Search Results (584)

Background: Locally advanced rectal cancer (LARC) management has evolved, but surgery (total mesorectal excision, TME) remains the curative cornerstone. Total neoadjuvant therapy (TNT) and organ preservation (OP) have emerged as response-adaptive strategies. We conducted a state-of-the-art systematic review to critically appraise TNT efficacy, trade-offs, OP feasibility, and emerging biomarkers. Methods: Following PRISMA 2020 guidelines, we searched PubMed, MEDLINE, Scopus, and EMBASE (1990–March 2026) plus ASCO/ESMO abstracts (2020–2026). We included phase II/III randomised controlled trials and major prospective studies evaluating neoadjuvant strategies in non-metastatic LARC. Risk of bias was assessed using RoB 2. Given heterogeneity, a narrative synthesis was performed (PROSPERO: CRD420251252675). Results: From 2847 records, 45 publications (30 trials) were included. For high-risk LARC (cT4, cN2, EMVI+, MRF+, tumour deposits), TNT improves disease-free survival and reduces distant metastases versus standard chemoradiotherapy (RAPIDO, PRODIGE 23, STELLAR, TNTCRT). However, TNT increases locoregional recurrence risk with short-course radiotherapy (RAPIDO: 10% vs. 6%; Polish II: no sustained overall survival benefit). Organ preservation is achievable in expert centres (OPRA: 54% 5-year TME-free survival; OPERA; CAO/ARO/AIO-16), but surgery remains the durable standard for most patients. De-escalation (PROSPECT, CONVERT, FOWARC, OCUM) avoids radiotherapy in low-risk (mrMRF−) patients without compromising local control. Lateral pelvic lymph node involvement (LPLN+) remains a negative prognostic factor even after TNT. Immunotherapy added to TNT (UNION, STELLAR II, SPRING-01, PRECAM) increases pCR rates (40–60%) but remains investigational. ctDNA-guided adaptation (CINTS-R) is feasible but requires mature data. Conclusions: Surgery (TME) is the definitive curative treatment for LARC. TNT is a preferred intensification strategy for high-risk patients, but trade-offs between systemic and local control must be individualised. Organ preservation is safe only for selected patients in expert centres. Immunotherapy-TNT combinations and ctDNA guidance are promising but not yet standard. This review provides an evidence-based roadmap for integrating these advances without losing sight of surgery’s central role. Full article

Aspergillosis encompasses a heterogeneous spectrum of diseases caused by filamentous fungi of the genus Aspergillus, ranging from allergic airway disorders and chronic pulmonary infection to rapidly progressive invasive disease. Aspergillus fumigatus is the predominant pathogen worldwide, although other species, including Aspergillus flavus, Aspergillus terreus and cryptic species, contribute to morbidity and may exhibit intrinsic or acquired antifungal resistance. Early and accurate laboratory diagnosis is essential for timely treatment, appropriate antifungal selection, and stewardship. Traditional culture remains foundational, enabling confirmation of viable organisms, species-level identification, and antifungal susceptibility testing, but sensitivity is limited and turnaround times are prolonged. Non-culture approaches—including galactomannan, β-D-glucan, lateral flow assays, PCR, and next-generation sequencing—enhance diagnostic sensitivity, facilitate early detection, and allow identification of resistance-associated mutations. Optimal diagnostic performance is achieved through integrated, multimodal strategies combining laboratory tests with clinical and radiological findings. In invasive disease, concurrent use of biomarkers and molecular assays improves specificity and positive predictive value, while in allergic bronchopulmonary aspergillosis, immunological markers remain central. Future directions include standardised molecular protocols, novel antigenic and host-based biomarkers, and cost-effective, risk-adapted diagnostic algorithms to refine detection, guide therapy, and improve patient outcomes. Full article

