Search Results (192)

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide belonging to the calcitonin family, discovered as a product of alternative splicing of the calcitonin gene. CGRP has emerged as a pleiotropic signaling molecule with widespread distribution in the central and peripheral nervous systems, particularly within primary sensory neurons. This narrative review synthesizes current knowledge on the CGRP system, integrating recent advances in its molecular structure, gene organization, and post-translational processing with high-resolution structural insights into its heterodimeric receptor complex (CLR-RAMP1) obtained through cryo-electron microscopy. We also include long-term safety data on anti-CGRP monoclonal antibodies, emerging cardiovascular risk signals, and novel therapeutic applications in vestibular migraine and pediatric populations. The intracellular signaling cascades activated by CGRP, including the canonical cAMP-PKA pathway, MAP kinase activation, and context-dependent calcium signaling, are discussed in relation to its diverse physiological functions. These encompass vasodilation, nociception modulation, neurogenic inflammation, gastrointestinal motility, bone metabolism, tissue regeneration, and energy homeostasis. The central role of CGRP in migraine pathophysiology is examined to understand the development of targeted therapies. The current pharmacological landscape is reviewed, including the evolution of small-molecule CGRP receptor antagonists (gepants) through three generations and the four approved monoclonal antibodies targeting CGRP or its receptor, with comparative analysis of their efficacy, safety profiles, and clinical positioning. Beyond migraine, emerging and predominantly preclinical roles of the CGRP system are discussed in chronic pain, osteoarthritis, cardiovascular diseases, sepsis, cancer (particularly bone metastases and tumor microenvironment immunomodulation), and neurodegenerative disorders such as Alzheimer’s disease. In these areas, the available evidence remains heterogeneous and, in most cases, is not yet sufficient to support clinical translation. Finally, future directions are discussed, including the development of stable CGRP analogs, allosteric modulators, and the potential expansion of therapeutic applications into oncology, intensive care medicine, and neuroprotection. Full article

Inflammatory bowel disease (IBD) with an onset in childhood is characterized by a more extensive phenotype, a more aggressive clinical course, and a higher risk of long-term complications, including growth retardation, compared to adult-onset disease. While tumor necrosis factor-alpha (TNF-α) inhibitors are the cornerstone of therapy, achieving sustained remission in children is often hindered by unique pharmacokinetic challenges, such as accelerated drug clearance and a higher propensity for immunogenicity. This review explores the evolving role of therapeutic drug monitoring (TDM), specifically the paradigm shift from reactive to proactive strategies. While proactive TDM remains a subject of debate in adult IBD, emerging pediatric data strongly support its routine use to optimize treatment durability and prevent secondary loss of response. Evidence-based target trough concentrations for pediatric patients are critical for achieving mucosal healing: 8–13 µg/mL at week 6 and >5–7 µg/mL during maintenance for infliximab, and >13–14 µg/mL post-induction for adalimumab. Beyond clinical outcomes, this review emphasizes the economic viability of proactive TDM, which has been shown to reduce total healthcare expenditures by 18–30% by minimizing hospitalizations and avoiding premature treatment switches. By integrating pharmacological data with clinical pathways, proactive TDM serves as an essential tool for personalized medicine, ensuring safer and more cost-effective management of pediatric IBD. Full article

Artificial intelligence (AI) is rapidly transforming cardiovascular medicine, with growing applications in pediatric cardiology. AI techniques, particularly machine learning and deep learning, enable the analysis of complex and heterogeneous data, supporting diagnosis, risk stratification, and clinical decision-making. This paper provides an overview of current AI applications in this field, discusses existing challenges, and explores future perspectives. In pediatric cardiology, AI has shown promising results across multiple domains. In electrocardiography, AI algorithms improve diagnostic accuracy and enable early detection of cardiac conditions, even in asymptomatic patients, while facilitating telecardiology-based care pathways. In cardiac auscultation, AI-assisted digital stethoscopes enhance the distinction between innocent and pathological murmurs, supporting primary care physicians and optimizing referral to pediatric cardiologic centers. Multimodality imaging represents one of the most advanced areas of AI applications. In echocardiography, magnetic resonance and computed tomography, AI improves image acquisition, view classification, and automated quantification, contributing to more standardized and reproducible assessments. Additionally, emerging technologies such as virtual reality, integrated with AI, offer innovative tools for education, surgical planning, and patient-specific modelling. Despite these advances, several limitations remain, including limited availability of large pediatric datasets, challenges in model generalizability and issues related to interpretability and integration into clinical workflows. In conclusion, AI represents a powerful complementary tool in pediatric cardiology, with the potential to improve diagnostic accuracy, optimize healthcare resources and support the transition toward precision medicine. Full article

