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Objective: The incidence of splanchnic vein thrombosis (SVT) is reported to be <25 times lower than that of deep vein thrombosis and pulmonary emboli, which occur in 70 to 270/100,000 cases in the general population. Current guidelines recommend initial treatment with therapeutic low-molecular-weight heparin followed by a transition to a vitamin K antagonist (VKA) or a direct oral anticoagulant (DOAC) in patients with cirrhosis who develop SVT without severe liver dysfunction. This, however, is based on observational data. This study aimed to evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhosis who present with SVT and receive either a DOAC or a VKA., Methods: This multicenter retrospective cohort study was conducted from December 2021 to November 2022. Patients between the ages of 18 and 75 years with cirrhosis and acute SVT who received either a VKA or a DOAC between July 2019 and July 2021 were eligible for inclusion. The primary outcome was the efficacy of treatment, defined as a new thrombotic event. The secondary outcome was the safety of treatment, defined as the development of major bleeding. Readmission data were followed up at 6 and 10 months. Bivariate analysis was conducted to assess the relationship between the medication groups and each outcome and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at 5% for all of the comparisons., Results: A total of 80 patients from 50 hospitals were included in this study. Sixty-one patients (59.02% male) received DOACs and 19 (57.89% male) received a VKA. Of the patients who received DOACs, 41 (67.21%) received apixaban, one (1.64%) received dabigatran, and 19 (31.15%) received rivaroxaban. The results from the bivariate analysis revealed no significant differences between DOACs and warfarin for both the efficacy (OR 1.46, 95% CI 0.44-4.84, P = 0.53) and safety outcomes (OR 1.03, 95% CI 0.04-26.43, P = 1) at 10 months., Conclusions: The use of DOACs in patients with cirrhosis who present with SVT may be efficacious and safe compared with warfarin. The findings from our study may inform power analyses for well-conducted randomized trials to confirm these findings.

Objectives: International trials have reported conflicting findings on whether the association between age and worse overall survival (OS) among children with Wilms tumor (WT) is due to age as an independent prognostic factor or the observation of more advanced disease at older ages. We sought to further elucidate this relationship using a population-based registry analysis., Methods: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with WT under the age of 20. The association between age and OS was assessed using multivariable Cox proportional hazards regression., Results: In this study, 3463 patients (54% female) were diagnosed with WT between 1975 and 2016. More advanced stage, larger primary tumor size, lymph node involvement, disease requiring radiotherapy, and omission of surgery were associated with worse OS ( P <0.05). More advanced stage, larger primary tumor size, and disease requiring radiotherapy were also associated with older age, whereas bilateral disease was associated with younger age ( P <0.001). On average, each year of age conferred an incremental hazard ratio (HR) of 1.07 (95% CI, 1.01 to 1.12, P =0.018) independent of relevant covariates. The rise in adjusted OS HR was most pronounced after the transitions in diagnosis age from 2 to 3 (HR age 3-15 vs. 0-2 1.77, 95% CI, 1.11 to 2.82, P =0.016) and from 15 to 16 (HR age 16-19 vs. 3-15 2.58, 95% CI, 1.06 to 6.25, P =0.036)., Conclusions: Diagnosis of pediatric WT at an older age was found to be independently associated with worse OS. Although additional prospective studies are warranted to examine tumor biology and other potential correlates, more aggressive treatment of older children based on age, especially as they approach early adulthood, may be considered in the multidisciplinary management of WT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases., Materials and Methods: Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA)., Results: From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P < 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P < 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA., Conclusion: This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG., (Copyright © 2022 Elsevier B.V. All rights reserved.)