET enzymes in intestinal epithelial biology, immune cell regulation, and host–microbiota interactions in colorectal inflammation and disease.

Journal of Personalized Medicine doi: 10.3390/jpm16070374

Authors: Gustavo Fabregat-Cid Natalia Escrivá-Matoses José De Andrés

Pain biomarkers have been proposed as potential tools to improve patient stratification, treatment selection, and individualized therapeutic strategies in chronic pain. However, despite an increasing volume of research across neuroimaging, electrophysiological, and molecular domains, their translation into clinical practice remains limited. A central challenge lies in the conceptual and methodological misalignment between biomarker discovery and clinical applicability. Many studies labelled as “predictive” rely on measurements obtained during or after intervention, small sample sizes, or lack of external validation, limiting their ability to inform real-world decision-making. In addition, the distinction between predictive, monitoring, and mechanistic biomarkers is often blurred, further complicating interpretation and implementation. This Perspective examines why many candidate pain biomarkers, although biologically informative, have not yet become clinically actionable tools for treatment selection. We distinguish between associative, mechanistic, monitoring, preventive, and truly predictive biomarkers using clinically relevant examples from pain research, and we outline the methodological requirements needed to translate biomarker discovery into precision pain medicine. We argue that the field requires a more rigorous framework for defining and validating predictive biomarkers, encompassing appropriate timing of measurement, robust study design, external validation, and patient-relevant endpoints. Without this framework, pain biomarker research risks continuing to generate biologically informative but clinically non-actionable findings that do not advance individualized therapeutic decision-making.

Journal of Personalized Medicine doi: 10.3390/jpm16070372

Authors: Ángela Solleiro-Vidal Diego Santos-García Alfredo Puy Núñez Teresa de Deus Fonticoba Pablo Mir Gracia Pons Pons Juan García Caldentey Nuria Caballol Jorge Hernández Vara Lydia López Manzanares Bárbara Vives Pastor Maria A. Ávila Rivera Isabel González Aramburu Rocío García-Ramos Carmen Borrué Julio Dotor García-Soto María Álvarez Sauco Iria Cabo Guillermo González Ortega COPPADIS Study Group COPPADIS Study Group

Background and Objective: Depression is frequent in Parkinson’s disease (PD), but it is unclear how mood changes and impacts patient’s quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients’ QoL. Patients and Methods: PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. Results: The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (p < 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [p = 0.896]). The prevalence of depression remained around 50–54% in the PwP group and 21–25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients’ QoL was associated with the depressive state throughout the entire follow-up period (p < 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N = 348). Conclusions: Mood change over time in PwP is associated with QoL.

Journal of Personalized Medicine doi: 10.3390/jpm16070373

Authors: Virginia Cinelli Federico Moretti Chiara Comisi Antonio Mascio Gloria Assegbede Vincenzo La Vergata Giulio Maccauro Carlo Perisano Tommaso Greco

Background: Fibular nonunion is an uncommon but clinically relevant complication following fractures or surgical procedures, often resulting in persistent pain and functional impairment. Due to its rarity, current evidence remains limited and no standardized treatment guidelines are available. Purpose: To systematically review the literature on fibular nonunion, focusing on clinical presentation, diagnostic approaches, and treatment outcomes. Methods: A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE, Scopus, and Web of Science were searched up to July 2025. Studies including adult patients (≥18 years) with fibular nonunion treated either conservatively or surgically were included. Data regarding demographics, clinical presentation, and treatment outcomes were extracted and analyzed descriptively. Results: Nineteen studies comprising 183 patients were included. The mean patient age was 45.7 years, with a predominance of males (58.4%). The distal third of the fibula was the most frequently involved site (75.9%). The mean time to diagnosis was 28.6 weeks. Surgical treatment was performed in 65.6% of cases, most commonly using open reduction and internal fixation. Among studies reporting union outcomes, favorable radiographic healing rates were observed following surgical treatment. Conservative treatment was primarily reserved for asymptomatic or minimally symptomatic patients. The overall complication rate was low (3.8%), mainly consisting of minor infections and hardware-related issues. Conclusions: Fibular nonunion is an uncommon but clinically significant condition. Available evidence suggests that surgical management may represent the most consistently successful treatment strategy in symptomatic and mechanically unstable cases, while nonoperative treatment may remain appropriate in carefully selected asymptomatic or minimally symptomatic patients. However, the available literature is limited by retrospective study designs, heterogeneous populations, inconsistent outcome reporting, and variable definitions of nonunion, highlighting the need for prospective multicenter studies and standardized treatment protocols.

Journal of Personalized Medicine doi: 10.3390/jpm16070371

Authors: Seung-Bo Lee

Background: Intraoperative hypotension (IOH) is the leading modifiable contributor to postoperative acute kidney injury (AKI), yet most evidence is associational and the heterogeneity of its effect is unknown. We estimated the causal effect of IOH burden on AKI and tested whether the most susceptible patients can be identified preoperatively. Methods: In a retrospective cohort of 2726 general-anesthesia cases from VitalDB, the exposure was the time-integrated mean arterial pressure (MAP) <65 mmHg burden (≥30, ≥60 and ≥120 mmHg·min) and the outcome was KDIGO-defined AKI within 7 days. The primary estimator was pre-treatment-adjusted augmented inverse-probability weighting (AIPW; doubly robust) with bootstrap 95% confidence intervals (CIs). Sensitivity analyses comprised a controlled-direct-effect model, negative control outcomes, E-values and vasopressor-stratified estimates. Effect heterogeneity was estimated with a causal forest; preoperative gradient-boosted models and decision-curve analysis assessed personalization and clinical utility. Results: AKI occurred in 205 (7.52%) cases. At 60 mmHg·min the AIPW risk difference was +3.00 percentage points (pp; 95% CI +0.84 to +5.26), with a monotonic dose–response (+2.78 to +7.62 pp across thresholds) and E-values rising from 2.08 to 3.44. The effect was concentrated in patients with elevated preoperative creatinine (conditional effect +9.86 pp, more than twice the cohort average). This susceptibility was recoverable from routine preoperative variables alone, with intraoperative waveform features conferring no measurable improvement (ΔAUROC −0.001). For predicting AKI itself, a parsimonious 4-feature preoperative score matched a 27-feature model (AUROC 0.775 vs. 0.768) and provided positive net benefit. Conclusions: Intraoperative hypotension burden shows a dose-dependent association with postoperative AKI that is consistent with a causal effect, concentrated in patients with reduced baseline renal reserve who are identifiable from routine preoperative data without intraoperative waveform infrastructure.

