International Journal of Translational Medicine

Background: Chronic shoulder pain is a frequent musculoskeletal complaint that significantly affects function, productivity, and quality of life. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential regenerative option due to their anti-inflammatory and tissue-repair properties. This study aims to evaluate the safety and short-term effectiveness of intra-articular injections of umbilical cord-derived MSCs (UC-MSCs) in patients with chronic shoulder pain. Methods: A retrospective pragmatic observational study was conducted at the Regenerative Medicine Institute in Costa Rica. Medical records were reviewed to extract clinical, sociodemographic, and treatment-related variables. The primary outcome was functional improvement measured with the American Shoulder and Elbow Surgeons (ASES) score. Changes between baseline and the 3-month follow-up were analyzed using paired tests, effect size calculations, and regression models to explore predictors of treatment response. Results: Twenty patients met the inclusion criteria. A significant improvement in shoulder function was observed, with a mean ASES increase of 17.17 points, exceeding the minimum clinically important difference of 12. Sixty percent of patients achieved clinically meaningful improvement. Effect size estimates indicated a large magnitude of change. Regression analyses showed that baseline ASES predicted follow-up scores, while higher UC-MSC doses were associated with greater functional improvement. No adverse events were documented during the study period. Conclusions: The study shows that UC-MSC therapy is a safe, minimally invasive, and clinically beneficial option for chronic shoulder pain. These findings support the therapeutic potential of MSCs and highlight the need for larger controlled studies to validate long-term efficacy and optimize treatment protocols. Full article

Introduction: Early HIV replication in the gastrointestinal tract plays an important role in HIV pathogenesis. We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US. Patients and Methods: We followed 34 adult HIV positive Veterans on cART comparing colon Innate Immune System (InImS) expression of a Paneth cell product (p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients and compare the expression to 2252 without HIV. Stool and colonoscopically obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93 ± 6.30 vs. 28.0 ± 6.13 kg/m²) p < 0.0001. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse, and descending colon (0.794 ± 0.890 vs. 0.170 ± 0.201 respectively; p < 0.000004; 1.062 ± 0.730 vs. 0.202 ± 0.377 respectively; p < 0.000003; and 0.611 ± 0.182 vs. 0.174 ± 0.251 respectively; p < 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% vs. 36%; p < 0.0002). We also ran these assays in cancer patients for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product, is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation. Full article

Zebrafish (ZF) have gained increasing attention in developmental neuroscience due to their experimental tractability, favorable ethical profile, and translational value. However, the expanding use of the ZF model has also highlighted the need to consider species-specific differences in relation to early social and emotional development. This review adopts a comparative and ethological perspective to examine early social interactions in ZF and mammals, integrating evidence from non-altricial vertebrates and teleost species with parental care (cichlids). Selected illustrative ZF papers were discussed, while Cichlids fish were chosen as a complementary, translationally consistent subject for developmental behavioral studies. The analysis focuses on developmental stages that are relevant for behavioral phenotyping in models of neuropsychiatric conditions. Zebrafish offer multiple methodological advantages, including suitability for high-throughput experimentation and substantial genetic and neurobiological homologies with humans. Nevertheless, the absence of mother–offspring bonding limits the modeling of neurodevelopmental processes shaped by early caregiving, such as imprinting and reciprocal regulatory interactions, instead observed in cichlids. Accumulating evidence indicates that early interactions among age-matched ZF are measurable, developmentally regulated, and sensitive to environmental and experimental manipulations. Within a comparative approach, these early conspecific interactions could be analogs of early social bonding observed in altricial mammals. Rather than representing a critical limitation, such species-specific features can inform the investigation of fundamental mechanisms of social development and support the complementary use of ZF and mammalian models. A contextualized and integrative approach may therefore enhance the translational relevance of ZF-based research, particularly for the study of neurodevelopmental disorders involving early social dysfunction. Full article

