Search Results (13,381)

Micro/nanorobotics is emerging as a promising biomedical technology because of its precision, minimal invasiveness, multifunctionality, and potential to mitigate systemic adverse effects. At these ultraminiaturized scales, unique physical constraints necessitate design principles and actuation strategies distinct from those of conventional robotic systems, making material choice, structural design, propulsion mechanisms, and fabrication methods central to overall performance. In this review, we examine recent trends in micro/nanorobot development, with particular emphasis on the advantages of employing hydrogels and the current technical limitations associated with their use. Magnetic, chemical, acoustic, optical, and biohybrid propulsion strategies are comparatively analyzed, together with the material requirements and biological compatibility associated with each approach. Representative applications in drug delivery, tissue regeneration, and cancer therapy are further discussed to highlight the broad medical potential of these systems. Finally, remaining challenges related to material limitations, actuation efficiency, biocompatibility, and manufacturing scalability are identified, and future directions toward clinical translation and practical deployment are outlined. Overall, this review provides an integrated perspective on how hydrogel properties, actuation physics, fabrication strategies, and translational considerations collectively shape the development of more adaptive, biocompatible, and clinically relevant microrobotic systems. Full article

Background/Objectives: Asthma, one of the most common chronic diseases in childhood, and acute bronchiolitis, a leading cause of hospitalization in early childhood, remain significant contributors to morbidity and mortality. Methods: This retrospective cohort study evaluated the efficacy and safety of intravenous magnesium sulfate (IV MgSO₄) as a secondary treatment in pediatric patients with acute asthma exacerbation unresponsive to first-line therapy and in patients with acute bronchiolitis unresponsive to supportive care. A total of 450 patients aged 6 months to 18 years, including 252 with acute asthma exacerbation and 198 with acute bronchiolitis, were included. Results: Significant improvements in peripheral capillary oxygen saturation were observed after IV MgSO₄ administration in both groups (p < 0.001). In the acute asthma exacerbation group, IV MgSO₄ also significantly reduced tachypnea compared to the acute bronchiolitis group (p < 0.001). No adverse effects related to IV MgSO₄ were observed. Conclusions: These findings suggest that IV MgSO₄ may be both beneficial and safe as an early secondary treatment in acute asthma exacerbations. Full article

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano–bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future. Full article

Individuals with cystic fibrosis (CF) face significant treatment burdens, and as life expectancy has increased, there is growing emphasis on their psychosocial well-being. Prevalence data indicate that approximately one-quarter to one-third of individuals with CF and their caregivers experience clinically significant anxiety or depression. Specifically, pooled global estimates report an anxiety prevalence of 24.9% (95% CI: 20.8–28.9%) and depression prevalence of 13–33% in adults with CF, with caregivers experiencing even higher rates (anxiety: 35–38%; depression: 20–35%). Depression is independently associated with a nearly twofold increase in mortality risk and substantially higher healthcare costs, underscoring its prognostic significance. These mental health comorbidities are consistently associated with reduced treatment adherence, diminished quality of life, increased healthcare utilisation, and decreased survival. Accordingly, psychological well-being has emerged as a key patient outcome that directly shapes engagement with care and the effectiveness of long-term CF management. International CF guidelines now recommend routine mental health screening within multidisciplinary care frameworks. Evidence-based interventions include cognitive–behavioural therapy (CBT), which is endorsed as a primary treatment, although access remains limited, and stepped-care pharmacotherapy, primarily selective serotonin reuptake inhibitors (SSRIs), for moderate to severe symptoms. Telemedicine and other digital health approaches have expanded access to psychological support, with remote CBT and online programmes demonstrating feasibility and symptom improvement during the COVID-19 pandemic and beyond. The advent of CFTR modulator therapies has significantly altered clinical outcomes, enabling many patients to achieve improved lung function and daily functioning. Nevertheless, mental health challenges persist, as individuals navigate new identity shifts and anxieties despite enhanced physical health. The implementation of mental healthcare remains inconsistent; while screening rates have increased, timely follow-up and integrated psychosocial support are frequently insufficient across care centres. This narrative review highlights the ongoing need to integrate mental health management into CF care to optimise adherence, patient outcomes, and long-term survival in the current therapeutic landscape. Full article