Journal of Personalized Medicine doi: 10.3390/jpm16070370

Authors: Theresa Mally Nina Rubicz Paul Martin Zwittag

Background: Migrated foreign bodies in the prevertebral region represent a rare but potentially serious condition. This case underscores the importance of thorough visual and digital intraoperative exploration for successful foreign body retrieval and highlights the potential diagnostic and surgical challenges associated with migrated foreign bodies in the cervical region. Case report: A 77-year-old female patient presented with dysphagia following the intake of an Angiotensin-Converting Enzyme (ACE) inhibitor. Due to hemodynamic instability and laboratory findings that indicated multiple organ failure, a computed tomography (CT) scan was performed, which revealed a left-sided prevertebral abscess with gas collections. Because of persistently elevated and fluctuating inflammatory markers, multiple CT scans were performed, which showed an obliquely oriented, wire-like tubular structure approximately 30 mm in length, 5 mm in width and 1 mm in diameter in the prevertebral region of the previous abscess cavity. Eventually, after three surgical interventions—one transoral and two transcervical approaches—the foreign body could be identified and removed. Afterwards, the patient’s inflammatory markers decreased and her dysphagia resolved. Conclusions: This case demonstrates that early diagnosis and timely removal of foreign bodies in the cervical space are essential to prevent complications such as retropharyngeal abscess formation or mediastinitis. A combination of careful clinical examination, endoscopic evaluation, and cross-sectional imaging—particularly CT scan—is crucial for accurate localization. Finally, this report highlights the importance of maintaining a high index of suspicion for migrated foreign bodies in patients presenting with persistent symptoms or unexplained cervical infections following suspected foreign body ingestion.

Journal of Personalized Medicine doi: 10.3390/jpm16070369

Authors: Kathleen D. McDaniel Neda Ghousifam Rodney A. Bowling Catherine Z. Chen Wei Zheng Zeenat A. Shyr

Background: Mucopolysaccharidosis type IIIB (MPSIIIB, Sanfilippo syndrome type B) is a rare lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU) enzyme, leading to progressive accumulation of heparan sulfate and severe neurological decline. MPSIIIB’s significant genetic heterogeneity presents a major barrier to developing broadly effective treatments and suggests a need for personalized therapeutic strategies. Methods: We established a personalized drug repurposing platform using high-content imaging with lysotracker dye as an indirect functional readout of lysosomal dysfunction to screen compounds that correct lysosomal defects in patient-derived fibroblasts. We screened 2807 compounds on cells from an MPSIIIB patient with a homozygous NAGLU p.Arg297Ter mutation. Hits that reduced lysosomal accumulation by at least 25% with minimal cytotoxicity were validated and subsequently tested for efficacy in fibroblasts from a second patient with a different, compound heterozygous NAGLU genotype. Results: The primary screen yielded 72 hits (2.6% hit rate), with 10 confirmed in dose–response assays. Notably, four clinically approved drugs—baclofen, dextrose, epalrestat and moxifloxacin—reduced lysosomal accumulation in the index patient’s cells. However, none of these four drugs were effective in the second patient’s cells, demonstrating a profound patient-specific effect. Only one non-clinical compound, 6-chlorothymol, showed a trend toward activity in both cell lines. Conclusions: Our study demonstrates a feasible framework for conducting rapid, N-of-1 drug repurposing screens for rare diseases. While we identified four promising candidates for the index patient, the lack of efficacy in a second patient cell line underscores that genetic heterogeneity may preclude a “one-size-fits-all” approach for MPSIIIB. These findings support the integration of individualized drug screening as a potential precision-medicine strategy, offering a potential path toward patient-specific therapies for rare diseases rather than traditional drug development.

Journal of Personalized Medicine doi: 10.3390/jpm16070368

Authors: Archana Ramgopal Tsuyoshi Fujita Breana K. Goscicki Shiva Sridar Daniel Klein Li Wang Ramasubramanian Kalpatthi Jignesh Dalal

