Long-Term Effectiveness and Safety of Ustekinumab in Crohn's Disease: Results from a Large Real-Life Cohort Study.

Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients.

Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients.

Hepatocellular carcinoma (HCC) is undergoing a transformative shift, with metabolic-associated fatty liver disease (MAFLD) emerging as a dominant etiology. Diagnostic criteria for MAFLD involve hepatic steatosis and metabolic dysregulation. Globally, MAFLD prevalence stands at 38.

The Impact of Radiofrequency Ablation on Survival Outcomes and Stent Patency in Patients with Unresectable Cholangiocarcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA.

Risk Stratification in Primary Biliary Cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and noninvasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients.

The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Treating Portal Hypertension in Patients with Hepatocellular Carcinoma.

Liver cancer is very frequent, and hepatocellular carcinoma (HCC) accounts for the majority of liver cancer cases. Its growing incidence has been greatly affected by the increasing prevalence of metabolic-associated fatty liver disease (MAFLD). The latter is a new epidemic in our era.

Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy.

Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments.

Gastrointestinal disorders as immune-related adverse events.

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care.

MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared.

Temporal and spatial variations of polycyclic aromatic hydrocarbon concentrations around a coke oven plant.

Unlabelled: From 1995 to 2004, in Genoa, Italy, daily concentrations of twelve polycyclic aromatic hydrocarbons (PAHs) were measured in particulate phase (PM10), around a coke oven plant in operation from the 1950s and closed in 2002. The study permitted to identify the coke oven as the main PAH source in Genoa, causing constant exceeding of benzo(a)pyrene (BaP) air quality target (1.0 ng/m3) in the urban area till 1,900 meters distance downwind the plant.

Effect of supplementation with vitamin D₃ on glucose production pathways in human subjects.

Scope: Research reports suggest that vitamin D affects glucose and insulin metabolism; however, the exact mechanisms are unclear. ²H NMR analysis of monoacetone glucose (MAG) after tracer administration provides a non-invasive method of profiling hepatic glucose metabolism. This study examined the effects of supplementation with vitamin D₃ on contribution of glycogenolysis to glucose production.

All trans-retinoic acid modulates the procoagulant activity of human breast cancer cells.

All trans-retinoic acid (ATRA) induces apoptosis and/or differentiation in solid tumors, including breast cancer, and has become a therapeutic tool in this disease. In human promyelocytic leukemia ATRA reduces the expression of cellular procoagulant activities (PCA), i.e.

A stereoselective synthesis of alpha-deuterium-labelled (S)-alpha-amino acids.

An atom-efficient and stereoselective synthesis has been developed for the preparation of alpha-2H-labelled (S)-alpha-amino acids, starting from a novel chiral diketopiperazine scaffold. Efficient mono-alkylation of the chiral template afforded the (S)-substituted adducts with the nature of the electrophile significantly effecting the stereochemical outcome. Subsequent alkylation was totally selective producing the 1,4-cis adduct as the sole diastereoisomer.

Chiral piperazine-2,5-dione derivatives as effective alpha-glucosidase inhibitors. Part 4.

The potential to inhibit alpha- and beta-glucosidases of a series of chiral piperazine-2,5-dione derivatives was investigated. Three of the seven compounds tested, viz., 1, 5b, and 5c, showed to be non competitive inhibitors of alpha-glucosidase, whereas they exhibited very low inhibitory activity towards beta-glucosidase.

(S)-alpha-methyl,alpha-amino acids: a new stereocontrolled synthesis.

A new and convenient stereocontrolled synthesis of the optically pure (S)-alpha-methyl,alpha-amino acids 6(a-d) that exploits the chiral synthon 1,4-N,N-[(S)-1-phenylethyl]-piperazine-2,5-dione (1) is described. The (S)-1-phenylethyl group, bonded to each of the N-atoms of the 2,5-diketopiperazine, acts as a chiral inductor in the first alkylation, while the steric hindrance appears to be the determining factor of stereocontrol in third and forth alkylation.

Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera.

We used the thrombin generation assay to evaluate the hypercoagulable state according to JAK2(V617F) mutational status in essential thrombocythemia (ET) and polycythemia vera (PV) patients. Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr). Tissue factor pathway inhibitor (TFPI), total and free protein S (PS), prothrombin (FII), factor V (FV), and neutrophil elastase were measured in plasma; CD11b was measured on neutrophils.

Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin.

Background: Clinical studies suggest a survival advantage in cancer patients receiving low molecular weight heparin (LMWH). A suggested mechanism for this beneficial effect may reside in the antiangiogenic activity of heparins.

Objectives: In this study we investigated whether two different LMWHs, i.

V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules.

Objective: This article evaluates patients with essential thrombocythemia (ET) to determine whether the V617F mutation in the JAK2 gene affects platelet hemostatic and adhesive molecules, platelet-polymorphonuclear leukocyte (PMN) interactions, and PMN-activation characteristics, as well as plasma hypercoagulation markers.

Patients And Methods: Thirty-seven ET patients with V617F JAK2 mutation and 38 wild-type, and 50 healthy controls were studied.

Results: Platelets from overall ET patients, compared to controls, expressed significantly higher membrane tissue factor (TF) and P-selectin (p < 0.

[Conservative treatment using mesalazine in ischemic colitis].

The authors propose the conservative treatment of ischemic colitis using slow-release mesalazine and enema. The excellent tolerability of the treatment and the good level of therapeutic efficacy was confirmed in 13 cases treated without signs of recurrence of disease.

Differential effect of the low-molecular-weight heparin, dalteparin, and unfractionated heparin on microvascular endothelial cell hemostatic properties.

Background And Objectives: Heparins, including unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), are glycosaminoglycans that are largely used as anti-thrombotic drugs. While the mechanisms of their anticoagulant actions in blood have been extensively studied, their effects on the hemostatic properties of the endothelium are still under investigation. The aim of this study was to compare the antithrombotic effects of a LMWH, i.

Clotting mechanisms and cancer: implications in thrombus formation and tumor progression.

Development of cancer is associated with activation of blood coagulation. The results of laboratory tests clearly demonstrate that fibrin formation and dissolution is continuously ongoing at different rates in these patients, who are at increased risk of secondary thrombosis. Notably, fibrin formation is also involved in the process of tumor spread and metastasis.

Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera.

Objective: Circulating polymorphonuclear leukocyte (PMN) activation occurs in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We want to define whether this phenomenon plays a role in the formation of circulating PMN-platelet aggregates in these conditions.

Methods: In 80 patients (46 ET and 34 PV) and 50 control subjects, we conducted a flow cytometric analysis to evaluate the levels of PMN-platelet aggregates (defined as the percentage of CD11b-positive PMN coexpressing a platelet-specific marker, i.

Personal daily exposures to benzo(a)pyrene of taxi drivers in Genoa, Italy.

Twenty-four hour personal exposures (both occupational and environmental) to benzo(a)pyrene (BaP) of 15 taxi drivers working in Genoa, Italy, were monitored in May-July 1998 (15 samplings), February 1999 (7 samplings) and June 1999 (7 samplings). The mean BaP exposures measured at these different times were 1.4 ng/m3, 1.