Background: Cannabis legalization has raised concerns regarding its potential influence on injury patterns, particularly among children. However, evidence on pediatric trauma remains limited. Objective: To examine trends in pediatric trauma incidence, injury mechanisms, healthcare utilization, and socioeconomic characteristics before and after recreational cannabis legalization in Nevada. Methods: A retrospective repeated cross-sectional study of trauma registry data was conducted using pediatric trauma activations recorded between 2013 and 2023. Incidence rates per 100,000 population were calculated using census data. Pre-legalization (2013–2016) and post-legalization (2017–2023) periods were compared using incidence rate ratios (IRRs) and bivariate tests. Socioeconomic status was assessed using the Distressed Communities Index (DCI). Results: Among 1772 pediatric trauma activations, overall incidence remained stable (21.6 vs. 21.4 per 100,000; IRR = 0.99, 95% CI: 0.90–1.09). Post-legalization, motor vehicle collision-related injuries increased (49.3% vs. 41.3%, p = 0.002), while pedestrian injuries declined (25.5% vs. 32.4%). ICU admissions decreased (19.5% vs. 27.3%, p < 0.001), although ICU length of stay increased (5.9 vs. 4.0 days, p = 0.005). A higher proportion of patients originated from less distressed communities post-legalization (p = 0.021), alongside shifts in insurance coverage (p < 0.001). Conclusions: Pediatric trauma incidence remained stable following cannabis legalization in Nevada; however, shifts in injury mechanisms, healthcare utilization, and socioeconomic patterns were observed. Because cannabis legalization was assessed at the population level and individual cannabis exposure was not directly measured, findings should be interpreted as temporal associations rather than causal effects. These findings highlight the need for ongoing surveillance and targeted, equity-focused injury prevention strategies. Full article

Pulmonary vein stenosis (PVS) is a rare and devastating condition affecting infants and children, characterized by progressive intimal hyperplasia, myofibroblast proliferation, and extracellular matrix deposition, leading to pulmonary hypertension and right heart failure. Despite multimodal interventions including surgery and catheter-based approaches, long-term outcomes remain poor due to high rates of restenosis and disease progression. The development of representative animal models has been instrumental in unraveling the complex pathophysiology of PVS and identifying potential therapeutic targets. This review comprehensively examines the evolution of PVS animal models—from large animals to recently established rodent models—and synthesizes insights gained regarding key pathogenic pathways and their therapeutic implications in guiding associated clinical trials in pediatric patients. We discuss evidence supporting mammalian target of rapamycin (mTOR) inhibition, TGF-β, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) targeting, and emerging strategies including fibroblast activation protein (FAP) inhibition and YAP/β-catenin pathway modulation. The recent development of neonatal rat PVS models has accelerated translational research by enabling cost-effective, high-throughput evaluation of candidate therapies. We propose a mechanistic framework integrating these pathways and discuss future directions for precision medicine approaches in PVS. Full article

Background: Antibiotic resistance (ABR) is a critical global health threat, disproportionately affecting low- and middle-income countries (LMICs) where systemic constraints, economic pressures and sociocultural factors drive inappropriate antibiotic use. While quantitative studies describe prevalence patterns, they fail to capture the underlying motivations and contextual barriers influencing prescribing and dispensing behaviors. This systematic review synthesizes qualitative evidence on the perceptions of healthcare professionals, patients, and caregivers regarding antibiotic use and explores the barriers and facilitators for implementing antibiotic stewardship programs in LMIC healthcare settings. Methods: We conducted a systematic review following PRISMA 2020 guidelines, based on a registered protocol in PROSPERO ID: CRD42024583749. Searches were performed in Medline, Embase, Cochrane Library, Web of Science, and Google Scholar for English-language studies published between 2014 and 2024. Qualitative and mixed-method studies examining stakeholder perspectives on antibiotic use and antibiotic stewardship implementation in LMICs were included. Studies were excluded if they focused exclusively on pediatric or neonatal populations, veterinary medicine, or quantitative outcomes without qualitative components. The data were analyzed using thematic analysis to identify and categorize codes and identify themes following methodological quality assessment of included studies using the Critical Appraisal Skills Programme Qualitative Studies Checklist by two independent reviewers. Results: Out of 2214 studies screened, a total of 119 studies from 33 LMICs were included, encompassing over 4000 participants across hospital, primary care, and community settings. Five interlinked themes emerged: (1) antibiotic use as a pragmatic response to diagnostic uncertainty and resource constraints; (2) financial and commercial drivers shaping prescribing and dispensing practices; (3) the disconnect between knowledge, sociocultural norms, and clinical behavior; (4) multi-level structural and professional barriers to antibiotic stewardship implementation; and (5) the critical role of health system vulnerabilities in perpetuating misuse. Conclusions: Inappropriate antibiotic use in LMICs reflects rational adaptations to systemic limitations rather than isolated knowledge gaps. Effective ABS strategies must address structural deficiencies, economic incentives, and sociocultural norms, while integrating context-specific interventions that strengthen health systems and engage all levels of care. The findings should, however, be evaluated in light of the geographic unevenness of the evidence base, the exclusion of non-English and gray literature, and lack of certainty assessments for synthesized themes. Full article

Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular pathways, including lysosomal degradation, mitochondrial oxidative phosphorylation, peroxisomal lipid metabolism, and myelin maintenance. This comprehensive review synthesizes current knowledge regarding the epidemiology, molecular classification, pathophysiology, and emerging therapeutic strategies of major pediatric neurodegenerative disorders. Epidemiological data indicate a “rare-but-many” landscape, where individually uncommon diseases collectively impose a measurable population burden. Mechanistically, disease progression reflects converging processes such as toxic substrate accumulation, impaired autophagy–lysosome flux, mitochondrial bioenergetic failure, oxidative stress, neuroinflammation, and glial dysfunction. Representative groups discussed include lysosomal storage disorders, leukodystrophies, mitochondrial encephalopathies, peroxisomal disorders, and other monogenic neurodegenerative syndromes. Advances in next-generation sequencing, metabolic profiling, and neuroimaging have substantially improved diagnostic accuracy and enabled earlier detection, including through newborn screening programs. Therapeutic paradigms are shifting from primarily supportive care toward mechanism-based interventions, including enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction strategies, and gene therapy approaches. Early molecular diagnosis is increasingly recognized as critical for optimizing outcomes, particularly in disorders amenable to presymptomatic intervention. Continued integration of genomic medicine, standardized epidemiologic surveillance, and translational research will be essential to refine disease classification, improve prognostication, and expand access to targeted therapies. Collectively, pediatric neurodegenerative diseases exemplify the intersection of developmental neurobiology and inherited metabolic dysfunction, underscoring the need for multidisciplinary, precision-based clinical strategies. Full article