Background: The prognostic significance of histological transformation (HT) in treatment-naive diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate the clinical outcomes and failure patterns of treatment-naive transformed DLBCL (trDLBCL) compared with de novo DLBCL using a large-scale cohort. Methods: We retrospectively analyzed 1735 consecutively enrolled treatment-naive DLBCL patients (118 trDLBCL and 1617 de novo). Propensity score matching (PSM) was performed to balance baseline characteristics. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models. Subgroups were defined by pathology (t-FL vs. t-MZL) and pattern: concurrent (synchronous indolent lymphoma and DLBCL components at diagnosis) vs. pure transformation (DLBCL occurring as the sole histology in patients with a prior history of untreated indolent lymphoma). Results: In the overall cohort, trDLBCL was associated with significantly inferior progression-free survival (PFS) compared with de novo disease and remained an independent adverse prognostic factor in multivariable analysis (HR 1.754, p < 0.001). These findings were confirmed in a 1:1 propensity score-matched cohort (108 pairs), where trDLBCL continued to show worse PFS (p < 0.01), while overall survival (OS) was comparable (p = 0.99). Within trDLBCL patients, the underlying indolent subtype (t-FL vs. t-MZL) did not significantly affect survival (PFS p = 0.17, OS p = 0.35), whereas “pure transformation” was associated with markedly inferior PFS (p = 0.005) and OS (HR 2.56, p = 0.02) compared with concurrent transformation. Failure pattern analysis revealed a higher risk of early progression in trDLBCL (POD24: 30.56% vs. 18.52%; OR 1.94, 95% CI: 1.05–3.56), whereas central nervous system (CNS) involvement was low and comparable between groups (2.78% vs. 0.93%, p = 0.62). Conclusions: Treatment-naive trDLBCL is associated with inferior PFS driven by early progression, whereas OS is comparable due to effective salvage therapies. Pure transformation appeared to define a higher-risk subgroup with inferior disease control, supporting the need for future prospective studies to evaluate risk-adapted frontline, consolidation, or maintenance strategies. Full article

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Long-term survival after solid organ transplantation remains limited by chronic remodeling, fibrosis, vascular complications, and malignancy despite advances in immunosuppressive therapy. Current monitoring strategies primarily rely on functional and immunological parameters that often identify complications only after irreversible injury has occurred. There is a critical need for earlier, mechanistically informative biomarkers that can predict survival outcomes. Many platelet-associated growth factors (PDGF, TGF-β, VEGF, EGF, and IGF-1) are stored in platelet α-granules but can also originate from immune, endothelial, and stromal cells, regulate angiogenesis, extracellular matrix deposition, immune modulation, and tissue repair—processes central to graft adaptation and chronic injury. In this review, we propose the growth factor signaling network as a conceptual framework that potentially links platelet biology, ischemia-reperfusion injury, alloimmune responses, and chronic immunosuppression to sustained growth factor signaling and maladaptive graft remodeling. This framework should be interpreted as a biologically plausible integrative model rather than a fully validated mechanistic pathway in transplant recipients. Importantly, direct clinical evidence linking platelet activation markers (e.g., P-selectin, PF4, β-thromboglobulin) with circulating growth factor levels and long-term transplant outcomes remains limited, highlighting a critical gap in current biomarker research. Emerging clinical evidence suggests their potential prognostic relevance in transplant outcomes. Elevated TGF-β levels have been associated with increased risk of opportunistic infections, while early postoperative IGF-1 concentrations predict short-term survival. Increased VEGF-A levels correlate with primary graft dysfunction and cardiac allograft vasculopathy, while PDGF isoforms contribute to fibrotic and vascular progression across transplanted organs. However, their clinical applicability is limited by methodological variability and lack of large-scale validation. Rather than serving solely as markers of rejection, platelet-associated growth factors may reflect dynamic processes involved in transplant remodeling and mortality risk. Incorporating growth factor profiling into multiparametric survival prediction models may improve early risk stratification and support precision post-transplant management strategies. Full article

Background/Objectives: Skeletal Class II malocclusion due to mandibular retrusion is frequently treated with functional appliances, yet their impact on temporomandibular joint (TMJ) structures, specifically the articular disc, remains debated. This systematic review aimed to critically assess quantitative morphological and positional TMJ changes (disc, condyle and glenoid fossa) evaluated with CBCT or MRI in growing skeletal Class II patients treated with functional appliances and to explore whether these changes are associated with the onset or prevention of temporomandibular disorders (TMDs). Methods: The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251028803). Electronic searches were performed in PubMed, Scopus, Web of Science, Cochrane Library, and Embase from inception to December 2025, complemented by manual screening. Inclusion criteria comprised controlled clinical studies in patients aged 8–16 years with skeletal Class II malocclusion due to mandibular deficiency, treated with removable or fixed functional appliances, with pre- and post-CBCT/MRI quantitative TMJ assessment. Risk of bias was evaluated using RoB 2 (RCTs) and ROBINS-I (non-randomized studies); overall certainty was appraised with GRADE. Results: From 937 records, 8 studies met the inclusion criteria. Articular disc outcomes were reported in fewer studies: disc position/morphology was generally stable, and when changes were observed they were favourable (partial improvement/normalization in selected cases). Importantly, no included study reported new treatment-induced disc displacement or new-onset TMD symptoms at the end of treatment. Across studies, the most consistent findings concerned condylar adaptations, commonly described as anterior and/or superior positional changes and remodelling of the condyle–fossa unit. Evidence certainty was limited by heterogeneity and methodological constraints, resulting in low to very low confidence for several outcomes. Conclusions: Functional appliance therapy in growing skeletal Class II patients may be associated with TMJ adaptations, predominantly involving the mandibular condyle, while limited available data may suggest disc stability and no reported short-term clinical TMD onset in included controlled studies. However, due to the limited and heterogeneous evidence base, these findings should be interpreted cautiously, and well-designed prospective studies with standardized 3D imaging outcomes and longer follow-up are needed, particularly for disc-specific endpoints. Full article

