Journal of Personalized Medicine doi: 10.3390/jpm16090467

Authors: Eszter Hódi Éva Horváth-Varga Márta Katona Hajnalka Orvos Áron Lajkó Zsófia Fritsch Szabolcs Várbíró Zita Gyurkovits

Importance: Congenital heart defects constitute the most prevalent developmental abnormality. Among these, critical congenital heart defects are associated with substantial morbidity and mortality if not promptly identified. Objective: To evaluate the screening performance of a newborn protocol combining prenatal ultrasonography, postnatal physical examination, and pulse oximetry screening, with particular attention being paid to the timing of the postnatal examination. This is an evaluation of screening performance in a single centre and not a study of birth prevalence. Methods: We performed a retrospective cohort study of all live-born infants delivered at University of Szeged, Hungary, between 2019 and 2024. Screening comprised prenatal ultrasonography, postnatal physical examination within 24 h and at a 48–72 h range, and pulse oximetry screening at 24 ± 6 h. The primary outcome was an echocardiographically confirmed congenital heart defect, classified as critical, severe, requiring surgical correction after one year of age, or minimal. Isolated patent foramen ovale, isolated patent ductus arteriosus when the only echocardiogram was performed before 21 days of age, and a patent duct in preterm infants were classified as transitional findings and were excluded. Proportions are reported with exact (Clopper–Pearson) 95% confidence intervals and groups were compared using Fisher’s exact test. Results: Among 13,979 live births, 123 infants had an echocardiographically confirmed structural defect of the heart or great vessels detected through screening; a further 39 infants had transitional findings. Postnatal physical examination accounted for 107/123 (87.0%, 95% confidence interval range: 79.7–92.4) of the cases detected by screening; because echocardiography was not performed in screen-negative infants and defects presenting after discharge were not systematically traced, this is the share of screen-detected cases and not the sensitivity of the examination. The second examination at the 48–72 h range accounted for 92/123 (74.8%, 66.2–82.2), including 3 critical and 5 severe defects in which the first examination had shown no abnormality. Prenatal ultrasonography identified 6/16 (37.5%, 15.2–64.6) of critical and severe defects, and 15/123 (12.2%, 7.0–19.3) of all structural defects. The latter figure is not a prenatal detection rate, since there are lesions that cannot be identified before birth. Pulse oximetry screening identified 1/123 (0.8%, 0.0–4.4) after negative prenatal ultrasonography and no clinical signs. The combined protocol detected 123 of the 124 infants known to have a structural defect (99.2%) before discharge; this is a detection rate among known cases. Critical defects were identified in at least 0.50 per 1000 live births and critical plus severe defects in at least 1.14 per 1000; these are lower limits for live births in one centre, not birth prevalence estimates. Interpretations: Repeated postnatal physical examination provided the highest yield, while prenatal ultrasonography contributed mainly to severe and critical defect detection; pulse oximetry screening added few additional cases but remains an important modality. Where discharge occurs before 48 h, a second cardiac examination should be arranged at a range of 48–72 h of age, and a cardiology review between two and six weeks is advisable, since small muscular ventricular septal defects and duct-dependent left-heart obstruction may not be apparent in the first days of life.

Journal of Personalized Medicine doi: 10.3390/jpm16090466

Authors: Guido Gembillo Concetto Sessa Luca Zanoli Luca Visconti Maria Federica Ricca Lorenzo Lo Cicero Andrea Corsonello Salvatore Petrina Antonino Nicosia Luca Soraci Giuseppe Fede Guglielmo Piccione Sebastiano Lumera Walter Morale Domenico Santoro

Heart failure affects more than 64 million people worldwide, and admissions for acute decompensation account for a substantial proportion of cardiovascular healthcare expenditure. Achieving complete decongestion remains the principal objective of inpatient management, yet many patients are discharged with persistent volume overload, a consistent predictor of early rehospitalization and mortality. Loop diuretics have remained the cornerstone of decongestive therapy for more than six decades; however, their effectiveness is frequently limited by diuretic resistance, leaving many patients incompletely decongested despite dose escalation. Diuretic resistance reflects adaptive sodium retention distributed across multiple nephron segments, a process that extends well beyond the loop itself. Distal-tubular-remodeling-enhanced proximal sodium reabsorption, neurohormonal activation, post-diuretic sodium retention, and impaired tubular drug delivery collectively blunt natriuretic responsiveness, explaining why progressive loop–dose escalation often yields diminishing returns. Sequential nephron blockade provides a physiology-based strategy that matches the adjunct agent to the predominant mechanism of sodium retention. We integrate contemporary randomized evidence with renal tubular physiology to propose a mechanism-based approach: acetazolamide for patients with hypochloremic metabolic alkalosis and enhanced proximal sodium reabsorption, thiazide-type diuretics when distal cotransporter escape predominates, vasopressin antagonists for dilutional hyponatremia complicating congestion, and sodium–glucose cotransporter 2 inhibitors as foundational therapy that combines modest acute natriuresis with durable cardiorenal protection. Early assessment of natriuretic response using spot urine sodium further enables individualized treatment escalation. Together, these concepts move sequential nephron blockade beyond empirical combination diuretic therapy toward a mechanism-based strategy for overcoming diuretic resistance. We propose a personalized, phenotype-driven framework in which early urinary sodium response, kidney function, serum chloride, acid–base status, serum sodium, background SGLT2 inhibitor therapy, and venous congestion imaging guide the selection, escalation, and de-escalation of adjunctive therapy, with the goal of more complete and safer decongestion in acute decompensated heart failure. Matching adjunct choice to a patient’s individual biochemical phenotype, rather than applying diuretics in a fixed sequence, exemplifies precision medicine applied to acute decongestive therapy.

Journal of Personalized Medicine doi: 10.3390/jpm16090465

Authors: Vanesa García-del-Castillo Mónica Alamo-Peña César Albarrán-Diego Cecilia Arnaiz-Schmitz Nuria Garzón María García-Montero

Background/Objective: Binocular summation, the improvement in visual performance under binocular compared with monocular viewing, depends on the visual task and the degree of optical degradation of the retinal image. Its behavior across the full defocus curve in presbyopia remains poorly characterized. The purpose is to quantify binocular summation in healthy presbyopic adults by assessing contrast sensitivity (CS) at intermediate and near distances and by comparing monocular and binocular defocus curves to evaluate the effect of binocularity on depth of focus, the area under the curve (AUC), and the binocular summation ratio (BSR). Methods: Thirty healthy presbyopic participants (mean age 53.7 ± 5.7 years, range 45–64) were included in this observational, cross-sectional study. CS was measured with the Pelli–Robson chart at 1 m and 40 cm, and monocular and binocular defocus curves were obtained from −3.50 D to +1.50 D in 0.50 D steps. BSR, AUC and depth of focus at the 0.2 and 0.1 logMAR thresholds were calculated. Monocular and binocular values were compared with paired t-tests, applying a Bonferroni correction. Results: Binocular CS was significantly higher than monocular CS at both distances (adjusted p < 0.025), with a large, distance-independent BSR (1.68 at 1 m, 1.69 at 40 cm). BSR exceeded unity at every defocus level (10–21% gain), but after correction the binocular advantage in visual acuity remained significant only within the central range (−0.50 D to +1.00 D). At the participant level, binocularity increased the AUC at the 0.1 logMAR threshold (+50.5%, p = 0.037, d = 0.40), whereas the increase at the 0.2 logMAR threshold (+52.2%) did not reach statistical significance (p = 0.107). Conclusions: Binocularity consistently enhances visual performance in presbyopic adults, for contrast sensitivity and, with a pattern of significant improvement concentrated in the central defocus range, for visual acuity, supporting a more personalized evaluation of presbyopia.

Journal of Personalized Medicine doi: 10.3390/jpm16090464

Authors: Maria Rogalidou Christina Kanaka-Gantenbein

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the most common chronic liver disease in childhood, paralleling the global increase in pediatric obesity and metabolic dysfunction. Once considered a benign condition, pediatric MASLD is now recognized as a heterogeneous and potentially progressive disease that may advance from simple steatosis to steatohepatitis, fibrosis, and, rarely, cirrhosis, with lifelong hepatic and cardiometabolic consequences. Its pathogenesis is multifactorial, involving insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, genetic and epigenetic susceptibility, environmental factors, and alterations in the gut microbiome. Most affected children are asymptomatic, and diagnosis is often prompted by elevated liver enzymes or incidental imaging findings. Noninvasive tools, including ultrasonography, elastography, serum biomarkers, and emerging multi-omics approaches, are improving disease detection and risk stratification, although liver biopsy remains the reference standard in selected cases. Lifestyle modification, including dietary optimization, increased physical activity, and gradual weight reduction, remains the cornerstone of management, while pharmacological therapies are still under investigation in pediatric populations. The marked variability in disease susceptibility; progression; and treatment response underscores the need for a personalized medicine approach. Integrating clinical characteristics with genomic, epigenomic, metabolomic, and microbiome data may enable early identification of high-risk children, more accurate prognostic assessment, and individualized preventive and therapeutic strategies. Early detection and multidisciplinary care involving pediatricians, hepatologists, endocrinologists, dietitians, and families may help reduce disease progression and the risk of long-term hepatic and cardiometabolic complications. This review summarizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pediatric MASLD, with a particular emphasis on precision diagnostics, biomarker discovery, and personalized therapeutic approaches. It also discusses current challenges and future directions for implementing personalized medicine to improve outcomes and reduce the lifelong burden of pediatric MASLD.

Journal of Personalized Medicine doi: 10.3390/jpm16090463

Authors: Ioanna Koniari Andreas Gerakaris Efthimia Kapsali Stamatios Kanellopoulos Georgia Xygka Asimenia Katsea Eftychia Petropoulou Anastasia Mavromati Rafail Koros Georgios Leventopoulos Angelos Perperis Georgios Kollias Periklis Davlouros

Heart failure remains a major cause of morbidity and mortality despite advances in guideline-directed medical therapy and device-based treatment. Cardiac resynchronization therapy delivered by conventional biventricular pacing constitutes an established therapeutic strategy for selected patients with heart failure with reduced ejection fraction and electrical desynchrony. Left bundle branch area pacing has emerged as a physiological pacing strategy that directly engages the conduction system, providing more effective electrical and mechanical resynchronization. Current evidence from observational studies, randomized pilot trials, and recent multicentre data suggest that left bundle branch pacing may achieve greater QRS narrowing, more favourable pacing thresholds, improved left ventricular ejection fraction, and reduced heart failure hospitalizations compared with conventional biventricular pacing in selected patients. This review summarizes the rationale, implantation criteria, patient selection, and current clinical evidence supporting left bundle branch pacing as an alternative pacing modality in heart failure patients. Despite encouraging available data, larger randomized trials with longer follow-up and broader patient populations are required to clarify long-term safety and to determine whether left bundle branch pacing should be adopted as a routine alternative to conventional cardiac resynchronization therapy. From a personalized medicine perspective, the choice between conduction system pacing and conventional biventricular pacing should be guided by individual patient characteristics, including conduction phenotype, QRS morphology and duration, myocardial scar burden, heart failure aetiology, coronary venous anatomy, and the chance of achieving confirmed conduction-system capture. This review therefore renders left bundle branch pacing within an individualized, phenotype-guided resynchronization strategy rather than as a universal replacement for biventricular pacing.

Journal of Personalized Medicine doi: 10.3390/jpm16090462

Authors: Elisa Garbin Nicola Cavasin Luca Basaldella Salima Magrini

Background: Ruptured isolated spinal artery aneurysms (SAAs) are not common. Posterior spinal artery aneurysms (PSAAs) are less common. Either is rarely the cause of spontaneous spinal subarachnoid hemorrhage (sSAH). Due to a few published reports, the natural course, diagnosis and optimal therapeutic strategy remain debatable and challenging. We report the case of a 60-year-old male presenting with lumbar and abdominal pain, which swiftly became associated with headache, photophobia and worsening neck pain. Spinal MRI revealed an intradural hemorrhage collection from the T9 level to the T10 level; the spinal DSA confirmed a fusiform dissecting PSAA originating from the T11 level. He was managed conservatively and recovered completely. We have reviewed the few cases reported in the literature. Results: Except for the present case, there are 29 reported cases of isolated PSAAs and 69 cases of isolated SAAs. The patients’ ages ranged from 16 to 88 years, and common presenting symptoms were headache and back/abdominal pain. The PSAAs were commonly located at the lower thoracic level or lumbar level. The most common PSAA treatment was surgery; among the 29 cases, 85% reported favorable outcomes regardless of the type of treatment. Conclusions: Ruptured spinal artery aneurysms are prone to spontaneous thrombosis. Given the lack of standardized guidelines, a personalized medicine approach is essential, requiring a detailed, patient-specific risk assessment. Conservative management could be an appropriate treatment option with a favorable outcome. Further understanding may help guide future clinical decision-making and tailored treatment planning according to patient-specific features.

Journal of Personalized Medicine doi: 10.3390/jpm16090461

Authors: Wiktor Śliwiński Weronika Pura Dominika Matecka Mateusz Kosowski Daniel Chołuj Jakub Marciniak Jakub Mazur Karolina Zarówna Laavanya Damodaran Natalia Szejko

Background: Pediatric inflammatory multisystem syndrome (PIMS), also referred to as multisystem inflammatory syndrome in children (MIS-C), is a rare but serious post-infectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection characterized by systemic hyperinflammation and multiorgan involvement. New-onset neurological and psychiatric symptoms have emerged as critical clinical features, occurring in approximately 12–27% of pediatric patients aged 2–15 years (median age, 10 years) and often indicating a more severe disease course. This narrative review aims to provide a comprehensive overview of the current literature regarding the neurological and psychiatric manifestations of PIMS/MIS-C, focusing on epidemiology, pathophysiology, clinical presentation, neuroimaging findings, biomarkers, treatment strategies, and outcomes. Methods: A narrative literature review was conducted to synthesize current evidence on the neurological and psychiatric spectrum of PIMS/MIS-C. Evaluated parameters included clinical presentations ranging from common symptoms (such as headache, encephalopathy, altered mental status, and seizures) to rare complications (such as ischemic stroke, acute disseminated encephalomyelitis, Guillain–Barré syndrome, and cerebral edema), alongside associated psychiatric disturbances, diagnostic findings, and therapeutic approaches. Results: Neurological and psychiatric manifestations significantly impact the clinical trajectory of PIMS/MIS-C. Acute symptoms include headache, encephalopathy, seizures, and psychiatric disturbances like behavioral changes, hallucinations, delirium, anxiety, and sleep disorders. Neuroimaging in many cases reveals reversible lesions of the splenium of the corpus callosum, while electroencephalography typically demonstrates diffuse slowing consistent with encephalopathy. Early recognition and prompt administration of immunomodulatory therapy—primarily intravenous immunoglobulin and corticosteroids—correlate with favorable neurological recovery in the majority of patients. However, current evidence remains largely observational and heterogeneous, precluding definitive causal conclusions regarding this treatment–outcome relationship. Affected children more frequently require intensive care unit admission and remain at risk for persistent cognitive, behavioral, and psychiatric sequelae. Conclusions: Neurological and psychiatric complications in PIMS/MIS-C are clinically significant indicators of disease severity that require vigilant monitoring and early immunomodulatory intervention. Continued multidisciplinary follow-up and prospective studies are essential to elucidate the long-term neurodevelopmental and psychiatric consequences and to optimize therapeutic strategies for these patients.

Journal of Personalized Medicine doi: 10.3390/jpm16090460

Authors: Nikola Popovski Nikoleta Stoyanova Rebecca Caiulo

Background: Congenital abdominal wall defects (CAWDs), primarily gastroschisis and omphalocele, result from disturbances in early embryonic folding and midgut development and are routinely detected during prenatal ultrasound screening. Despite advances in prenatal imaging, considerable heterogeneity in clinical presentation, severity, and outcomes necessitates structured risk stratification to optimize prenatal and perinatal management. Objectives: We aimed to present a series of prenatally diagnosed congenital abdominal wall defects and integrate current evidence into a clinically applicable, risk-adapted framework for prenatal assessment and perinatal management. Materials and Methods: Three pathological cases of CAWDs diagnosed between 2025 and 2026 were retrospectively analyzed. Two additional first-trimester ultrasound examinations demonstrating physiological midgut herniation were included as illustrative examples of an important differential diagnosis during early pregnancy. Prenatal assessment included systematic evaluation of bowel dilatation, bowel wall thickness, liver herniation, and associated structural anomalies. Established risk stratification systems—including the distinction between simple and complex gastroschisis and the classification of omphalocele according to defect size and associated anomalies—were applied. A narrative review of the literature was performed to contextualize the clinical findings and support the development of a practical ultrasound-based diagnostic and management algorithm. Results: The pathological cases illustrated the broad clinical spectrum of CAWDs, ranging from isolated omphalocele to lethal body stalk anomaly, while the illustrative examples emphasized the importance of distinguishing physiological midgut herniation from pathological abdominal wall defects during the first trimester. Prenatal risk stratification based on ultrasound findings may inform surveillance strategies, delivery planning, and parental counseling. In particular, associated anomalies and liver herniation in omphalocele, as well as progressive bowel abnormalities in gastroschisis, were identified as key determinants of prognosis and clinical management. Based on the literature review and the illustrative institutional cases, an educational ultrasound-based diagnostic and management framework was proposed to summarize the current evidence and support a structured diagnostic approach. Conclusions: Congenital abdominal wall defects should be considered a spectrum of disorders with varying embryological origins, clinical manifestations, and prognostic implications. A standardized prenatal assessment combined with risk-adapted management can improve prognostic accuracy, optimize perinatal planning, and support informed parental counseling. Implementation of structured diagnostic frameworks may enhance clinical decision making and improve outcomes in affected pregnancies.

