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Inelastic nuclear interaction probability of 400 GeV/c protons interacting with bent silicon crystals was investigated, in particular for both types of crystals installed at the CERN Large Hadron Collider for beam collimation purposes. In comparison to amorphous scattering interaction, in planar channeling this probability is ∼36% for the quasi-mosaic type (planes (111)), and ∼27% for the strip type (planes (110)). Moreover, the absolute inelastic nuclear interaction probability in the axial channeling orientation, along the ⟨110⟩ axis, was estimated for the first time, finding a value of 0.6% for a crystal 2 mm long along the beam direction, with a bending angle of 55 μrad. This value is more than two times lower with respect to the planar channeling orientation of the same crystal, and increases with the vertical angular misalignment. Finally, the correlation between the inelastic nuclear interaction probability in the planar channeling and the silicon crystal curvature is reported.

BackgroundInterstitial lung disease (ILD) related to rheumatoid arthritis (RA) significantly impacts on quality of life and survival of the patients. Data about prevalence and natural history of RA-ILD are only partially known and mainly based on retrospective studies. The recent introduction of antifibrotic drugs have allowed for the first time the opportunity to treat ILD in RA patients; in fact, INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing ILD different than idiopathic pulmonary fibrosis (IPF), including RA-ILD, but the prevalence of RA-ILD patients that may potentially benefit from nintedanib therapy remain unknown.ObjectivesAim of the present multicenter Italian study was to investigate the prevalence of fibrosing progressive patterns in a cross-sectional cohort of non-selected RA-ILD patients.MethodsWe enrolled in the study all RA patients according to 2010 EULAR/ACR classification criteria, with an ILD confirmed at high resolution computed tomography (HRCT) and with a follow-up of at least 24 months.According to the current indication of nintedanib, patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity (FVC) ≥10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24 month-period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnoea.ResultsOne hundred and thirty-four RA-ILD patients were enrolled in the study (males/females 54/80, mean age 72±9.5 years, mean RA and ILD duration 13.1±9.5 and 4.6±4.1 years, respectively. Anticitrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were recorded in 76.2% and 87.6% of cases, respectively.According to radiologic features, ILD was classified as probable or definite usual interstitial pneumonia (UIP) in 50.7% of patients, NSIP in 19.4% and other patterns in 29.8%. A fibrosing pattern was reported in 73.9% of cases (all patients with UIP pattern, 57.7% of patients with NSIP and 40% with other pattern). A relative decline of 6.8% of forced vital capacity (FVC) was recorded during the follow-up, without significant difference between fibrosing and non-fibrosing ILD (6.3%±13.8 vs 5.9%±21.3, respectively). A relative FVC decline ≥ 10% and/or a progression of radiologic fibrotic involvement was observed in 38.8% of patients. As expected, a significant difference in relative decline of FVC was recorded between progressive and non-progressive ILD (15.7%±16.4 vs -1.3%±8.3, respectively). Globally, a fibrosing progressive pattern was recorded in 35.8% of patients (48/134, 48.5% of patients with fibrosing pattern). Of interest, also 11.4% of patients with a non-fibrosing pattern showed a progressive behavior of disease (see Figure 1).ConclusionThe recent introduction of nintedanib for the treatment of fibrosing progressive ILD different by IPF has potentially changed the paradigm for the treatment of RA-ILD. In fact, for the first time, rheumatologist has a therapy available with efficacy on RA related lung involvement.This study shows some limitations. The retrospective design and the need of serial HRCT and FVC could induce an overestimation of progressive disease (pulmonary function could not have been properly evaluated in asymptomatic patients). On the other hand, the exclusion of symptoms, such as a worsening of dyspnea and cough, might underestimate the prevalence of progressive lung disease. Finally, some patients were already treated with antifibrotic drugs, possibly influencing the evolution of lung disease in the last 2 years.In conclusion, about a third of RA-ILD patients shows a fibrosing progressive pattern of ILD and might benefit of antifibrotic treatment, alone or in combination with anti-rheumatic drugs. For RA patients with progressive non-fibrosing ILD, we need more studies to establish the best therapeutic approach.References[1] Flaherty KR et al. N Engl J Med 2019;381:1718-1727[2] Manfredi A, et al. Expert Rev Clin Immunol. 2021;17:485-97Figure 1.AcknowledgementsI have no acknowledgement to declare.Disclosure of InterestsAndreina Manfredi Speakers bureau: BMS, Lilly, and.Boehringer-Ingelheim, Vincenzo Venerito: None declared, Massimiliano Cazzato: None declared, Stefano Gentileschi: None declared, Laura La Corte: None declared, Anna Maria Iuliano: None declared, Giulia Cassone: None declared, Caterina Vacchi: None declared, Caterina Tomassini: None declared, Alessandra Rai: None declared, Marlea Lavista: None declared, Dario Andrisani: None declared, Elenia Laurino: None declared, Claudia Canofari: None declared, elisa pedrollo: None declared, Fabiola Atzeni: None declared, Gian Domenico Sebastiani: None declared, Bruno Frediani: None declared, Marta Mosca: None declared, Florenzo Iannone: None declared, Marco Sebastiani Speakers bureau: BMS, Pfizer, and Boehringer-Ingelheim, Consultant of: Lilly, Grant/research support from: BMS, Pfizer.

