Development and validation of comprehensive nomograms from the SEER database for predicting early mortality in metastatic rectal cancer patients.

BACKGROUND: Metastatic rectal cancer is an incurable malignancy, which is prone to early mortality. We aimed to establish nomograms for predicting the risk of early mortality in patients with metastatic rectal cancer. METHODS: In this study, clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database.We utilized X-tile software to determine the optimal cut-off points of age and tumor size in diagnosis. Significant independent risk factors for all-cause and cancer-specific early mortality were determined by the univariate and multivariate logistic regression analyses, then we construct two practical nomograms. In order to assess the predictive performance of nomograms, we performed calibration plots, time-dependent receiver-operating characteristic curve (ROC), decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: A total of 2570 metastatic rectal cancer patients were included in the study. Multivariate logistic regression analyses revealed that age at diagnosis, CEA level, tumor size, surgical intervention, chemotherapy, radiotherapy, and metastases to bone, brain, liver, and lung were independently associated with early mortality of metastatic rectal cancer patients in the training cohort. The area under the curve (AUC) values of nomograms for all-cause and cancer-specific early mortality were all higher than 0.700. Calibration curves indicated that the nomograms accurately predicted early mortality and exhibited excellent discrimination. DCA and CIC showed moderately positive net benefits. CONCLUSIONS: This study successfully generated applicable nomograms that predicted the high-risk early mortality of metastatic rectal cancer patients, which can assist clinicians in tailoring more effective treatment regimens.

Blast phase of chronic myeloid leukemia with concurrent BCR::ABL1 and SET::NUP214: A report of two cases.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm defined by the presence of t(9;22)(q34;q11.2)/BCR::ABL1. Additional chromosomal abnormalities play an important role in the progression to CML. However, the additional fusion gene was rarely reported such as CBFB::MYH11. In this report, we described two cases of the co-occurrence of BCR::ABL1 and SET::NUP214 in CML-BP for the first time, which is associated with poor outcomes during tyrosine kinase inhibitor (TKI) treatment. Meanwhile, we retrospectively analyzed SET::NUP214 fusion transcript of the two cases at initial diagnosis of the CML chronic phase by quantitative RT-PCR, and detected at a ratio of 1.63% and 1.50%, respectively. SET::NUP214 may promote disease progression during the transformation of CML. This study highlights the importance of extended molecular testing at the initial diagnosis of CML-CP at TKI resistance and/or disease transformation.

circPTK2 promotes proliferation, migration and invasion of trophoblast cells through the miR-619/WNT7B pathway in preeclampsia.

It has been shown that the circular RNA (circRNA) circPTK2 modulates many types of diseases. However, the possible functions as well as the molecular mechanisms of circPTK2 in preeclampsia (PE) and their effects on trophoblast are unknown. Herein, we obtained the placental tissues from 20 pregnant women with PE who delivered in the Yueyang Maternal Child Medicine Health Hospital between 2019 and 2021 to serve as the PE group, and a normal group was composed of 20 healthy pregnant women with normal prenatal examinations. The circPTK2 level was significantly reduced in tissues from the PE group. The expression and localization of circPTK2 were verified using RT-qPCR. CircPTK2 silencing inhibited HTR-8/SVneo growth and migration in vitro. To investigate the underlying mechanism of circPTK2 in PE progression, dual-luciferase reporter assays were conducted. It was found that circPTK2 and WNT7B could bind directly to miR-619, and that circPTK2 affected WNT7B expression by sponging miR-619. To conclude, this study identified the functions and mechanisms of the circPTK2/miR-619/WNT7B axis in PE progression. In this way, circPTK2 has the potential to be used both in diagnostic and therapeutic settings for PE.

Erythritol aggravates gut inflammation and anxiety-like behavioral disorders induced by acute dextran sulfate sodium administration in mice.

Erythritol is a widely used sugar substitute in food and beverages with beneficial and detrimental roles in obesity and cardiovascular diseases, respectively; however, its influence on inflammatory bowel disease (IBD) and related behavioral disorders is not well understood. Here, we found that erythritol exacerbated gut inflammation by promoting macrophage infiltration and inducing M1 macrophage polarization, thus increasing gut leakage during colitis triggered by acute dextran sulfate sodium (DSS) treatment. Increased gut permeability can cause neuroinflammation and anxiety-like behavioral disorders. In conclusion, our results revealed a negative role for erythritol in gut inflammation and anxiety-like behavioral disorders induced by erythritol administration in a mouse model of acute colitis, suggesting that erythritol intake control may be necessary for IBD treatment.

LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors.

LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis, at least, in part, through inhibition of let-7 microRNA biogenesis. Here, we report that overexpression of either wild-type (WT) LIN28B or a LIN28B mutant that is unable to inhibit let-7 processing increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts, and drives distant metastases in vivo. Genome-wide chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) and coimmunoprecipitation experiments show that LIN28B binds active gene promoters in neuroblastoma cells through protein-protein interaction with the sequence-specific zinc-finger transcription factor ZNF143 and activates the expression of downstream targets, including transcription factors forming the adrenergic core regulatory circuitry that controls the malignant cell state in neuroblastoma as well as GSK3B and L1CAM that are involved in neuronal cell adhesion and migration. These findings reveal an unexpected let-7-independent function of LIN28B in transcriptional regulation during neuroblastoma pathogenesis.

The relationship between eHealth literacy and palliative care knowledge, attitudes, and practice among nurses: a cross-sectional study.

BACKGROUND: The crucial role that nurses play in offering palliative care to patients with life-threatening diseases is widely acknowledged, but the correlation between their eHealth literacy and their knowledge, attitudes, and practice in this domain has yet to be investigated. This study is conducted to investigate the status of eHealth literacy and knowledge, attitudes, and practice regarding palliative care among nurses, and to examine their relationship. METHODS: A cross-sectional study design was conducted among 546 nurses selected from the first-class tertiary hospitals located both inside and outside of Zhejiang Province between May 12 and May 20, 2022. The online survey of eHealth literacy scale (eHEALS) and scale of knowledge, attitudes, and practice (KAP) regarding palliative care was performed using snowball sampling through the WeChat mini program "Questionnaire Star". The Spearman rank correlation and binary logistic regression model were used to analyze the independent association between eHealth literacy and KAP toward palliative care. RESULTS: The median scores of eHEALS and KAP regarding palliative care were 32 (interquartile range[IQR] 29 to 38) and 82 (IQR 54 to 106) points. The results of correlation analysis showed that the KAP regarding palliative care was significantly correlated with eHEALS (rho = 0.189, P < 0.001). In addition, the results of binary logistic regression analysis demonstrated that the eHEALS score was independently associated with the KAP score regarding palliative care when controlling for sociodemographic factors (OR = 2.109; P < 0.001). CONCLUSION: Nurses who worked in first-class tertiary hospitals have good levels of eHealth literacy, while the overall level of KAP regarding palliative care is moderate. Our findings highlight that the eHEALS score is independently associated with the KAP score regarding palliative care. Therefore, nursing managers should adopt multiple measures to comprehensively improve eHealth literacy among nurses, further enrich their knowledge of palliative care, promote a positive transformation of attitudes towards palliative care, and efficiently implement palliative care practice, in order to promote high-quality development of palliative care.

PP2Acα regulates epidermal cell proliferation via the EGFR/AKT/mTOR pathway in psoriasis-like skin lesions caused by PPP2CA deficiency.

Psoriasis, a common skin disease, endangers human physiological and mental health; however, its pathogenesis remains unclear. Keratinocyte proliferation is a typical pathological characteristic of psoriasis. Serine/threonine protein phosphatase 2A (PP2A) is one of the most important phosphatases for maintaining normal phosphorylation levels in humans. PP2Acα is the alpha subtype of the PP2A C subunit (encoded by PPP2CA), which maintains the catalytic functions of PP2A. Epidermal growth factor receptor (EGFR) is activated by phosphorylation (p-EGFR) to regulate the downstream signalling pathway to promote epidermal cell proliferation. Previous studies have found that PPP2CA induced epidermal hyperplasia, keratinization and other pathological phenomena similar to those in mouse models of psoriasis. The present study showed that PP2Acα negatively regulated EGFR phosphorylation and epidermal cell proliferation, and EGFR inhibitors could alleviate PP2Acα by inhibiting epidermal cell proliferation. This study further examined the effect of mechanisms on epidermal cell proliferation and the downstream signalling pathway of EGFR using molecular technological methods to explore new ideas for treating psoriasis.