Background/Objectives: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a serious complication of hematopoietic stem cell transplantation (HSCT), particularly in high and very high-risk pediatric patients. Despite known risk factors, U.S. data remain limited. The benefit of prophylactic defibrotide is uncertain, with prior trials yielding inconclusive results. This study evaluates its use and association with SOS incidence, healthcare burden, and outcomes. Methods: We performed a retrospective cohort study of 10,250 pediatric HSCT encounters using the Pediatric Health Information System. Patients were stratified as high-risk (n = 9584) or very high-risk (n = 666) per HARMONY criteria. Prophylactic defibrotide was used in 344 encounters; 9906 received none (therapeutic use allowed after SOS diagnosis). Outcomes included SOS incidence, length of stay (LOS), ICU admission, mortality, acute GVHD, and costs. Mixed-effects logistic regression models with patients as a random intercept were used (p < 0.05). Results: SOS incidence differences between the defibrotide prophylaxis and non-prophylaxis groups were not statistically significant in either risk category (high-risk: 26% [n = 79/302] vs. 7.1% [n = 663/9282] p = 0.495, OR 1.457, 95% CI 0.494–4.296; very high-risk: 31.0% [n = 13/42] vs. 21.6% [n = 135/624], p = 0.970, OR 1.081, 95% CI 0.019–60.769). The extremely wide confidence intervals indicate that the data are consistent with both benefit and harm of prophylaxis. Median LOS was longer in the prophylactic group (40 vs. 33 days, p < 0.001; 56 vs. 49 days, p = 0.296, respectively). ICU admissions (50.7% vs. 32.8%; 69.0% vs. 50.8%), mortality (7.9% vs. 3.5%; 23.8% vs. 10.9%), and costs ($443,537 vs. $205,325; p < 0.001) were also higher in the prophylaxis group. Acute GVHD incidence differences were not statistically significant, with contradictory directions between risk subgroups. Conclusions: Prophylactic defibrotide was not associated with reduced SOS incidence and was associated with higher ICU use, longer LOS, increased mortality, and greater costs. These findings represent associations, not causation, and likely reflect residual confounding by indication—as defibrotide prophylaxis was preferentially administered to patients perceived to be at highest clinical risk. Prospective studies with appropriate confounding adjustment are needed to clarify the role of defibrotide in SOS prevention.

Journal of Personalized Medicine doi: 10.3390/jpm16070367

Authors: Daniele Salvatore Paternò Luigi La Via Marco Lo Presti Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Emilia Concetta Lo Giudice Giordana Russo Mattia Pratini Paolo Tummino Giuseppe Scibilia Marco Barbanti Massimiliano Sorbello

Cardiac arrhythmias complicate 20–50% of surgical procedures and contribute substantially to perioperative morbidity, mortality, and healthcare costs, with postoperative atrial fibrillation (POAF) being the most frequent form. Their genesis reflects the convergence of surgical stress, anaesthetic agents, autonomic imbalance, systemic inflammation, and electrolyte disturbances, explaining the limited efficacy of single-mechanism interventions. This narrative review synthesises contemporary evidence on pathophysiology, risk stratification, prevention, acute management, and emerging technologies, emphasising individualised, patient-tailored approaches. MEDLINE, Embase, and Cochrane CENTRAL were searched (January 2010–January 2026), prioritising randomised trials, meta-analyses, and guidelines. Contemporary risk stratification integrates clinical scores, biomarkers, and electrocardiographic parameters; machine-learning models show moderate discrimination (pooled AUC 0.84) and may enable more personalised prediction pending external validation. Evidence-based prophylaxis—beta-blockade, magnesium, selective amiodarone, and emerging anti-inflammatory strategies such as colchicine—reduces POAF in high-risk populations, while acute management is guided by haemodynamic status and individual risk. Anticoagulation follows CHA2DS2-VASc stratification, although optimal timing and duration remain undefined. Wearable monitoring, AI-based detection, and atrial-selective agents show clinical promise. Systematic, personalised integration of risk assessment, prophylaxis, monitoring, and management offers the clearest path to reducing arrhythmia-associated morbidity.

Journal of Personalized Medicine doi: 10.3390/jpm16070366

Authors: Berkan Aliev Boyko Atanasov

Enhanced Recovery After Surgery (ERAS) pathways have improved perioperative outcomes by standardizing evidence-based interventions across the surgical continuum. However, substantial variability in postoperative recovery persists, even within well-implemented ERAS programs. This heterogeneity reflects differences in clinical risk, functional reserve, biological response to surgical stress, treatment responsiveness, and contextual factors that are not fully captured by uniform protocols. Precision medicine provides a potential framework for refining ERAS by integrating patient-specific data into perioperative risk assessment, intervention selection, patient monitoring, and recovery planning. Nevertheless, most precision medicine tools remain insufficiently validated for routine ERAS implementation, and their clinical utility is limited by heterogeneous evidence, data integration challenges, costs, workflow complexity, and equity concerns. Future progress will require prospective validation, pragmatic implementation studies, interoperable data systems, and evaluation of patient-centered outcomes. This narrative review examines the emerging role of precision medicine tools in perioperative practice and proposes an idealized conceptual model of “precision ERAS” in which standardized evidence-based care is preserved as the foundation, while selected interventions are adapted according to individual risk, biological phenotype, and recovery trajectory.

Journal of Personalized Medicine doi: 10.3390/jpm16070365

Authors: Bradley C. Nelson Mark J. Lambrechts

Technological advances in spine surgery have allowed for significantly improved precision. Perhaps no technology has allowed for more personalized and precise surgery than endoscopic spine surgery. Although this technology has been around for decades, advancements in camera resolution have led to enhanced magnification and visualization of nerve root compression. Given our improved understanding of the interplay between spinal stability, spine pain, and muscle health, minimizing muscle disruption and bone resection has now become a key principle in spinal care. This narrative review will talk about common lumbar spine pathologies and how spinal endoscopy can be implemented to potentially improve patient care and outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16070364

Authors: Isolina Riaño-Galan Corsino Rey María Bogaerts Marquez Laura Muñoz Rebeca García César Bazó Julián Rodríguez