Objectives: To evaluate how often pain is assessed and treated in pediatric trauma patients transported by Emergency Medical Services (EMS) to a pediatric emergency department (ED), and to compare current practice with national recommendations of the Polish Ministry of Health for prehospital pediatric pain management. Methods: We conducted a retrospective analysis of EMS and ED documentation for all trauma patients under 18 years of age transported to the Pediatric Teaching Hospital of the University Clinical Center of the Medical University of Warsaw between 1 January and 31 December 2021. A total of 981 patients with injury or suspected injury or burns were included without exclusion criteria. For patients with documented pain scores, we analyzed pain intensity (0–10), the scales used [Visual Analog Scale (VAS), Numerical Rating Scale (NRS), Wong–Baker Faces Pain Rating Scale (FACES)], body region injured, Glasgow Coma Scale (GCS) score, suspected alcohol or psychoactive substance use, and type and route of analgesic administration. We further evaluated non-pharmacological interventions, pain reassessment, and achievement of at least 50% pain reduction, as defined in national guidelines. Statistical analysis included Student’s t-test or ANOVA for quantitative variables and maximum likelihood chi-square tests for qualitative variables (α = 0.05). Results: Pain was assessed in 839/981 (85.5%) patients; 651/839 (77.6%) reported pain, most frequently of moderate intensity. Despite this, only 208/981 (21.2%) patients received analgesics prehospitally. Morphine and paracetamol were the most frequently used drugs, predominantly administered intravenously, while non-opioid monotherapy was commonly used in patients with lower baseline pain scores. Less than half of all patients received any non-pharmacological intervention whatsoever. Pain was reassessed in 734/839 (87.5%) patients, with a mean reassessment time of approximately 10 min; however, in many cases reassessment occurred earlier than the expected onset of analgesic action. Overall, only 29.4% of patients with pain and documented reassessment achieved the recommended ≥50% reduction in pain intensity, and at least 70.2% of the cohort had no documented evidence of treatment fully complying with national recommendations. Conclusions: In this real-world prehospital and ED cohort, pediatric trauma pain remains under-treated, and adherence to national guidelines on opioid-based analgesia and pain reassessment is suboptimal. Further efforts are needed to improve documentation, expand the recommended pharmacological options for mild pain, and strengthen education on guideline-concordant pediatric pain management in EMS. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalization for acute respiratory tract infection (ARTI) in young children. Respiratory viral coinfections are frequently identified in RSV-related ARTIs, yet their impact on disease severity remains controversial and may vary according to the co-pathogen involved. In the context of evolving RSV prevention strategies, a clearer understanding of RSV coinfection phenotypes is needed. Methods: We conducted a multicenter retrospective cohort study of children aged ≤ 5 years hospitalized for ARTI at two Italian tertiary-care pediatric hospitals between 1 September 2022 and 30 April 2025. Children with laboratory-confirmed RSV infection detected by multiplex polymerase chain reaction were included. Patients were classified as having RSV monoinfection, RSV–rhinovirus coinfection, or RSV–non-rhinovirus coinfection. Severe disease was defined as a composite outcome including intensive care unit (ICU) admission, need for respiratory or hemodynamic support, or death. Association between infection status and severe disease was evaluated using a Poisson regression model with robust variance, adjusted for age, sex, and comorbidities. Results: Among 231 RSV-related hospitalizations, 118 (51.1%) were classified as RSV monoinfection, 65 (28.1%) as RSV–rhinovirus coinfection, and 48 (20.8%) as RSV–non-rhinovirus coinfection. Children with RSV–rhinovirus coinfection were older and had shorter hospital stays. Severe disease occurred in 80.5% of RSV monoinfections, 70.8% of RSV–rhinovirus coinfections, and 75.0% of RSV–non-rhinovirus coinfections. After adjustment, neither RSV–rhinovirus coinfection (adjusted risk ratio [aRR]: 0.93; 95% confidence interval [95% CI]: 0.80–1.13) nor RSV–non-rhinovirus coinfection (aRR: 0.99; 95% CI: 0.83–1.18) was associated with increased disease severity compared with RSV monoinfection. Conclusions: RSV–rhinovirus and RSV–non-rhinovirus coinfections were not associated with greater disease severity compared with RSV monoinfection in hospitalized children. These findings support pathogen-specific interpretation of multiplex diagnostic results and inform clinical risk stratification in the era of expanding RSV prevention strategies. Full article

Background/Objectives: Inflammatory bowel disease (IBD) management has evolved from conventional therapies to advanced biologics and targeted small molecules; however, clinical practice often relies on empirical treatment sequencing rather than individualized approaches. The heterogeneity of IBD phenotypes, variable treatment responses, and expanding therapeutic options necessitate a shift toward precision medicine. This review aims to synthesize current evidence on personalizing IBD therapy and provide an implementation framework for clinical practice. Methods: A narrative review was conducted encompassing peer-reviewed literature, recent network meta-analyses, and clinical guidelines. Evidence was gathered on treat-to-target strategies, therapeutic drug monitoring (TDM), clinical decision support systems, artificial intelligence applications, multi-omics platforms (genomics, transcriptomics, microbiome, metabolomics), advanced imaging modalities, and special populations including pediatric patients and pregnant women. Results: Treat-to-target strategies incorporating endoscopic and biochemical endpoints improve long-term outcomes when individualized to patient-disease factors. TDM-guided optimization enhances biologic efficacy and reduces immunogenicity. Emerging AI tools and multi-omics platforms show promise in predicting treatment response and patient stratification. Network meta-analyses provide comparative effectiveness estimates guiding advanced therapy selection in both Crohn’s disease and ulcerative colitis. Implementation of precision medicine frameworks remains constrained by regulatory, economic, and technical barriers. Conclusions: Personalizing IBD therapy through integration of precision medicine tools, patient-specific factors, and comparative effectiveness data represents the future of IBD management. Overcoming implementation barriers through standardized frameworks and multidisciplinary collaboration is essential to translate these advances into routine clinical practice. Full article

The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the “collateral damage” of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase IIβ inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools—specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping—has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity. Full article