Background: Scattering of the sclera limits optical coherence tomography (OCT) imaging of deeper targets including lesions, malignancies, and other surgical targets. While existing applications of fluorescein dye are currently focused on fluorescence properties for tissue labeling, the absorption characteristics of the dye also hold potential for scleral tissue clearing. Methods: Fluorescein is investigated here to gauge the potential impact of its optical clearing on intrasurgical OCT guidance. Fluorescein was applied topically to ex vivo porcine and human eye models. OCT imaging was conducted over time to assess the increases in imaging depth due to fluorescein clearing. High-speed microscope-integrated OCT was used during pilot trabeculectomy surgery on cleared eye models to assess clearing applications in a surgical context. Results: The OCT depth of imaging increased with fluorescein concentration and application time. The effect saturates at a near-20% concentration with 50 min of application time, with a maximum signal increase of +15 dB. Reversal of the effect was observed following 10 min of rinsing. Conclusions: High-concentration fluorescein dye has novel applications as an optical clearing agent, increasing the OCT imaging depth through highly scattering biological tissue. These properties can be leveraged for improved image guidance in surgical contexts. Full article

Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particularly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to a pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a subpopulation of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The goal of this review is the following: (i) comprehensively examine the multifaceted nature of oncofetal reprogramming; (ii) elucidate its underlying molecular mechanisms, including its regulators and effectors; and (iii) evaluate its consequences for the therapeutic response in different cancer types. We comprehensively integrate the latest findings from colorectal, breast, lung, liver, and other cancers to provide a detailed understanding of how oncofetal programs interfere with tumor response to treatment. Among the candidates, YAP1 and AP-1 have emerged as central transcriptional drivers of this reprogramming process, especially in colorectal and breast cancers. We also explore the distinct expression patterns of oncofetal genes across different tumor types and how these patterns correlate with treatment outcomes and patient survival. Lastly, we propose a dual-targeting therapeutic strategy that simultaneously targets both cancer stem cells and oncofetal-reprogrammed populations as a more effective approach to overcome resistance and limit recurrence. Full article

Background: We describe the post-mortem analysis of a CARD11 variant allele, p.Ser995Leu, identified in fraternal twins who died in early infancy with no identifiable cause of death. CARD11 variants through varied inheritance models can alter immune function through loss- or gain-of-function mechanisms, involving distinct protein domains; yet the significance of GUK domain variants remains poorly characterized. Twin autopsies showed non-specific findings, such as pulmonary macrophage accumulation and splenic white pulp expansion, but without infection or structural abnormalities. Methods: Whole-exome sequencing, performed as part of molecular autopsies, identified the shared CARD11 p.Ser995Leu variant, previously classified as a variant of uncertain significance (VUS). We assessed evolutionary conservation across CARD family proteins and species and predicted functional impact using in silico tools, which estimate the likelihood that a variant is deleterious. AlphaFold-based structural modeling emphasized qualitative biophysical assessment. Using epidemiological data, population allele frequency, and Bayesian ACMG variant classification, we assessed competing hypotheses under an autosomal dominant model. Results: The p.Ser995Leu substitution affects a conserved, surface-exposed β-sheet within the GUK domain. While CADD scores exceeded 20, other predictive algorithms offered only partial support of pathogenicity. Structural modeling suggested a potential GUK domain destabilization. Integrating genetic, pathologic, immunologic, and probabilistic modeling, we propose a biologically plausible model in which the variant, like other GUK variants, may alter NF-κB or other signaling pathways and is likely pathogenic. Conclusions: While the CARD11 p.Ser995Leu variant’s contribution to disease is uncertain without functional validation or parental testing, and phenotypic findings are non-specific, the presence of an ultra-rare GUK domain variant in both twins, combined with in silico and statistical modeling, supports its interpretation as likely pathogenic or high risk. The results highlight the challenges of data-limited post-mortem variant interpretation. Full article