Journal of Personalized Medicine doi: 10.3390/jpm16090459

Authors: Sherlyn Chng Omar Shadid Ishith Seth Warren M. Rozen

Background: Flexor tendon rupture is a rare but potentially disabling complication following minimally invasive treatment of Dupuytren’s disease. This meta-analysis compared rupture incidence after collagenase Clostridium histolyticum (CCH) injection and percutaneous needle fasciotomy/aponeurotomy (PNF/PNA). Methods: PubMed, MEDLINE, and Embase were systematically searched for randomised trials, cohort studies, clinical trials, and case series reporting complications after CCH or PNF for Dupuytren’s disease. Case reports and secondary evidence were excluded from incidence calculations, although reference lists of reviews were screened for eligible primary studies. Flexor tendon rupture events and study denominators were extracted as reported. Pooled incidence was estimated using random-effects proportional meta-analysis with logit transformation and continuity correction. Separate pooled estimates were generated for CCH and PNF, followed by subgroup comparison. Results: Forty-one studies were included. Across eligible studies, 68 flexor tendon ruptures were identified, including 62 after CCH and 6 after PNF. Ruptures most commonly involved the flexor digitorum profundus, affected the small finger, and occurred early, with a median time to rupture of 8 days, where reported. Fourteen PNF cohorts comprising 6058 treated units reported 6 ruptures, producing a pooled incidence of 0.32% (95% CI: 0.18–0.55%) with no observed heterogeneity. Twenty-nine CCH cohorts comprising 60,949 treated units reported 62 ruptures, producing a pooled incidence of 0.83% (95% CI: 0.42–1.64%) with substantial heterogeneity. Subgroup comparison demonstrated a higher pooled rupture incidence following CCH than PNF. Conclusions: Flexor tendon rupture is uncommon after both CCH and PNF. Characterisation of anatomical and treatment-related patterns of rupture may support more individualised risk counselling and treatment selection in Dupuytren’s disease. Future studies are required to develop clinically meaningful risk-stratification strategies.

Journal of Personalized Medicine doi: 10.3390/jpm16090458

Authors: Akshay Soni Ishith Seth Kaiyang Lim Alexander Phan Richard J. Ross Mathew Lee Warren M. Rozen

Background: Thoracic air complications after autologous breast reconstruction (ABR) are uncommon and incompletely characterised. A personalised perioperative approach requires integration of patient anatomy, reconstructive technique, anaesthetic exposures and the postoperative clinical trajectory rather than reliance on population-level estimates alone. Methods: We report a 41-year-old woman in whom pneumomediastinum was identified after bilateral DIEP flap reconstruction and performed a focused literature review restricted to primary studies of pneumothorax or pneumomediastinum following autologous flap breast reconstruction. Searches across MEDLINE-Ovid, PubMed and Wiley Online Library using predefined MeSH terms were conducted. Data extraction focused on study characteristics, incidence, mechanism of injury, perioperative factors, and management. Results: The patient developed postoperative hypotension and persistent tachycardia, followed by pleuritic chest pain. CT excluded pulmonary embolism and oesophageal perforation but demonstrated Moderate volume pneumomediastinum without pneumothorax. She was managed conservatively and discharged on postoperative day 7. Five primary studies met the eligibility criteria. Study-specific pneumothorax frequencies were 1/463 (0.22%) after rib-sparing free-flap reconstruction, 3/749 (0.4%) after extended latissimus dorsi reconstruction, and 4/180 patients (2.2%; 1.4 per 100 internal mammary vessel dissections). Reported mechanisms included pleural injury during internal mammary vessel dissection, inadvertent puncture during regional anaesthesia, barotrauma under positive-pressure ventilation, and drain-related barotrauma. No previous primary report of pneumomediastinum after autologous flap breast reconstruction was identified. Conclusions: Pneumothorax and pneumomediastinum are uncommon but potentially serious complications of ABR. They are rarely documented postoperatively; however, surgeons and anaesthetists must remain vigilant, particularly during exposure of the internal mammary vessels and airway management. Patient-specific assessment, symptom-directed imaging and multidisciplinary management may support early recognition to prevent morbidity and preserve the outcomes of reconstructive procedures.

Journal of Personalized Medicine doi: 10.3390/jpm16090457

Authors: Ángela Morell Alberto Morell Ainhoa Aranguren Jacobo Rogado Miguel Sampedro Rebeca Mondéjar Ramón Colomer M. Paz Lorenzo Esther Ramírez

Background/Objectives: Immunotherapy using immune checkpoint inhibitors has transformed the treatment of multiple solid tumours. However, the clinical response to programmed death receptor (PD-1) and its ligand (PD-L1) inhibitors remains heterogeneous. We have previously shown that host-related factors such as body mass index (BMI) may modulate the efficacy of immunotherapy. The aim of this study was to determine whether body composition, measured with bioelectrical impedance analysis (BIA) before treatment initiation, is a prognostic factor for survival outcomes in patients treated with PD-1/PD-L1 inhibitors, independently of tumour type and stage. Methods: In this prospective, single-centre observational study, patients with solid tumours underwent baseline body composition assessment using multifrequency bioelectrical impedance analysis (BIA) before initiation of PD-1/PD-L1 inhibitor therapy. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events were evaluated using Kaplan–Meier analyses and multivariable Cox regression models adjusted for tumour stage and metastatic status. Results: A total of 80 patients with solid tumours were included in the study. The median age was 67 years, and 48 (60.0%) were male. Higher BMI (≥25 kg/m2) and elevated body fat percentage (%BF) were associated with more favourable survival outcomes. After adjustment for tumour stage and metastatic status, BMI ≥ 25 kg/m2 was associated with a lower risk of death (HR 0.286, 95% CI 0.087–0.941; p = 0.039). Similar results were observed for elevated %BF (HR 0.289, 95% CI 0.087–0.963; p = 0.036). Neither BMI nor %BF was significantly associated with the occurrence of confirmed immune-related adverse events. Conclusions: Baseline BMI and body fat percentage were associated with survival outcomes in this exploratory cohort of patients receiving PD-1/PD-L1 inhibitors. These findings should be considered exploratory and hypothesis-generating and require confirmation in larger, tumour-specific prospective studies.

Journal of Personalized Medicine doi: 10.3390/jpm16090456

Authors: Anna Grimaldi Diego Lopane Stefano Mancin Orsola Agorini Vincenzo Di Nuzzo Giuseppe Frattolillo Domenico Di Sivo Giovanni Gavarro Incoronata Chiusolo Ciro Pozzuoli Sara Morales Palomares Italian Society of Nephrology Nurses (SIAN) Board of Directors Group Italian Society of Nephrology Nurses (SIAN) Board of Directors Group Giovanni Cangelosi Alessandro Stievano

Background/Objectives: Fluid balance management is a core nursing competency, particularly in high-acuity settings. However, the assessment of insensible water loss remains challenging due to the lack of standardized methods, which may increase variability in clinical reasoning. In this context, digital tools may support a more structured and personalized approach. This study aimed to assess nurses’ knowledge of fluid balance and insensible water loss [perspiratio insensibilis (PI)] and to evaluate the usability and perceived quality of a pilot digital clinical decision-support tool (CareBalance-N). Secondary analyses explored differences across clinical settings and the association between knowledge level and app evaluation. Methods: A cross-sectional observational study was conducted among 50 nurses working in three clinical settings: hemodialysis (n = 20; 40%), internal medicine (n = 15; 30%), and intensive care (n = 15; 30%). Knowledge was assessed using a structured questionnaire (score range: 0–100), while the usability and perceived quality of the digital application for fluid balance were evaluated using the User Version of the Mobile App Rating Scale (uMARS). Differences between settings were analyzed using ANOVA, and correlations were assessed using Pearson’s correlation coefficient. Results: The mean knowledge score was 67.6 ± 7.7, with significant differences across clinical settings [F(2, 47) = 28.4; p < 0.001]: hemodialysis 73.6 ± 6.0, intensive care 66.9 ± 4.7, and internal medicine 60.3 ± 5.1. The mean uMARS score was 3.91 ± 0.17, with particularly high ratings for functionality (4.19 ± 0.17) and perceived impact (4.17 ± 0.16). A strong positive correlation was found between knowledge scores and app evaluation (r = 0.943; p < 0.001). Conclusions: These findings highlight variability in nursing knowledge across clinical settings and suggest that digital tools such as CareBalance-N may represent a promising approach to facilitate more structured clinical reasoning and fluid balance assessment. However, these potential benefits require validation in real-world clinical settings. Further studies are needed to evaluate their impact on decision-making processes, the accuracy of fluid balance assessment, patient safety, and clinical outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16090455

Authors: Daniele Salvatore Paternò Luigi La Via Rossella Moltisanti Antonio Putaggio Angela Maria Piccolo Giorgia Maria Noce Roberta Scuto Gilberto Duarte-Medrano Natalia Nuño-Lámbarri Emilia Concetta Lo Giudice Massimiliano Sorbello

Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO2 retainers, underscoring the value of continuous CO2 monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity.

Journal of Personalized Medicine doi: 10.3390/jpm16090454

Authors: Paul R. Walker

Molecular residual disease (MRD) testing approaches with plasma next-generation sequencing (NGS) testing to identify circulating tumor DNA (ctDNA) in resectable-stage non-small cell lung cancer (NSCLC) are evolving. The MRD concept is to better guide perioperative systemic treatment and identify recurrent NSCLC before symptomatic radiographic recurrences. Multiple tumor-informed assays are available with technology driving lower levels of ctDNA detection. However, it remains unclear that individual patients derive survival outcome benefit from MRD testing. NSCLC tumor biology of spatial heterogeneity, early parallel metastases, and recurrence clonal evolution can impact tumor-informed approaches irrespective of specific assay level of ctDNA detection. Clinical decision making guided by tumor-informed MRD testing to date have been limited by recurrence risks of up to 20% when landmark MRD-negative, improved outcomes benefit of adjuvant treatment even when landmark MRD-negative, and lead times with longitudinal MRD-positive conversion of several months or longer before overt radiographic recurrences with no proven strategy of survival benefit with intervening treatment. Cautionary tumor biology and clinical issues remain in the clinical utility of tumor-informed MRD testing in resected NSCLC. These need to be clarified with certainty before MRD testing should step beyond a technology-driven prognostic recurrence risk indicator before becoming an absolute clinical guide to meaningfully impact individual patient management and outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16090453

Authors: Luisa M. Rizzo Matilde Petz Federico Carlini Susanna Esposito

Telemedicine is increasingly transforming pediatric cardiology by expanding access to specialized care, supporting early diagnosis, and improving longitudinal monitoring of children with cardiovascular disease. This narrative review summarizes current applications of digital health in pediatric cardiology, with emphasis on congenital heart disease, pediatric hypertension, and arrhythmia management. Tele-echocardiography represents one of the most established telehealth tools, enabling remote interpretation of fetal, neonatal, and pediatric echocardiographic images and improving referral appropriateness, particularly in peripheral or resource-limited settings. In infants with complex congenital heart disease, especially those with single-ventricle physiology during the interstage period, home monitoring programs using mobile applications, pulse oximeters, digital scales, and structured caregiver reporting may facilitate early recognition of clinical deterioration and reduce avoidable transfers. In non-congenital cardiovascular disease, home blood pressure monitoring can improve diagnostic accuracy by reducing white-coat effects and supporting repeated measurements in real-life settings. Smartphone-enabled electrocardiographic devices and wearable technologies may enhance detection of intermittent arrhythmias and strengthen outpatient management. Despite these advantages, challenges remain, including data fragmentation, limited pediatric validation of consumer devices, interoperability issues, privacy concerns, and socioeconomic disparities in technology access. Properly integrated telemedicine may promote more timely, equitable, and patient-centered pediatric cardiovascular care.

Journal of Personalized Medicine doi: 10.3390/jpm16090452

Authors: Gonçalo Nunes Marta Guimarães Sofia S. Pereira Ivo Mendes Francisco Vara-Luiz Cátia Oliveira Marta Gonçalves Patrícia Mendes Rute Santos Tânia Meira Jorge Fonseca

Introduction: Refeeding syndrome (RS) is a life-threatening metabolic complication of nutritional support. Prolonged fasting, frequently observed in malnourished patients referred for percutaneous endoscopic gastrostomy (PEG), may induce histological and ultrastructural changes in the intestinal mucosa, potentially influencing metabolic adaptation during nutritional reintroduction. Mixed-Meal Tolerance Tests (MMTT) combined with targeted metabolic profiling allow dynamic assessment of serum glucose, gastrointestinal hormones and metabolites, which may help to elucidate the metabolic adaptations associated with fasting and refeeding. Objective: The present study aims to perform MMTT in PEG patients to characterize enteroendocrine hormone responses and metabolomic profiles following a prolonged period of reduced nutritional intake and subsequent enteral refeeding. Methods: This prospective, single-center study includes adults referred for PEG after at least one month of oral intake below 50% of energy needs. The MMTT will be performed at PEG placement and after 3–6 months of enteral nutrition. Serial blood samples will be collected from baseline up to 120 minutes post-meal to measure serum glucose, insulin, C-peptide, electrolytes and gastrointestinal hormones (GLP-1, GIP, ghrelin and PYY), and for targeted metabolomic profiling by spectroscopy. Clinical and nutritional data will be prospectively recorded. Exploratory analyses will assess metabolic and hormonal changes over time and their potential associations with relevant clinical characteristics. The study was approved by the institutional ethics committee, and patient informed consent will be obtained. Conclusion: This study integrates MMTT and targeted metabolomic profiling to characterize hormonal and metabolic responses during fasting and refeeding in PEG patients considered at increased risk of RS due to prolonged markedly reduced oral intake. The findings may improve understanding of metabolic adaptations associated with nutritional reintroduction and may identify candidate hormonal and metabolic signatures to support future studies on RS pathophysiology and risk assessment.

Journal of Personalized Medicine doi: 10.3390/jpm16090451

Authors: Christos Verras Ioannis Ventoulis Sofia Bezati John Parissis Effie Polyzogopoulou

Prompt diagnosis and treatment of sepsis and septic shock is crucial due to the persistently high rates of morbidity and mortality associated with the disease. Recently, research efforts have focused on identifying novel biomarkers that would detect, classify, and assess the severity of sepsis in a timely manner, thereby allowing for expeditious and precise treatment of sepsis and septic shock. Among these biomarkers, proenkephalin (PENK) has gained considerable attention. Accordingly, this narrative review aims to consolidate current evidence on the clinical utility of PENK in patients with sepsis and septic shock, with emphasis on its role as a biomarker of renal dysfunction and as a predictor of sepsis-associated acute kidney injury (AKI) and mortality in both the emergency department (ED) and intensive care unit (ICU) settings.

Journal of Personalized Medicine doi: 10.3390/jpm16090450

Authors: Johanna Broman Niklas Nielsen Anna K. M. Persson

Background: Large prospective studies on the prevalence of acute and persistent pain in children are limited, and risk factors associated with post-surgical pain in children remain unclear. Objective: To examine the incidence of pediatric acute (APOP) and persistent postoperative pain (PPOP) and to determine whether factors such as age, sex, preoperative anxiety/sleep disturbance, preoperative pain and parental stress are associated with increased risk. Design: Prospective observational multicenter study. Setting: Hospitals performing pediatric surgery in southern Sweden. Patients: 601 children aged 1–17 years planned for one of the European Society of Pediatric Anesthesia (ESPA) pre-defined surgical procedures: inguinal hernia, circumcision/hypospadias/retentio testis, adenoidectomy/tonsillectomy/tonsillotomy, appendectomy and orthopedic acute fracture surgery. Main outcome measures: Postoperative pain in PACU after 24 h and 3, 6 and 12 months, level and description of the pain and effect on the child. Results: The incidence of APOP in the postoperative care unit was 0–27%, increasing to 13–58% after 24 h depending on surgery type. The incidences of PPOP were 4–24%, 4–30%, and 0–19% at 3, 6, and 12 months, respectively, depending on surgery type. Older age was a risk factor for APOPPACU (OR 1.2, p < 0.001) and APOP24h (OR 1.3, p < 0.001), whereas female sex was a risk factor only for PPOP6months (OR 2.1, p = 0.028). Self-reported parental stress was a significant risk factor for postoperative pain at all follow-ups, exhibiting increasing influence (APOP24h OR 1.2, p = 0.001; 3months OR 1.5, p < 0.001; 6months OR 1.3, p < 0.001; 12months OR 1.5, p < 0.001). Preoperative anxiety/sleep disturbance only affected APOPPACU (OR 2.0, p = 0.008), whereas preoperative pain was not a risk factor. Conclusions: The incidences of APOP and PPOP were lower than in previous studies. Possible risk factors for acute pain include older age and preoperative anxiety/sleep disturbance. Only self-reported parental stress was a consistent risk factor for persistent pain.

Journal of Personalized Medicine doi: 10.3390/jpm16090449

Authors: Renée E. W. M. van de Vorst Sophie S. M. Pelk Eelke H. Gort Petronella O. Witteveen Ronald P. Zweemer Cornelis G. Gerestein

Background: Secondary cytoreductive surgery (SCS) followed by postoperative chemotherapy is a recognized option for select patients with platinum-sensitive first recurrent epithelial ovarian cancer (EOC), supported by the DESKTOP-III and SOC-1 trials. Neither trial reported chemotherapy rates stratified by lesion number or resection status. As a result, the added value of postoperative chemotherapy after complete resection of a unifocal recurrence remains unclear. This study aimed to evaluate current clinical practice and factors influencing this decision. Methods: A cross-sectional survey was conducted among gynecological and medical oncologists from international expert oncological centers, assessing definitions of unifocal recurrence, current postoperative chemotherapy practice after complete SCS, perceived clinical value and strength of the supporting evidence, and factors influencing decision-making. Results: Twenty of 48 invited experts responded (41.7%). Respondents applied different definitions of unifocal recurrence, leading to variable estimates of the annual number of patients undergoing SCS. Respondents perceived postoperative chemotherapy to have meaningful clinical value, despite rating the supporting evidence as weak. A proportion did not routinely administer postoperative chemotherapy after complete SCS, managing patients with observation alone. Decisions to omit chemotherapy were influenced by institutional, clinical, and patient-related factors. Overall, 82% of respondents considered a randomized trial comparing chemotherapy with observation clinically valuable. Conclusions: Clinical practice regarding postoperative chemotherapy after complete SCS for a first unifocal recurrence of EOC varies among international expert oncological centers. The absence of a uniform definition of unifocal recurrence and lack of direct evidence regarding postoperative chemotherapy omission highlight the need for standardized definitions and prospective randomized evaluation of chemotherapy versus observation.