Growth impairment is a clinical manifestation frequently observed in pediatric patients with cardiomyopathy associated with various inherited disorders, including RASopathies, lysosomal storage diseases, neuromuscular disorders, and metabolic conditions. In this narrative review, we explored the genetic and pathophysiological mechanisms underlying the development of both growth and myocardial impairment in Noonan syndrome (NS)—the most common RASopathy—Duchenne and Becker muscular dystrophies, Pompe disease, mucopolysaccharidoses, and mitochondrial diseases. For each condition, we described the cardiac and growth phenotypes, focusing on epidemiology, clinical implications, and disease-specific therapeutic strategies. In the era of precision medicine, innovative etiologic treatments targeting the underlying molecular mechanisms have emerged. Therefore, elucidating the molecular pathways responsible for growth impairment in pediatric inherited cardiomyopathies remains essential for optimizing multidisciplinary management and improving patient outcomes. Full article

Background/Objectives: Topical treatment efficacy is fundamentally dependent on effective delivery of the active pharmaceutical ingredient and its compatibility with the compromised skin barrier. Many commercially available industrial formulations contain poorly tolerated excipients or lack essential therapeutic combinations, frequently leading to complex polypharmacy and reduced patient adherence. In contrast, magistral galenic preparations offer a degree of therapeutic personalization unmatched by standardized products, positioning the compounding laboratory as a strategic resource in dermatological care. This analysis aims to identify and evaluate ten indispensable magistral formulations selected based on their high clinical frequency and the absence of equivalent, globally available commercial alternatives. Materials and Methods: Each formulation was according to four strategic pillars: (i) dosage customization, (ii) excipient modification (removing allergens like parabens or fragrances), (iii) synergistic ingredient association, and (iv) vehicle optimization. The dermatological conditions addressed include pediatric scabies, melasma, hidradenitis suppurativa, and autoimmune mucosal diseases. Key selections include Kligman’s formula for hyperpigmentation and personalized trichological preparations. Results: The identified “top 10” magistral formulation reveals significant gaps within the standardized pharmaceutical market. In pediatric scabies (specifically patients < 15 kg), benzyl benzoate and precipitated sulfur demonstrate superior efficacy over permethrin, addressing emerging resistance patterns. For acute inflammatory dermatoses, Hoffmann Paste and Lime Liniment provide effective protective barriers while neutralizing local acidity. Antiseptic and astringent solutions, including Burow’s and Silver Nitrate (AgNO₃) offer targeted mechanisms and biocidal activity, often absent in standardized topicals. Furthermore, specialized adhesive oral pastes for autoimmune conditions minimizing systemic absorption and associated risks. Conclusions: Magistral compounding represents a cornerstone of precision medicine in dermatology enabling tailored therapies that bridge critical gaps left by standardized formulations, particularly in complex cases and vulnerable populations. Full article

The underlying metabolism of tumor cells in gliomas has become an area of focus secondary to the difficulties in diagnosis and treatment of these tumors. Heterogeneity in both molecular and phenotypic features of tumor cells in pediatric and adult gliomas presents a significant barrier to traditional treatment options such as radiotherapy and chemotherapy. Low-grade gliomas in pediatric and adult populations have relatively high survival rates, while high-grade gliomas have no effective treatments. Recent advancements in metabolomic techniques have uncovered key metabolic abnormalities, such as increased glutamine and creatinine in invasive edge cells and increased purines in viable tumor cells, distinguishing tumor cells in gliomas. Spatial metabolic heterogeneity and metabolic plasticity enable gliomas to adapt to diverse microenvironments and oxidative stress, necessitating precision medicine approaches that target subtype-specific metabolic vulnerabilities. Further, gliomas are characterized by high intratumoral heterogeneity, with metabolic distinctions between core, edge, viable, and necrotic regions. Altered metabolism of tumor cells has an impact on cells within the tumor microenvironment, resulting in a dysfunctional phenotypic state in resident cells. These metabolic abnormalities differentiate tumor cells from the surrounding microenvironment. Enhanced understanding of the metabolic abnormalities in gliomas could inform targeted therapies, increasing therapeutic response in patients. This review synthesizes emerging evidence on intratumoral and intertumoral heterogeneity in gliomas, highlights the role of tumor-immune cell crosstalk in shaping the metabolic landscape, and discusses how these vulnerabilities may be exploited to develop novel therapies. Full article