Background: Telemedicine complements traditional healthcare delivery and may improve access, continuity of care, and patient engagement, particularly in chronic conditions requiring regular follow-up. Video consultation is a widely adopted telemedicine modality and is increasingly integrated into hybrid care models. Methods: This real-world implementation project describes scheduled video consultations embedded in a hybrid care model for children and adolescents with type 1 diabetes using continuous glucose monitoring (CGM) and integrated insulin delivery technologies as part of routine clinical care. A total of 38 families were offered video consultations as part of routine care; 18 adopted the hybrid model. Video consultations were used for routine follow-up, shared review of device data, treatment adjustment, and diabetes education. Family experience was assessed using a voluntary 5-point Likert-scale satisfaction questionnaire. Complete longitudinal CGM data were available for 13 participants, all of whom were established users of the same automated insulin delivery (AID) platform (MiniMed™ 780G (Medtronic MiniMed, Inc. Minneapolis, MN, USA) integrated with Guardian™ 4 (Medtronic MiniMed, Inc. Minneapolis, MN, USA) continuous glucose monitoring). Results: Between 2022 and 2024, 162 video consultations were conducted. Acceptability was high, with 95% (17/18) of respondents reporting high satisfaction (score ≥ 4 on the 5-point Likert scale). 89% (16/18) of families perceived the quality of care as comparable to face-to-face visits for routine follow-up. Families highlighted convenience, reduced travel burden, and flexibility, as well as the value of shared review of CGM and AID system data. Group-level CGM-derived metrics appeared descriptively similar across sequential face-to-face visits and video consultations. Individual patient trajectories showed expected variability but no consistent pattern of deterioration during periods of remote follow-up. Conclusions: Video consultation is a feasible and well-accepted complementary modality within hybrid care models for pediatric type 1 diabetes. When integrated with CGM and automated insulin delivery systems, it supports personalized, data-driven clinical decision-making and continuity of care. Structured implementation and systematic evaluation are essential for sustainable integration into routine practice.

Journal of Personalized Medicine doi: 10.3390/jpm16070363

Authors: Joana O. Pinto Bruno Peixoto Artemisa R. Dores Fernando Barbosa

The main purpose of this work is to critically review the literature on neurocognitive disorders (ND) diagnosis. A critical review was conducted in PubMed, Scopus, and EBSCO. Systematic reviews and meta-analyses focusing on ND diagnosis were included. The selected studies were critically analyzed and conceptually integrated to identify relevant dimensions for the diagnosis of ND. The review included 88 studies. Most studies focused on Alzheimer’s disease and mild cognitive impairment. The literature remained predominantly centred on isolated diagnostic domains, and important limitations were consistently identified, including methodological heterogeneity, lack of standardized thresholds, and reduced clinical applicability. Based on the identified conceptual and methodological limitations, a Multidimensional Model of Neurocognitive Disorders (MOND model) for ND diagnosis was proposed. The MOND model was developed as a multidimensional, multilevel, transdiagnostic model integrating biological, neurocognitive, neuropsychiatric, motor, functional, frailty, reserve-related, and socio-environmental dimensions. The model may contribute to research, symptom classification, severity characterization, prognosis, and personalized intervention planning across different ND trajectories. Future studies using the MOND model should focus on refining algorithms to estimate the risk of ND.

Journal of Personalized Medicine doi: 10.3390/jpm16070362

Authors: Ourania S. Kotsiou Georgios I. Barkas Konstantinos I. Gourgoulianis Zoe Daniil

Background: Biologic therapies have transformed severe asthma management, but real-world evidence comparing phenotypes, lung function trajectories, and persistence across biologic classes remains limited. Objective: To characterize a real-world cohort of biologic-treated severe asthma patients, focusing on baseline phenotypes, longitudinal post-bronchodilator spirometry (including a spirometric surrogate suggestive of small airways involvement), and discontinuation/switching patterns. Methods: In this retrospective observational study at a tertiary referral center, adults with severe asthma treated with benralizumab, mepolizumab, omalizumab, or tezepelumab were included. Demographic, clinical, biomarker, and functional data were collected at baseline and follow-up. Post-bronchodilator FEV1 and FEF25–75 (% predicted) were assessed at baseline, 6 months, 12 months, and 24–36 months when available. Longitudinal outcomes were analyzed using multivariable linear mixed-effects models; discontinuation and switching were recorded. Results: Eighty-seven patients were included (benralizumab n = 13, omalizumab n = 10, mepolizumab n = 30, tezepelumab n = 34), representing 10.9% of the clinic’s population. Most had long-standing disease, elevated body mass index, and a T2-high profile. Baseline characteristics were generally similar across groups, with expected differences in total IgE (p = 0.007) and blood eosinophils (p < 0.001). The primary endpoint (FEV1 % predicted change from baseline to 12 months) showed adjusted mean changes of +12.46 (95% CI +1.63 to +19.29; p = 0.020) with benralizumab, +15.82 (+8.35 to +23.64; p < 0.001) with mepolizumab, +16.65 (+1.58 to +31.71; p < 0.001) with omalizumab, and +15.69 (+6.52 to +24.87; p = 0.030) with tezepelumab; trajectories differed by biologic class (time × biologic p = 0.019). Although the interaction term indicated heterogeneous temporal patterns, these adjusted findings should be interpreted as associative in the context of biomarker-driven treatment selection and not as evidence of comparative superiority of any biologic class. Discontinuation occurred in 15/87 (17.2%), with switching most commonly due to inadequate control. Conclusions: Real-world severe asthma patients demonstrate heterogeneous phenotypes and spirometric trajectories on biologics. Integrating biomarkers with longitudinal lung function monitoring, including small-airway spirometric surrogates, supports individualized management.