Background: Although survival rates for patients with malignant bone tumors have improved significantly, complications following tumor resection and limb-sparing reconstruction remain a major clinical challenge, particularly in young individuals. Intercalary resection often results in large bone defects, necessitating complex reconstructions. Fibula grafts offer biological advantages; however, their long-term outcomes, especially regarding mechanical complications and comprehensive patient-reported well-being, require further detailed exploration, particularly in cohorts utilizing non-vascularized grafts. Objective: This retrospective study evaluated the complication rates, bone hypertrophy, limb function, and quality of life following non-vascularized fibular graft reconstruction for malignant bone tumors in a single-center cohort. This study offers insights into long-term success and patient well-being, with a particular focus on correlations with systemic therapy and defect size, factors that remain insufficiently explored in the current literature. Methods: In this single-center retrospective study, twenty-four non-vascularized fibular grafts were used to reconstruct intercalary bone defects following malignant tumor resection. Complications were categorized using the Clavien–Dindo classification. Graft hypertrophy was evaluated according to the method described by Weiland and de Boer. Functional outcomes were assessed using the MSTSs and TESSs, while quality of life was measured using the SF-36 questionnaire. Notably, the cohort analyzed represents a relatively large single-center series focusing exclusively on the outcomes of non-vascularized fibular grafts. Results: Our findings revealed significant rates of mechanical complications, with osteosynthesis material failure occurring in 50.0% of cases, pseudarthrosis in 47.6%, and fractures of the fibular grafts in 38.1% of cases. Importantly, there were significant correlations between mechanical complications and systemic therapy (p = 0.017), as well as between defect size and fractures (p = 0.013), identifying critical risk factors. Despite these considerable complication rates, patients achieved satisfactory limb function (MSTS: 74 ± 17; TESS: 83 ± 15) and quality of life scores comparable to national norms, with notably higher mental health indices, highlighting their psychological resilience. Conclusions: Non-vascularized fibular graft reconstruction, despite high mechanical complication rates, significantly facilitates long-term functional recovery and psychological well-being. These findings emphasize the necessity of risk-adapted surgical strategies and long-term follow-up protocols to mitigate complications, optimize long-term function, and ultimately advance patient-centered care. Full article

Arrhythmogenic cardiomyopathy (ACM) is a genetic myocardial disorder marked by progressive cardiomyocyte loss, fibro-fatty replacement, ventricular arrhythmias, and risk of sudden cardiac death. Traditionally considered a structural and electrical disease driven by desmosomal dysfunction, emerging evidence redefines ACM as an inflammatory cardiomyopathy in which immune activation plays a central role. This review integrates genetic, molecular, experimental, and clinical data to highlight inflammation as a unifying feature of ACM. Desmosomal gene variants impair cell adhesion and also activate cardiomyocyte-intrinsic inflammatory pathways, including nuclear factor of kappa B (NFκB) and glycogen synthase kinase 3β (GSK3β) signaling, promoting cytokine release, immune cell recruitment, and fibrotic remodeling. Preclinical studies suggest inflammation precedes structural changes, indicating it may be an initiating event rather than a secondary response. Clinical and pathological findings support this model, with inflammatory infiltrates, circulating cytokines, and autoantibodies observed across disease stages. These processes often present as episodic “hot phases” resembling myocarditis, thus complicating diagnosis. The inflammatory landscape involves both innate and adaptive immunity, along with stromal and neuronal remodeling, contributing to arrhythmogenesis through gap junction disruption, calcium-handling abnormalities, and fibrosis. Environmental factors such as exercise, stress, and metabolic disturbances further modulate inflammatory pathways and disease expression. Therapeutically, this evolving perspective supports immunomodulatory approaches, including inhibition of NFκB, GSK3β, and cytokine signaling. Early clinical data on immunosuppressive and cytokine-directed therapies are promising, especially during active inflammatory phases, while gene-based strategies specifically address the underlying genetic defects. In conclusion, ACM should be recognized as an inflammatory cardiomyopathy shaped by interactions between genetic susceptibility and immune dysregulation. Integrating genetic and immunologic profiling may improve diagnosis, risk stratification, and treatment, ultimately leading to refined personalized therapeutic strategies. Full article

HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are central to modern antiretroviral therapy (ART) because of their high potency and durable effect on viral suppression. However, drug resistance mutations (DRMs) within HIV-1 IN emerge, which can compromise long-term treatment efficacy. Many distinct DRMs that arise under INSTI therapy have been extensively tabulated in public repositories and literature. However, the timelines over which they emerge, accumulate, and consolidate in patients have not been systematically integrated across clinical and experimental studies. In this review, we synthesize current evidence on the temporal evolution of DRMs within HIV-1 IN by examining mutational kinetic data from viruses derived from people living with HIV/AIDS (PLWH) and from in vitro selection experiments. We compare experimental timelines to recent computational predictions derived from Potts-based fitness landscapes coupled with kinetic Monte Carlo simulations and identify reproducible kinetic classes that distinguish fast-, intermediate-, and slow-emerging DRMs. Rapidly emerging DRMs such as E92Q and N155H typically appear early under drug pressure and often represent low-barrier adaptive responses, whereas the most clinically consequential mutations, such as Q148H/K/R, G140A/S, and E138K, arise only after extended therapy and generally require compensatory mutational backgrounds to persist. Although absolute emergence times vary substantially between in vivo and in vitro systems, consistent temporal trends across datasets support the existence of underlying epistatic constraints that shape drug resistance evolution. Understanding DRM timelines is clinically relevant because it provides a framework for interpreting resistance detected at virological failure, informs optimal timing of resistance testing, and may enable earlier identification of high-risk evolutionary trajectories before durable resistance is established. Full article

Background/Objectives: Eravacycline is a fluorocycline antibiotic increasingly used for drug-resistant or difficult-to-treat infections, including off-label indications, with limited real-world clinical data. This study aimed to characterize the effectiveness, safety, and overall risk-benefit profile of eravacycline using an adapted Desirability of Outcome Ranking (DOOR) framework. Methods: We conducted a retrospective, single-center observational study of adult patients who received ≥48 h of eravacycline at an academic medical center between May 2022 and October 2023. Clinical response was assessed at the end of therapy, alongside 30-day all-cause mortality. Treatment-emergent adverse events (TEAEs) were recorded and normalized per 100 eravacycline-days. An adapted DOOR framework integrated efficacy, toxicity and mortality into an ordinal composite outcome, with analyses stratified by pathogen and site of infection. Results: A total of 140 patients contributed 151 eravacycline courses. Intra-abdominal (41.7%) and lower respiratory tract infections (27.8%) were the most common indications. Treatment success was observed in 69.5% of courses, while 30-day all-cause mortality was 23.6%. TEAEs occurred in 52.3% of courses and frequently led to eravacycline discontinuation. Exposure-normalized TEAE rates were highest in shorter courses, with gastrointestinal intolerance predominating early, while hepatoxicity and coagulation abnormalities were more frequent with intermediate treatment durations. DOOR analysis demonstrated highly desirable outcomes in 48.3% of courses, with more favorable profiles observed in carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant Enterococci (VRE) and nontuberculous mycobacteria (NTM) infections. Bloodstream infections were associated with less desirable outcomes. Conclusions: Eravacycline demonstrated meaningful real-world activity across complex infections but was limited by frequent toxicity. The DOOR framework provided a patient-centered context for organism- and site-specific risk-benefit assessment. Full article