Stereoconvergent Synthesis of Monofluoroalkenes via Photoinduced Dual Decarboxylative Cross-Coupling of α-Fluoroacrylic Acids with Redox-Active Esters.

Herein, a new strategy for the synthesis of monofluoroalkenes via employing α-fluoroacrylic acids and N-hydroxyphthalimide (NHPI) redox-active esters as coupling partners has been developed. This decarboxylative reaction enabled the formation of C(sp2)-C(sp3) bonds to provide a practical and efficient approach for the construction of a variety of monofluoroalkenes, which are key structural motifs in organic chemistry, under mild reaction conditions. The protocol exhibited excellent functional group compatibility and delivered monofluoroalkene products with excellent Z-stereoselectivity. This work also provides a platform for the modification of complex biologically active molecules containing carboxylic acids.

Pediatric Hepatic Cystic Lesions: Differential Diagnosis and Multimodality Imaging Approach.

When a pediatric hepatic cystic lesion is identified at imaging, the differential diagnosis may be broad, including developmental, infectious, neoplastic, and posttraumatic or iatrogenic causes. The location of a cystic lesion and its number, size, composition, and relationship to the biliary system are features that help in narrowing the differential diagnosis. An incidentally detected simple hepatic cyst is the most commonly encountered. Ciliated foregut cysts are typically located in hepatic segment IVa. The presence of multiple cysts should raise suspicion for fibropolycystic liver disease, a group of related lesions-including biliary hamartoma and choledochal cyst-caused by abnormal embryologic development of the ductal plate. Communication of the cystic lesion with the biliary tree can confirm the diagnosis of choledochal cyst. In a neonate with jaundice, a cystic lesion at the porta hepatis should raise suspicion for choledochal cyst versus cystic biliary atresia. Hepatic abscess can appear cystlike, though typically with internal contents. In an immunocompromised child, multiple cystlike lesions should raise concern for fungal microabscesses. A complex cystic mass in a young child should raise suspicion for mesenchymal hamartoma, which can evolve into undifferentiated embryonal sarcoma if untreated. Hepatic hematoma and biloma can appear cystlike in children with a history of trauma or recent intervention. In neonates with an umbilical vein catheter (UVC), an intrahepatic cyst along the course of the UVC should raise concern for infusate extravasation. Familiarity with imaging findings and clinical features is essential for achieving accurate diagnosis of pediatric hepatic cystic lesions, which in turn can guide appropriate clinical management. Online supplemental material is available for this article. ©RSNA, 2022.

The ß-1,3-glucan synthase gene GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis in Grifola frondosa.

ß-1,3-Glucans are well-known biological and health-promoting compounds in edible fungi. Our previous results characterized a glucan synthase gene (GFGLS) of Grifola frondosa for the first time to understand its role in mycelial growth and glucan biosynthesis. In the present study, we identified and functionally reannotated another glucan synthase gene, GFGLS2, based on our previous results. GFGLS2 had a full sequence of 5944 bp including 11 introns and 12 exons and a coding information for 1713 amino acids of a lower molecular weight (195.2 kDa) protein with different conserved domain sites than GFGLS (5927 bp with also 11 introns and a coding information for 1781 aa). Three dual-promoter RNA-silencing vectors, pAN7-iGFGLS-dual, pAN7-iGFGLS2-dual, and pAN7-CiGFGLS-dual, were constructed to downregulate GFGLS, GFGLS2, and GFGLS/GFGLS2 expression by targeting their unique exon sequence or conserved functional sequences. Silencing GFGLS2 resulted in higher downregulation efficiency than silencing GFGLS. Cosilencing GFGLS and GFGLS2 had a synergistic downregulation effect, with slower mycelial growth and glucan production by G. frondosa. These findings indicated that GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis and provides a reference to understand the biosynthesis pathway of mushroom polysaccharides. KEY POINTS: • The 5944-bp glucan synthase gene GFGLS2 of G. frondosa was cloned and reannotated • GFGLS2 showed identity and significant differences with the previously identified GFGLS • GFGLS2 played a major role in fermentation and glucan biosynthesis.