Idiopathic inflammatory myopathies (IIM) comprise a heterogeneous group of autoimmune disorders with variable systemic involvement. Among them, dermatomyositis (DM) is the subtype with the most extensive biomarker characterization due to its defined immunopathology and frequent association with interstitial lung disease (ILD). This narrative review summarizes studies retrieved from PubMed, Scopus, and Web of Science up to March 2025, focusing on non-autoantibody biomarkers in DM. Reported categories include soluble proteins, cytokines, chemokines, muscle-specific microRNAs, and transcriptomic signatures reflecting interferon activation, tissue injury, and fibrotic remodeling. Among the most validated molecules, interferon-stimulated genes, ferritin, KL-6, SP-D, and CXCL10 demonstrate diagnostic and prognostic value, particularly in anti-MDA5-positive DM, where they support early identification of patients at risk for rapidly progressive ILD. However, despite increasing evidence, most biomarkers lack disease specificity, standardized cutoffs, and multicenter validation, while molecular assays remain confined to specialized laboratories. Clinically accessible markers such as ferritin, KL-6, and CXCL10 currently offer the highest translational potential. Nevertheless, the heterogeneity of study designs and analytical methods continues to limit comparability and routine clinical integration. Future research should prioritize the validation of composite biomarker panels through standardized, multicentric studies to enhance diagnostic precision and enable precision medicine approaches in DM and related inflammatory myopathies. Full article

Background/Objectives: GATA-binding protein 3 (GATA-3) is a crucial transcription factor that drives type 2 immune responses, and it is actively involved in allergic conditions such as asthma, allergic rhinitis (AR), and atopic dermatitis (AD). However, the molecular mechanisms GATA-3 uses to modulate immune responses and its potential therapeutic targeting are not fully understood. This systematic review aimed to summarize studies on the role of GATA-3 in immune responses, particularly in allergic diseases, and evaluate GATA-3’s potential as a therapeutic target. Methods: We searched PubMed, Scopus, Web of Science, Cochrane, and Science Direct for studies published before April 2025. Articles were sifted through using predefined criteria, and risk of bias was measured with RoB 2 for clinical trials and SYRCLE for animal models and in vitro studies; evidence was graded using the GRADE system. Results: Twenty-nine eligible studies reported that GATA-3 is a key regulator of Th2 and ILC2 differentiation, promoting the production of IL-4, IL-5, and IL-13. Animal models and in vitro studies demonstrated its role in exacerbating allergic inflammation and highlighted the promise of targeting strategies such as DNAzymes and nanocapsules. Clinical trials showed that targeting GATA-3, particularly with DNAzymes, can reduce allergic responses in asthma. Conclusions: GATA-3’s role in driving allergic inflammation through Th2 and ILC2 pathways suggests it as a promising therapeutic target. Understanding its broader regulatory mechanisms is imperative for designing effective GATA-3 targeting-based therapies. Full article

Background/Objective: Early hemodynamic instability in sepsis arises from endothelial dysfunction and vasoplegia before capillary leakage and organ failure occur. Albumin administration guided by serum concentration or shock criteria has not improved outcomes. This review synthesized evidence supporting an early, physiology-guided framework for albumin and norepinephrine use in pre-δ vasoplegic sepsis. Methods: A narrative synthesis of experimental and clinical studies examined endothelial injury, sepsis phenotypes, hemodynamic monitoring, biochemical markers, and intravascular albumin mass. Evidence from phenotype cohorts was integrated to construct a physiology-based therapeutic framework. Results: The δ phenotype consistently emerged as a vasoplegic, hyperinflammatory endotype with hypoalbuminemia, elevated lactate, and the highest mortality. Studies showed 20–25% of patients with community-acquired sepsis exhibit early vasoplegia, with low systemic vascular resistance and high cardiac output. Mass-balance analyses showed intravascular albumin mass declines early in sepsis, correlate inversely with fluid balance, and predict mortality. These findings suggest early low-dose norepinephrine may stabilize perfusion pressure, while albumin use should follow intravascular albumin mass trajectories. A dynamic exclusion concept proposes withholding albumin during capillary leak and reintroducing it when intravascular albumin mass stabilizes. Conclusions: Albumin therapy in sepsis should shift from late concentration-based to early physiology-guided endothelial protection. Monitoring intravascular albumin mass, lactate, and fluid balance may guide targeted norepinephrine and albumin use before δ-type endothelial failure occurs. This framework needs phenotype-stratified validation. Full article