Background and AimsEndoscopic Submucosal Dissection (ESD) is an endoscopic procedure to remove gastrointestinal tumors [1]. It lasts 90 minutes or longer and general anaesthesia or deep sedation [2] are required to ensure comfort and immobility. Pain is evoked by intestinal insufflation and external compression manoeuvres. We evaluated the use of neuraxial blockades to perform colorectal ESD.MethodsWith informed consent, we performed neuraxial blocks for five colorectal ESD. Spinal anaesthesia (SA) and combined spinal-epidural (CSE) anaesthesia at T11-T12 level with spinal bolus of 0,3% ropivacaine, 4 ml + fentanyl 20mcg. Epidural anaesthesia (EA) at T10-T11 level with bolus of 0,4% ropivacaine, 12 ml + fentanyl 50mcg. Data regarded: patient; procedure; anaesthetic technique; SpO2; NIBP; intraprocedural pain (NRS); additional sedation or analgesia; patient’s and operator’s satisfaction.ResultsAll patients were elder and had comorbidities.Tumour site: 1 rectum; 2 descending colon; 2 ileocecal valve.Procedure’s duration: between 120 and 375 minutes.Anaesthesia: 2 SA, 1 CSE; 2 EA.SpO2: always stable between 97% and 100%.NIBP: 2 episodes of mild hypotension were registered.NRS: always 0; patients who received spinal anaesthesia complaint of abdominal pain after 200/240 minutes. They received additional IV fentanyl and deep propofol sedation.Patients’ and operators’ degree of satisfaction: 4 or 5Results are summarized in table 1.Abstract 46 Figure 1Abstract 46 Table 1ConclusionsCentral neuraxial blocks could be alternative techniques for colorectal ESD procedures, especially for fragile patients [3]. Procedure duration could not be accurately predicted, thus continuous epidural or CSE, should be preferred. Research trials are needed to corroborate our thoughts.

Chronic hepatitis B virus infection is strongly associated with the development of hepatocellular carcinoma (HCC). Epithelial tumors are frequently characterized by loss of cadherin expression or function. Cadherin-dependent adhesion prevents the acquisition of a migratory and invasive phenotype, and loss of its function is itself enough for the progression from adenoma to carcinoma. The HBx protein of hepatitis B virus is thought to contribute to the development of the carcinoma, however, its role in the oncogenic and metastatic processes is far from being fully understood. We report herein the ability of HBx to disrupt intercellular adhesion in three different cell lines stably transfected with an inducible HBx expression vector. The linkage between the actin cytoskeleton and cadherin complex, which is essential for its function, is disrupted in the presence of HBx, as indicated by detergent solubility and immunoprecipitation experiments. In addition, beta-catenin was tyrosine phosphorylated in HBx-expressing cells. Inhibition of the src family of tyrosine kinases resulted in the prevention of the disruption of adherens junctions. These results suggest that HBx is able to disrupt intercellular adhesion in a src-dependent manner, and provide a novel mechanism by which HBx may contribute to the development of HCC.