Journal of Personalized Medicine doi: 10.3390/jpm16070361

Authors: Behrouz Ebrahimi Albert K. Dadzie Mansour Abtahi Masrur A. Sadhin Daniel Kim Srishti Kolla Baoxin Li R. V. Paul Chan Michael J. Heiferman Xincheng Yao

Objective: To predict pixel-wise retinal thickness maps from near-infrared (NIR) fundus images using deep learning (DL), and to identify image features in NIR fundus photographs serving as surrogate markers of retinal thickness, with implications for decentralized diabetic macular edema (DME) screening, progression monitoring, and treatment assessment. Methods: A DL model based on a U-Net architecture was trained on paired NIR fundus and OCT images from 531 eyes across three groups: healthy controls, diabetic retinopathy (DR) without DME, and DME. Model performance was evaluated using mean absolute error (MAE), root mean squared error (RMSE), structural similarity index (SSIM), and center-involved DME (ci-DME) classification at a central subfield thickness threshold of 300 µm. Controlled image manipulation experiments, including spatial disruption of vascular patterns, relocation of hard exudates, and contrast enhancement, were performed to identify image-level features serving as surrogate markers of retinal thickness. Results: The model achieved an MAE of 30.41 ± 18.68 µm, RMSE of 36.14 ± 21.05 µm, and SSIM of 0.87 ± 0.04 across the macula, with consistent performance across ETDRS subfields. For ci-DME classification, it achieved an accuracy of 84.1%, sensitivity of 69.1%, and specificity of 88.7%. Interpretability analyses were performed as qualitative assessments to visualize image regions contributing to model predictions. These analyses highlighted retinal vascular structures, hard exudates, and local contrast variations as visual features observed in relation to model outputs. Conclusions: NIR fundus images contain sufficient structural information to support pixel-wise retinal thickness estimation, with vascular architecture, hard exudates, and local contrast variations identified as image features potentially associated with model predictions. These findings suggest that NIR-based deep learning approaches may have potential applications in the assessment of diabetic macular edema and warrant further prospective and external validation to determine their role in screening, triage support, longitudinal monitoring, and treatment-related assessment, particularly in decentralized and re-source-limited care environments.

Journal of Personalized Medicine doi: 10.3390/jpm16070360

Authors: Joanna Zygadło Leszek Blicharz Joanna Czuwara Joanna Nowaczyk Karolina Makowska Małgorzata Olszewska Lidia Rudnicka

Background/Objectives: Facial discoid dermatosis is a rare inflammatory dermatosis presenting with round, superficial erythematous lesions located on the face. Diagnosis may be challenging and often requires careful clinicopathological correlation due to overlapping clinical and histopathological features. Skin lesions are typically resistant to a wide range of topical and systemic treatments. From the perspective of personalized medicine, improved phenotyping of rare inflammatory dermatoses may support more precise diagnosis, individualized therapeutic decisions, and non-invasive disease monitoring. This study aimed to characterize facial discoid dermatosis using line-field confocal optical coherence tomography and reflectance confocal microscopy and to discuss its differential diagnosis and therapeutic implications. Methods: We report a case of facial discoid dermatosis in a 35-year-old patient examined with line-field confocal optical coherence tomography and reflectance confocal microscopy. The imaging findings were interpreted in correlation with clinical and histopathological features. A literature review was performed to summarize differential diagnoses, therapeutic perspectives, and the proposed relationship between facial discoid dermatosis and pityriasis rubra pilaris. Results: Non-invasive imaging revealed morphological features consistent with a psoriasiform inflammatory dermatosis and provided additional in vivo information supporting the diagnosis. The literature review showed limited evidence for a direct association between facial discoid dermatosis and pityriasis rubra pilaris, with only isolated reports suggesting possible overlap or progression. Conclusions: Facial discoid dermatosis appears to represent a distinct psoriasiform dermatosis. Line-field confocal optical coherence tomography and reflectance confocal microscopy may contribute to a personalized diagnostic approach by supporting differential diagnosis and potentially guiding individualized monitoring in rare inflammatory facial dermatoses.

Journal of Personalized Medicine doi: 10.3390/jpm16070359

Authors: Panagis Lykoudis Maria Papadoliopoulou Alexios Kozonis Georgios Kirkilesis Marios-Konstantinos Tasoulis Mahrokh Nohadani Mihir A. Gudi

Background/Objectives: Immunohistochemistry is an integral component of the diagnostic approach in breast cancer and remains essential for tumor characterization and therapeutic decision-making. p63 gene expression may have potential diagnostic and prognostic roles in breast cancer patients. Methods: In this study, 127 specimens of invasive breast carcinoma and 50 control cases were evaluated for p63 gene expression and compared to other pathology factors. Results: None of the 50 control cases was assessed as positive for p63 expression. Progesterone and estrogen receptor status were the only factors that demonstrated a statistically significant negative correlation with p63 expression (p = 0.005 and p = 0.017, respectively). Tumor size demonstrated a marginally non-significant correlation with p63 expression (p = 0.051). None of the remaining factors was significantly correlated with p63 expression. Conclusions: In conclusion, p63 expression is inversely correlated with estrogen and progesterone receptor status, and type, size and grade of the tumors are not correlated with the gene’s expression, nor is HER2 status. This conclusion might impact genotype-based stratification pertinent to diagnosis and tailored treatment.

Journal of Personalized Medicine doi: 10.3390/jpm16070358

Authors: Mariangela Pati Immacolata Blasi Giovanna Botticelli Andrea Musarò Flavio Vanacore Giulia Galeati Lorenzo Aguzzoli Maria Paola Bonasoni

Background: Trisomy 21 (T21) is strongly associated with congenital heart disease, particularly atrioventricular septal defect (AVSD), ventricular septal defect (VSD), atrial septal defect (ASD) and selected conotruncal and arch anomalies. First- and second-trimester ultrasound, Doppler and fetal cardiac MRI enable increasingly early and detailed characterization of these lesions, while advances in molecular cardiogenesis have linked specific phenotypes to dosage-sensitive genes on chromosome 21. Methods: This narrative review synthesizes contemporary evidence on structural and functional cardiovascular anomalies in T21 fetuses in the first and second trimester, integrating fetal echocardiography, Doppler assessment and fetal cardiac MRI with embryologic and molecular insights, and summarizing trimester-specific detectability and pathophysiologic links to candidate genes in the Down syndrome-critical region. Approximately one quarter to one third of T21 fetuses have major congenital heart disease on high-quality prenatal echocardiography, with AVSD representing about half of all lesions and VSD, tetralogy of Fallot (TOF), arch anomalies, venous return abnormalities and functional markers (increased nuchal translucency, tricuspid regurgitation, ductus venosus abnormalities) comprising the remainder. Results: First-trimester detection relies on functional markers and early four-chamber and outflow-tract views, whereas second-trimester studies refine anatomic definition and hemodynamics, with MRI reserved for complex cases. Overexpression of genes such as DSCAM, COL6A1/COL6A2, DYRK1A and RCAN1 perturbs endocardial cushion, conotruncal and vascular development. Conclusions: Early, protocol-driven cardiac imaging in T21 supports timely diagnosis, risk stratification and multidisciplinary counselling, and links fetal imaging phenotypes with chromosome 21 gene dosage to advance personalized management and future genotype–phenotype research.