SIRT5 promotes non-small cell lung cancer progression by reducing FABP4 acetylation level.

This study evaluates the role of SIRT5 in non-small cell lung cancer (NSCLC) progression and explores the underlying mechanism. The expression and correlation of SIRT5 and FABP4 in lung cancer were analyzed by the GEPIA database. The expression levels of SIRT5 and FABP4 in NSCLC cells were measured by qRT-PCR and western blot. The effect of SIRT5 and FABP4 on NSCLC cell development was determined. The interaction between SIRT5 and FABP4 was analyzed by co-immunoprecipitation (Co-IP). Tumor mass and volume were measured in nude mice to study the effect on the growth of NSCLC transplanted tumors. GEPIA database analysis showed that SIRT5 was highly expressed, while FABP4 was lowly expressed in lung cancer, which was consistent with the detection results of SIRT5 and FABP4 expressions in NSCLC cell lines. The expression of SIRT5 was negatively correlated with FABP4. Transfection of sh-SIRT5 in NSCLC cells led to a decrease in NSCLC cell malignancy, which was counteracted by sh-FABP4 transfection. Western blot and Co-IP showed that SIRT5 reduced FABP4 expression by inducting the deacetylation of FABP4. Nude mice in the sh-SIRT5 + sh-FABP4 group had significantly reduced tumor mass and volume compared with those in the sh-FABP4 group, while the tumor mass and volume in the sh-SIRT5 + sh-FABP4 group were increased in comparison to those in the sh-SIRT5 group. To conclude, collected evidence showed that SIRT5 promoted NSCLC cell development by reducing FABP4 acetylation level.

Loss of atrx cooperates with p53-deficiency to promote the development of sarcomas and other malignancies.

The SWI/SNF-family chromatin remodeling protein ATRX is a tumor suppressor in sarcomas, gliomas and other malignancies. Its loss of function facilitates the alternative lengthening of telomeres (ALT) pathway in tumor cells, while it also affects Polycomb repressive complex 2 (PRC2) silencing of its target genes. To further define the role of inactivating ATRX mutations in carcinogenesis, we knocked out atrx in our previously reported p53/nf1-deficient zebrafish line that develops malignant peripheral nerve sheath tumors and gliomas. Complete inactivation of atrx using CRISPR/Cas9 was lethal in developing fish and resulted in an alpha-thalassemia-like phenotype including reduced alpha-globin expression. In p53/nf1-deficient zebrafish neither peripheral nerve sheath tumors nor gliomas showed accelerated onset in atrx+/- fish, but these fish developed various tumors that were not observed in their atrx+/+ siblings, including epithelioid sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma and rare types of carcinoma. These cancer types are included in the AACR Genie database of human tumors associated with mutant ATRX, indicating that our zebrafish model reliably mimics a role for ATRX-loss in the early pathogenesis of these human cancer types. RNA-seq of p53/nf1- and p53/nf1/atrx-deficient tumors revealed that down-regulation of telomerase accompanied ALT-mediated lengthening of the telomeres in atrx-mutant samples. Moreover, inactivating mutations in atrx disturbed PRC2-target gene silencing, indicating a connection between ATRX loss and PRC2 dysfunction in cancer development.

Whole Genome Sequencing and CRISPR/Cas9 Gene Editing of Enterotoxigenic Escherichia coli BE311 for Fluorescence Labeling and Enterotoxin Analyses.

Some prevention strategies, including vaccines and antibiotic alternatives, have been developed to reduce enterotoxigenic Escherichia coli proliferation in animal production. In this study, a wild-type strain of BE311 with a virulent heat-stable enterotoxin gene identical to E. coli K99 was isolated for its high potential for gene expression ability. The whole genome of E. coli BE311 was sequenced for gene analyses and editing. Subsequently, the fluorescent gene mCherry was successfully knocked into the genome of E. coli BE311 by CRISPR/Cas9. The E. coli BE311−mCherry strain was precisely quantified through the fluorescence intensity and red colony counting. The inflammatory factors in different intestinal tissues all increased significantly after an E. coli BE311−mCherry challenge in Sprague−Dawley rats (p < 0.05). The heat-stable enterotoxin gene of E. coli BE311 was knocked out, and an attenuated vaccine host E. coli BE311-STKO was constructed. Flow cytometry showed apoptotic cell numbers were lower following a challenge of IPEC-J2 cells with E. coli BE311-STKO than with E. coli BE311. Therefore, the E. coli BE311−mCherry and E. coli BE311-STKO strains that were successfully constructed based on the gene knock-in and knock-out technology could be used as ideal candidates in ETEC challenge models and for the development of attenuated vaccines.

