A Case of Severe Transaminase Elevation Following a Single Ustekinumab Dose with Remission After Drug Withdrawal.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody which binds Interleukin (IL)-12/23. It is indicated for the treatment of moderate-severe psoriasis and active psoriatic arthritis. Few data are available about the possibility of an interaction between ustekinumab and the liver. CASE DESCRIPTION: We reported a case of a 61-year old woman admitted to our Unit for severe transaminase elevation (aspartate transaminase 756 IU/l, alanine transaminase 1212 IU/l) occurred after a single Ustekinumab infusion for psoriasis. All other possible causes of liver damage, including drugs, hepatitis viruses, auto-antibodies and metabolic disorders were excluded. Liver biopsy showed lymphocytic infiltration, biliary duct damage and piecemeal necrosis. On the bases of the nonspecific histological picture and Rucam score, we accomplished the diagnosis of "liver injury of iatrogenic origin". After drug withdrawal, a spontaneous normalization of liver enzymes occurred within six months.

The Role of Gender-specific Cytokine Pathways as Drug Targets and Gender- specific Biomarkers in Personalized Cancer Therapy.

The definition of personalized treatments in tumor disease could lead to an improvement of the therapeutic success rate. Therefore, biomarkers are urgently required in order to select the patients that could benefit from adjuvant therapies in the initial phase of the disease and to better define and treat the clinical/therapeutic subgroups in the advanced pathological phases. Disregulation of cytokine physiological network is directly involved in the genesis and progression of tumors. Cytokines are of central importance in the regulation of immune system, but they are rarely released singly: each cytokine is able to induce the production of many other factors leading to a network in which they cooperate with other cell regulators such as hormones and neuropeptides. For these reasons the research must be directed to the evaluation of the interrelationships between the different cytokines and their respective pathways, as well as their contribution to the disease aetiology and progression in order to identify real and effective drug targets and biomarkers. The T CD4+ helper cells (Th) have various subpopulations, among which Th1, Th2, Th3, Th9 and Th17, respectively produce cytokines. It has become clear that disorders within the interactions of the network of these cytokines can produce neoplastic diseases. Furthermore, studies focusing on gender have shown that the homeostasis of the immune system is controlled by pathways of cytokines that are different between sexes and defined for this reason "genderspecifics". Therefore, this perspective article aims to highlight the significance of these cytokine pathways in order to identify new clinical strategies and personalized therapy in neoplastic diseases.

Mucosal molecular pattern of tissue transglutaminase and interferon gamma in suspected seronegative celiac disease at marsh 1 and 0 stages.

BACKGROUND/AIM: In celiac disease (CD), there is increased mRNA coding for tissue transglutaminase (tTG) and interferon gamma (IFNα). In seronegative celiac patients, the mucosal immune complexes anti-tTG IgA/tTG are found. We assayed tTG- and IFNα-mRNA in the mucosa of patients with a clinical suspicion of seronegative CD and correlated the values with intraepithelial CD3 lymphocytes (IELs). MATERIALS AND METHODS: Distal duodenum specimens from 67 patients were retrieved and re-evaluated for immunohistochemically proven CD3 IELs. Five 10 µm sections were used for the extraction and assay of tTG and IFNα coding mRNA levels using reverse transcriptase real-time polymerase chain reaction (RT-PCR). Samples from 15 seropositive CD patients and 15 healthy subjects were used as positive and negative controls. Results were expressed as fold-change. RESULTS: Our series was divided into three groups based on IEL count: >25 (14 patients: group A), 15-25 (26 patients: group B), and 0-15 (27 patients: Group C). tTG-mRNA levels were (mean ± SD): CD = 9.8 ± 2.6; group A = 10.04 ± 4.7; group B = 4.99 ± 2.3; group C = 2.26 ± 0.8, controls = 1.04 ± 0.2 (CD = group A > group B > group C = controls). IFNα-mRNA levels were: CD = 13.4 ± 3.6; group A = 7.28 ± 3.6; group B = 4.45 ± 2.9; group C = 2.06 ± 1.21, controls = 1.04 ± 0.4. CONCLUSIONS: Our results suggest that tTG- and IFNγmRNA levels are increased in both seropositive and potential seronegative patients with CD, showing a strong correlation with the CD3 IEL count at stage Marsh 1. An increase in both molecules is found even when IELs are in the range 15-25 (Marsh 0), suggesting the possibility of a "gray zone" inhabited by patients which should be closely followed up in gluten-related disorders.

Computer-based simulator for catheter insertion training.

Minimally invasive surgery procedures are getting common in surgical practice; however the new interventional procedure requires different skills compared to the conventional surgical techniques. The need for training process is very important in order to successfully and safely execute a surgical procedure. Computer-based simulators, with appropriate tactile feedback device, can be an efficient method for facilitating the education and training process. In addition, virtual reality surgical simulators can reduce costs of education and provide realism with regard to tissues behaviour and real-time interaction. This work take into account the results of the HERMES Project (HEmatology Research virtual MEdical System), conceived and managed by Consorzio CETMA-Research Centre; the aim of this project is to build an integrate system in order to simulate a coronary angioplasty intervention.