Journal of Personalized Medicine doi: 10.3390/jpm16090448

Authors: Siddharth Gandhi Michael Balas

Objective: The objective was to quantify whether demographic and social attributes that were irrelevant to stated clinical need, prognosis, and expected benefit altered resource-allocation decisions made by a general-purpose large language model (LLM). Methods: We conducted a cross-sectional audit of the gpt-5-chat-latest API model alias on 8 October 2025, across seven clinical vignettes, generating 30,618 forced-choice comparisons between patient profiles. Profiles varied across a full-factorial combination of eight demographic and social attributes while clinical need, prognosis, and expected benefit were held constant. Forced choices were analyzed using pooled logistic regression with separate Patient A and Patient B attribute terms and vignette-specific position effects; position-averaged odds ratios and position-balanced absolute probabilities were derived from this model. Priority-score differences were analyzed using an analogous linear model. Results: The model showed large position-averaged associations between non-clinical patient attributes and allocation decisions. Indigenous and Black race were associated with substantially higher odds of selection relative to White race (Indigenous: OR 16.48, 95% CI 14.85–18.28; Black: OR 8.07, 95% CI 7.32–8.90), corresponding to position-balanced absolute increases in selection probability of 30.7 and 16.3 percentage points, respectively. Conversely, high-status occupation (OR 0.064, 95% CI 0.058–0.071), friendship with institutional leadership (OR 0.121, 95% CI 0.111–0.131), and major donor status (OR 0.092, 95% CI 0.084–0.101) were associated with markedly lower odds of selection. Choice-score concordance was 95.1%. Conclusions: In this controlled audit, the LLM’s allocation decisions varied substantially according to demographic and social characteristics despite identical stated clinical need, prognosis, and expected benefit. Although some patterns could be interpreted differently under competing ethical frameworks, their implicit and unexplained incorporation into resource-allocation decisions raises concerns regarding transparency, accountability, and clinical governance. Clinical use of LLM-based allocation support should therefore require explicit safeguards and systematic auditing for non-clinical influences.

Journal of Personalized Medicine doi: 10.3390/jpm16090447

Authors: Athanasios Kranas Evgenia Paxinou Ioannis Bazakidis Christina Koufopoulou Petros Koufopoulos Georgios Feretzakis Vassilios S. Verykios

Background/Objectives: Assessment of Internet Gaming Disorder (IGD) relies on retrospective self-reports and clinical interviews, which may be affected by recall and social desirability biases and may be insensitive to behavioral change. This study evaluated an artificial intelligence (AI)-enabled, privacy-preserving digital phenotyping framework for personalized IGD risk stratification under controlled simulation assumptions. Methods: A synthetic dataset of 1000 virtual user profiles was generated with a 20% elevated-risk prevalence and 5% balanced stochastic label noise. Four aggregated telemetry features were modeled: average session duration, sessions per week, Late-Night Index, and application-switching rate. Random Forest, Logistic Regression, and Gradient Boosting classifiers were evaluated using a stratified 80:20 hold-out split, five-fold cross-validation, playtime-only baselines, label-noise sensitivity analysis, and 200 synthetic realizations. Results: The primary Random Forest model achieved a balanced accuracy of 0.850, a sensitivity of 0.800, a specificity of 0.900, an area under the receiver operating characteristic curve (ROC-AUC) of 0.909, an average precision (AP) of 0.779, and a Brier score of 0.089. As an internal consistency check under the pre-specified synthetic signal structure, all-feature models showed higher performance than playtime-only baselines, and feature importance analyses recovered the encoded signal hierarchy. Performance declined with increasing label noise. Across 200 realizations, mean ROC-AUC values for the three all-feature models ranged from 0.888 to 0.904, with overlapping empirical 95% intervals. Conclusions: The framework demonstrates the methodological feasibility of transforming aggregated telemetry into interpretable risk signals while avoiding content-level monitoring. These findings are hypothesis-generating and do not establish clinical validity or diagnostic performance. Longitudinal validation in clinically characterized cohorts is required before deployment.

Journal of Personalized Medicine doi: 10.3390/jpm16090446

Authors: Meghan MacNeal Nathan A. Bihlmeyer Susanne B. Haga

Background/Objectives: Rural populations remain underrepresented in genomic research and may face unique barriers to accessing genetic and precision medicine services. This study evaluated knowledge, attitudes, beliefs, and perceived barriers related to genetics and precision medicine among rural participants enrolled in OneDukeGen (ODG), a large academic biobank and precision medicine research initiative. Methods: This mixed-methods study included rural ODG participants identified using U.S. Census Bureau rural classification code. Participants completed an online survey assessing genetics knowledge, attitudes toward genetic testing and precision medicine, healthcare utilization, and internet use. Semi-structured interviews were conducted with a subset of survey participants to further explore perceptions of genetics research, barriers to care, privacy concerns, and educational needs. Results: Among 10,305 ODG participants, 3268 (31.7%) were classified as rural, representing 97 of North Carolina’s 100 counties. A total of 111 rural participants completed surveys and 14 participated in qualitative interviews. Participants generally demonstrated favorable attitudes toward genetics and precision medicine despite moderate genetics knowledge scores. Most participants believed genetic testing could improve disease prevention and treatment selection, particularly for cancer care and pharmacogenomics applications. Qualitative interviews identified three major thematic domains: (1) perceived value and promise of genetics, (2) concerns regarding privacy, trust, and misuse of genetic information, and (3) barriers and facilitators to accessing genetic services. Participants generally viewed genetics research positively but expressed concerns regarding cost, insurance coverage, privacy, and genetic discrimination. Conclusions: Rural participants generally expressed positive attitudes toward genetics and precision medicine; however, substantial barriers related to cost, trust, privacy, awareness, and digital access remain. Community-engaged approaches emphasizing accessibility, provider education, and culturally appropriate communication may be critical for equitable implementation of precision medicine in rural communities.

Journal of Personalized Medicine doi: 10.3390/jpm16090445

Authors: Anna Paspala Dimitrios K. Vlachos Dionysios Prevezanos Panagiotis Dorovinis Nikolaos Machairas Stylianos Kykalos Evangelos Tagkalos Georgios C. Sotiropoulos

Background/Objectives: Primary biliary neuroendocrine tumors (PBilNETs) are exceptionally rare biliary tract neoplasms that are frequently misdiagnosed preoperatively as cholangiocarcinoma because of overlapping clinical and radiological findings. This systematic review aimed to summarize overall evidence regarding presentation, diagnostic evaluation, surgical management, and outcomes of PBilNETs. Methods: A systematic search of PubMed, Scopus, and Embase databases was performed according to PRISMA guidelines for studies published between January 2000 and December 2025. Studies including adult patients with histologically confirmed and surgically treated PBilNETs were eligible. Data regarding demographics, symptoms, imaging findings, surgical treatment, histopathology, immunohistochemistry, and outcomes were extracted and analyzed. Results: Fifty-eight studies involving 79 patients met the inclusion criteria. Median age at diagnosis was 49 years, with female predominance. Obstructive jaundice, abdominal pain, and pruritus were the most common presenting symptoms. Most tumors originated from the hilar or extrahepatic bile ducts. Preoperative diagnosis was challenging, as most lesions were initially considered cholangiocarcinomas. Surgical resection was the main therapeutic approach and included bile duct excision with biliary reconstruction, pancreaticoduodenectomy, or hepatic resection according to tumor location. Histopathological analysis demonstrated predominantly well- or moderately differentiated neuroendocrine neoplasms with frequent chromogranin A and synaptophysin positivity. Favorable long-term outcomes were reported, with high postoperative survival and limited recurrence during follow-up. Conclusions: PBilNETs remain diagnostically challenging because of their rarity and nonspecific presentation; however, they appear to exhibit a less aggressive biological behavior than conventional biliary adenocarcinomas. Surgical resection remains the cornerstone of treatment, while further multicenter studies are required to optimize diagnostic and therapeutic strategies. The findings also support an individualized multidisciplinary approach integrating clinical presentation, advanced imaging, histopathological grading, and immunohistochemical profiling to optimize personalized management of these rare tumors.

Journal of Personalized Medicine doi: 10.3390/jpm16090444

Authors: Antoine Yanni Géraldine Descamps Fabrice Journe Edward Boutremans Isabelle Loeb Sven Saussez Didier Dequanter

Background: The immune landscape in head and neck squamous cell carcinoma (HNSCC) has been widely investigated. However, the crucial role played by the lymph node microenvironment in metastatic and non-metastatic HNSCC remains unknown. This systematic review aims to discuss the immunological crosstalk between the tumor and the nodal microenvironment and to describe the distribution of immune cells in metastatic and non-metastatic lymph nodes. Methods: A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus, and the Cochrane Library were searched for studies published between 1990 and 2025, with the final search performed in December 2025. Prospective and retrospective studies evaluating immune cell infiltration in metastatic and non-metastatic cervical lymph nodes were included, whereas studies focusing exclusively on non-cellular biomarkers and non-English publications were excluded. The risk of bias was assessed using the Newcastle–Ottawa Scale. The results were synthesized narratively, and no meta-analysis was performed. Results: The screening process identified 608 articles, of which 27 met our predefined inclusion criteria. These studies focused on macrophages, dendritic cells, neutrophils, natural killer cells, T helper cells, cytotoxic T cells, regulatory T cells, B cells, total lymphocytes, and surface markers. This systematic review provides a well-structured analysis of current knowledge on the impact of the innate and adaptive immune systems on the response against cancer cells and the recruitment of immune cells in lymph nodes. The most significant findings highlight the crucial role of antigen presentation in the antitumor response, particularly through the recruitment and activation of dendritic cells and subcapsular sinus macrophages in tumor-draining lymph nodes. It also presents in a fairly comprehensible manner that the density of mature dendritic cells, cytotoxic T cells, and B cells is higher in non-metastatic lymph nodes. Discussion: The lymph node microenvironment is highly enriched with immune cell infiltration, and their distribution between metastatic and non-metastatic lymph nodes can contribute to a better understanding of the underlying pathological processes. Particular attention should be given to the innate immune system cells and their implication in antigen presentation. Our findings suggest that identifying immunological profiles of lymph nodes may provide a rationale for treatment de-escalation protocols and raise the question of lymph node preservation in antitumor immune responses. However, the heterogeneity and bias assessment of the included studies warrant a cautious interpretation of these findings. Another important limitation is the limited number of studies comparing the immune microenvironment of primary tumors and lymph nodes.

Journal of Personalized Medicine doi: 10.3390/jpm16090443

Authors: Andrea Franchini Giuseppe Rovere Felice Barletta Franco Lucio Gorgoglione Giovanni Noia Giuseppe Maccagnano Andrea Perna

Introduction: Degenerative lumbar kyphosis (DLK) is a common cause of sagittal imbalance, pain, and functional disability. While three-column osteotomies provide powerful correction, they are associated with substantial morbidity. We evaluated the radiographic and clinical outcomes of a novel posterior-based correction strategy combining Posterior Interpedicular Osteotomy (PIO), bilateral discectomy, and hyperlordotic transforaminal lumbar interbody fusion (TLIF) in patients with DLK. Materials and Methods: A retrospective single-center case series was conducted including 215 consecutive patients with symptomatic DLK and pelvic incidence–lumbar lordosis (PI–LL) mismatch >10° treated between 2019 and 2023. All patients underwent PIO combined with bilateral discectomy and insertion of a 20° hyperlordotic TLIF cage. Radiographic parameters, including lumbar lordosis (LL), pelvic tilt (PT), and sacral slope (SS), were assessed preoperatively and up to 24 months postoperatively. Clinical outcomes were evaluated using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Short Form-36 (SF-36). Complications were systematically recorded. Results: Mean lumbar lordosis improved from 15.7° ± 8.3° preoperatively to 45.4° ± 11.6° at 24 months, corresponding to a mean correction of 29.7° ± 10.1° and 12.4° ± 2.9° per treated level (p < 0.001). Significant improvements were observed in PT, SS, VAS, ODI, and SF-36 scores (all p < 0.001), with maintenance of correction throughout follow-up. Mean operative time was 218.4 ± 47.3 min and mean blood loss was 483.2 ± 195.7 mL. The overall complication rate was 16.3%, with incidental durotomy being the most common event (14.9%). No cases of cage migration, deep infection, neurological deterioration, or radiographic pseudarthrosis were identified among patients who underwent CT evaluation. Conclusions: PIO combined with bilateral discectomy and hyperlordotic TLIF achieved substantial and durable sagittal correction with significant clinical improvement and an acceptable safety profile. By combining extensive posterior release with preservation of the anterior tension band, this technique may represent an effective intermediate alternative between conventional posterior column osteotomies and more invasive three-column deformity correction procedures.

Journal of Personalized Medicine doi: 10.3390/jpm16090442

Authors: Bita Rashed Naimi David B. Hom

Cannabis use has increased substantially in the United States, driven by broader legalization, decriminalization, and expanding medical and recreational availability. For facial plastic surgeons, the clinical implications remain difficult to define because “cannabis use” encompasses heterogeneous products and routes, including smoked flower, vaping, concentrates, edibles, pharmaceutical cannabinoids, topical cannabidiol (CBD), and frequent co-use with tobacco or nicotine. Current evidence suggests that systemic cannabis use, particularly inhaled or heavy perioperative use, may be associated with increased surgical complications in selected populations; however, existing studies are limited by retrospective design, inconsistent exposure definitions, inadequate dose and route characterization, and confounding by tobacco use and comorbidities. Cannabinoids exert biologic effects through the endocannabinoid system, particularly CB1 and CB2 receptors, which are expressed in the central nervous system, immune cells, vasculature, and skin. These pathways influence inflammation, keratinocyte proliferation, fibroblast activity, angiogenesis, immune surveillance, pain signaling, and tissue remodeling. The net effect of cannabinoid exposure on wound healing is likely context dependent, varying based on receptor expression, wound-healing phase, route of administration, cannabinoid composition, local tissue environment, and patient-specific risk factors. Preclinical and early dermatologic literature suggests potential therapeutic roles for topical cannabinoids, especially CBD, in modulating inflammation and epithelial repair. In contrast, systemic perioperative cannabis use has been associated in several surgical cohorts with infection, delayed healing, hematoma, nonunion, and reoperation. Evidence specific to facial plastic surgery remains sparse. The most directly relevant study evaluated cannabis and tobacco use in patients undergoing operative mandibular fracture repair. Cannabis-only use was not associated with increased complications, although the cohort was small; concurrent cannabis and tobacco use was associated with higher rates of surgical site infection, facial nonunion, abscess, debridement, and malocclusion. To date, no published studies address cannabis-associated outcomes in rhinoplasty, rhytidectomy, blepharoplasty, browlift, or facial rejuvenation. This review summarizes the biologic rationale, available surgical evidence, and clinical considerations for incorporating cannabis use into individualized perioperative risk assessment in facial plastic surgery.

Journal of Personalized Medicine doi: 10.3390/jpm16090441

Authors: Truc Thanh Nguyen Huong Tu Lam Thong Duy Vo

Background and aims. Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease associated with cirrhosis, hepatocellular carcinoma, and increased risks of liver-related and cardiovascular mortality. Many patients, however, remain asymptomatic until advanced stages. The gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-C) ratio is a simple, noninvasive marker reflecting hepatic dysfunction and cardiometabolic imbalance. This study assessed its association with NAFLD and determined an optimal cutoff for identifying NAFLD. Methods. We conducted a cross-sectional analysis of 575 adults undergoing routine health examinations at the University of Medicine and Pharmacy Hospital in Ho Chi Minh City between 2021 and 2023. Participants with significant alcohol intake, viral hepatitis, or other chronic liver diseases were excluded. NAFLD was diagnosed by standardized abdominal ultrasonography based on increased hepatic echogenicity relative to the renal cortex or spleen. Associations between GGT/HDL-C and NAFLD were assessed by logistic regression (both as a continuous variable and by quartiles), and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Statistical significance was defined as a two-tailed p-value < 0.05. Results. Individuals with NAFLD showed significantly higher BMI, prevalence of hypertension and diabetes, and elevated glucose, HbA1c, AST, ALT, GGT, cholesterol, triglycerides, and LDL-C, along with lower HDL-C. Each unit increase in the GGT/HDL-C ratio was associated with a 2% increase in the odds of NAFLD based on univariate logistic regression analysis. However, after adjustment for demographic and metabolic covariates, the GGT/HDL-C ratio was no longer independently associated with NAFLD. The highest quartile had an odds ratio of 7.05 (95% CI: 4.2–11.83) compared to the lowest. The area under the ROC curve for GGT/HDL-C was 0.72, outperforming GGT or HDL-C alone. A cutoff of 32.47 UI/mmol had 72.4% sensitivity and 63.3% specificity. Conclusions. The GGT/HDL-C ratio showed a significant unadjusted association with NAFLD and moderate discriminatory performance. However, because the association was no longer significant after full adjustment, the ratio should currently be considered a simple laboratory-based screening marker that requires further validation before routine clinical application.