Background: Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, is an acute but reversible form of left ventricular dysfunction, most commonly triggered by physical or emotional stress. Although well documented in cardiology practice, its occurrence following hepatobiliary surgery is rarely reported. Case presentation: We describe the case of a 67-year-old woman with a history of arterial hypertension and prior cholecystectomy who was admitted for elective hepatobiliary surgery due to choledocholithiasis complicated by a liver abscess. She underwent laparotomy with choledocholithotomy, hepaticojejunostomy, and abdominal drainage. The postoperative course was complicated by intra-abdominal bleeding, requiring reoperation, and subsequent intestinal leakage, necessitating a second re-laparotomy. On the tenth postoperative day after the second surgery, she developed chest discomfort and dyspnea upon minimal exertion. Electrocardiography revealed T-wave inversions in leads V3–V6, while echocardiography demonstrated a reduced ejection fraction of 45% with apical akinesis. Plasma levels of N-terminal pro-B-type natriuretic peptide (NT–proBNP) were elevated, whereas troponin remained within normal limits. Coronary angiography excluded obstructive coronary artery disease, and ventriculography confirmed apical ballooning consistent with Takotsubo cardiomyopathy. Conclusions: This case highlights Takotsubo cardiomyopathy as a rare but important postoperative complication of major hepatobiliary surgery. Awareness of this condition in surgical patients presenting with acute chest symptoms is essential, as timely recognition and differentiation from acute coronary syndrome directly influence management and prognosis. Full article

Background/Objectives: Understanding the pharmacokinetics (PK) of antiepileptic and anti-inflammatory drugs under different physiological conditions is essential for optimizing therapy. Phenytoin, a widely used antiepileptic, and indomethacin, a nonsteroidal anti-inflammatory drug, are frequently prescribed in women of reproductive age. This study aimed to evaluate the influence of age, pregnancy, and dosing regimens on the PK of both drugs, as well as to investigate potential drug–drug interactions (DDIs). Methods: PK parameters of phenytoin and indomethacin were systematically analyzed in women aged 20–45 years under non-pregnant and pregnant conditions. Different dosing regimens were compared, and coadministration studies were conducted to assess DDI. Results: Phenytoin demonstrated stable absorption and bioavailability across ages and during pregnancy. Single daily dosing (300 mg once daily) yielded slightly higher peak concentration (C_max) values, while fractionated dosing (100 mg q8h) produced significantly higher drug exposure (AUC) and absorption fraction, particularly with prolonged administration, reflecting saturable metabolism. During pregnancy, systemic exposure (C_max and AUC) was modestly reduced, while absorption and distribution remained unchanged. Indomethacin showed minimal age-related variability and linear pharmacokinetics across dosing regimens. In pregnancy, exposure was reduced (lower C_max and AUC) with delayed T_max, indicating slower absorption. Importantly, no PK DDI was observed, as indomethacin parameters remained unchanged except for T_max, which was lower in the interaction scenario compared with baseline, suggesting a faster absorption rate without affecting overall exposure or peak concentration in the presence of phenytoin. Conclusions: Phenytoin and indomethacin exhibit stable and predictable PK across ages and during pregnancy, with dose-dependent characteristics that align with their known metabolic profiles. The absence of clinically relevant DDI supports their safe concomitant use. These findings provide preliminary reassuring evidence for clinicians and contribute to a better understanding of their pharmacological behavior in diverse patient populations. Full article

Background: Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder. This study aims to demonstrate the potential of comprehensive polygenic scores (PGSs) as clinical biomarkers for stratifying individuals with ASD and for advancing the understanding of ASD’s heterogeneous etiology. Methods: We calculated 2602 PGSs—representing all publicly available, license-cleared PGSs in the PGS Catalog—for 75 individuals with ASD by utilizing the database of the Tohoku Medical Megabank Birth and Three-generation cohort study. Results: Unsupervised clustering revealed three ASD subgroups. We identified twenty PGSs with the most significant differences among these subgroups as distinctive PGSs for each subgroup. PGS set enrichment analysis associated these distinctive PGSs with different traits in each subgroup: high-density lipoprotein cholesterol measurements, urea measurement, and body mass index. Furthermore, distinctive PGSs indicated consistent genetic predisposition directions: lower high-density lipoprotein cholesterol levels in subgroup 1, higher urea levels in subgroup 2, and lower body mass index in subgroup 3. Conclusions: Comprehensive PGSs extending beyond psychiatry-related traits represent promising clinical biomarkers for identifying ASD subgroups with different genetic predispositions. Such stratification may enhance understanding of heterogenous genetic backgrounds and targeted drug development. Full article