Radiotherapy remains one of the main pillars of cancer treatment and is used in more than half of all oncological patients. Despite continuous technological improvements, ionizing radiation inevitably causes damage to surrounding healthy tissues, leading to acute and chronic complications affecting multiple organs, including the skin, mucosa, heart, lungs, bones and gastrointestinal tract. Radiation-induced injuries significantly impair patients’ quality of life, limit therapeutic doses, and represent a major unmet clinical challenge. Hydrogels have emerged as promising biomaterials for managing radiation-induced damage due to their high content of water, tunable mechanics, and ability to mimic the extracellular matrix. Recent innovations have introduced functional systems, including stimuli-responsive, injectable, and bioactive hydrogels, capable of delivering antioxidants, growth factors, or living cells. Unlike traditional material-based reviews, this work proposes a novel classification framework based on the hydrogel’s mechanism of action within the pathophysiology of radiation injury. We evaluate how specific designs, such as ROS-scavenging matrices, barrier-forming injectable shields, and bioactive delivery vehicles, address distinct phases of inflammation and fibrosis. By providing a comprehensive overview of radiation-induced injuries across different organs, this review summarizes current hydrogel-based strategies for both prevention and therapy. We highlight the potential of these mechanistically aligned systems to protect healthy tissues, suppress chronic inflammation, and promote effective tissue regeneration. Full article

Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Growing evidence indicates that metabolic syndrome components, including obesity, insulin resistance, and hyperglycemia, contribute to PCa development, and progression to more aggressive form. At the same time, standard treatments such as androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) significantly improve oncologic outcomes but are associated with adverse metabolic effects, including increased fat mass, insulin resistance, and sarcopenia, potentially worsening patients’ overall metabolic profile and quality of life. Tumor progression in PCa is strongly driven by androgen receptor (AR) signaling, which is closely linked to cellular metabolic reprogramming, highlighting metabolism as a potential therapeutic target. Aim: The aim of this study was to evaluate and synthesize current evidence on the role of the ketogenic diet (KD) in PCa, with particular emphasis on its interaction with hormonal therapies, underlying metabolic and endocrine mechanisms, and its potential application as an adjunctive strategy in integrated oncologic care. Results: The KD, characterized by high fat and very low carbohydrate intake, induces a metabolic state of ketosis that reduces circulating glucose, insulin, and insulin-like growth factor 1 (IGF-1), potentially counteracting metabolic alterations associated with PCa and its treatments. Preclinical studies consistently demonstrate that carbohydrate restriction and KD can slow tumor growth, modulate key oncogenic pathways such as PI3K/AKT/mTOR, reduce systemic insulin signaling, and enhance survival in prostate cancer models. Additionally, emerging evidence suggests possible synergistic effects when KD is combined with standard therapies, including ADT and immunotherapy. Clinical data, although limited, indicate that low-carbohydrate dietary interventions may improve metabolic parameters and could delay biochemical progression, as suggested by increased prostate-specific antigen (PSA) doubling time. However, results across studies remain heterogeneous, and robust evidence on long-term oncologic outcomes is lacking. Conclusions: Overall, the KD represents a promising but still experimental strategy in PCa management, requiring careful nutritional supervision to avoid adverse effects such as unintended weight loss or sarcopenia. Further well-designed randomized clinical trials are needed to clarify its safety, efficacy, and role in routine clinical practice. Full article