Journal of Personalized Medicine doi: 10.3390/jpm16090439

Authors: Grigory Demyashkin Anastasiia Buianova Nathalia Pyatigorskaya Olga Filippova Galina Brkich Zhanna Aladysheva Vasiliy Belyaev Vladimir Shchekin

Radiation-induced liver disease (RILD) remains a clinically significant complication of radiotherapy for malignant neoplasms of the liver and upper abdomen, restricting achievable therapeutic doses and adversely affecting patient outcomes. Conventional photon-based radiotherapy (X-rays/γ-rays) exposes substantial volumes of healthy liver parenchyma and adjacent organs to ionizing radiation, increasing the risk of hepatocellular damage, inflammation, and progressive fibrosis. Electron irradiation (β-particles) represents a promising alternative owing to its limited tissue penetration (~2–3 cm) and steep dose fall-off, which significantly reduces exit dose and may reduce exit dose and limit exposure of paratumoral healthy tissues compared with photon therapy. However, the molecular mechanisms underlying electron-induced hepatic damage and strategies for its prevention remain insufficiently characterized. This review systematically analyzes the pathogenesis of radiation-induced liver damage, encompassing direct DNA damage, oxidative stress, mitochondrial dysfunction, NF-κB-mediated inflammation, cellular senescence, and TGF-β/Smad-driven fibrosis. The comparative dosimetric and radiobiological advantages of electron irradiation over photon therapy are discussed, with particular attention to intraoperative radiotherapy, FLASH, and very high-energy electron techniques. Current radioprotective strategies are critically evaluated, with emphasis on the limitations of amifostine and the multifunctional radioprotective potential of ascorbic acid, including free radical scavenging, attenuation of lipid peroxidation, stimulation of endogenous antioxidant defense, and direct inhibition of radiation-induced DNA strand breaks. Existing gaps in the evidence base are identified, and recommendations for future experimental and clinical research are proposed.

Journal of Personalized Medicine doi: 10.3390/jpm16090440

Authors: Andrea Bruno Antonio Meola Stefano Di Bella Leonello Tacconi

Background/Objectives: Surgical indications for spondylodiscitis are controversial, particularly when epidural extension and evolving neurological compromise are present. This study aimed to describe the clinical, neurological, pain-related, and inflammatory outcomes of patients with spondylodiscitis treated with decompressive laminectomy without spinal stabilization, at a single tertiary center. Methods: We retrospectively reviewed 15 consecutive patients with spondylodiscitis who underwent decompressive laminectomy at the University Hospital of Trieste between January 2017 and December 2023. Inclusion required at least 6 months of clinical and laboratory follow-up. Patients treated with acute vertebral stabilization were excluded. Collected data included spinal level, timing from diagnosis to surgery, visual analog scale (VAS) pain score, Cooper Scale grade, modified Japanese Orthopedic Association score (mJOA), white blood cell count, and C-reactive protein (CRP). Assessments were performed preoperatively (T0), 1 week after surgery (T1), and at 6 months (T2). Imaging findings from representative cases were reviewed to illustrate the radiographic evolution after decompression combined with antibiotic therapy and orthotic support. Results: The cohort included 8 women and 7 men with a mean age of 57.33 years. Twelve patients (80%) underwent surgery within 48 h because of neurological deterioration or urgent compressive findings. Thoracic involvement was predominant (11 cases, 73%), whereas cervical and lumbar disease accounted for 1 and 3 cases, respectively. Intraoperative cultures were positive in 9 patients (60%), and Staphylococcus aureus was isolated in 7 of these 9 cases (77.8%). Mean VAS pain score improved from 6.3 at T0 to 4.3 at T1 and 1.4 at T2. Mean lower-extremity Cooper Scale grade improved from 2.7 to 2.1 to 0.6; mean upper-extremity Cooper Scale grade improved from 1.3 to 1.0 to 0. Mean mJOA improved from 10.3 to 11.4 to 16.0. Mean white blood cell count declined from 11.58 to 8.35 to 6.14 × 103/µL, and mean CRP declined from 123.9 to 72.81 to 19.44 mg/L. No patient worsened neurologically after surgery. No patient required acute stabilization or delayed arthrodesis during follow-up. Conclusions: In our case series of patients with compressive or progressive neurological spondylodiscitis, decompressive laminectomy combined with antibiotic treatment, bracing, and rehabilitation was associated with early neurological stabilization, substantial pain relief, and marked reduction in inflammatory markers, without subsequent need for instrumented stabilization. These data support the role of spinal decompression as part of a personalized, effective treatment strategy in patients with neurological decline.

Journal of Personalized Medicine doi: 10.3390/jpm16080438

Authors: Julia Kościanek Natalia Zabawa Anna Stanaszek Michał Maślanka Hubert Mączka Martyna Pniaczek Aleksandra Bołoz Jadwiga Nessler Jarosław Zalewski Konrad Stępień

Type 2 myocardial infarction (T2MI) occurs secondary to an imbalance between myocardial oxygen supply and demand, with systemic conditions serving as the primary precipitating factors. T2MI predominantly affects older adults and is frequently accompanied by multiple chronic comorbidities. Therefore, it often has an atypical clinical course and remains a significant diagnostic and therapeutic challenge, particularly given the lack of standardized clinical guidelines. Furthermore, the diagnosis of T2MI in women is especially challenging due to sex-related differences in biomarker kinetics and atypical symptom presentation. The aim of this review is to summarize current knowledge on T2MI, discuss modern diagnostic tools, and analyze sex-related differences in this context in order to identify future directions for the development of therapeutic guidelines. The review emphasizes the need for a multimodal approach, integrating biomarkers, individualized clinical decision-making and advanced cardiac imaging, as differentiation between T2MI and T1MI remains a significant challenge. Therefore, both non-invasive and invasive diagnostic strategies may be required to accurately identify patients with T2MI. Although routine coronary angiography in T2MI is not clearly supported by current evidence, it may be useful as a decisive tool for reclassification, particularly when the clinical presentation is ambiguous.

Journal of Personalized Medicine doi: 10.3390/jpm16080437

Authors: Arkadeep Dhali Jyotirmoy Biswas Fayaz Khan Dushyant Singh Dahiya Saikat Mandal

Background: GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity and metabolic disease, but their use in people with chronic pancreatitis is not a chronic pancreatitis-directed indication and direct evidence is limited. We described recorded outcomes among non-diabetic adults carrying a chronic pancreatitis diagnosis who did or did not have recorded GLP-1 RA exposure. Methods: We performed a retrospective propensity score-matched cohort study using the TriNetX Collaborative Network. Chronic pancreatitis was identified from a recorded diagnosis; supporting imaging, histological, functional, or specialist-confirmation criteria were unavailable. The exposed cohort included patients receiving dulaglutide, semaglutide, or tirzepatide (n = 1441 before matching), and the comparator cohort included patients without recorded GLP-1 RA exposure (n = 142,047 before matching). One-to-one propensity score matching generated 1422 patients in each cohort. Outcomes were assessed from 1 to 1095 days after the index date using risk comparisons and time-to-event analyses. Results: Mean follow-up after matching was 458.8 days in the exposed cohort and 664.4 days in the comparator cohort. Recurrent acute pancreatitis was recorded in 19/799 (2.4%) versus 76/704 (10.8%) patients (HR 0.247, 95% CI 0.149–0.409), pancreatic cancer in 10/1373 (0.7%) versus 40/1345 (3.0%) (HR 0.255, 95% CI 0.128–0.511), and all-cause mortality in 21/1419 (1.5%) versus 157/1416 (11.1%) (HR 0.167, 95% CI 0.105–0.263). A similar direction was observed across several coded outcomes. Vitamin D deficiency showed a higher hazard (HR 1.556, 95% CI 1.129–2.145), although its risk comparison was not significant. Conclusions: These estimates describe outcomes in a selected treatment-exposed phenotype of chronic pancreatitis. The findings are hypothesis-generating and should not guide prescribing decisions. Further prospective studies are required to confirm this hypothesis.

Journal of Personalized Medicine doi: 10.3390/jpm16080436

Authors: Panagiotis Dorovinis Konstantinos Kossenas Anna Paspala Dimitrios Papaconstantinou Myrto D. Keramida Dimitrios K. Vlachos Dionysios Prevezanos Stylianos Kykalos Nikolaos Machairas Georgios C. Sotiropoulos

Background/Objectives: Liver metastasis develops in approximately 50% of patients with colorectal cancer. Invasion of the biliary tract from colorectal liver metastasis (CRLM) is rarely reported. Preoperative diagnosis remains elusive, prohibiting optimal surgical management. The objective of this systematic review was to summarize the clinical, radiological, pathological, and treatment characteristics of ibCRLM and describe the reported outcomes. Methods: A systematic literature search of the Medline, Embase, Web of Science, CENTRAL, and CINAHL databases was undertaken for studies reporting clinical outcomes of patients with ibCRLM, up to May 2026. An individual patient data analysis approach was utilized. Results: Thirty-eight case reports and 10 case-series, incorporating 228 patients with biliary involvement from CRLM, were identified. Mean age was 62.4 ± 10.9 years, with a male-to-female ratio of 3.2:1. The majority of metastatic lesions were metachronous in 71.1% and solitary in 59.1% of patients. Surgical treatment was implemented in 89.2% of patients. Major hepatectomy was the most common procedure, being performed in 46.2% of patients, followed by minor hepatectomy in 38.7% and pancreatoduodenectomy in 4.3%. After a median follow-up of 52.5 months (range 2–164 months), the survival rate was 60.5%. Non-survivors were found to have significantly more synchronous CRLM (50% versus 0, p = 0.008), while a single patient did not receive any curative-intent treatment and died 20 days following CRLM presentation. Conclusions: IbCRLM is a distinct clinicopathological presentation of CRLM with characteristic radiological and pathological features. The available evidence suggests that selected patients may achieve favorable long-term outcomes following complete surgical resection, although these findings should be interpreted with caution given the limitations of the available literature.

Journal of Personalized Medicine doi: 10.3390/jpm16080435

Authors: Celine Carmen Akta Maximilian Muellner Kai-Uwe Lewandrowski Lukas Schönnagel Anika Mueller Michael Putzier Matthias Pumberger Thilo Khakzad

Background/Objectives: Total en bloc spondylectomy (TES) remains one of the most invasive and selectively used procedures in spine oncology. Its role has become more selective in the modern era of stereotactic body radiotherapy, separation surgery, targeted systemic therapy, immunotherapy, and multidisciplinary cancer care. This study evaluated long-term survival, imaging-defined systemic disease burden, operative morbidity, patient-reported outcomes, and frailty-related variables after TES in a rare single-center cohort, with the goal of identifying selection-relevant survival and treatment-burden signals rather than developing a validated decision algorithm. Methods: We performed a retrospective single-center cohort study of consecutive adults who underwent TES for spinal tumors between 2011 and 2022. Of the 36 screened patients, 30 had sufficient clinical and survival data for analysis; patients without reliable survival or last-contact data were not included. Contrast-enhanced CT and PET-CT were reviewed for extraspinal metastases, lymphadenopathy, pleural effusion, and soft-tissue extension. Survival was analyzed using Kaplan–Meier methods, log-rank testing, and exploratory univariate Cox regression. Patient-reported outcomes included the Oswestry Disability Index (ODI) and SF-36 when available; frailty was summarized with the modified frailty index-5 (mFI-5) when component data were present. Results: The cohort included 13 men and 17 women with a mean age of 54.8 ± 15.2 years. At final follow-up, 18 patients had died, and 12 were alive. Five-year overall survival was approximately 76% in the full cohort. Extraspinal metastases were present in 72.2% of deceased patients compared with 8.3% of survivors and showed the clearest exploratory association with increased mortality (HR 3.46, 95% CI 1.23–9.78; p = 0.019). Metastatic disease demonstrated inferior survival compared with primary bone or soft-tissue tumors. Perioperative blood loss and transfusion burden were substantial but were not associated with survival in univariate analysis. ODI and SF-36 data were available only in small subsets and were therefore interpreted as descriptive signals of treatment burden. Conclusions: TES remains relevant in modern spine oncology, but only as an increasingly selective intervention. In this rare cohort, systemic disease burden, particularly extraspinal metastases, was the clearest selection-relevant survival signal, while blood loss, transfusion requirements, complications, and limited patient-reported outcomes illustrated substantial treatment burden. These findings do not establish a validated selection algorithm but support a contemporary decision threshold that integrates tumor biology, systemic disease status, anticipated margins, physiologic reserve, operative morbidity, and patient goals.

Journal of Personalized Medicine doi: 10.3390/jpm16080434

Authors: Michele Salati Alberto Roncon Gian Marco Guiducci Michela Tiberi Mara Romito Anna Chiara Nanto Francesco Xiumè Rosanna Coltrinari Stefano Falcetta Paolo Gentili Abele Donati Majed Refai

Background/Objectives: Prolonged postoperative air leak (PAL) remains one of the most common complications after lung resection, significantly affecting postoperative recovery and healthcare utilization. While several preoperative risk factors have been identified, reliable intraoperative predictors are still lacking. This study aimed to evaluate whether intraoperative ventilator-derived parameters—volume decay (Vol-Decay) and pressure decay (Pres-Decay)—are associated with the development of PAL following uniportal video-assisted thoracic surgery (VATS) lung resection. Methods: We conducted a single-center study including 277 consecutive patients undergoing uniportal VATS lung resection for neoplastic disease between May 2023 and April 2024. At the end of the surgical procedure, intraoperative Vol-Decay and Pres-Decay were measured using the mechanical ventilator under standardized conditions. PAL was defined as an air leak persisting for more than 5 days within 30 days after surgery. Univariate and multivariate analyses were performed to identify independent predictors of PAL, and the optimal Vol-Decay cut-off was determined using Youden’s index. Results: PAL occurred in 18 patients (6.5%). At univariate analysis, higher smoking exposure, lower FEV1, lower FEV1/FVC ratio, and higher Vol-Decay were significantly associated with PAL. At multivariable analysis, only FEV1 (p = 0.013) and Vol-Decay (p = 0.038) remained independent predictors. The optimal Vol-Decay cut-off was 22 mL (AUC 0.64), with high specificity (0.94) but low sensitivity (0.34). Patients with Vol-Decay > 22 mL showed a significantly higher incidence of PAL compared to those with lower values (27.3% vs. 4.7%). Conclusions: Intraoperative Vol-Decay represents a simple, objective, and reproducible parameter associated with the development of prolonged air leak after uniportal VATS lung resection. Its measurement may enable real-time risk stratification and support personalized intraoperative decision-making, potentially guiding targeted corrective strategies. Further prospective multicenter studies are warranted to validate these findings and confirm their clinical applicability.

Journal of Personalized Medicine doi: 10.3390/jpm16080433

Authors: Takeshi Osonoi Shinichiro Shirabe Miyoko Saito Mitsuru Hosoya Satako Douguchi Kensuke Ofuchi Makoto Katoh

Background: Imeglimin is a novel oral antidiabetic agent that improves mitochondrial function and glucose metabolism in patients with type 2 diabetes mellitus (T2DM). Its effects on liver enzymes remain unclear. We investigated the effects of imeglimin on hepatic biomarkers, particularly γ-glutamyl transpeptidase (γ-GTP), and the reversibility of these changes after treatment discontinuation. Methods: This post hoc analysis of the prospective INFINITY Study included 25 patients with T2DM who completed 6 months of imeglimin treatment followed by a 3-month withdrawal period. Clinical parameters were averaged within predefined 3-month study phases. Changes during treatment and after discontinuation were analyzed. Results: Imeglimin significantly improved glycemic control. The geometric mean γ-GTP decreased from 36.2 (27.1–48.4) U/L during the Baseline Phase to 31.1 (23.5–41.1) U/L during the Late Treatment Phase (p < 0.05). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed downward trends, although these changes were not statistically significant. During the Withdrawal Phase, γ-GTP returned to 35.6 (26.4–48.5) U/L (p < 0.05 vs. Late Treatment Phase). Patients with baseline γ-GTP >50 U/L showed larger but non-significant changes. Changes during treatment and after discontinuation were inversely correlated (r = −0.480, p = 0.015). Only total cholesterol correlated with γ-GTP during both treatment (r = 0.554, p = 0.005) and withdrawal (r = 0.450, p = 0.024). Conclusions: γ-GTP levels showed a significant decrease during imeglimin treatment and increased during the post-treatment observation period in patients with T2DM. Exploratory analyses identified an association between changes in γ-GTP and total cholesterol; however, these findings should be interpreted cautiously and require confirmation in prospective studies with prespecified endpoints.

Journal of Personalized Medicine doi: 10.3390/jpm16080432

Authors: Andrea Coello Hidalgo Ana Alvear Miquilena Domenica Yepez Zamora Diego Quiguango Farias Luis Chauca Bajaña Maria Rodriguez Tates Byron Velasquez Ron

Background: Temporomandibular disorders (TMD) comprise a heterogeneous group of musculoskeletal conditions that may manifest during childhood and adolescence. However, standardized information regarding TMD-related clinical findings in pediatric populations remains limited because of methodological heterogeneity and the inconsistent application of validated diagnostic protocols. Objective: The aim of this study was to characterize clinical findings related to temporomandibular disorders in schoolchildren and to explore their potential contribution to individualized assessment strategies within the framework of personalized pediatric oral healthcare. Methods: A multicenter cross-sectional study was conducted in 1052 schoolchildren recruited from participating educational institutions. All participants underwent a standardized clinical examination that included assessment of masticatory muscle tenderness, temporomandibular joint tenderness, joint sounds, pain intensity, and perceived stress using an adapted pediatric DC/TMD protocol. Categorical variables were summarized as frequencies, percentages, and 95% confidence intervals (95% CIs). Associations between categorical variables were evaluated using Pearson’s chi-square test, and multivariable logistic regression was performed to identify factors independently associated with pain. Results: Pain during clinical examination was identified in 111 participants (10.6%; 95% CI: 8.8–12.6%), whereas temporomandibular joint sounds and myofascial pain were detected in 1.4% and 0.3% of participants, respectively. Most pain was classified as mild, and the masseter muscle was the most frequently affected anatomical site. Increasing age and female sex were independently associated with pain. Compared with children aged 4–6 years, participants aged 10–12 years (adjusted OR = 9.61; 95% CI: 2.22–41.51) and 13–16 years (adjusted OR = 35.49; 95% CI: 8.59–146.61) showed significantly greater odds of pain. Female participants also demonstrated higher odds of pain than males (adjusted OR = 7.49; 95% CI: 3.68–15.21; all p < 0.05). Conclusions: Clinically detectable TMD-related findings were generally uncommon among schoolchildren aged 4–16 years and were predominantly mild and muscular. Increasing age and female sex were independently associated with pain, emphasizing the importance of demographic factors in the early clinical expression of TMD. Standardized pediatric clinical examination protocols may facilitate early identification of TMD-related findings and support preventive strategies during childhood and adolescence. These findings support the implementation of individualized clinical assessment strategies for early identification of children at risk of temporomandibular disorders, contributing to personalized preventive and therapeutic approaches in pediatric oral healthcare.