Journal of Personalized Medicine doi: 10.3390/jpm16070357

Authors: Luis Chauca Bajaña Tatiana Cruz Moreno Diego Quiguango Farias Sandra Vélez Cevallos Eliana Pazmiño Troncoso Alisson Juiña Jaime Mauricio Rosales Pavón Byron Velásquez Ron

Background: Temporomandibular disorders (TMD) are multifactorial musculoskeletal conditions frequently associated with chronic pain, inflammation, and functional impairment. Increasing evidence suggests that oxidative stress may contribute to the pathophysiology of TMD, and salivary biomarkers have emerged as a promising non-invasive approach for evaluating these biological alterations. Objective: This systematic review and meta-analysis aimed to systematically evaluate and quantitatively synthesize the available evidence regarding salivary oxidative stress biomarkers in patients with temporomandibular disorders compared with healthy controls. Materials and Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. Electronic searches were performed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases. Observational studies and clinical trials evaluating salivary oxidative stress biomarkers in patients with TMD were included. The primary biomarkers assessed were malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). Data extraction and risk of bias assessment were independently performed by two reviewers using the Newcastle–Ottawa Scale and RoB 2 tool when applicable. Random-effects meta-analyses were conducted using weighted or standardized mean differences with 95% confidence intervals. Included studies demonstrated substantial methodological variability regarding TMD diagnostic criteria, saliva collection protocols, biomarker assays, and sampling conditions. Results: Pooled analyses showed significantly elevated salivary malondialdehyde levels in patients with TMD compared with healthy controls, suggesting increased lipid peroxidation and oxidative stress activity. In contrast, total antioxidant capacity and catalase activity demonstrated inconsistent and non-significant findings across studies. Considerable heterogeneity was identified among studies, limiting the comparability and interpretability of pooled estimates. Salivary oxidative stress biomarkers, particularly malondialdehyde, appear to be associated with temporomandibular disorders and may reflect underlying oxidative and inflammatory mechanisms. Conclusions: However, substantial methodological heterogeneity and lack of standardized protocols currently limit their clinical applicability. Future well-designed longitudinal studies using harmonized diagnostic and analytical methodologies are required to clarify their translational value in TMD assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16070356

Authors: Federica Zito Marino Carminia Maria Della Corte Vincenza Ciaramella Stefania Erra Andrea Ronchi Alfonso Fiorelli Giovanni Vicidomini Mario Santini Giosuè Scognamiglio Floriana Morgillo Fortunato Ciardiello Renato Franco Marina Accardo

The journal retracts the article titled “AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma” [...]

Journal of Personalized Medicine doi: 10.3390/jpm16070355

Authors: Isabel Dirven Marre W. Kamminga Lise M. Verhoef Rogier M. Thurlings Ruben L. Smeets Arjan van Caam Madelon C. Vonk

Background: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by inflammation, vasculopathy, and fibrosis. It is associated with the highest mortality among rheumatic diseases. Very early SSc may represent a critical phase with risk of developing progressive disease. Although timely treatment may be effective in patients with progressive disease, it carries risks of adverse events, underscoring the need for early identification of individuals at risk. Biomarkers for progression in the early stage offer opportunities for timely intervention and improved long-term outcomes. Therefore, validating biomarkers that predict progression is an important research priority. In this narrative literature review, we summarize and evaluate blood circulating biomarkers associated with different progression endpoints in (very) early SSc. Methods: The literature search was conducted using PubMed. Eligible studies assessed biomarkers in very early SSc or early SSc cohorts with longitudinal follow-up and progression-related outcomes. Results: The identified studies investigated biomarkers associated with interstitial lung disease (ILD), skin progression, overall disease progression, and mortality. Anti-topoisomerase I was associated with ILD development. A high interferon score was linked to reduced lung function and mortality. KL-6 was associated with progression in early SSc-ILD. PRO-C3 and PRO-C6 showed the strongest associations with skin involvement. Finally, IgG anti-centromere antibody was associated with organ involvement and progression to definite SSc. CXCL10 and TNFRII were linked to progression and significant survival differences in the discovery and replication cohorts. However, effect sizes were often modest, and findings were inconsistent across cohorts. Substantial heterogeneity in study design, populations, endpoints, and biomarker assessment methods limited comparability. Moreover, most biomarkers demonstrated associations at the group level but lacked sufficient discriminatory power for individual risk prediction. Only a minority of studies included validation cohorts, and replication of findings was limited. Conclusions: Multiple biomarkers show promising associations with progression in very early and early SSc, but a single biomarker is unlikely to reliably predict disease progression.