Background/Objectives: Gliomas are among the most aggressive primary brain tumors in adults, characterized by profound molecular heterogeneity and poor response to conventional therapies. Immunotherapy has transformed outcomes in several cancers, yet glioma remains largely refractory, due in part to an immunosuppressive tumor microenvironment. Post-transcriptional regulation of gene expression is increasingly recognized as a key mechanism controlling immune cell function in tumors. Regnase-1, an endoribonuclease regulating the stability of inflammation- and immunity-related mRNAs, is a central modulator of immune responses; however, its role in glioma progression and immune modulation remains poorly understood. This study aimed to evaluate Regnase-1 expression in glioma and investigate its association with tumor grade, prognosis, and immune microenvironment characteristics. Methods: Regnase-1 transcript levels were evaluated by RT-PCR in tumor samples from 40 Moroccan glioma patients and validated using transcriptomic data from The Cancer Genome Atlas (TCGA, n = 672) and the Chinese Glioma Genome Atlas (CGGA, n = 959). Bioinformatic analyses and statistical assessments were performed using established pipelines. Results: Regnase-1 expression was significantly elevated in glioblastoma, IDH-wildtype tumors, and higher tumor grades, correlating with poorer overall survival, and emerging as an independent prognostic factor in the CGGA cohort. High Regnase-1 expression was associated with enrichment of pathways related to angiogenesis, hypoxia, invasion, and immune evasion. Tumors with elevated Regnase-1 showed reduced infiltration of effector immune cells (CD8⁺ T cells, Th1 cells) and increased presence of immunosuppressive populations, including regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages. Single-cell analyses further highlighted exhausted CD8⁺ T cells and regulatory T cells as major populations linked to Regnase-1 expression. Notably, Regnase-1 expression also exhibited strong positive correlations with multiple inhibitory immune checkpoint pathways. Conclusions: Elevated Regnase-1 expression defines an aggressive, immunosuppressive glioma phenotype and is associated with poor prognosis, supporting its potential as a prognostic biomarker and a target for immunomodulatory strategies. Full article

Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide despite advances in screening, navigational bronchoscopy, and systemic therapies. Diagnostic and therapeutic limitations persist, including uncertainty regarding intraprocedural tissue adequacy during biopsy sampling and constraints of existing ablative modalities for tumors located near critical thoracic structures. This review examines two emerging technologies: Full-Field Optical Coherence Tomography-based Dynamic Cell Imaging (DCI) and monopolar biphasic Pulsed Electric Field (PEF) ablation as complementary emerging technologies that may address these gaps. The Van Gogh™ Microscopy System (CellTivity Scientific, Inc.) utilizes DCI to enable real-time visualization of cellular metabolic activity without tissue destruction, providing functional information regarding tissue viability and microstructural morphology. The Aliya^® PEF ablation system (Galvanize Therapeutics, Inc.) delivers biphasic high-voltage electrical pulses that induce non-thermal tumor cell death while preserving extracellular matrix architecture, potentially allowing treatment near sensitive thoracic structures such as airways, vasculature, and pleura. Early preclinical studies and initial clinical experience suggest that DCI can facilitate rapid intraprocedural assessment of biopsy adequacy, while PEF ablation may provide reproducible focal tumor destruction with a favorable safety profile near critical structures. Although the current evidence base remains limited to early-phase studies and feasibility trials, the convergence of real-time biologic tissue assessment with structurally preserving ablation technologies introduces the possibility of integrating diagnostic confirmation and local therapy within a single procedural workflow. This review summarizes the mechanistic rationale, emerging evidence, and potential clinical applications of these technologies and proposes a conceptual “See and Strike” framework within these two emerging technologies. The methodological limitations, workflow considerations, and future research directions required to validate this approach are also discussed. Prospective multicenter trials and long-term oncologic outcomes will be necessary before widespread clinical adoption. Full article

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive myeloproliferative neoplasm of early childhood characterized by constitutive activation of the RAS-MAPK signaling pathway. RASopathies are a heterogeneous group of complex genetic disorders arising from germline mutations that dysregulate RAS-MAPK signaling. Noonan syndrome, CBL syndrome, and neurofibromatosis type 1 (NF1) are the three major RASopathies predisposing to JMML. More than 90% of JMML cases harbor germline or somatic mutations in one of five canonical driver genes—PTPN11, NRAS, KRAS, NF1, or CBL—establishing JMML as the prototypical malignant manifestation of RASopathy biology. The fifth edition of the World Health Organization Classification of Tumours reclassified JMML as a myeloproliferative neoplasm while the International Consensus Classification adopted JMML under pediatric and/or germline mutation-associated disorders, introducing a JMML-like category for cases lacking five canonical mutations but harboring emerging drivers such as SH2B3::LNK alterations and ALK::ROS1 fusions. The distinction between germline and somatic mutations profoundly influences prognosis: e.g., germline PTPN11-associated myeloproliferations and many germline CBL cases undergo spontaneous resolution, whereas somatic PTPN11- and NF1-mutated JMML is more aggressive and requires prompt allogeneic hematopoietic stem cell transplantation. DNA methylation profiling has emerged as the most robust prognostic framework, with consensus defining high-, intermediate-, and low-methylation subgroups that independently predict outcome. Both genotype and DNA methylation subclassification have been integrated into clinical decision-making, incorporating pretransplant azacitidine, watch-and-wait approaches for favorable-risk patients, and emerging targeted therapies including MEK inhibitors. This review synthesizes recent advances in understanding JMML as a bona fide RASopathy; provides a diagnostic algorithm, molecular landscapes, and prognostic models; and highlights opportunities for molecularly targeted therapeutic intervention. Full article

