Long Term Follow-Up of the Endovascular Trans-Vessel Wall Technique for Parenchymal Access in Rabbit with Full Clinical Integration

OBJECTIVE: Endovascular techniques are providing options to surgical/percutaneous cell transplantation methods. Some cells, e.g. insulin producing cells, are not suitable for intra-luminal transplantation and for such cells, other options must be found. We have constructed a "nanocatheter" with a penetrating tip for vessel perforation, thereby creating a working channel for parenchymal access by endovascular technique. To finish the procedure safely, the distal tip is detached to provide a securing plug in the vessel wall defect. MATERIALS AND METHODS: We have performed interventions with full clinical integration in the superior mesenteric artery (SMA), the subclavian artery and the external carotid artery in rabbits. No hemorrhagic- or thromboembolic events occurred during the procedure. Stenosis formation and distal embolisation were analyzed by angiography and macroscopic inspection during autopsy at five, 30 and 80 days. All animals and implanted devices were also evaluated by micro-dissections and histochemical analysis. RESULTS: In this study we show safety data on the trans-vessel wall technique by behavioral, angiographical and histological analysis. No stenosis formation was observed at any of the follow-up time points. No animals or organs have shown any signs of distress due to the intervention. Histological examination showed no signs of hemorrhage, excellent biocompatibility with no inflammation and a very limited fibrous capsule formation around the device, comparable to titanium implants. Further, no histological changes were detected in the endothelia of the vessels subject to intervention. CONCLUSIONS: The trans-vessel wall technique can be applied for e.g. cell transplantations, local substance administration and tissue sampling with low risk for complications during the procedure and low risk for hemorrhage, stenosis development or adverse tissue reactions with an 80 days follow-up time. The benefit should be greatest in organs that are difficult or risky to reach with surgical techniques, such as the pancreas, the CNS and the heart

P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

open access articleDuchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target

Patient Safety in Internal Medicine

AbstractHospital Internal Medicine (IM) is the branch of medicine that deals with the diagnosis and non-surgical treatment of diseases, providing the comprehensive care in the office and in the hospital, managing both common and complex illnesses of adolescents, adults, and the elderly. IM is a key ward for Health National Services. In Italy, for example, about 17.3% of acute patients are discharged from the IM departments. After the epidemiological transition to chronic/degenerative diseases, patients admitted to hospital are often poly-pathological and so requiring a global approach as in IM. As such transition was not associated—with rare exceptions—to hospital re-organization of beds and workforce, IM wards are often overcrowded, burdened by off-wards patients and subjected to high turnover and discharge pressure. All these factors contribute to amplify some traditional clinical risks for patients and health operators. The aim of our review is to describe several potential errors and their prevention strategies, which should be implemented by physicians, nurses, and other healthcare professionals working in IM wards

Recurrent venous thromboembolism and major bleeding in patients with localised, locally advanced or metastatic cancer: an analysis of the Caravaggio study

Background: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear.Methods: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation.Results: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ra-tio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The ef-ficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study.Conclusions: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding. (c) 2022 Published by Elsevier Ltd.Thrombosis and Hemostasi