Journal of Personalized Medicine doi: 10.3390/jpm16070354

Authors: Christos Tsilivigkos Eleftherios Ferekidis Marios Stavrakas

Introduction: Cochlear implantation is a well-established treatment for adults with bilateral postlingual deafness. In recent years, increasing research attention has focused on its use in patients with single-sided deafness (SSD) with or without tinnitus. Restoration of binaural auditory input through cochlear implantation may partially reestablish binaural processing. Methods: We conducted a narrative review of the literature focusing on studies examining the basic mechanisms associated with hearing impairment in SSD, as well as cochlear implantation outcomes in this population, including hearing performance, tinnitus suppression, and quality of life (QoL). We also reviewed comparative studies between cochlear implants (CIs) and alternative hearing devices, along with current candidacy criteria and the challenges associated with cochlear implantation in this patient group. Results: Current evidence suggests that CIs can provide significant benefits in this population, including tinnitus reduction or suppression, improved speech perception in both quiet and noise, enhanced sound localization, and better disease-specific and overall QoL. Furthermore, numerous studies—despite some variability in outcomes—indicate that CIs may offer superior performance compared with alternative options, such as contralateral routing of signals hearing aids (CROS-HAs) and bone-conduction devices, particularly in terms of speech perception, localization, tinnitus control, and aspects of QoL. Nevertheless, appropriate candidacy criteria and key challenges—most notably device non-use—should be carefully considered when evaluating cochlear implantation in this patient population. Conclusions: Further research is required to address these challenges and to advance a more personalized approach to cochlear implantation in individuals with SSD, with the aim of optimizing outcomes and reducing cochlear implant non-use.

Journal of Personalized Medicine doi: 10.3390/jpm16070353

Authors: Daniela Valle Almeida Figueredo Silvia de Lourdes Loreto Faquini Edward Araujo Júnior Tammy Caram Sabatine Gustavo Yano Callado Antonio Braga Roberta Granese Alex Sandro Rolland Souza

Objective: To review the literature on palliative care protocols and models of care for pregnant women and their fetuses with life-limiting conditions. Methods: A narrative literature review was conducted in the PubMed/MEDLINE and Virtual Health Library (VHL)—BIREME/SciELO/LILACS, using the descriptors “palliative care” and “prenatal care”. Studies of all designs published between February 2015 and May 2025 were considered for inclusion. Articles in languages other than Portuguese, English, and Spanish, duplicates, and those that did not discuss care protocols or experiences in perinatal palliative care for life-limiting fetal conditions starting from prenatal care were excluded. Articles were selected through title, abstract, and full-text screening. Results: Twenty-one studies focused on prenatal care were selected, presenting protocols and experiences of care in palliative fetal medicine. Most addressed the diagnosis of life-limiting fetal malformations, prenatal care, birth and delivery plan, perinatal grief and the puerperium. Across the included studies, a recurring emphasis on individualized, patient and family-centered approaches was identified, reflecting core principles of personalized medicine. Tailoring communication, care planning, and bereavement support to the specific clinical, genetic, cultural, and psychosocial profile of each dyad emerged as a structural characteristic of effective perinatal palliative care models. Conclusions: There is a scarcity of specific palliative care protocols for pregnancy, indicating a need to expand studies. The reviewed literature can contribute to the creation and adaptation of palliative care protocols and models for pregnant women and their fetuses with life-limiting conditions, may support more consistent care planning, improved communication, and better alignment with parental values.

Journal of Personalized Medicine doi: 10.3390/jpm16070352

Authors: Johannes Moritz Mittendorfer Zehra Duezguen Lukas Horak Andreas Gahleitner Elisabeth Marlene Mandler Lena Hirtler

Background/Objectives: Accurate identification of the functional femoral attachment of the anterior (ACL) and posterior cruciate ligament (PCL) is essential for anatomic reconstruction and for patient-specific femoral tunnel planning, yet correct intraoperative localization remains inconsistent. This anatomical study investigated whether subcortical bone features provide evidence of functional cruciate ligament attachment and whether surrounding osseous ridges are reliable landmarks. Methods: Computed tomography (CT) scans of 20 paired, fresh-frozen distal femora (10 body donors) were processed using 3D volume rendering to visualize the intercondylar fossa walls and to assess the presence of four characteristic ridges: lateral intercondylar ridge (LIR), lateral bifurcate ridge (LBR), medial intercondylar ridge (MIR) and medial bifurcate ridge (MBR). In addition, thin-ground section histology of the femoral insertion sites was performed to characterize insertion morphology. Results: Histology demonstrated distinct direct and indirect insertions for both ligaments; the direct insertion exhibited a characteristic four-layer transition (ligament, non-calcified fibrocartilage, calcified fibrocartilage, bone), whereas the indirect insertion showed collagen fibers attaching directly to bone. The LIR and MIR were present in 85% and 80% of specimens, respectively, while the LBR and MBR were less frequent (LBR 25%, MBR 10%). No significant associations were found between ridge presence and age, sex or laterality. Conclusions: These findings support the direct insertion as the functional cruciate attachment and suggest that the LIR and MIR—due to their consistent occurrence and location at the rim of the direct insertion—are the most useful bony landmarks for individualized femoral tunnel orientation, whereas bifurcate ridges should be considered adjunctive when present. The observed variability provides a rationale to stratify cases requiring adjunct imaging or navigation.