G protein-coupled receptors (GPCRs) are the largest family of diverse receptors in eukaryotic organisms, playing a critical role in modulating human physiology. It therefore comes as no surprise that about 36% of all currently available drugs target this superfamily. When an agonist binds to a GPCR, it induces conformational changes in the receptor that allow it to interact with intracellular proteins. This interaction triggers downstream signaling cascades that alter the cell’s activity. GPCR signaling is complex, as GPCRs transmit signals through coupling with G proteins, arrestins, and numerous other intracellular effectors. Different ligands, receptor subtypes, and cellular environments can result in the activation of distinct signaling pathways. Biased signaling through GPCRs has emerged as a frontier area in pharmacological research efforts towards designing targeted therapeutic interventions and enhancing drug efficacy and safety. This review presents the types of bias associated with GPCRs and the mechanisms underlying biased signaling. Examples of biased ligands and their therapeutic implications will be discussed. In addition, the inherent challenges in measuring signaling bias, and especially the translational gap between in vitro and in vivo assays and clinical outcomes, will be outlined. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with poor survival even after surgical resection. Clinical stages include resectable (R-PDAC), borderline resectable (BR-PDAC), locally advanced, and metastatic disease. Neoadjuvant therapy (NAT)—chemotherapy or chemoradiotherapy before surgery—has emerged as a promising strategy to improve outcomes by increasing margin-negative resection rates and enhancing overall survival. For R-PDAC, surgery followed by adjuvant chemotherapy remains the standard, but NAT may be considered in high-risk patients, such as those with severe pain, elevated CA 19-9, or large tumors. For BR-PDAC, NAT is the primary approach, significantly increasing R0 resection rates and prolonging survival. Common regimens include mFOLFIRINOX and gemcitabine-based combinations. NAT also carries risks, including disease progression during therapy, loss of resectability, and uncertainty in evaluating response. Current tools, such as imaging and CA 19-9, offer limited predictive value. The role of NAT in R-PDAC remains under debate, while its benefits in BR-PDAC are more established. This review summarizes current evidence and guidelines on NAT in PDAC, with a focus on treatment strategies, patient selection, and emerging approaches. Full article

Background: Terminal ileum inflammation and surgical resections impair absorption of vitamin B12 and D in patients with Crohn’s disease (CD) and Ulcerative Colitis (UC). We assessed differences in subclinical deficiencies of vitamin B12 (<350 pg/mL) or D (<50 nmol/L), by lesion localization (namely non-ileal CD, ileal CD, and UC) and surgical resection status (namely no resection, non-ileal small bowel resections, ileocecal resections, and colonic resections) in CD and UC patients. Methods: We analyzed data from 571 patients (17–93 years), with UC (51%) and CD (49%, including 47 non-ileal (8%), 244 ileal-CD (46%)) managed at the University of Missouri Health Care System (Jan 2017–April 2022). Results: Prevalence of vitamin B12 and vitamin D deficiencies was 19% and 83%, respectively. Prevalence of resection was 26%, including 5% with non-ileal small bowel resections, 11% with ileocecal resections, and 10% with colonic resections. CD with ileal involvement was associated with a 3-fold elevated risk of B12 deficiency (p = 0.004), but not vitamin D. Ileocecal resections were associated with a >3-fold increase in both B12 deficiency (OR = 3.53, p = 0.001) and D deficiency (OR = 3.35, p = 0.044). Conclusions: CD patients with ileal involvement and ileocecal resections have an elevated risk of vitamin B12 and D deficiency, and may benefit from adjunctive supplementation. Full article

Background: Neuraxial anesthesia (NA) is increasingly utilized across various surgical specialties, particularly for abdominal procedures, making it a potential alternative to general anesthesia (GA). Methods: This narrative review was conducted following the PRISMA guidelines for systematic reviews to report on the application of NA worldwide and across various surgical fields. Results: The findings indicate that while NA is gaining popularity, its adoption varies significantly by procedure type and specialty. Evidence supporting its use in major abdominal surgeries remains limited, with most studies focusing on pelvic and minor procedures. The emerging concept of awake surgery under NA shows promising potential, as preliminary data suggest benefits in reducing perioperative morbidity and enhancing recovery. Despite these advancements, gaps in the literature highlight the need for further high-quality trials to establish NA as a safe and routine alternative to GA. Conclusions: NA is increasingly explored across different surgical specialties as a feasible and effective option for abdominal procedures. However, despite this growing interest, solid evidence supporting its use in major abdominal surgery remains limited. Full article

