Acute leukemias with chimeric fusion genes involving FET (FUS, EWSR1, and TAF15) family proteins and ETS (E26 transformation-specific)-like transcription factors often present with unique clinical and pathological characteristics. This mini-review aims to summarize the clinical and pathological features of acute leukemia cases harboring rearrangements involving the fused in sarcoma (FUS) or Ewing sarcoma breakpoint region 1 (EWSR1) genes.

An extensive literature review was performed on reported acute leukemia cases with fusions involving FUS or EWSR1. The details of the reported cases, as well as summarized information, are presented.

Rare cases of acute leukemia have been found to harbor either FUS or EWSR1 gene rearrangements with ETS or non-ETS proteins as partners and demonstrate heterogeneous clinical and pathological features. Acute leukemias carrying FUS gene rearrangements present with diverse immunophenotypes and are predominantly, but not exclusively, acute myeloid leukemia (AML), with ERG as the most frequent fusion partner. In contrast, acute leukemias with EWSR1 gene rearrangements more commonly present as B-cell acute lymphoblastic leukemia (ALL) and mixed phenotypic acute leukemia (MPAL), with ZNF384 as the predominant partner. At present, FUS::ERG-positive AML is the only specific entity with a FET::ETS fusion that is formally recognized in the World Health Organization 5th edition hematolymphoid tumor classification (WHO-HEM5) and the International Consensus Classification (ICC) systems. Cytogenetic karyotyping and fluorescence in situ hybridization remain crucial tools for detecting chromosomal translocations in over half of acute leukemias harboring FUS or EWSR1 gene rearrangements. However, a subset of patients may exhibit a normal karyotype and require advanced molecular diagnostic methods. EWSR1-rearranged leukemias can be difficult to distinguish from Ewing sarcoma and therefore require particular attention.

As more cases and additional data become available, it may be justified to expand this category of acute leukemias to include other specific acute leukemia entities with fusions involving FET::ETS, such as FUS::FLI1 and FUS::FEV, in addition to FUS::ERG-positive AML. However, additional data are required to support such subclassification. In contrast, AML cases with EWSR1 rearrangements are exceedingly rare and display considerable variability. Cases of B-ALL or B/myeloid MPAL with the EWSR1::ZNF384 fusion may be more appropriately classified together with other ZNF384-rearranged leukemia subtypes. Advanced molecular diagnostic methods, especially RNA-based next-generation sequencing, are suggested to improve the accurate diagnosis of acute leukemias with FUS or EWSR1 fusions. Additional pathologic workup, particularly immunohistochemical staining with hematopoietic markers, is highly recommended to differentiate EWSR1-rearranged leukemia from Ewing sarcoma.

The optimal surgical management for spontaneous supratentorial intracerebral hemorrhage (SSICH) remains controversial because conventional approaches often fail to balance rapid decompression with effective hematoma evacuation. This study aimed to evaluate the efficacy and safety of new combined surgical strategies (“two-in-one” and “three-in-one”) versus conventional methods for SSICH.

This retrospective cohort study included 451 SSICH patients treated between January 2019 and December 2023. Based on clinical severity, patients were stratified into Group I (non-herniation, n = 374) and Group II (herniation, n = 77). Within each subgroup, patients were further categorized by treatment period: a historical control cohort (2019–2020) receiving conventional surgery, and an intervention cohort (2021–2023) receiving combined strategies (“two-in-one” for Group I; “three-in-one” for Group II). Outcomes included decompression time, hematoma evacuation rate, complications, and six-month functional recovery (Glasgow Outcome Scale/modified Rankin Scale), were compared.

In Group I, the “two-in-one” strategy achieved faster decompression (4.65 min) and a high evacuation rate (92.15%), which was comparable to neuroendoscopy alone (90.58%) and significantly higher than stereotactic aspiration alone (44.55%). This was associated with improved six-month outcomes (poor outcome rates were 39.39%, 54.35%, and 42.86% in Groups I-A, I-B, and I-C, respectively, overall P = 0.034). In Group II, the “three-in-one” strategy demonstrated shorter decompression time (4.73 vs. 37.85 min, P < 0.001) and higher evacuation rates (80.51% vs. 63.50%, P < 0.001) than decompressive craniectomy alone. Logistic regression further supported the prognostic advantage of the “two-in-one” strategy in Group I.

These combined strategies may integrate the advantages of multiple techniques to enable rapid decompression and effective hematoma clearance in SSICH. Prospective studies are warranted.

Steatotic donor livers are highly susceptible to post-transplant dysfunction; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate the role of galectin-3 (LGALS3)-mediated pyroptosis in steatotic liver graft injury and explore its therapeutic potential.

A mouse model of steatotic liver transplantation was established. Graft tissues were subjected to RNA sequencing to identify key regulators. In vitro, LGALS3 was modulated in steatotic hepatocytes under ischemia/reperfusion stress to assess its impact on the NLRP3 inflammasome and pyroptosis. The regulatory mechanism by which LGALS3 modulates NLRP3 ubiquitination was further examined. Finally, the therapeutic efficacy of LGALS3 inhibition was evaluated in an orthotopic liver transplantation model.