Journal of Personalized Medicine doi: 10.3390/jpm16080431

Authors: Hugo A. Sanchez Guillermo Ponce de Leon-Ballesteros Miguel F. Herrera

Introduction: Gastrojejunal anastomosis (GJA) stricture is an important complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). The impact of suture material on stricture rate when performing a hand-sewn GJA is not well established. Methods: This is a retrospective analysis of a prospectively maintained database that includes 882 patients who underwent primary or revisional LRYGB with a minimum 12-month follow-up. We compared two consecutive groups of patients who underwent hand-sewn gastrojejunal anastomosis: group 1 (n = 426), utilizing a multifilament non-absorbable/absorbable suture combination (silk/Vicryl®), whereas group 2 (n = 456) received an absorbable monofilament suture (Monocryl®). The primary outcome was the incidence of symptomatic GJA stricture, defined as an inability to pass a 10 mm gastroscope associated with dysphagia, vomiting, or food intolerance. Results: The symptomatic stricture rate was significantly lower in group 2 (0.7% vs. 6.8%; p < 0.001). On multivariate analysis, the use of monofilament sutures was a stronger protective factor (OR 0.09; 95% CI 0.03–0.30; p < 0.001), whereas revisional surgery was associated with an increased risk of symptomatic stricture (OR 2.61; 95% CI 1.05–6.50; p = 0.03). Type 2 diabetes mellitus and gender were not independent predictors. One-year weight loss was similar between patients who developed symptomatic strictures (and required dilations) and those who did not (p > 0.05). Conclusion: The use of absorbable monofilament sutures for hand-sewn GJA in LRYGB reduces the risk of symptomatic stricture without compromising weight loss outcomes. These findings support a personalized suture strategy, especially in high-risk patients undergoing revisional surgery.

Journal of Personalized Medicine doi: 10.3390/jpm16080430

Authors: Georgios P. Georghiou Klitia Socratous Sotiris Kyriakou Konstantinos Lampropoulos Panos Georghiou Amalia Georgiou Marilina Neokleous Iakovos Ttofi Nikolas Iosif Filippos Triposkiadis

Aortitis—inflammation of the aortic wall—presents at the interface of vasculitis, infection, structural aortic disease, and cardiovascular risk. It may occur in giant cell arteritis (GCA), Takayasu arteritis, immunoglobulin G4 (IgG4)-related disease, drug-induced injury, infection, or as an isolated finding after aortic surgery. Modern imaging detects aortic inflammation more frequently, but the main challenge is classification rather than detection: determining whether disease is infectious or immune-mediated, active or dominated by fixed structural damage, systemic or isolated, and whether the dominant threat is aneurysm, dissection, undertreated infection, or avoidable immunosuppression. This review considers aortitis as a high-risk vascular syndrome requiring aetiology-first classification rather than descriptive labelling. Before escalating immunosuppression, infection must be actively excluded and inflammatory activity distinguished from fixed vascular damage. Treatment should be individualised according to phenotype, age, vascular territory, comorbidity, and toxicity risk, with surveillance continuing even after symptoms and inflammatory markers improve. Optimal care depends on multidisciplinary assessment integrating rheumatology, infectious diseases, vascular surgery, radiology, and cardiology expertise. Progress will require standardised imaging definitions, registries linking inflammatory control with structural vascular outcomes, and validation of artificial intelligence (AI) tools before clinical adoption.

Journal of Personalized Medicine doi: 10.3390/jpm16080429

Authors: Patrycja Brzóska-Ritter Piotr Żarczyński Maciej Haberka

Background: Familial hypercholesterolemia (FH) is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease. Aims: To evaluate circulating biomarkers of inflammation and atherosclerosis in patients with clinically suspected FH stratified according to the Dutch Lipid Clinic Network (DLCN) criteria. Methods: This cross-sectional study included 80 patients (mean age, 53.4 [13.2] years; 58% women) receiving maximally tolerated lipid-lowering therapy (statins ± ezetimibe). Serum concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2), tumor necrosis factor-α (TNF-α), apolipoprotein B (ApoB), oxidized low-density lipoprotein (oxLDL), and monocyte chemoattractant protein-1 (MCP-1) were measured. Participants were classified as definite FH (DLCN score > 8; n = 45) or non-definite FH (DLCN score ≤ 8; n = 35). Biomarker concentrations were analyzed according to the above subgroups and sex. Results: Patients with definite FH had significantly higher serum Lp-PLA2 concentrations (62.2 [33.8] vs. 46.5 [19.9] ng/mL; p = 0.03) and TNF-α concentrations (6.94 [4.53] vs. 4.51 [2.93] pg/mL; p = 0.02) compared to non-definite FH, whereas ApoB, oxLDL, and MCP-1 concentrations did not differ significantly between the subgroups. Women had significantly higher TNF-α concentrations compared to men (6.57 [4.74] vs. 4.60 [2.20] pg/mL; p = 0.04) with no differences among other cytokines. Conclusions: Patients with definite FH exhibited persistently higher circulating Lp-PLA2 and TNF-α concentrations despite maximally tolerated lipid-lowering therapy, suggesting ongoing activation of specific inflammatory pathways. These findings support further investigation of Lp-PLA2 and TNF-α as candidate biomarkers for cardiovascular risk assessment in FH.

Journal of Personalized Medicine doi: 10.3390/jpm16080428

Authors: Andrej Belančić Marin Golčić Almir Fajkić Vlatka Bračić Marko Skelin Antonio Markotić Ivan Ćavar Dragan Trivanović Ivana Mikolašević

Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy—particularly with fluoropyrimidines, platinum compounds, and anthracyclines—show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care.

Journal of Personalized Medicine doi: 10.3390/jpm16080427

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

Background/Objectives: Polyetheretherketone (PEEK) implants are increasingly being used for mandibular reconstruction and augmentation, yet predicting the resulting facial soft tissue changes remains challenging. Accurate pre-operative prediction of soft tissue deformation is essential for surgical planning and patient counselling. To the best of our knowledge, this study presents the first application of a computational model for predicting three-dimensional facial soft tissue deformation induced by PEEK implants. Methods: Four patient cases with pre-operative and post-operative cone-beam computed tomography scans were analysed. A mass tensor model was employed to predict soft tissue changes based on the pre-operative soft tissue shape, mandibular anatomy, and the designed PEEK implant. Model accuracy was quantified by comparing predicted outcomes to post-operative scans using landmark-based analysis of chin and jaw positions, as well as surface distance mapping, with a mean error below 2 mm adopted as the criterion for clinically acceptable accuracy. Results: Landmark-based analysis revealed a mean absolute error of 0.9 ± 0.8 mm between the predicted and actual positions. The mean surface distances were 1.3 mm for the jaw–chin region and 1.0 mm for the entire facial region. Conclusions: These results demonstrate the potential of a computational approach for real-time prediction of facial soft tissue changes following PEEK implant placement, achieving clinically relevant accuracy at the cohort level, with a tendency towards under-prediction and one case exceeding the threshold.

Journal of Personalized Medicine doi: 10.3390/jpm16080426

Authors: Alireza Sharafshah Colin Hanna Kai-Uwe Lewandrowski Mark S. Gold Brian Fuehrlein Panayotis K. Thanos Igor Elman Eliot L. Gardner Jag Khalsa David Baron Abdalla Bowirrat Albert Pinhasov Edward J. Modestino Rossano Kepler Alvim Fiorelli Sergio L. Schmidt Morgan P. Lorio Keerthy Sunder Lyle Fried Michael Slifer Frank Fornari Shaurya Mahajan Yatharth Mahajan Marco Lindenau Álvaro Dowling Rafaela Dowling João Paulo Bergamaschi Kyriaki Z. Thanos Paul R. Carney Kenneth Blum

Background/Objectives: Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition with a strong polygenic and stress-related biological basis. Although Genome-Wide Association Studies (GWAS) have acknowledged abundant risk variants, translating these findings into biologically meaningful candidates remains challenging. This study introduces an integrative computational approach from raw file preparation by python-coded application into downstream in-depth silico analyses designed to systematically refine GWAS signals for PTSD using fine-mapping, linkage disequilibrium (LD), and haplotype analyses. Methods: GWAS source file for PTSD was obtained from the GWAS Catalog (EFO_0001358) and analyzed using a custom Python pipeline integrating data harmonization, genome-wide visualization, LD estimation via 1000 Genomes reference panels, approximate Bayesian fine-mapping, and Haploview-inspired haplotype inference. SNPs were filtered based on statistical significance, LD structure, and posterior inclusion probability. Downstream systems’ biology analyses included protein–protein interaction modeling and pharmacogenomics (PGx) annotations. Results: From the primary GWAS dataset, 100 top-ranked SNPs were selected, leading to the identification of 58 significant loci. LD and haplotype analyses refined these signals to 93 candidate SNPs (66 genes). Following the exclusion of non-protein-coding genes, 45 genes remained, and network-based prioritization generated a final list of 20 biologically connected and pharmacogenetically relevant genes associated with PTSD. Conclusions: This integrative approach provided a robust and reproducible framework for GWAS fine-mapping and variant prioritization, effectively reducing large-scale GWAS outputs to biologically interpretable PTSD risk loci and genes.

Journal of Personalized Medicine doi: 10.3390/jpm16080425

Authors: Alma Nurtazina Valeriia Koss Ivan Voitsekhovskiy Maxat Toishimanov Daulet Dautov Kairat Karibayev Victoria Shender Georgij Arapidi

Background: Metabolic syndrome (MetS) is a heterogeneous cardiometabolic group of conditions in which early disturbances of glucose homeostasis are not always adequately captured by routine clinical tests. Methods: In this pilot study, liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based blood serum peptidomics was applied to identify circulating peptide signatures associated with MetS and progressive glycemic impairment. Serum samples from healthy donors and patients with MetS, including subgroups with normoglycemia, prediabetes, and diabetes mellitus, were subjected to peptide enrichment by ultrafiltration and solid-phase extraction prior to LC-MS/MS analysis. Results: Overall, 6754 unique peptides derived from 1820 precursor proteins were identified, and 32 peptides were significantly overrepresented in patients with MetS relative to healthy donors. Eight precursor proteins and five identified peptides showed significant positive correlations with glycemic stage, likely indicating progressive remodeling of the circulating serum peptidome during disease progression. A separate analysis of patients with prediabetes revealed additional candidate markers associated with early metabolic alterations. Moreover, multivariate logistic regression identified a four-peptide panel with good discriminatory performance for differentiating healthy donors from patients with MetS, yielding a leave-one-out cross-validated area under the curve of 0.91. Conclusions: Collectively, these findings indicate that serum peptidome profiling can reveal biologically and clinically relevant possible candidate biomarkers associated with MetS and early dysglycemia.

Journal of Personalized Medicine doi: 10.3390/jpm16080424

Authors: Cheedy Jaja Daniel M. Sop Andrew Campbell Wally R. Smith

Pain is a leading cause of morbidity and healthcare utilization in sickle cell disease (SCD), and opioids remain central to treating vaso-occlusive and chronic pain. Yet opioid response varies widely, raising the question of whether pharmacogenetic testing should inform opioid prescribing. Our review examined the PubMed literature on pharmacogenomics and opioid efficacy in SCD. We focus on CYP2D6 as the clearest current pharmacogenetic signal for codeine and tramadol, and assess SCD-specific implementation studies, preemptive testing, and African pharmacoequity. The current evidence supports targeted CYP2D6-informed prescribing in selected contexts rather than universal testing for all opioids, while highlighting the need to integrate genotype with pain phenotype, drug–drug interactions, liver function, and clinically grounded implementation studies, and better characterize African and African-ancestry pharmacogene variation.

Journal of Personalized Medicine doi: 10.3390/jpm16080423

Authors: Alifa Nasrin Muhammad Bin Asif Ramasamy Naidu Afzal Haq Asif Muhammad Shahzad Chohan Gausal Azam Khan Md Arifuzzaman Akm Azad Muhammad Ali Martuza

Background: Diabetes mellitus affects over 500 million people worldwide, yet many machine learning prediction models remain difficult to interpret, limiting their clinical applicability. This study proposes an explainable machine learning framework integrating the Marine Predators Algorithm (MPA) for hyperparameter optimization with SHAP-based explainability to diabetes prediction. Methods: Logistic Regression (LR), Random Forest (RF), and MPA-optimized XGBoost were evaluated using a publicly available Kaggle diabetes dataset of approximately 100,000 records. Statistical significance was assessed using Wilcoxon signed-rank tests with Bonferroni correction for fold-wise cross-validation results, while McNemar’s and DeLong’s tests were employed for paired comparison of independent test-set predictions and ROC-AUC values, respectively. Performance was assessed using accuracy, precision, recall, F1-score, specificity, ROC-AUC, and Brier score. SHAP was used to provide global and local model explanations. Results: The MPA-optimized XGBoost model achieved the highest performance, with 96.72% accuracy, 97.70% precision, 95.70% recall, 96.71% F1-score, and 99.56% ROC-AUC, significantly outperforming LR and RF (p < 0.001). The model demonstrated good calibration with a Brier score of 0.0262. SHAP analysis identified HbA1c level, blood glucose level, and age as the most influential predictors, while interaction analysis indicated a synergistic relationship between HbA1c and blood glucose. Conclusions: The proposed framework demonstrated strong predictive performance and interpretable model behavior on the publicly available diabetes dataset used in this study. These findings indicate the potential of MPA-based optimization combined with SHAP explainability for supporting transparent machine learning research in diabetes prediction. However, additional external validation using independent clinical datasets is required before considering the framework for clinical decision support or real-world deployment.

Journal of Personalized Medicine doi: 10.3390/jpm16080422

Authors: Alan Sinclair Ffion James Aswani Muraleedharan Ahmed Abdelhafiz

Introduction: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. Methods: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. Results: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. Conclusions: Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients.

Journal of Personalized Medicine doi: 10.3390/jpm16080421

Authors: Adil Sarvar Mohammed Sai Priyanka Mellacheruvu Zainab Gandhi Sai Prasanna Lekkala Suvidha Manne Umera Yasmeen Iramunisa Begum Rupak Desai Shrinivas Kambali Lakshmi Sai Meghana Kodali Shiny Teja Kolli Shaylika Chauhan Shweta Kambali

Background: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. Methods: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. Results: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (p < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. Conclusions: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine.

Journal of Personalized Medicine doi: 10.3390/jpm16080420

Authors: Ioannis Mykoniatis Athanasios Papatzelos Damianos Damon Dejan Nikolaou Nikolovski Asterios Symeonidis Christos Roidos Chrysovalantis Toutziaris Ioannis Vakalopoulos Petros Sountoulides

Background: Active surveillance (AS) represents a cornerstone of personalized medicine in uro-oncology, offering an individualized management strategy for low- and selected favourable intermediate-risk prostate cancer that aligns treatment intensity with patient-specific risk profiles; however, real-world adherence data from southern European academic centres remain scarce. This study aimed to evaluate AS discontinuation rates, reasons for transition to active treatment, and quality of life (QoL) in a single-centre Greek university hospital cohort. Methods: This is an observational retropective cohort study of patients enrolled in an AS protocol at the First Department of Urology, Aristotle University of Thessaloniki, between October 2016 and July 2022. Treatment-free survival (TFS) was estimated using Kaplan–Meier analysis. Associations between AS discontinuation and age at diagnosis, PSA level, and Charlson Comorbidity Index (CCI) were explored using univariable and multivariable Cox proportional hazards regression. QoL, erectile function, and anxiety were assessed cross-sectionally in patients remaining on AS using SF-12, IIEF-6, STAI-6, and MAX-PC. Results: Thirty-six patients were included (32 low-risk; 4 favourable intermediate-risk), with a median age of 69.5 years, median PSA of 6.92 ng/mL, and median CCI of 3. After a median follow-up of 24 months (IQR 21–45), 19 patients (52.8%) transitioned to active treatment; the median time to treatment was 21 months (IQR 17–34). Among the 10 patients with a known reason for discontinuation, 6 (31.6% of all discontinued) showed histopathological or clinical disease progression, 3 (15.8%) had a PSA increase alone, and 1 (5.3%) transitioned due to urinary symptoms; the reason was unknown in 9 cases (47.4%). In exploratory Cox regression, PSA ≥ 7.0 ng/mL was the only factor with complete documented output significantly associated with transition to active treatment (univariable HR 3.70, 95% CI 1.35–10.1, p = 0.011; multivariable HR 3.93, 95% CI 1.42–10.9, p = 0.008). Cross-sectional QoL assessment in 10 patients remaining on AS demonstrated median scores above established population norms for SF-12 and below clinical anxiety thresholds on STAI-6 and MAX-PC. Conclusions: In this single-centre cohort, AS discontinuation occurred early and at a rate higher than that of established international programmes, consistent with the institution’s initial AS experience. Higher PSA at diagnosis was the only factor with complete analytical documentation to be significantly associated with earlier transition.