Artificial intelligence (AI) is increasingly transforming gastrointestinal endoscopy by supporting lesion detection, lesion characterization, quality assessment, and clinical risk prediction. Hemostatic decision-making represents a particularly complex field for AI integration, as therapeutic decisions are often made rapidly in the presence of active bleeding, impaired visualization, unstable patients, and variable lesion accessibility. This review critically examines the current evidence for AI-assisted decision-making in gastrointestinal endoscopy and endoscopic hemostasis, with emphasis on gastrointestinal bleeding, prediction of hemostatic therapy requirements, bleeding-risk stratification, rebleeding prediction, transfusion support, and post-procedural monitoring. Available studies suggest that machine learning and deep learning models may outperform conventional scoring systems in selected retrospective or validation cohorts, improve recognition of high-risk lesions, support less experienced endoscopists, and contribute to more individualized management of non-variceal bleeding, variceal bleeding, and capsule endoscopy findings. However, prospective interventional evidence remains sparse, and most available models are limited by retrospective design, single-center datasets, incomplete external validation, black-box decision-making, heterogeneous reporting, workflow barriers, and uncertain cost-effectiveness. AI should therefore be regarded as an adjunctive decision-support tool rather than an autonomous replacement for clinical judgment. Its future value will depend on prospective multicenter validation, explainability, real-time usability, regulatory clarity, post-deployment surveillance, and evidence of improved patient-centered outcomes before widespread implementation in emergency endoscopy practice. Full article

The overdose crisis in North America is increasingly driven by illicitly manufactured fentanyl and other high-potency synthetic opioids, which are associated with severe and unpredictable opioid-induced respiratory depression (OIRD). Current pharmacologic strategies to prevent fatal overdose have largely emphasized downstream rescue through opioid antagonism (e.g., naloxone), leaving limited attention to upstream pharmacologic modification of respiratory risk. In this Opinion article, we argue that buprenorphine should be reframed not only as a treatment for opioid use disorder (OUD), but also as a pharmacologic modifier of OIRD risk in fentanyl-dominant drug markets. Drawing on its partial μ opioid receptor agonism, ceiling effect on respiratory depression, and exceptionally high receptor affinity, we describe how buprenorphine can displace full agonists while limiting respiratory suppression. We further situate this pharmacology within emerging population-level observations from North American fentanyl contexts, suggesting reduced overdose mortality among individuals receiving opioid agonist therapy, particularly buprenorphine. In fentanyl-dominant drug markets, reframing buprenorphine as a modifier of respiratory risk has direct implications for clinical messaging about overdose protection, medication selection for individuals with ongoing illicit opioid use, and policy approaches aimed at reducing opioid-related mortality. Full article