Identification of a Novel ß-Thalassemia Mutation at Codon 130 (+T) (HBB: c.391insT) in Han Chinese.

ß-Thalassemia (ß-thal) is an inherited blood disorder characterized by reduced or absent synthesis of the ß chains of hemoglobin (Hb). Although more than 900 ß-globin gene mutations around the world have been identified, here we report a novel mutation detected in a Chinese subject of Han ethnicity. This allele develops by insertion of one nucleotide (+T) at codon 130 (HBB: c.391insT) in the third exon of the ß-globin gene. The mutation causes a frameshift that leads to a termination codon at codon 139. The identification of the novel mutation will facilitate future diagnosis of ß-thal and will also be useful the genetic counseling and prenatal diagnosis.

Safety of gadoterate meglumine in children younger than 2 years of age.

BACKGROUND: Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age. OBJECTIVE: To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration. MATERIALS AND METHODS: Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. RESULTS: One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. CONCLUSION: No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis.

Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer.

Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3.

Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis.

A MicroRNA302-367-Erk1/2-Klf2-S1pr1 Pathway Prevents Tumor Growth via Restricting Angiogenesis and Improving Vascular Stability.

RATIONALE: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367 cluster in angiogenesis and tumors has not yet been fully evaluated. OBJECTIVE: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases. METHODS AND RESULTS: Here, we show that miR302-367 elevation in endothelial cells reduces retinal sprouting angiogenesis and promotes vascular stability in vivo, ex vivo, and in vitro. Erk1/2 is identified as direct target of miR302-367, and downregulation of Erk1/2 on miR302-367 elevation in endothelial cells increases the expression of Klf2 and in turn S1pr1 and its downstream target VE-cadherin, suppressing angiogenesis and improving vascular stability. Conversely, both pharmacological blockade and genetic deletion of S1pr1 in endothelial cells reverse the antiangiogenic and vascular stabilizing effect of miR302-367 in mice. Tumor angiogenesis shares features of developmental angiogenesis, and endothelial specific elevation of miR302-367 reduces tumor growth by restricting sprout angiogenesis and decreasing vascular permeability via the same Erk1/2-Klf2-S1pr1 pathways. CONCLUSIONS: MiR302-367 regulation of an Erk1/2-Klf2-S1pr1 pathway in the endothelium advances our understanding of angiogenesis, meanwhile also provides opportunities for therapeutic intervention of tumor growth.

Diagnostic accuracy of non-contrast magnetic resonance enterography in detecting active bowel inflammation in pediatric patients with diagnosed or suspected inflammatory bowel disease to determine necessity of gadolinium-based contrast agents.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime. OBJECTIVE: To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD. MATERIALS AND METHODS: We conducted a retrospective study of 77 patients (7-18 years; 68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30 days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (κ), Fleiss kappa, (κF), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard). RESULTS: The pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%; κ 0.713, P<0.001; P-value 0.549). Compared to combined endoscopy/histopathology, pre- vs. pre-/post-contrast sensitivity (67%, confidence interval [CI] 0.53-0.79 vs. 67%, CI 0.53-0.79) and specificity (80%, CI 0.59-0.92 vs. 68%, CI 0.46-0.84) varied little (κ 0.42, P<0.001 and κ 0.32, P=0.003, respectively). The three readers had moderate agreement (85.2%; κ 0.695, P=0.001; P-value 0.625). More penetrating complications were identified following contrast administration (P-value 0.04). CONCLUSION: Use of a contrast agent does not improve the detection of active inflammation in the terminal ileum and colon compared to non-contrast MRE, although use of a contrast agent does aid in the detection of penetrating disease.