Journal of Personalized Medicine doi: 10.3390/jpm16080419

Authors: Sergey Yu. Muraviev Zakhar A. Akulov Maria A. Sukhanova Miroslava O. Pilipenko Evgeniy A. Tarabrin Zelimkhan G. M. Berikkhanov Milena Yu. Ivanova Andrey M. Nikolaev Vadim S. Razumovsky Vladislav S. Rakintsev Aleksey G. Kotelnikov Sara Nourmahal Alexey L. Shestakov

Objectives: To assess whether muscle morphology and metabolism can inform personalised care in ventral hernias and to define which parts of a proposed postoperative remodelling model are supported by direct evidence. Methods: We conducted a structured narrative review of PubMed/MEDLINE, Scopus and Web of Science from 1 January 2010 through 30 April 2026. Two authors selected 38 publications. Evidence was classified as direct when generated in ventral or incisional hernia cohorts and indirect when drawn from inguinal hernia, transplantation, geriatric, oncological, animal or general muscle studies. No quantitative synthesis was undertaken. Results: Direct studies document lateral muscle displacement, impaired abdominal wall function, inconsistent associations between low muscle mass and clinical outcomes, and CT-derived increases in muscle cross-sectional areas after transversus abdominis release (TAR). The evidence for anterior abdominal wall myosteatosis, biomarker-guided care and the three proposed remodelling trajectories remains largely indirect. In a 37-patient TAR series, the median rectus abdominis cross-sectional area increased by 16.1% (IQR 11.4–27.0%); muscle function and metabolic recovery were not measured. Conclusions: Routine CT can yield muscle area, attenuation and intermuscular adipose tissue measures without further imaging. No anterior abdominal wall-specific thresholds or biomarker cut-offs have been validated, so these measures should not determine current treatment in isolation. Prospective studies should test whether combined imaging, functional and clinical phenotyping improves the selection of prehabilitation and follow-up.

Journal of Personalized Medicine doi: 10.3390/jpm16080418

Authors: Maria Efenesia Baffa Roberto Maglie Stefano Colabrese Carlo Pipitò Vincenzina Rubino Sasha Visinoni Lucrezia Cerchiai Marzia Caproni Emiliano Antiga

Vitiligo is an autoimmune depigmenting disorder characterized by marked heterogeneity in therapeutic response, both between patients and among lesions within the same individual. While current therapies primarily target interferon-γ (IFN-γ)-driven inflammation, clinical outcomes remain variable and frequently incomplete, suggesting that additional lesion-specific biological factors contribute to repigmentation potential. In this narrative review, we propose the concept of repigmentation competence to describe the capacity of an individual lesion to achieve clinically meaningful repigmentation under therapy. We hypothesize that this competence emerges from the interaction of four interconnected biological axes: (i) cytokine network and immune memory, (ii) local immune regulation, (iii) regenerative capacity, and (iv) microenvironmental permissiveness. A targeted search of PubMed/MEDLINE and ClinicalTrials.gov up to March 2026 was conducted to identify translational studies, mechanistic models, and clinical trials relevant to these pathways. Evidence was synthesized thematically with emphasis on cytokine-mediated mechanisms and their interaction with regenerative and tissue-context processes. The IFN-γ/CXCL9/CXCL10 axis and tissue-resident memory T cells (TRM) represent the most clinically validated drivers of disease persistence, as demonstrated by the therapeutic efficacy of JAK inhibitors, although immune suppression alone often fails to achieve complete or durable repigmentation. In contrast, regulatory pathways involving PD-1/PD-L1 signaling, regulatory T cells (Tregs), IL-10, TGF-β, and IL-2–based strategies remain biologically compelling but only partially translated into effective therapies. Regenerative capacity has also emerged as an important determinant of treatment response, with growing evidence supporting the role of melanocyte stem cell niches, follicular regeneration, and Wnt/β-catenin signaling. Accordingly, regenerative approaches such as non-cultured epidermal cell suspension (NCES) are increasingly being integrated into combination therapeutic strategies. The lesional microenvironment remains the least therapeutically developed axis despite growing experimental evidence supporting its importance in melanocyte survival and migration. Collectively, these observations suggest that the variable efficacy of current therapies may reflect different combinations of lesion-specific biological constraints. The emerging benefit of combination strategies may therefore derive not simply from additive effects, but from the simultaneous engagement of multiple axes involved in repigmentation competence. Our review supports a shift from a predominantly drug-centered model toward a lesion-oriented framework integrating immune, regenerative, regulatory, and microenvironmental determinants of response.

Journal of Personalized Medicine doi: 10.3390/jpm16080417

Authors: Aris Kaltsas Andreas Koumenis Evangelos N. Symeonidis Fotios Dimitriadis Nikolaos Sofikitis

Background/Objectives: Varicocele is usually clinically left-sided, but imaging and mechanistic studies suggest that contralateral venous reflux or bilateral testicular effects may be more common than physical examination indicates. This narrative review critically examines whether varicocele-associated infertility is better conceptualized as an asymmetric disorder with potential bilateral anatomical or functional involvement and considers the implications for diagnosis and treatment. Methods: PubMed/MEDLINE and Scopus were searched from inception to 21 June 2026 for studies on varicocele laterality, bilateral and subclinical disease, color Doppler ultrasonography, venography, and unilateral versus bilateral repair. Reference lists and contemporary clinical guidelines were also reviewed. Because the included studies differed substantially in patient selection, age, operator technique, diagnostic criteria, and reference standards, reported bilateral rates were not interpreted as head-to-head estimates of diagnostic sensitivity or as pooled prevalence estimates. Results: Physical examination identifies predominantly left-sided clinical disease. Bilateral involvement is reported more frequently when both sides are assessed using Doppler ultrasonography or venography, but estimates vary widely across referral-enriched and highly selected cohorts. Human and experimental evidence supports several mechanisms by which a clinically unilateral lesion may have bilateral functional effects, including shared scrotal hyperthermia, oxidative stress, endocrine disturbance, and venous cross-communication. Bilateral repair is consistent with standard treatment criteria when both varicoceles are clinically palpable. In men with a clinical left varicocele and non-palpable right-sided reflux, comparative evidence is mixed, and current guidelines do not support routine treatment of imaging-only disease. Conclusions: Varicocele is best viewed as an asymmetric disorder that may be anatomically or functionally bilateral in selected men, rather than as a universally bilateral disease. Deliberate bilateral clinical assessment and standardized bilateral ultrasonography when imaging is clinically indicated may improve phenotyping and operative planning. However, contralateral imaging abnormalities should not automatically be converted into a surgical indication.

Journal of Personalized Medicine doi: 10.3390/jpm16080416

Authors: Coco Ng Gurpreet K. Singhera Ea Chung Chang Amrit Samra Katherine A. Adolphs Evan H. Phillips Jamil Bashir Zachary Laksman Honglin Luo Gordon A. Francis Chi Lai Ying Wang

Background: Although cardiovascular disease (CVD) significantly impacts the quality of life of millions of patients worldwide, the high costs of developing new drugs and conducting clinical trials for CVD hinder therapeutic development in this field. Repurposing approved drugs, of which the safety has already been tested can significantly reduce the time and cost required for treating CVD. From the perspective of pharmacology, repurposed drugs are selected to specifically target CVD patients carrying the matching drug targets, enabling tailored, personalized intervention. In the context of drug repurposing, therapeutic target mapping is a process used to assess the enrichment of molecules that can be affected by a drug in order to produce a therapeutic effect. Methods: This narrative review summarizes the workflows and challenges of performing therapeutic target mapping to assess the potential of repurposing existing drugs for treating CVD. We also share our perspective of how retrospective studies of human specimens can contribute to therapeutic target mapping based on experience from the Bruce McManus Cardiovascular Biobank (BMCB), a large explanted heart biobank located in Vancouver, Canada. The literature we discuss was identified by non-systematic searches of PubMed, using search terms “human-derived specimens”, “drug repurposing”, and “cardiovascular disease”. We reviewed articles from 2012 to 2026 and prioritized studies conducted after 2019 to discuss recent advances in the field. Conclusions: Human specimens of high molecular quality are needed for evaluating the enrichment of drug targets in CVD. Therapeutic target mapping in diseased cardiovascular tissue requires integrated expertise from medical, translational, and applied sciences to identify suitable human specimens for molecular phenotyping, and to design hypothesis-driven approaches to validate the drugs suggested for repurposing.

Journal of Personalized Medicine doi: 10.3390/jpm16080415

Authors: Electra Chatzidimitriou Georgios Ntritsos Eleni Poptsi Emmanouil Tsardoulias Andreas L. Symeonidis Magda Tsolaki Panos Charalambous Chrissa Sioka Eleni Aretouli Ioannis Iakovou Katherine P. Rankin Panagiotis Ioannidis Despina Moraitou

Background and Objectives: Functional decline is a major determinant of disability, caregiver burden, and loss of independence in behavioral variant frontotemporal dementia (bvFTD). Although bvFTD is characterized by early and rapidly progressive deterioration in everyday functioning, the multimodal contributors associated with longitudinal functional change remain insufficiently understood. The present study aimed to identify the strongest cognitive, behavioral, personality, and neuroimaging correlates of longitudinal functional deterioration in bvFTD using an integrated multimodal framework over a 12-month follow-up period. Methods: Twenty-seven patients diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of the “AHEPA” University Hospital in Thessaloniki, Greece, and underwent comprehensive face-to-face neuropsychological assessment for the evaluation of a wide range of cognitive domains, alongside caregiver-based evaluations of behavioral disturbances, personality changes, and functional abilities, at baseline, 6 months, and 12 months. Brain perfusion single-photon emission computed tomography (SPECT) was acquired only at baseline, with regional cerebral blood flow (rCBF) quantified using a Brodmann area (BA)-based approach. Functional status was assessed using the Disability Assessment for Dementia (DAD) as the primary outcome, while the Frontotemporal Dementia Rating Scale (FRS) served as a secondary measure. Repeated-measures analysis of variance (ANOVA) was used to characterize longitudinal changes across cognitive, behavioral, personality, and functional domains, while linear mixed-effects (LME) models were applied to identify longitudinal correlates of functional decline and sources of inter-individual variability in functional outcomes. Results: Significant progressive decline in functional abilities was observed over the 1-year follow-up period, consistent with an aggressive and rapidly deteriorating clinical course in bvFTD. Reductions in functional performance were evident across both basic and instrumental activities of daily living, with deterioration being more pronounced in instrumental activities. Based on the final LME model, greater apathy-related (negative) behavioral symptoms, global cognitive impairment, attentional and processing speed deficits, and impaired inhibitory control were independently associated with poorer longitudinal functional outcomes (p < 0.001). At the neuroimaging level, reduced baseline perfusion in the right BA 24 within the anterior cingulate cortex was also significantly associated with greater loss of functional independence over time (p < 0.001). Conclusions: Longitudinal functional decline in bvFTD reflects the combined disruption of behavioral regulation, global cognition, executive control, and frontal–cingulate network integrity. The findings provide a preliminary foundation for future research investigating factors associated with accelerated functional decline. Further validation in larger, multicenter longitudinal cohorts is needed to determine the prognostic relevance of these factors and their potential applicability to patient stratification and individualized care planning.

Journal of Personalized Medicine doi: 10.3390/jpm16080414

Authors: Christian D’Elia Edda Russo Giada Santagata Riccardo Terenzi Francesca Li Gobbi Emanuele Antonio Maria Cassarà Elisa Cioffi Valentina Grossi Francesca Romano Barbara Lari Maria Infantino Mariangela Manfredi Serena Guiducci Maurizio Benucci

Background: Polymyalgia rheumatica (PMR) is a clinically heterogeneous inflammatory disorder in which conventional acute-phase reactants may inadequately reflect the complexity and biological variability of disease activity. Precision medicine approaches integrating multidimensional clinical and laboratory data may offer a more comprehensive characterization of inflammatory phenotypes. This study investigated whether the combined assessment of cytokine profiles, routine laboratory biomarkers, ultrasound findings, and clinical variables could improve disease activity stratification in PMR. Methods: A total of 103 consecutive patients with PMR were retrospectively analyzed. Disease activity was assessed using the PMR Activity Score (PMR-AS) and, for exploratory purposes, dichotomized according to the cohort median (≥11 vs. <11). Group differences were evaluated using non-parametric statistical methods. The multidimensional structure of the dataset was explored through Spearman correlation analysis, principal component analysis (PCA), and unsupervised clustering. Predictive models, including logistic regression, random forest, and gradient boosting, were developed to evaluate the potential contribution of integrated analytical approaches to patient stratification. Results: The study cohort included 103 patients (63.1% female), with a median age of 76 years (IQR 71–81); 57 patients (55.3%) presented PMR-AS ≥11. Patients with higher disease activity exhibited significantly increased levels of CRP, fibrinogen, platelet count, IL-6, serum amyloid A (SAA), and myeloid-related protein (MRP), together with a higher prevalence of joint effusion and Power Doppler positivity. Among the evaluated biomarkers, SAA demonstrated the strongest correlation with disease activity (Spearman ρ = 0.878; p < 0.001). Multivariate predictive modeling showed high discriminative performance, with random forest achieving the highest cross-validated AUC (0.934), whereas gradient boosting demonstrated the best overall accuracy (0.883). Unsupervised clustering analysis identified a subgroup characterized by a more pronounced inflammatory signature associated with higher PMR-AS values. Conclusions: These findings support the concept that disease activity in PMR may be more effectively represented through an integrated multidimensional inflammatory profile rather than isolated biomarkers. The combined evaluation of routine laboratory parameters, cytokines, and imaging features may contribute to more refined patient stratification within a precision medicine framework. Although exploratory, these results highlight the potential value of advanced data integration strategies for supporting biologically informed disease characterization in PMR, while underscoring the need for external validation before translation into clinical practice.

Journal of Personalized Medicine doi: 10.3390/jpm16080413

Authors: Luigi Angelo Vaira Hareem Qadeer Fabio Maglitto Giuseppe Consorti Giulio Cirignaco Giovanni Salzano Giacomo De Riu

Background/Objectives: Osteoradionecrosis of the jaws remains a severe late complication of head and neck radiotherapy. Current preventive strategies are still frequently based on population-level dose thresholds and broadly standardized dental-clearance protocols, despite substantial heterogeneity in individual risk. This comprehensive review aimed to integrate established preventive guidance with emerging tooth-level, spatial-dosimetric, prognostic, and causal approaches within an integrative conceptual framework for personalized osteoradionecrosis prevention. Methods: Structured searches of five databases were completed on 30 May 2026. Evidence sources were selected and mapped across six a priori thematic domains, with the selection process summarized in a simplified flow diagram and an evidence map. Priority was given to guidelines, systematic reviews, large cohorts, externally validated prediction models, and clinically actionable studies. Results: Osteoradionecrosis risk is determined by interactions among tumor site, surgical anatomy, mandibular dose distribution, dental and periodontal disease, smoking, diabetes, nutritional status, biological susceptibility, and expected survival. Tooth extraction is not uniformly protective, and its potential benefit depends on tooth prognosis, local radiation dose, oncological urgency, and patient-level vulnerability. Dose–volume parameters and site-specific mapping provide more clinically relevant information than prescribed dose alone. Contemporary normal tissue complication probability and machine-learning models increasingly support individualized risk estimation, although calibration, external validation, data quality, and workflow integration remain limiting. Competing-risk and causal-inference approaches may further distinguish baseline risk from the expected benefit of specific preventive interventions. Conclusions: The evidence reviewed can be organized within an integrative conceptual framework combining tooth-level prognosis, spatial dosimetry, systemic susceptibility, competing mortality, and intervention burden. This framework synthesizes and reorganizes existing evidence; it is not a validated clinical model and requires prospective validation and clinical-impact evaluation before routine implementation. Until then, available prediction models should support, rather than replace, multidisciplinary clinical judgement.

Journal of Personalized Medicine doi: 10.3390/jpm16080412

Authors: Cristina Stanescu Catalina Teodora Pintilie Roxana Elena Bogdan Goroftei Madalina Nicoleta Matei Iulia Chiscop Monica Boev Florina Popa Camelia Tamas

Background: Chronic wounds pose a persistent therapeutic challenge. Type I collagen and hyaluronic acid (HA) support tissue repair, but real-world evidence for describing their combined use in padformulations is limited. This study provides a real-world description of clinical outcomes observed within a tailored management, including Type I Collagen–Hyaluronic Acid pads (HCHA), on healing trajectories across diverse chronic wound etiologies. Methods: This retrospective observational analysis included 64 patients treated between 2017 and 2024 for chronic wounds, including burns (n = 32) and trophic ulcers of various etiologies (n = 32). Clinical data, including wound characteristics, daily healing rate (DHR), and procedural pain assessed using repeated VAS measurements, were extracted from medical records. Results: The daily healing rate (DHR) ranged from 3.22% in neglected burn wounds to 2.03% in non-burn chronic wounds. Percent area reduction (PAR) analysis at 7, 14, and 30 days showed greater wound area reduction in burn wounds (20%, 36%, and 62%) compared with non-burn wounds (13%, 25%, and 45%). Procedural pain decreased in both cohorts, with burn injuries presenting higher baseline VAS scores but following a similar downward trajectory over time (p < 0.001), converging to comparably low levels by day 30. Overall, the findings describe the outcomes observed within an individualized, multimodal wound care approach, which incorporates HCHA pads tailored to wound-specific characteristics. Conclusions: In this retrospective observational study, patients treated with HCHA pads as part of individualized multimodal wound care exhibited progressive granulation, favorable wound-healing trajectories, and lower procedural pain levels. Further controlled studies are warranted to validate these results and refine the patient selection criteria.

Journal of Personalized Medicine doi: 10.3390/jpm16080411

Authors: Alice B. Popejoy Deborah Cragun Megan C. Roberts Lisa M. Bendz Sarah Gonzales Susanne B. Haga R. Ryanne Wu Natasha J. Petry Laura B. Ramsey Ryley Uber Kaniz Momin Nina R. Sperber

Background: Pharmacogenetic (PGx) testing could identify actionable drug–gene interactions, reducing the risks of inappropriate prescribing of certain medications in some patients. An area of growing public health concern is rising global rates of depression and antidepressant use over the last two decades. Prior research has elucidated perspectives of healthcare providers who prescribe antidepressants regarding the clinical utility of genetic information, including PGx testing, but there is a gap in understanding how individual perspectives and systemic contextual factors may combine to influence PGx testing adoption. Objective: The objective of this study was to elucidate combinations of individual and contextual conditions associated with willingness to adopt PGx testing for Cytochrome P450 Subfamily IID, Polypeptide 6 (CYP2D6) and Subfamily IIC, Polypeptide 19 (CYP2C19) among antidepressant prescribers. Methods: We conducted a cross-sectional, mixed-methods study using structured questionnaires and semi-structured interviews with healthcare providers who prescribe antidepressants within their scope of practice across four healthcare systems in the United States. We collected data on implementation science concepts from the Theoretical Domains Framework, the Consolidated Framework for Implementation Research (CFIR), and the Implementation Outcomes Framework. Coincidence analysis (CNA), a case-based, Boolean logic-based method that identifies minimally sufficient combinations of conditions that lead to a particular outcome, was used to identify combinations of conditions for PGx test adoption among antidepressant prescribers. Interviews were also conducted with 10 patients who received pharmacogenetic testing within these healthcare systems to contextualize findings with patient perspectives. Results: Prescribers adopted PGx testing when they believed it would be beneficial to patients and were not deterred by cost-related concerns; the combination of these conditions led to PGx adoption in the most highly supported CNA model. Patient perspectives were also consistent with the selected model, with data suggesting they may have greater willingness to tolerate costs when they perceived or experienced benefits from testing. Conclusions: Insights from this study may be used by health system administrators and public health policymakers to inform future PGx implementation strategies that enhance uptake and awareness of existing evidence for clinical benefits of PGx testing and mitigate cost-related barriers to adoption.