Journal of Personalized Medicine doi: 10.3390/jpm16070351

Authors: Dmitry Oskin Stanislav Kotlyarov

Background/Objective: Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) are among the most prevalent respiratory disorders worldwide and frequently coexist in the same patient. However, the contribution of active TB and post-tuberculosis lung disease to COPD exacerbations and long-term prognosis remains incompletely defined. This paper aim to evaluate the prevalence, clinical correlates, and prognostic significance of tuberculosis and its sequelae in patients with COPD. Materials and methods: We conducted a population-based retrospective cohort study using de-identified data from the regional healthcare information system. The cohort included all adults aged 18 years or older with a recorded diagnosis of COPD (ICD-10 code J44). Tuberculosis was identified by codes A15–A19 and B90. The primary outcomes were COPD exacerbations and all-cause mortality. Group comparisons, cluster analysis, Kaplan–Meier survival analysis, Cox proportional hazards modeling, and multivariable logistic regression were performed. Results: Tuberculosis and/or its sequelae were identified in 267 of 16,714 patients (1.60%): post-TB sequelae (B90) in 197 (73.8%), active TB (A15–A19) in 22 (8.2%), and both in 48 (18.0%). Compared with patients without TB, those with COPD-TB were younger (63.5 ± 14.2 vs. 65.7 ± 14.7 years; p = 0.018), more often male (75.3% vs. 52.0%; p < 0.001), and had higher mortality (16.5% vs. 10.6%; p = 0.003). COPD-TB was associated with bronchiectasis (OR = 6.07; 95% CI, 3.03–12.16), pulmonary fibrosis (OR = 5.67; 95% CI, 3.40–9.45), and pneumonia (OR = 2.01; 95% CI, 1.50–2.71), but with lower prevalences of obesity, diabetes mellitus, and hypertension. Patients with TB experienced more COPD exacerbations, including recurrent exacerbations. In multivariable models, tuberculosis was associated with COPD exacerbations after adjustment for age and sex (adjusted OR = 1.43; 95% CI, 1.05–1.96); this association was attenuated and lost significance after further adjustment for post-tuberculosis structural lung disease, indicating that it is largely mediated by post-TB sequelae. Tuberculosis remained associated with mortality after adjustment for available covariates, both in logistic regression (adjusted OR = 1.61; 95% CI, 1.14–2.28) and in Cox analysis (hazard ratio = 1.37; 95% CI, 1.01–1.85). Conclusions: Tuberculosis and post-tuberculosis lung disease are clinically accessible risk markers associated with COPD exacerbations and mortality. These findings support recognizing patients with COPD and a history of TB as a high-risk subgroup requiring intensified follow-up, proactive exacerbation prevention, and prioritized vaccination counseling. In the context of personalized medicine, a documented history of tuberculosis and post-tuberculosis lung changes represents a clinically accessible marker that can be used to stratify individual risk and to tailor monitoring and prevention in patients with COPD.

Journal of Personalized Medicine doi: 10.3390/jpm16070350

Authors: Thomas Karagkounis Angeliki Alifragki Ioannis Zoupas Sofia Sarantou Nikolaos Schizas Konstantinos S. Mylonas Dimitrios C. Iliopoulos

Background/Objectives: Minimally invasive (MIS) mitral valve surgery has been proven to be a safe and effective alternative to median sternotomy (ST), with advantages in postoperative recovery and morbidity. However, its role in the setting of infective endocarditis (IE) remains uncertain. This meta-analysis aims to evaluate the outcomes of MIS in mitral valve surgery for infective endocarditis. Methods: A PRISMA-compliant search for studies including patients undergoing MIS for mitral valve IE was performed through 14 January 2026, in PubMed, Scopus and Cochrane. Time-to-event data were reconstructed from published Kaplan–Meier curves. A secondary comparative analysis focusing on MIS versus ST techniques was conducted. Results: Fourteen retrospective studies comprising 949 patients were analyzed. In the MIS cohort, early mortality was 4.2% (95%CI: 1.8%, 7.4%). Overall survival was 86.7% at 1 year, 75.2% at 5 years and 56.2% at 10 years. Freedom from IE-related reoperation remained high at 97.5%, 95.9%, and 90.7% at 1, 5, and 10 years, respectively. Mitral valve repair was performed in 52.5% of patients. In secondary comparative analyses, overall survival at 4-year follow-up was not different between MIS and ST [HR: 0.82 (95%CI: 0.43, 1.57), p = 0.55]. MIS was associated with a significantly shorter intensive care unit (ICU) stay [MD: −1.52 days (95%CI: −2.08, −0.97), p < 0.01]. Conclusions: MIS for mitral valve IE is associated with favorable early and long-term outcomes, comparable survival with sternotomy, and reduced ICU stay. These findings suggest that MIS may be considered as a feasible and potentially effective alternative for the management of mitral valve IE in carefully selected patients. Further prospective comparative studies are warranted.

Journal of Personalized Medicine doi: 10.3390/jpm16070349

Authors: Ahmad I. Kamaludin Ashwin Kumaria Keyoumars Ashkan

Background: Neuromodulation is a rapidly developing field with growing interest in its application in neuro-oncology, particularly since the publication of the EF-14 trial which demonstrated a survival benefit conferred by tumour treating fields (TTF) in patients with glioblastoma. In addition, the emerging field of cancer neuroscience has postulated the role of neural–tumour communication in tumour aetiology, which is theoretically targetable by neuromodulation strategies. This scoping review therefore aims to comprehensively evaluate current or future applications of neuromodulation in managing patients with brain tumours, encompassing preclinical and clinical studies. Methods: The MEDLINE database was queried for all relevant articles from inception to 1 December 2024. A synthesis of findings was performed, broadly categorised to preclinical and clinical research. Findings: The database search returned 3296 results, from which 187 full-text articles were further assessed. A total of 79 studies met the inclusion and exclusion criteria and were included. The results from preclinical studies (n = 18) were stratified according to modality which included electrical therapy, electroporation, electromagnetic field (EMF) and deep brain stimulation (DBS). Similarly, clinical studies (n = 61) were classified to preoperative modalities such as transcranial magnetic stimulation (TMS) and transcranial direct stimulation (tDCS), and postoperative modalities such as TMS, TTF, EMF and spinal cord stimulation (SCS). Interpretation: The application of neuromodulation as adjunctive therapy in the context of neuro-oncology is an emerging field, with encouraging results in various modalities across a wide range of applications from surgical planning and functional rehabilitation, to its therapeutic potential. Further research is urgently needed to harness the potential of neuromodulation in improving patient outcomes.

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 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.