The Earlier You Find, the Better You Treat: Red Flags for Early Diagnosis of Inflammatory Bowel Disease.

Delayed diagnosis is a challenge in the management of inflammatory bowel disease (IBD). Several studies show a significant association between diagnostic delay and disease progression to complications and surgery, especially in Crohn's disease (CD). What risk factors are associated with diagnostic delay in IBD remains unclear.

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

Background: The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD.

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer.

Background: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking.

Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells.

Background: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage.

Hindlimb Ischemia Impairs Endothelial Recovery and Increases Neointimal Proliferation in the Carotid Artery.

Peripheral ischemia is associated with higher degree of endothelial dysfunction and a worse prognosis after percutaneous coronary interventions (PCI). However, the role of peripheral ischemia on vascular remodeling in remote districts remains poorly understood. Here we show that the presence of hindlimb ischemia significantly enhances neointima formation and impairs endothelial recovery in balloon-injured carotid arteries.

Inflammation and macrophage polarization in cutaneous melanoma: Histopathological and immunohistochemical study.

Tumor-associated macrophages (TAMs) are considered to affect tumor growth and progression. Macrophages can be classified into two states of polarized activation, namely classically activated M1 macrophages and alternatively activated M2 macrophages. The dynamic balance between TAMs and tumor cells has an important impact on tumor homeostasis and progression.

Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months).

A reappraisal of macrophage polarization in glioblastoma: Histopathological and immunohistochemical findings and review of the literature.

The survival rate in glioblastoma multiforme patients has scarcely improved in the last decades; however, many new therapeutic strategies have been theorized or developed for these neoplasias. Recently, the inverse correlation observed between patient prognosis and tumor-associated macrophages (TAMs) density in solid tumors has encouraged the development of anti-tumor strategies aiming to target TAMs. As expected, TAMs polarization is influenced by both macrophage localization and tumor microenvironment signals, resulting in a more complex scenario than the simple M1/M2 activation status.

A case of intravascular large B cell lymphoma: New clinical and immunohistochemical findings.

Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non-Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the CNS and the skin. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist of neurological and cognitive impairment, fever of unknown origin and cutaneous lesions, lacking of a typical neuroimaging pattern. For all these reasons the diagnosis is commonly missed and the exitus is frequent, therefore post mortem evaluation is necessary to clarify the clinical history.

Circulating non-hematological cells during cardiopulmonary bypass: new findings in cardiac surgery procedures.

Background: Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation.

AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells.

The mTOR signaling pathway and neuronal stem/progenitor cell proliferation in the hippocampus are altered during the development of absence epilepsy in a genetic animal model.

Hyperactivation of mammalian target of rapamycin (mTOR) signaling pathway occurs after an epileptogenic insult and, its inhibition prevents the development of spontaneous seizures. We have recently demonstrated that mTOR's inhibition by rapamycin (started before seizure onset), permanently reduces the development of spontaneous absence seizures in WAG/Rij rats, an animal model of absence epilepsy; furthermore, mTOR phosphorylation was increased in adult WAG/Rij rats' cortex, but not other brain areas. However, it was not clear whether this hyperphosphorylation was a cause or a consequence of absence seizure.

mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy.

Several signaling pathways are believed to be involved in the epileptogenic process that triggers the subsequent changes in the brain causing epilepsy. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that in the brain, regulates several important physiological functions such as neuronal development and synaptic plasticity, and also seems to be involved in many pathologies, including epilepsy and psychiatric disorders. Previous work in animal models of both genetic and acquired generalized convulsive epilepsies, has suggested that modulators of the mTOR signaling pathway may have beneficial neuroprotective and antiepileptogenic effects.

New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review.

Aims: Calcific aortic stenosis is a progressive disease characterized by massive fibrosis andmineralization of the valve leaflets. The aim of this study was to determine whether the onset of native calcific aortic stenosis is associated primarily with matrix remodelling events, and particularly with elastin degradation.

Methods And Results: The immunohistochemical expression profile of matrix degradating enzymes and tenascin-C was investigated in both healthy and native calcified aortic valves.