Journal of Personalized Medicine doi: 10.3390/jpm16080410

Authors: Michele Salati Anna Chiara Nanto Mara Romito Alberto Roncon Michela Tiberi Gian Marco Guiducci Francesco Xiumè Francesca Barbisan Gaia Goteri Majed Refai

Background: Tumor Spread Through Air Spaces (STAS) is a histopathological pattern of invasion associated with aggressive behavior in lung adenocarcinoma. Its prognostic impact and implications for surgical strategy remain controversial. This study evaluated the impact of STAS on survival and recurrence outcomes in patients undergoing uniportal video-assisted thoracoscopic surgery (U-VATS) for lung adenocarcinoma. Methods: We retrospectively analyzed consecutive patients with histologically confirmed lung adenocarcinoma who underwent U-VATS resection between January 2020 and January 2023 at a single tertiary referral center. Propensity score matching (1:1) was performed to reduce selection bias between STAS-positive and STAS-negative patients. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier estimates and log-rank tests. Multivariable Cox proportional hazards regression models were used to identify independent predictors of survival. Subgroup analyses were performed according to the type of resection. Results: Among 365 included patients, 111 (30.4%) were STAS-positive. After propensity score matching, 222 patients were analyzed (111 STAS-positive and 111 STAS-negative). STAS-positive patients showed a higher overall recurrence rate compared with STAS-negative patients (36.9% vs. 27.9%, p = 0.15), with a significantly increased rate of local parenchymal recurrence (18.9% vs. 9.0%, p = 0.03). No significant differences in OS or RFS were observed between matched groups. Multivariable Cox regression analysis confirmed that STAS was not independently associated with OS (HR 0.88, 95% CI 0.50–1.53, p = 0.643). In STAS-positive patients, sublobar resection was associated with significantly worse survival outcomes compared with lobectomy and emerged as an independent predictor of mortality (HR 2.61, 95% CI 1.14–5.97, p = 0.02). Conclusions: STAS was associated with an increased risk of local recurrence but was not independently associated with overall survival after U-VATS resection for lung adenocarcinoma. However, in STAS-positive patients, sublobar resection was independently associated with worse survival outcomes, suggesting that surgical extent plays a critical role in this subgroup. These findings support consideration of a personalized surgical approach in patients with STAS-positive lung adenocarcinoma.

Journal of Personalized Medicine doi: 10.3390/jpm16080409

Authors: Gilberto Gremese Matteo Comuzzi Matteo Danielis Tommaso Piani Daniele Guerino Biasucci Giuseppe Cuttone Ciro Fittipaldi Francesca Lucchese Luigi Vetrugno Cristian Deana

Background: Critically ill patients undergo rapid and clinically significant skeletal muscle loss during the first week of ICU admission, driven by a complex interplay of systemic inflammation, neuroendocrine dysregulation, and accelerated protein catabolism. While CRP is an established marker of the inflammatory response, its temporal relationship with early muscle wasting—specifically whether the initial inflammatory peak or its subsequent persistence most strongly determines muscle loss—remains poorly characterised. This study investigated the serial dynamics of inflammatory biomarkers and their correlation with skeletal muscle changes during the first seven ICU days. Methods: This is a post hoc analysis of the NUTRITI prospective observational cohort, conducted at a single academic ICU in Udine, Italy (Ethics Committee approval: CEUR-2019-Os-17). Sixty-six adult critically ill patients with an anticipated ICU stay exceeding 72 h and requiring artificial nutritional support were included; patients on renal replacement therapy or with contraindications to bioelectrical impedance analysis (BIA) were excluded. Body composition—skeletal muscle mass (MM, kg) and phase angle (PA°)—was assessed by single-frequency BIA (50 kHz) on Day 1 and Day 7. The primary outcome was ΔMM%, the percentage change in muscle mass between admission and Day 7, calculated as ΔMM% = [(MMd − MMa)/MMa] × 100. Daily inflammatory biomarkers—CRP (mg/L), total WBC (×103/mm3), and lymphocyte count (×103/mm3)—were collected throughout. Spearman rank correlations between ΔMM% and serial biomarkers were computed for each day. Given the large number of tests (42 total), Bonferroni false discovery rate corrections were applied. Results: The cohort had a median age of 68.5 years (IQR 61–77.8), was predominantly male (71.2%), with median APACHE II 21.5 and SOFA 7. Median muscle mass declined significantly from 34.3 kg (IQR 29.9–39.5) at Day 1 to 30.6 kg (IQR 26.5–34.9) at Day 7 (p < 0.001), corresponding to a median MM% of −8.45% (IQR −14.2% to −1.52%). Phase angle also declined significantly (4.9° to 4.5°; p < 0.01). CRP showed no significant correlation with ΔMM% at Days 1 or 2, but a negative correlation emerged at Day 3 (ρ = −0.297; p = 0.020) and peaked at Day 4 (ρ = −0.355; p = 0.006), attenuating thereafter. CRP at Days 5 and 6 correlated with phase angle changes (p = 0.017 and p = 0.022, respectively). WBC showed no significant correlations at any time point. Day-7 lymphocyte count was nominally correlated with ΔMM% (ρ = −0.314; p = 0.040). Neither APACHE II nor SOFA at admission correlated with ΔMM%. No test survived correction for multiple comparisons. Conclusions: The kinetics of CRP—rather than its initial intensity—seem to be associated with early skeletal muscle catabolism in critically ill patients, with a temporally specific signal emerging at Days 3–4 of ICU admission. Although these findings are exploratory and did not survive multiple testing correction, their biological plausibility—grounded in the known kinetics of ubiquitin-proteasome activation and NF-κB signalling—and their alignment with the emerging concept of inflammation-guided nutritional timing both support their value as a hypothesis-generating observation. Serial CRP monitoring may represent a pragmatic candidate biomarker to identify the optimal window for nutritional escalation, pending prospective validation in adequately powered trials.

Journal of Personalized Medicine doi: 10.3390/jpm16080408

Authors: Pennipat Nabheerong Phuwadon Duangto Suttiwat Jeamtrakool Chairat Charoemratrote Pornpat Theerasopon

Background/Objectives: Dental age estimation is widely used in clinical and forensic practice. The Demirjian four-teeth methods were developed to simplify age assessment; however, their accuracy varies among populations and requires validation before use in specific ethnic groups. This study aimed to evaluate and compare the accuracy of Demirjian’s four-teeth methods I and II for dental age estimation in Southern Thai children and adolescents aged 7–15 years. Methods: This retrospective cross-sectional study included 360 digital panoramic radiographs (180 males and 180 females) from Southern Thai individuals aged 7–15 years. Dental age was estimated using Demirjian’s four-teeth method I (teeth 34, 35, 36, and 37) and method II (teeth 31, 34, 35, and 37). Estimated dental ages were compared with chronological ages using the Wilcoxon signed-rank test. Accuracy was assessed by mean error (ME), mean absolute error (MAE), and root mean square error (RMSE). Intra- and inter-observer reliability were evaluated using weighted kappa statistics. Results: Intra- and inter-observer agreement were excellent, ranging from 0.957 to 1.000 and 0.895 to 0.956, respectively. The mean chronological age was 11.53 ± 2.55 years. Both methods overestimated chronological age in males and females. ME ranged from 0.54 to 0.75 years, while MAE ranged from 0.97 to 1.01 years. Method II produced slightly lower estimation errors than method I. Significant differences between dental and chronological ages were found for both methods in both sexes (p < 0.05). Conclusions: Both methods overestimated chronological age by approximately one year in Southern Thai children and adolescents. Method II showed marginally lower errors; however, population-specific calibration may improve age estimation in Thai populations. These findings support the need for population-specific dental age estimation strategies, contributing to more personalized and accurate age estimation for Thai children in both clinical and forensic settings.

Journal of Personalized Medicine doi: 10.3390/jpm16080407

Authors: Nazym Sagandykova Madina Baurzhan Alexandr Gulyayev Sayagul Kairgeldina Shyngys Sergazy Gulnur Daniyarova Karlygash Absattarova Liudmila Kovalenko Akmaral Izbassarova

Background/Objectives: Chronic dust-induced lung diseases, including pneumoconiosis and asbestosis, require long-term monitoring and individualized management. Conventional rehabilitation and follow-up often depend on in-person visits and may not provide continuous assessment outside clinical settings. This scoping review mapped evidence on digital technologies used to monitor patients, assess respiratory symptoms and functional status, and support rehabilitation follow-up in chronic dust-induced lung diseases. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute methodology. PubMed, Scopus, and Web of Science were searched from inception to 29 June 2026 without language restrictions. Five eligible publications were included. Results: The evidence was grouped into three categories: wearable monitoring of activity and respiratory symptoms, analysis of data from a digital rehabilitation platform, and electronic medical record (EMR) analysis. Wearable sensors showed high performance in recognizing basic activity states and cough events under controlled conditions. Platform- and EMR-based approaches showed potential for using clinical and functional data to support patient stratification and monitoring. However, most studies were limited to early technical or algorithmic validation and did not assess long-term home use, patient adherence, integration into clinical workflows, or clinical and rehabilitation outcomes. Conclusions: Digital technologies may support objective monitoring and rehabilitation follow-up in chronic dust-induced lung diseases, but the evidence base remains small and clinically immature. Prospective studies in real-world settings should evaluate usability, external validity, workflow integration, and clinically meaningful outcomes.

Journal of Personalized Medicine doi: 10.3390/jpm16080406

Authors: Alessandro Girombelli Piergiuseppe Volpe Francesco Saglietti Dana Shiffer Giulia Sette Raymond M. Planinsic Francesco Vetrone

Introduction: Neuromonitoring during general anesthesia (GA) is recommended to reduce the incidence of postoperative delirium and intraoperative awareness, particularly during total intravenous anesthesia. Guidelines emphasize that anesthesiologists should not rely solely on processed depth-of-anesthesia indices such as the Bispectral Index or Patient State Index but should also interpret the raw electroencephalographic (EEG) waveform and the density spectral array (DSA). Although EEG patterns associated with individual anesthetic agents or combinations of hypnotics and opioids have been described, limited evidence exists regarding EEG activity during multimodal anesthetic regimens. This systematic review aimed to evaluate DSA patterns as pharmacodynamic markers of the cortical effects of GABAergic anesthetics, opioids, and ketamine. Methods: PubMed, Embase, and the Cochrane Library were searched without date restrictions up to September 2025. Eligible studies included adult patients undergoing general anesthesia and reporting raw EEG data or specific DSA patterns associated with the investigated drugs. Risk of bias was assessed using RoB 2 and ROBINS-I according to study design. Owing to the limited number of eligible studies, findings were synthesized narratively. Results: Out of 273 papers screened, 3 studies met the inclusion criteria, comprising 72 patients. The studies achieved an appropriate and stable effect-site concentration of propofol–remifentanil GA, demonstrated by a baseline DSA recorded before ketamine administration. Ketamine administration produced a shift from the baseline alpha–delta pattern to a beta–delta DSA pattern. Conclusions: Ketamine administration during stable propofol–remifentanil anesthesia produces a characteristic shift towards a beta–delta DSA pattern, which may increase processed EEG indices, leading to misinterpretation of anesthetic depth. Further studies are needed to characterize DSA signatures associated with multimodal anesthesia and to identify patterns indicative of adequate anesthetic depth when multiple agents are administered.

Journal of Personalized Medicine doi: 10.3390/jpm16080405

Authors: Takeshi Osonoi Shinichiro Shirabe Miyoko Saito Mitsuru Hosoya Norie Watahiki Nana Shiozawa Satako Douguchi Kensuke Ofuchi Makoto Katoh

Background: Patients with type 2 diabetes (T2D) frequently exhibit impaired erythrocyte deformability, which contributes to microvascular dysfunction. We previously reported that imeglimin, a mitochondrial-targeted antidiabetic agent, prolongs erythrocyte lifespan. This study investigated the effects of imeglimin on whole-blood fluidity and its clinical implications in patients with T2D. Methods: This post hoc analysis of the INFINITY study included 25 patients with T2D who completed 6 months of imeglimin treatment (2000 mg/day) followed by a 3-month follow-up. Whole-blood fluidity was assessed by measuring whole-blood passage time using a microchannel array flow analyzer (MC-FAN). Hematological parameters, glycemic markers, and vascular indices, including brachial-ankle pulse wave velocity (baPWV) and toe-brachial index (TBI), were also assessed. Results: Whole-blood fluidity, assessed by 3-month averages of whole-blood passage time, showed an improvement trend at Months 1–3 (p = 0.058) and a significant improvement at Months 4–6 (p = 0.016) compared with baseline; this effect was reversed after discontinuation. Erythrocyte lifespan significantly increased by 10–20% during treatment and remained prolonged after discontinuation. Conversely, red blood cell count, hemoglobin, and hematocrit decreased during treatment and returned toward baseline post-discontinuation. At Month 6, baPWV increased, and TBI decreased, both showing reversibility after treatment cessation. Conclusions: In this exploratory post hoc analysis, imeglimin treatment was associated with reduced whole-blood passage time measured using the MC-FAN system, suggesting improved whole-blood fluidity in patients with T2D. The clinical and mechanistic significance of this observation requires confirmation in future controlled prospective studies incorporating direct assessments of erythrocyte rheology and microvascular function.

Journal of Personalized Medicine doi: 10.3390/jpm16080404

Authors: Horia Tudor Stanca

The past decade has witnessed remarkable progress in the understanding and management of retinal diseases [...]

Journal of Personalized Medicine doi: 10.3390/jpm16080403

Authors: Sy Van Hoang Kha Minh Nguyen Hai Phuong Nguyen Tran Hung Phi Truong Tai Nhat Nguyen Sang Quang Ly

Background: Familial hypercholesterolaemia (FH) is a common monogenic cause of premature coronary artery disease (CAD), yet data from South-East Asia are sparse and the yield of family cascade screening has not previously been reported in Vietnam. Methods: In this prospective, single-centre cohort study (March 2023–September 2025), 500 consecutive patients with premature CAD (men < 55 years, women < 60 years) underwent targeted next-generation sequencing of LDLR, APOB and PCSK9, with Sanger confirmation of pathogenic or likely pathogenic (P/LP) variants. First-degree relatives of variant-positive index patients were offered structured counselling and cascade sequencing of the family-specific variant. Results: A P/LP variant was identified in 18 of 500 patients (3.6%; 95% CI 2.1–5.4%); 17 (94.4%) involved LDLR and one APOB. Nine distinct P/LP variants were observed, with several recurrent, consistent with possible founder effects. Two carriers were homozygous, including one with an APOB frameshift attributable to consanguinity. Variant carriers were younger (mean difference −5.6 years, 95% CI −9.2 to −2.0) with higher LDL-cholesterol (median 227.5 vs. 138 mg/dL) and more extensive coronary disease than non-carriers. Cascade screening was completed in 20 of 26 eligible families (77%); among 105 first-degree relatives tested, 46 (43.8%; 95% CI 34.7–53.4%) carried the family-specific variant, most of them young, asymptomatic offspring or siblings. Conclusions: Precise molecular diagnosis in a small number of index patients identified a much larger cohort of at-risk relatives who would otherwise have remained undiagnosed, providing the first Vietnamese evidence that hospital-anchored cascade screening is feasible and high-yielding in a resource-limited setting.

Journal of Personalized Medicine doi: 10.3390/jpm16080402

Authors: Teresa Sinicropi Carmelo Mazzeo Mariausilia Franchina Maria Iannello Francesco Fleres

Introduction: Desmoid fibromatosis (DF) is a rare, locally invasive, and typically non-metastatic neoplasm. Its pathophysiology is poorly understood, and the subtle clinical presentation makes diagnosis challenging. A multidisciplinary approach is necessary to achieve a definitive diagnosis and identify the most effective therapeutic strategy. Because of its heterogeneous presentation and unpredictable behavior, DF cannot be managed through a standardized protocol, and diagnostic and therapeutic decisions must instead be tailored to the individual patient, consistent with a personalized-medicine approach. We present an unusual case in which we aim to evaluate the diagnostic procedures and treatments used and determine whether they align with the recent literature. Materials and Methods: A case report. A 27-year-old man presented with fever and worsening abdominal pain, without clinical signs of intestinal obstruction. He had undergone a sleeve gastrectomy five years earlier. A computed tomography (CT) scan revealed an intra-abdominal mass in the mesohypogastric region, likely originating from the mesentery of the small intestine. The patient underwent a right hemicolectomy extended to the terminal ileum. Histopathological examination and immunohistochemistry confirmed the diagnosis of DF. The patient was discharged on the 5th postoperative day (POD) in good general clinical condition. To date, there are no signs of recurrence. Conclusions: The multidisciplinary approach is essential for managing DF and R0 surgical resection remains the gold standard. The diagnostic and therapeutic pathway followed in our patient appears consistent with the recent literature. This case illustrates how individualized clinical reasoning can be applied even to a rare, heterogeneous neoplasm for which no standardized protocol exists. Furthermore, an established post-surgical management protocol for DF has not yet been developed. Additionally, we observed a possible, hypothesis-generating association between bariatric surgery and the subsequent onset of an intra-abdominal desmoid tumor; given the rarity of desmoid fibromatosis relative to the high volume of bariatric procedures performed worldwide, this observation should not be interpreted as a confirmed correlation, and we conducted a literature review to explore it as a hypothesis. Numerous studies are needed on this matter, but we hope that this case can provide a small starting point for subsequent studies.