Background/Objectives: Small-cell prostate cancer (SCPC) is a rare, aggressive variant of prostate cancer with poor prognosis, arising “de novo” or through lineage plasticity from conventional adenocarcinoma under androgen receptor-targeted therapies. Characterized by low PSA levels despite high tumor burden and visceral metastases, SCPC poses diagnostic challenges with conventional and PSMA-targeted imaging due to variable tracer uptake. This narrative review aims to evaluate the role of PET/CT tracers in clinical and preclinical settings for SCPC diagnosis, staging, and management. Methods: A systematic literature search was conducted on PubMed and Scopus up to December 2025 using terms “PET OR positron emission tomography AND prostate OR prostatic AND small-cell NOT non-small-cell”. Eight studies (five clinical, three preclinical) on the role of PET/CT imaging in SCPC were included and analyzed for study design, population, tracers, and findings, with comparative evaluation of diagnostic performance across PET tracers. Results: Clinical studies showed that ¹¹C-choline detects progression at low PSA but misses SCPC; ¹⁸F-FDG exhibited a high SUVmax value for distinguishing SCPC from adenocarcinomas with neuroendocrine differentiation, predicting poor survival; ⁶⁸Ga-DOTATATE identified NEPC/SCPC with promising prognostic/therapeutic value for selected cases. Preclinical models evaluated ⁸⁹Zr-tracers targeting DLL3 or CDCP1 (an antigen expressed in aggressive neuroendocrine tumours) and ¹⁸F-BnTP (a target of mitochondrial activity) in SCPC subtypes, focusing on translational imaging. Conclusions: From this review, although still based on limited literature evidence and mostly derived from retrospective and small SCPC sub-cohorts,¹⁸F-FDG PET/CT currently appears as the most reliable tracer for SCPC, aiding tumor detection and prognostication when PSMA/choline imaging fails. In the preclinical setting, DLL3/CDCP1-targeted agents emerge as promising theranostics tools. Multimodal imaging approach and prospective trials are needed for standardization and patient-based SCPC management. Full article

Background/Objectives: In Europe, Pseudomonas aeruginosa is the second most common cause of ventilator-associated pneumonia in intensive care units. Intrinsic antibiotic resistance and acquired carbapenemases can lead to high mortality. To guide more targeted antimicrobial therapy and adequate infection control measures, we performed a multicenter study on the prevalence and genetic basis of carbapenem resistance among P. aeruginosa (CR-PA) across 17 community hospitals in Austria. Methods: During a 3-month period, we collected 621 P. aeruginosa isolates from 560 patients. Antibiotic susceptibility testing was performed according to EUCAST guidelines, and all CR-PA isolates were subjected to whole genome sequencing. Results: Antibiotic susceptibility testing revealed carbapenem resistance in 5.41% (36/621) of the investigated P. aeruginosa isolates. Only 3 produced a carbapenemase (2 Verona Integron-encoded Metallo- ß-lactamases and 1 Imipenemase Metallo-ß-lactamase) and carried a carbapenemase-encoding gene. Among the studied P. aeruginosa isolates there was a high genetic diversity, excluding a single driving epidemic lineage in the included Austrian hospitals. Conclusions: The absence of interhospital clonal dominance suggests that carbapenem resistance emerged independently in different centers, likely driven by local antibiotic selection pressures rather than regional clonal spread. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is a major cause of cancer-related morbidity and mortality, with incidence expected to increase. Liver transplantation is the most definitive curative option for early HCC, but many patients present beyond accepted transplant criteria, including the Milan criteria. Downstaging aims to reduce tumor burden and enable transplantation without compromising long-term outcomes. Methods: We reviewed the literature on liver transplantation, immune checkpoint inhibitors, immunotherapy–locoregional therapy combinations, and immune-related adverse events in HCC. Results: Immunotherapy-based strategies are emerging as downstaging approaches in selected patients. In advanced HCC, immune checkpoint inhibitor combinations have improved objective response rates compared with tyrosine kinase inhibitors, reaching approximately 20–36% in pivotal phase III trials. In the downstaging setting, early data suggest that immune checkpoint inhibitors, particularly with locoregional therapies, can achieve sufficient tumor regression to permit transplantation in patients initially beyond criteria. The ImmunoXXL trial reported successful downstaging and transplantation in all 16 patients treated with atezolizumab–bevacizumab, with 62.5% complete pathological responses, 2-year recurrence-free survival of 90%, and overall survival of 94%. The VITALITY study achieved successful downstaging in 75.6% of patients beyond Milan criteria, with 36.7% undergoing transplantation and 3-year post-transplant survival of 85%. However, pre-transplant immune checkpoint inhibitor exposure carries a clinically relevant risk of acute allograft rejection, reported in approximately 16–28% of transplanted patients. Conclusions: Immunotherapy-based downstaging before liver transplantation is promising but remains non-standard. Its use should be restricted to carefully selected patients within multidisciplinary protocols, as evidence remains limited by small cohorts, heterogeneous regimens, uncertain washout intervals, and rejection risk. Full article