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Crohn's disease (CD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. With the increased availability of modalities in the last two decades, the treatment of CD has advanced remarkably. Although medical treatment is the mainstay of therapy, most patients require surgery during the course of their illness, especially those who experience complications. Nutritional optimization and ERAS implementation are crucial for patients with CD who require surgical intervention to reduce postoperative complications. The increased surgical risk was found to be associated with the use of corticosteroids, but the association of surgical risk with immunomodulators, biologic therapy, such as anti‐TNF mediations, anti‐integrin medications, and anti‐IL 12/23 was low in certainty. Decisions about preoperative medication must be made on an individual case‐dependent basis. Preoperative imaging studies can assist in the planning of appropriate surgical strategies and approaches. However, patients must be informed of any alterations to their treatment. In summary, the management of perioperative medications and surgery‐related decision‐making should be individualized and patient‐centered based on a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Introduction The canonical Wnt signaling pathway, also called the [beta]-catenin/ TCF pathway, controls various cellular events such as migration, proliferation, and differentiation throughout development. Dysregulation of Wnt signaling is thought [...], Dysregulation of canonical Wnt signaling is thought to play a role in colon carcinogenesis. [beta]-Catenin, a key mediator of the pathway, is stabilized upon Wnt activation and accumulates in the nucleus, where it can interact with the transcription factor T cell factor (TCF) to transactivate gene expression. Normal colonic epithelia express a truncated TCF-1 form, called dnTCF-1, that lacks the critical [beta]-catenin-binding domain and behaves as a transcriptional suppressor. How the cell maintains a balance between the two forms of TCF-1 is unclear. Here, we show that ERM-binding phosphoprotein 50 (EBP50) modulates the interaction between [beta]-catenin and TCF-1. We observed EBP50 localization to the nucleus of human colorectal carcinoma cell lines at low cell culture densities and human primary colorectal tumors that manifested a poor clinical outcome. In contrast, EBP50 was primarily membranous in confluent cell lines. Aberrantly located EBP50 stabilized conventional [beta]-catenin/TCF-1 complexes and connected [beta]-catenin to dnTCF-1 to form a ternary molecular complex that enhanced Wnt/[beta]-catenin signaling events, including the transcription of downstream oncogenes such as c-Myc and cyclin D1. Genome-wide analysis of the EBP50 occupancy pattern revealed consensus binding motifs bearing similarity to Wnt-responsive element. Conventional chromatin immunoprecipitation assays confirmed that EBP50 bound to genomic regions highly enriched with TCF/LEF binding motifs. Knockdown of EBP50 in human colorectal carcinoma cell lines compromised cell cycle progression, anchorage-independent growth, and tumorigenesis in nude mice. We therefore suggest that nuclear EBP50 facilitates colon tumorigenesis by modulating the interaction between [beta]-catenin and TCF-1.

Infants who are born to preeclamptic mothers have been shown to have higher risk for being small for gestational age (SGA) and having neonatal thrombocytopenia or neutropenia. (1-6) Neonatal thrombocytopenia [...], Objective. To investigate the relationship of neonatal platelet count and preeclampsia to levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (P1GF), and vascular endothelial growth factor (VEGF) in the cord blood of preterm infants. Methods. Sixty-nine preterm infants with a gestational age between 26 and 37 weeks at birth were enrolled, sFlt-1, P1GF, and VEGF levels in the cord blood of preterm neonates, with or without maternal preeclampsia, were measured using a standardized sandwich enzyme-linked immunosorbent assay method. Results. Infants with maternal preeclampsia had higher cord blood sFlt-1 but lower P1GF and VEGF levels. There was a significantly positive relationship between neonatal platelet count and birth weight and a significantly negative relationship between neonatal platelet count and cord blood sFlt-1 levels. Multiple regression analysis revealed that only birth weight and cord blood sFlt-1 levels were independently related to neonatal platelet count, whereas maternal preeclampsia, gestational age (GA), and small for GA (SGA) were not related. Neonates with thrombocytopenia had higher cord blood sFlt-1 levels but lower birth weight. A significant correlation was also found between birth weight and cord blood sFlt-1 levels. Multiple regression with birth weight as the dependent variable found that only GA and cord blood sFlt-1 levels were independently related. Furthermore, infants with high cord blood sFlt-1 were more likely to have lower platelet count and maternal preeclampsia, be SGA, and have a trend toward lower birth weight. Conclusion. Excess sFlt-1 may play an important role in the development of maternal preeclampsia- induced neonatal thrombocytopenia, and SGA. Pediatrics 2005; 116:468-472; sFlt-1, vascular endothelial growth factor, placenta growth factor, preeclampsia, platelets. ABBREVIATIONS. SGA, small for gestational age; VEGF, vascular endothelial growth factor; P1GF, placenta growth factor; sFlt-1, soluble fms-like tyrosine kinase 1; GA, gestational age; VLBW, very low birth weight; Tpo, thrombopoietin; Mk, megakaryocytic.