Journal of Personalized Medicine doi: 10.3390/jpm16080401

Authors: Marco Chiappetta Alessandra Cancellieri Carolina Sassorossi Filippo Lococo Teresa Ferrazzo Chiara Scognamiglio Alessia Senatore Adriana Nocera Qianqian Zhang Andrea Guarneri Silvia Taralli Maria Lucia Calcagni Flaminia Vocaturo Luca Boldrini Huong Elena Tran Isabella Sperduti Stefano Margaritora

Background: Spread through air spaces (STAS) is a prognostic factor for survival in non-small cell lung cancer (NSCLC), but the chance to identify it before surgery remains challenging. In this study, we consider clinical, pathological and metabolic factors, with the aim to identify possible STAS predictors in NSCLC. Methods: Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1 January 2018 to 31 December 2023 were retrospectively reviewed and analyzed. Patients with GGO, AIS, or MIA tumors, metastases, or undergoing neoadjuvant therapy were excluded. The parameters assessed by 18F-FDG PET/CT were: SUVmax, SUVmean, SUVpeak, TLG and MTV. The primary endpoint was the association between clinical, metabolic, and pathologic characteristics with the presence of STAS. A univariate and multivariate logistic regression model was developed to identify independent predictors of STAS. Results: The final analysis was conducted on 224 patients. Non-lepidic-acinar adenocarcinomas showed a statistically significant higher risk of STAS than the lepidic-acinar histotype: 20.8% vs. 4.3%, p = 0.003, OR 5.87, 95%CI 1.83–18.78. Furthermore, tumor grade was significantly associated with STAS: 4.6% in G1–G2 tumors vs. 23.5% in G3 tumors (p = 0.001, OR 5.79, 95%CI 2.12–15.78); as well as lymph vascular invasion (p = 0.034) and tumor size >2 cm (p = 0.017). Multivariate analysis confirmed high tumor grade as an independent risk factor (OR 4.73, 95%CI 1.16–19.23, p = 0.030). Conclusions: In our study, risk of STAS is not correlated with metabolic parameters, while adenocarcinoma subtypes and tumors grading seem to stratify the risk of STAS occurrence. These results may be consolidated in an external validation analysis to possibly better plan the extent of lung resection.

Journal of Personalized Medicine doi: 10.3390/jpm16080400

Authors: Stamatios Katsimperis Lazaros Tzelves Patrick Juliebø-Jones Andreas Skolarikos

Testicular germ cell tumors (TGCTs) are highly curable malignancies, yet their clinical management still relies heavily on conventional serum tumor markers, including alpha-fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase, which have limited sensitivity and specificity in several clinically relevant settings. Circulating microRNAs, particularly miR-371a-3p, have emerged as promising liquid biopsy biomarkers with potential applications across the TGCT disease continuum. This narrative review summarizes the current evidence on the biological basis, diagnostic performance, clinical utility, and limitations of circulating microRNAs in TGCTs. MiR-371a-3p demonstrates high diagnostic accuracy for viable non-teratomatous TGCTs and consistently outperforms classical serum tumor markers in primary diagnosis. Its rapid decline after effective treatment and its association with tumor burden support potential roles in chemotherapy monitoring, early relapse detection during surveillance, and the assessment of selected post-chemotherapy residual masses. However, its inability to detect teratoma remains a major biological limitation, particularly in non-seminomatous residual disease and surveillance settings. Additional barriers to implementation include assay heterogeneity, the lack of universally accepted cutoffs, the variable use of serum versus plasma, and the absence of broad regulatory approval. Emerging translational data suggest that miR-371a-3p may also contribute to tumor–microenvironment communication and cisplatin resistance, although these findings remain preclinical. Overall, miR-371a-3p represents one of the most promising biomarkers in TGCT management, but its routine clinical integration will require standardized analytical protocols and prospective validation in marker-guided decision pathways.

Journal of Personalized Medicine doi: 10.3390/jpm16080399

Authors: Athanasios Syllaios Dimitrios Schizas

Gastrointestinal (GI) diseases comprise a heterogeneous group of disorders that collectively account for a substantial proportion of global morbidity, mortality, and healthcare expenditure [...]

Journal of Personalized Medicine doi: 10.3390/jpm16080398

Authors: Emanuele Rocco Villani Rosa Liperoti Laura Franza Francesca Maria Secciani Antonella Di Paola Graziano Onder Angelo Carfì

Background/objective: Down syndrome (DS) is characterized by premature aging, with comorbidities observed in the older population without DS, a high prevalence of multimorbidity and cognitive decline. The use of multiple medications further increases clinical complexity. The objective of this paper is to evaluate anticholinergic use and the anticholinergic burden (ACB) in a sample of persons with DS. Methods: cross-sectional retrospective study involving community-dwelling persons with DS, afferent to the DS clinics of the Fondazione Policlinico Universitario “A. Gemelli” (Rome, Italy). Individuals were assessed through a standardized clinical protocol. ACB was evaluated according to the anticholinergic cognitive burden scale, with a score ≥ 3 indicating high risk of anticholinergic side effects. Results: 337 individuals were taking ≥ 1 chronic medication, mean age was 37.7 (±14.6), 158 (43.8%) were females. 143 (39.6%) individuals took ≥ 1 medication with known anticholinergic burden, 51 (14.1%) individuals showed high risk ACB score. High risk ACB score prevalence increased with age (<18 years n = 0, 0%; 18–39 years n = 14, 8.2%; 40+ years n = 37, 22.3% p < 0.001). Polypharmacy was more prevalent among individuals with high ACB score (n = 20, 39.2% vs. n = 23, 7.4%, p < 0.001). The most prevalent drugs in individuals with high risk ACB score were antipsychotics (n = 34, 66.6% vs. n = 17, 33.3%, p < 0.001). The most prevalent comorbid condition was psychosis (n = 34, 66.6% vs. n = 16, 33.3%, p < 0.001). Discussion: individuals with DS show a high prevalence of anticholinergic drug use, increasing with age and associated with polypharmacy and psychiatric conditions. These medications are directly addressing the underlying psychiatric or neurological conditions in DS, rather than causing them. Nevertheless, these medications are often essential for managing psychiatric disorders, simultaneously increasing ACB, posing a risk of exacerbating pre-existing vulnerabilities (e.g., cognitive decline), which warrants the need for a more personalized strategy. Conclusions: A thorough assessment of drug history is mandatory in the DS population, to apply deprescribing, pharmacological switches, non-pharmacological approaches, to lower or even prevent high ACB, promoting overall a personalized and tailored approach to this population.

Journal of Personalized Medicine doi: 10.3390/jpm16080397

Authors: Pasquale Niscola Valentina Gianfelici Roberta Laureana Marco Giovannini Carla Mazzone Fabio Efficace Maria Ilaria Del Principe

Acute Myeloid Leukemia (AML) is a heterogeneous group of aggressive blood-related cancers that arise from the hematopoietic system, requiring specific treatments due to their genetic diversity and complexity. Artificial intelligence (AI) has emerged as a transformative technology in healthcare, with considerable potential to help manage AML. The application of AI approaches, such as Machine Learning (ML) models and Deep Learning (DL) algorithms, has been shown to aid risk stratification, diagnosis, treatment planning, and surveillance. This review highlights recent developments in AI applications for the personalized management of AML. We focus specifically on three major axes of personalization in AML: (1) the use of predictive models combining different data sources to improve prognostic assessment and guide risk-adaptive treatments; (2) prediction of treatment responses to various therapies based on data analysis; and (3) the use of AI for monitoring and adaptive trials in AML patients.

Journal of Personalized Medicine doi: 10.3390/jpm16080396

Authors: Tianyi Shen Nicholas Kai Yi Tan Wen Xuan Chew Matthias Yi Quan Liau Vor Luvira Vinay K. Kapoor Orestis Ioannidis Vishal G. Shelat

Gallbladder cancer (GBC) is the most common biliary tract malignancy and is among the most lethal gastrointestinal cancers. Since its inclusion in cancer staging manuals, the GBC Tumour–Node–Metastasis (TNM) classification has undergone repeated revisions intended to improve anatomical precision and prognostic discrimination. This narrative review traces the evolution of GBC staging across AJCC editions and the 2025 UICC TNM update and critically examines whether these refinements have translated into clinically meaningful risk stratification. In the 2025 UICC TNM 9 grouping, Stage IA corresponds to T1aN0M0 and Stage IB to T1bN0M0, while T2aN0M0 and T2bN0M0 remain Stage IIA and IIB, respectively. Structured literature searches were performed to identify historical staging documents, population-based analyses, validation studies, and prognostic reports relevant to stage migration, survival discrimination, and emerging staging modifiers. Successive changes, including T-category refinement and the transition from nodal location to nodal burden, have improved anatomical resolution. However, available validation studies suggest that gains in overall prognostic performance remain modest, with reported concordance indices often remaining near 0.66. Contemporary evidence increasingly shows that tumour location, adequacy of lymphadenectomy, number of positive lymph nodes, lymph node ratio, log odds of positive lymph nodes, obstructive jaundice, residual disease status, and selected molecular alterations may capture inter-patient heterogeneity beyond anatomy alone. Future staging refinement should therefore preserve TNM as a common anatomical language while developing validated parallel modifiers that support more individualized prognostication and treatment selection.

Journal of Personalized Medicine doi: 10.3390/jpm16080395

Authors: Costanza Martorelli Alessandra Monzio Compagnoni Matteo Massa Gianluigi Pasta Federico Alberto Grassi Michela Saracco Eugenio Jannelli

Background: Obesity is increasingly prevalent among patients undergoing total hip arthroplasty (THA). While outcomes are well reported, fewer studies assess postoperative BMI trends, digital templating accuracy, and biomechanical restoration. Purpose: To evaluate BMI evolution, templating accuracy, restoration of limb length and femoral offset, and clinical outcomes after primary THA in obese patients, compared with normal-weight controls. Methods: Retrospective comparative cohort including 75 obese patients (BMI ≥ 30 kg/m2) undergoing primary THA between July 2021 and December 2024. BMI was recorded preoperatively and at last follow-up. OrthoView™ 7.1 digital templating guided preoperative planning; accuracy was defined as implanted versus planned component sizes. Radiographic assessment of limb length and femoral offset was performed in 60 obese patients and 60 normal-weight controls. Clinical outcomes included Harris Hip Score (HHS), Oxford Hip Score (OHS), and EQ-5D-5L. Postoperative complications were recorded in the obese cohort. Results: BMI remained stable postoperatively (33.68 ± 2.57 vs. 34.06 ± 2.78 kg/m2; p = 0.138). Templating accuracy within ±1 size was high (femoral stem 80.2%; acetabular cup 94.7%). Limb-length discrepancy was low and comparable between obese and normal-weight patients (3.55 vs. 3.78 mm; p = 0.687). Femoral offset restoration was similarly comparable. Patient-reported outcomes improved significantly in both groups, with no significant differences in postoperative scores. Conclusions: In obese patients, THA provides reliable digital planning accuracy, satisfactory biomechanical reconstruction, and substantial functional improvement comparable to normal-weight patients. BMI remains essentially unchanged after surgery, indicating THA does not substantially influence postoperative weight trajectory in this population.

Journal of Personalized Medicine doi: 10.3390/jpm16070394

Authors: Clayton Peixoto Melanie Navarro Carolina Gomes Carrilho Antonio José Grande Antonio Egidio Nardi Adriana Cardoso André Barciela Veras

Background: Sexual function in postmenopausal women is influenced by both hormonal and psychological factors. This study investigates the associations between sex hormones, sexual function, and sexual beliefs in this population. Objective: This research seeks to assess the relationship between sex hormones, sexual function, and dysfunctional sexual beliefs in postmenopausal women. Methods: A cross-sectional study was conducted with 42 postmenopausal women aged 45–65 years. Instruments included the FSFI and SDBQ. Hormones assessed were testosterone, estradiol, progesterone, prolactin, DHEA, SHBG, and LH. Blood samples were collected in the morning and analyzed using chemiluminescence or radioimmunoassay. Pearson correlation tests were used, with Bonferroni adjustment applied to control for multiple comparisons. Results: Free testosterone was positively correlated with sexual desire and negatively associated with dysfunctional beliefs regarding sexual desire. Estradiol also showed a positive correlation with desire, while prolactin was negatively associated. No other FSFI domains showed significant hormonal associations. Conclusions: Findings suggest that testosterone may influence both sexual desire and the internalization of dysfunctional sexual beliefs in postmenopausal women, highlighting the interplay between biological and psychological dimensions of sexuality, which may be relevant for a more comprehensive clinical assessment of sexual function in this population.

Journal of Personalized Medicine doi: 10.3390/jpm16070393

Authors: Stefano Pagano Sebastian Dendorfer Tobias Renkawitz

Background/Objectives: Commercial wearables are increasingly used after total hip and knee arthroplasty (THA/TKA) to record activity and gait outside the clinic and may help tailor recovery pathways. We reviewed the evidence on commercial devices, digital phenotyping, and data-informed rehabilitation after arthroplasty. Methods: We performed a structured narrative search of PubMed and Google Scholar. Of 916 records, 63 duplicates were removed, 853 were screened, 245 full texts were assessed, and 76 publications were included. Findings were synthesized thematically; no formal risk-of-bias assessment or evidence grading was undertaken. Results: Recovery differed by outcome and procedure. PROMs commonly improved within 1–3 months, while gait-quality measures recovered over about 7–13 weeks after THA and 13–24 weeks after TKA. Frequency-domain gait features, sample entropy, and machine-learning models provided information beyond step counts. Tracker-based interventions most consistently increased postoperative steps when introduced early and combined with behavior-change support, while digital rehabilitation was generally non-inferior to conventional rehabilitation. Wrist-worn consumer devices remained inaccurate with gait aids, compliance definitions varied, and higher step counts did not consistently correspond to better PROMs. Conclusions: Commercial wearables already support phenotyping and remote follow-up of individual recovery trajectories, but evidence for fully adaptive rehabilitation remains limited.

Journal of Personalized Medicine doi: 10.3390/jpm16070392

Authors: Theodora Palyvou Ioannis Stefanou Sotirios Kympouris Theodora Imant Dionysia Thermou Stavriella Seferli Vasiliki Kanellopoulou Despoina Chatzopoulou Katrin Spyropoulou Nikolaos Kardaras Milena Iotova Asimina Ntotsika Maria-Christina Kapoutsi Iasonas Priftis Mara Bouga Christina Bolanou Georgios Sygkounas Spyridon Volteas

Introduction: Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy arising from the smooth muscle tissue of the uterine wall. It typically presents with abnormal vaginal bleeding, pelvic pain, or a pelvic mass. In rare instances, symptoms may result from local invasion or metastasis. We report a case of uLMS initially diagnosed following colonic perforation due to direct tumor invasion, accompanied by a comprehensive narrative review of the literature on the incidental identification of uterine sarcomas during emergency general surgery to further emphasize the diagnostic challenges, treatment approaches, and need for individualized care in these complex cases. Case Presentation: A 45-year-old woman presented to the Emergency Department with acute abdominal pain of several hours’ duration, in the absence of other associated symptoms. An emergency exploratory laparotomy was performed, revealing feculent peritonitis secondary to sigmoid colon rupture, resulting from local invasion by a large uterine mass. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was undertaken, followed by en bloc resection of the sigmoid colon, appendectomy and construction of a terminal colostomy. Her postoperative course was uneventful, and she was discharged on postoperative day eight. Histopathological examination of the specimen revealed a high-grade uterine leiomyosarcoma. Following evaluation by a multidisciplinary oncology board, the patient received adjuvant chemotherapy. Methods and Results: A narrative review of the literature was performed to identify cases of uterine sarcomas incidentally diagnosed during emergency surgery performed by general surgeons. Including the present case, six cases were identified. Most patients presented with acute abdomen mimicking gastrointestinal pathology, with diagnosis established intraoperatively or postoperatively. Definitive surgical management was achieved during the initial emergency procedure in all cases. Conclusion: Although exceptionally rare, uterine sarcoma should be considered in the differential diagnosis of acute abdomen in female patients undergoing emergency surgery. Awareness of this atypical presentation, the appropriate diagnostic approach, real-time intraoperative adaptability, and individualized multidisciplinary management are essential for ensuring appropriate surgical management and optimizing patient care.

Journal of Personalized Medicine doi: 10.3390/jpm16070391

Authors: Rebecca L. Beres Kenneth D. R. Setchell Marialena Mouzaki Xueheng Zhao

Pruritus is a debilitating symptom frequently affecting patients with cholestatic liver disease, often resistant to conventional antipruritic therapies. The pathogenesis of cholestatic pruritus (CP) is multifactorial, implicating not only bile acids but also a complex array of other potential pruritogenic mediators and neural signaling pathways. Identification of the exact pruritogen has been elusive, and gaps remain in understanding the pathogenesis of pruritus, so developing targeted treatments is critical. The stratum corneum (SC), the outermost lipid-rich layer of the skin, may act as a reservoir for circulating pruritogens, offering a novel window to explore the pathogenesis of CP. Recent advancements in lipidomics and non-invasive tape stripping have enabled detailed profiling of SC lipid alterations in disease states. In this review, we synthesize the current understanding of CP and its candidate pruritogens and describe state-of-the-art approaches for SC lipid analysis, combining tape stripping to sample the skin surface with mass spectrometry-based lipidomics. Finally, we summarize cutaneous molecular findings and discuss how these techniques are facilitating biomarker discovery and informing therapeutic development. This review discusses the paradigm shift from a single-molecule perspective to a more integrated view of CP as a product of complex mediator interactions and highlights the potential of SC profiling to uncover novel targets for intervention strategies.

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.