Transcriptomic analysis identified LGALS3 as a key upregulated molecule in steatotic grafts, associated with pyroptosis pathways. In vitro, LGALS3 overexpression enhanced NLRP3 inflammasome activation and pyroptotic cell death, whereas LGALS3 knockdown exerted protective effects. Mechanistically, LGALS3 modulated NLRP3 inflammasome activity by regulating its ubiquitination. In vivo, pharmacological inhibition of LGALS3 significantly improved graft function, reduced histological injury, suppressed pyroptosis, and prolonged recipient survival.

This study demonstrates that LGALS3 drives steatotic graft injury by promoting NLRP3-mediated pyroptosis through the regulation of ubiquitination. These findings identify LGALS3 as a promising therapeutic target for improving the outcomes of liver transplantation using steatotic donor organs.

Fast inverse planning in radiosurgery planning is limited by an excessive number of isocenters, which is clinically hypothesized to be driven by the morphological irregularity of the target volume. This retrospective cross-sectional study aimed to empirically evaluate this hypothesis in vestibular schwannoma cases.

Consecutive patients diagnosed with vestibular schwannoma and receiving Gamma Knife radiosurgery in 2023 were included, and their treatment plans designed using the GammaPlan planning system were collected. Morphological irregularity–related parameters, including standard sphericity (SS), volume ratio sphericity (VRS), and the coefficient of variance of diameters (DCV), were calculated based on parameters provided by the system. Basic demographic and clinical data were collected to evaluate their impact on sphericity. The effects of different sphericity assessment methods on common treatment plan parameters were analyzed.

Treatment plans of 280 patients with vestibular schwannoma were collected. The SS, VRS, and DCV of the tumors were 0.85 (0.77–0.91), 0.46 ± 0.16, and 0.22 (0.14–0.34), respectively. Multivariate analysis showed that lesion volume, acoustic neuroma consensus on systems for reporting results grade, and age were significant factors influencing sphericity. All other planning parameters, except prescription dose and homogeneity index, were significantly correlated with sphericity. DCV was more closely correlated with SS than with VRS.

DCV may serve as a simple quantitative metric of target morphological irregularity, showing strong consistency with SS. Incorporating morphological irregularity into Gamma Knife treatment plan evaluation may help improve future planning strategies and support optimization of isocenter utilization.

The current criterion of biochemical response to ursodeoxycholic acid in primary biliary cholangitis is an alkaline phosphatase (ALP) level of ≤1.67 × the upper limit of normal (ULN) after 12 months of treatment. However, a proportion of patients who meet this parameter may still progress to liver decompensation. This study aimed to optimize the clinical management of primary biliary cholangitis by (1) establishing ALP normalization as a core treatment target, (2) identifying early intervention windows, and (3) developing risk stratification criteria.

This multicenter retrospective study included an internal cohort and an external validation cohort. We assessed the prognostic impact of ALP normalization with Kaplan-Meier and Cox regression. Sankey diagrams and segmented Poisson regression analysis mapped dynamic risk transitions to identify critical intervention windows. Predictive performance (sensitivity/specificity/positive predictive value/negative predictive value [NPV]) of Mayo, Paris II, and Toronto criteria for 12-month ALP normalization was compared.

Patients achieving ALP normalization showed significantly higher complication-free survival versus those with ALP 1.0–1.67 × ULN (89.8% vs. 79.8%; P = 0.016). Segmented Poisson regression identified significant change points at 3.73 and 5.5 months for high-to-medium and medium-to-low risk transitions, respectively. Failure to meet the Toronto criteria at month 3 predicted non-normalization with 95% NPV, whereas Paris II criteria at month 6 provided optimal specificity (73%) for identifying patients who failed to achieve ALP normalization.

ALP normalization significantly improves clinical outcomes. Two subgroups demonstrate low normalization probability and warrant early intervention: (1) patients with ALP ≥ 1.67 × ULN after 3 months and (2) those not meeting Paris II criteria by month 6.

Irinotecan is a camptothecin derivative that exerts its antitumor effects after conversion into the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), and it is widely used for the treatment of various advanced solid tumors. However, irinotecan-induced neutropenia (IIN) remains one of its most common and clinically significant hematological toxicities, increasing the risk of infection, treatment interruption, dose reduction, and poor therapeutic outcomes. This review aims to summarize the pathogenesis, risk factors, and management strategies of IIN to provide practical guidance for its clinical prevention and standardized management. Current evidence suggests that IIN is mainly associated with SN-38-mediated topoisomerase I inhibition and mitochondrial injury in hematopoietic stem cells, leading to impaired neutrophil production. The risk of IIN is influenced by irinotecan dosage, UGT1A and transporter gene polymorphisms, baseline patient characteristics, organ function, and concomitant chemotherapy. Preventive and therapeutic strategies include genotype-guided dose adjustment, careful dose optimization, oral alkalinizing agents, granulocyte colony-stimulating factor support, and modulation of intestinal microbiota. In conclusion, IIN is a multifactorial and potentially manageable adverse reaction. Integrating pharmacogenetic testing, individualized dosing, supportive care, and emerging approaches such as microbiota-based interventions may improve the safety and continuity of irinotecan-based chemotherapy.