With the widespread use of antenatal steroids, exogenous surfactant therapy, and improvements in neonatal care, the survival rate of very low birth weight infants has increased, but bronchopulmonary dysplasia (BPD) [...], Objective. To determine whether an elevated placenta growth factor (PlGF) level in cord blood is associated with increased risk for preterm infants to develop bronchopulmonary dysplasia (BPD). Methods. Sixty-three preterm infants who were born at 34 weeks' gestation or earlier were enrolled. Two infants who died before 28 days' postnatal age could not be assigned a BPD status and were excluded. PlGF levels in cord blood were measured using enzyme-linked immunosorbent assay. Mann-Whitney rank sum test, Spearman correlation coefficients, and multivariable linear or logistic regression analyses were used for statistical analysis. Results. The BPD group had a higher PlGF level, lower gestational age, lower birth weight (BW), higher incidence of endotracheal tube intubation, and longer duration of intubation. The PlGF levels in cord blood correlated negatively with gestational age and BW. However, multivariable logistic regression analyses revealed that only elevated cord blood PlGF levels and BW were associated with BPD after adjusting for all contributing factors. Furthermore, an increased PlGF level in cord blood was significantly correlated with the clinical severity of BPD, as measured by duration of intubation. At 17 mg/dL, the specificity of cord blood PlGF level in predicting BPD was 95%, the sensitivity was 53%, the positive predictive value was 83%, and the negative predictive value was 82%. Conclusions. Measuring cord blood PlGF level at birth might be a biological marker for predicting the occurrence of BPD and allowing early therapeutic intervention. Pediatrics 2004;113:1348-1351; bronchopulmonary dysplasia, cord blood, placenta growth factor. ABBREVIATIONS. BPD, bronchopulmonary dysplasia; PlGF, placenta growth factor; VEGF, vascular endothelial growth factor; GA, gestational age; RDS, respiratory distress syndrome; BW, birth weight.

Abstract Background Notch and TLR pathways were found to act cooperatively to activate Notch target genes and to increase the production of TLR-induced cytokines in macrophages. However, the mechanism of LPS-induced Notch activation and its role in sepsis still remains unclear. Methods We analyzed the expression patterns of Notch components in a LPS-stimulated murine macrophage cell line using real-time PCR and western blotting. The role of DAPT, a gamma-secretase inhibitor that is known to be a potent Notch inhibitor, in LPS-induced cytokine release and experimental sepsis in mice was also explored. Student's t-test was used to analyze the difference between the two groups. Results We found that Notch signaling was activated after LPS stimulation. The expression of Jagged 1, a Notch ligand, induced by LPS occurred in a JNK-dependent manner. In addition, Notch target genes were upregulated by early Notch-independent activation followed by delayed Notch-dependent activation after LPS stimulation. Disruption of Notch signaling by DAPT attenuated the LPS-induced inflammatory responses, including vascular endothelial growth factor (VEGF) and high-mobility group box chromosomal protein 1 (HMGB1), both in vitro and in vivo and partially improved experimental sepsis survival. Conclusions These findings support the existence of a synergistic effect of Notch signaling and the LPS pathway both in vitro and in vivo. Therefore, in the future Notch inhibitors may be utilized as adjunctive agents for the treatment of sepsis syndrome.