Frontotemporal lobar degeneration (FTLD) represents a heterogeneous group of neurodegenerative disorders with overlapping clinical, pathological, and genetic characteristics. Increasing evidence indicates that disease mechanisms begin decades before the appearance of clinical symptoms, highlighting the importance of identifying preclinical and prodromal stages. This review provides a comprehensive synthesis of current knowledge on the complexity of FTLD, emphasizing early detection and intervention strategies. It integrates findings from neuropathological, neuroimaging, fluid biomarker, genetic, and clinical studies in both familial and sporadic forms, with particular attention to gene-specific trajectories, biomarker evolution, and emerging therapeutic approaches targeting presymptomatic and prodromal phases. Recent advances in biomarker discovery and neuroimaging are enabling earlier diagnosis and intervention, offering the potential to delay phenoconversion and preserve brain function. Full article

Background: Cerebrospinal fluid (CSF) shunting remains a crucial intervention in the treatment of paediatric hydrocephalus. Overdrainage syndrome is a well-recognised but potentially severe complication, in which hyperostosis cranii ex vacuo—diffuse thickening of the cranial bones—emerges as an adaptive response to chronic intracranial hypotension. Currently, no established diagnostic criteria exist to reliably identify and classify this phenomenon, nor are there defined strategies to prevent associated complications of reduced intracranial compliance. Objective: This study aimed to characterise the morphoradiological and clinical phenotype of hyperostosis cranii ex vacuo in paediatric patients with long-term shunt dependency and to propose its classification as a fifth subtype of CSF overdrainage syndrome with direct implications for long-term neurosurgical care. Methods: A retrospective observational study was conducted on nine paediatric patients with radiologically confirmed diffuse calvarial thickening secondary to surgical treatment of hydrocephalus. Quantitative morphometric analysis of frontal, parietal, and occipital bones, sella turcica dimensions, and dural enhancement was performed using high-resolution neuroimaging. Clinical records were reviewed for hydrocephalus aetiology, shunt revision history, and neurological impairment. Results: All patients exhibited a mean two-fold increase in age-adjusted calvarial thickness. Premature craniosynostosis was identified in 33.3% of cases. Diffuse pachymeningeal enhancement was noted in all patients with contrast-enhanced imaging. Neurological comorbidities included epilepsy, spastic paraparesis, and features of Chiari type I malformation. Conclusions: Hyperostosis cranii ex vacuo represents a distinct and underrecognised consequence of chronic CSF overdrainage. We propose preliminary diagnostic criteria and a structured management pathway—from radiological recognition through ICP assessment to tiered surgical intervention. Formal recognition of this entity as a fifth subtype of CSF overdrainage syndrome may enhance early diagnosis, improve risk stratification, and guide long-term surveillance of shunted children. Full article

Background: Radiation therapy is a key treatment modality for brain metastases. While providing a treatment alternative, post-treatment imaging often presents diagnostic challenges, particularly in distinguishing tumor recurrence from radiation-induced changes such as necrosis. Advanced imaging techniques and artificial intelligence (AI)-based radiomic analyses emerge as alternatives to help lesion characterization. The objective of this study was to assess the capacity of machine learning algorithms to distinguish between brain metastases recurrence and radiation necrosis. Methods: The research was conducted in two phases and used publicly available MRI data from patients treated with Gamma Knife radiosurgery. In the first phase, 30 cases of local recurrence of brain metastases and 30 cases of radiation-induced necrosis were considered. Image segmentation and radiomic feature extraction were performed on these data using MatRadiomics_1_5_3, a MATLAB-based framework integrating PyRadiomics. Features were then selected using point-biserial correlation. In the second phase, a classification was performed using a Support Vector Machine model with repeated stratified cross-validation settings. Results: The results achieved an accuracy on the test set of 83% for distinguishing metastases from necrosis. Conclusions: The results of this feasibility study demonstrate the potential of radiomics and AI to improve diagnostic accuracy and personalized care in neuro-oncology. Full article