Background and Objectives: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin malignancy associated with high rates of recurrence and disease-specific mortality. Although adjuvant platinum–etoposide chemotherapy is used in high-risk disease, the optimal number of treatment cycles has not been established. Materials and Methods: This multicenter retrospective cohort study included 104 patients with resected high-risk MCC (pathological stage IIB–III) treated at Israeli medical centers between September 1985 and February 2021. Patients were assigned to one of three treatment groups: radiotherapy alone, four cycles of platinum–etoposide plus radiotherapy, or six cycles of platinum–etoposide plus radiotherapy. The chemotherapy regimen consisted of cisplatin or carboplatin combined with etoposide in 21-day cycles, with the first two cycles administered concurrently with radiotherapy. Primary endpoints were disease-free survival (DFS) and overall survival (OS), analyzed using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Results: Four cycles of adjuvant platinum–etoposide combined with radiotherapy were associated with the most favorable survival outcomes at all follow-up time points. Five-year DFS and OS in the four-cycle group were 65% (95% CI: 58–72%) and 75% (95% CI: 68–82%), respectively, compared with 55% and 60% in the six-cycle group, and 40% and 45% in the radiotherapy-only group (p < 0.001). The survival advantage of four cycles over radiotherapy alone was sustained at 10- and 20-year follow-up (p < 0.0001). In patients with stage III disease and nodal involvement, the four-cycle group achieved a median DFS of 93 months and a median OS of approximately 110 months, significantly exceeding outcomes in both the six-cycle and radiotherapy-alone groups. No statistically significant survival benefit from chemotherapy was identified in the small subgroup of patients with stage IIB/T4N0 disease. Conclusions: In patients with high-risk resected MCC, the addition of adjuvant platinum–etoposide chemotherapy to radiotherapy significantly improves DFS and OS, with the greatest benefit observed in patients with stage III disease and lymph node involvement. Four cycles represent an optimal treatment duration, delivering durable long-term survival benefit without the need for more prolonged chemotherapy exposure. These findings support a risk-adapted multimodality approach and provide real-world evidence to guide adjuvant therapy decisions in this rare and aggressive malignancy. Full article

Background/Objectives: The NETest is a blood-based, machine learning-enhanced multigene transcript assay designed to detect and monitor neuroendocrine tumors (NETs). This study evaluated the accuracy of the recently validated NETest2.0^® (2025) to (1) detect the presence of disease and (2) assess its utility as a clinically meaningful tool for monitoring NET status across diverse patient cohorts, including post-surgical surveillance, observation (“watch-and-wait”), and treatment settings. Methods: This registry study (NCT02270567) evaluated two objectives. For Objective 1, 1290 samples from 886 patients, of which 404 had paired follow-up samples, were analyzed for concordance between NETest2.0^® and imaging-detectable disease. For Objective 2, paired blood samples (n = 404; median interval 7 months [IQR 4–13.8]) from NET patients across specialized centers were assessed. NETest2.0^® scores were correlated with clinically adjudicated disease status using imaging as the comparator. Cohorts included post-surgical residual disease detection (n = 71), post-surgical recurrence monitoring (n = 44), observation (n = 72), and treatment monitoring (n = 217; somatostatin analogs, PRRT, and other therapies). Analyses were performed by cohort and in aggregate. Results: For Objective 1, NETest2.0^® (cut-off ≥ 50) demonstrated an AUC of 0.96, sensitivity of 91.9%, specificity of 94.9%, PPV of 98.4%, NPV of 77.1%, and overall accuracy of 92.5%. Performance was consistent across tumor grades and sites. For Objective 2, 286 patients (70.8%) were stable, and 118 (29.2%) had progression or recurrence. NETest2.0^® score changes correlated significantly with outcomes: scores decreased in stable patients (median −14.6%) and increased in progressive disease (median + 15.4%; p < 0.0001). Any increase (>0%) in score was associated with progression. Diagnostic performance for detecting progression reached a sensitivity of 78.0%, specificity of 98.3%, PPV of 91.1%, NPV of 90.2%, and accuracy of 83.9%. Conclusions: NETest2.0^® accurately detects disease and provides a clinically actionable tool for monitoring NETs. Its high specificity and predictive performance support risk-adapted surveillance, potentially reducing unnecessary imaging while identifying early progression across diverse clinical settings. Full article

Atezolizumab–bevacizumab is established as first-line therapy for unresectable hepatocellular carcinoma (HCC) based on phase III randomized evidence. Although overall safety outcomes were acceptable in the registration trial, the risk of gastrointestinal (GI) and variceal bleeding remains a clinically relevant concern, particularly in patients with cirrhosis and portal hypertension. Differences between trial-based safety estimates and observational data necessitate a focused evaluation of hemorrhagic risk in this setting. Randomized trial data indicate low rates of high-grade bleeding under protocol-driven endoscopic screening and predefined eligibility criteria. In contrast, real-world cohorts report higher incidences of GI and variceal hemorrhage, especially among patients with prior bleeding, untreated or high-risk varices, reduced hepatic reserve, and extensive portal vein tumor thrombosis. Pooled analyses confirm an increased prevalence of bleeding with atezolizumab–bevacizumab compared with non-antiangiogenic systemic therapies, although event rates vary across studies due to differences in patient selection and bleeding definitions. Severe and fatal hemorrhage occurs in a minority of cases and is concentrated in clinically high-risk subgroups. Bleeding during atezolizumab–bevacizumab therapy is influenced by baseline portal hypertension severity, hepatic functional status, and tumor-related vascular involvement. Trial-derived safety data reflect outcomes under controlled conditions and may underestimate risk in broader populations. Structured baseline assessment, endoscopic evaluation, and risk-adapted portal hypertension management are integral to clinical implementation. Prospective studies incorporating standardized hemorrhage definitions and predefined risk stratification frameworks are required to refine patient selection and optimize safety in routine practice. Full article

Background: Femoral pseudoaneurysms are clinically heterogeneous, with substantial variability in anatomical features and patient-related bleeding risk. Standard treatment algorithms may be inadequate, particularly in patients receiving anticoagulation or presenting with altered coagulation profiles. A personalized, risk-adapted interventional strategy may optimize outcomes while preserving procedural safety. This study compares ultrasound-guided compression with endovascular and percutaneous therapies and evaluates the safety of minimally invasive approaches across different risk profiles to support individualized management. Methods: This single-center retrospective cohort study included 65 consecutive patients treated for femoral pseudoaneurysms between January 2019 and May 2025. Treatment modalities comprised ultrasound-guided compression, endovascular embolization (coils, covered stents, NBCA–Lipiodol), percutaneous glue injection, and hybrid approaches. Primary endpoints were technical and clinical success. Safety was assessed using pre- and post-procedural INR, platelet count, and hemoglobin levels. High-risk status was defined as ongoing anticoagulation or antiplatelet therapy, INR > 1.5, or platelet count <50 × 10⁹/L. Results: Endovascular and percutaneous approaches achieved significantly higher technical (100% vs. 68.5%, p = 0.006) and clinical success rates (100% vs. 77.8%, p = 0.009) compared with ultrasound-guided compression. In minimally invasive cohorts, INR and platelet counts remained stable after treatment, while hemoglobin showed an expected post-procedural decrease (p < 0.001). High-risk patients demonstrated technical success rates comparable to standard-risk patients, with no significant differences in laboratory trends. Favorable outcomes were observed across different embolic materials. Conclusions: Endovascular and percutaneous therapies provide superior effectiveness compared with ultrasound-guided compression while maintaining a reassuring safety profile, even in patients at increased bleeding risk. These findings support a personalized, patient-tailored interventional approach based on individual anatomical and clinical characteristics. Full article

Acute lymphoblastic leukemia (ALL) is a genetically and epigenetically heterogeneous malignant disease characterized by different subtypes with varying sensitivities to conventional chemotherapy. Despite significant improvements in survival rates, relapse remains the primary cause of treatment failure, often associated with intrinsic or acquired drug resistance. First-line therapy at diagnosis represents a major determinant of relapse in ALL. In this study, we performed a transcriptome and drug response profiling analysis to identify subtype-specific cell surface proteins that are overexpressed in patients with poor response to induction therapy. We summarize the current state of knowledge regarding chemotherapy responses, resistance mechanisms to standard cytostatic drugs and the increasing importance of cell biomarkers as predictors of an adverse disease course and potential therapeutic targets. We discuss the results of clinical and molecular studies linking specific genomic alterations—such as KMT2A-rearrangements, Ph-like, DUX4-rearrangements and T-ALL—to drug resistance and highlight surface antigens like CSPG4, HER2, MCAM and ROR1 that define high-risk leukemia phenotypes. The integration of transcriptomic, immunophenotypic and drug response data could enable a new generation of risk-adapted, surface-directed strategies for relapse treatment in ALL. Our analysis therefore provides subtype-specific predictive therapeutic targets for relapse treatment in ALL. Full article