Computational studies of oxygen transport in arterio-venous fistulae

Arterio-venous-fistulae (AVF) are surgically-formed connections between an artery and a vein and are regarded as the “gold standard” method of vascular access, for haemodialysis. Nonetheless, up to 60% fail within three months of creation. Their principal failure mechanism is intimal hyperplasia (IH), an adverse inflammatory process causing AVF to block and fail. Evidence suggests that IH is a multifactorial process, attributable to an altered vascular environment, including increased metabolic stress, flow disturbances, mechanical stress, and wall hypoxia (low oxygen levels). The present work focuses on studying wall hypoxia in idealised AVF. Vascular walls are oxygenated by transport from both luminal oxygenated blood and adventitial vasa vasorum (VV), the microvascular network supplying large vessels. Luminal oxygen supply is affected by the altered AVF haemodynamics, while altered wall-mechanics can prevent adequate VV perfusion. The aim of this thesis is to ascertain what is most important in determining wall-oxygen levels: (i) modified luminal flow field; (ii) mechanically-modified VV perfusion. Hence, a model of oxygen transport, capable of accounting for VV damage/hypoperfusion, was developed. Geometries and VV perfusion fields obtained from mechanical simulations were used to provide the oxygen transport model with a VV oxygen source. Results suggest that for a given set of wall parameters, the local wall-oxygen levels are governed by the flow field, while spatial distributions of mechanically-modified VV perfusion are shown to have negligible effects on the local wall-oxygen levels. However, overall wall-oxygen levels are highly sensitive to changes in bulk wall parameters, particularly oxygen consumption rates. Finally, these results were used to develop a simplified oxygen transport model, that is combined with a mesh-adaptive-direct-search approach to identify an optimal AVF configuration with reduced hypoxia levels. The configuration features a non-planar anastomosis and a helical shaped vein.Open Acces

Antithrombotic therapy with rivaroxaban in five patients with paroxysmal nocturnal haemoglobinuria and thrombotic events

Five patients with paroxysmal nocturnal haemoglobinuria and thrombotic complications under oral antithrombotic treatment with vitamin K antagonist were switched to receive the direct oral anticoagulant rivaroxaban an factor Xa inhibitor. In all five patients haematological and biochemical parameters and adverse events were evaluated for a period of twelve months. Therapy with rivaroxaban was well tolerated in all cases and one patient showed a significant reduction of bleeding and transfusion requirement. All patients obtained a significant reduction in days of hospitalization with a consequent improvement in their quality of life after rivaroxaban treatment

Optimization Methods for the Same-Day Delivery Problem

In the same-day delivery problem, requests with restricted time windows arrive during a given time horizon and it is necessary to decide which requests to serve and how to plan routes accordingly. We solve the problem with a dynamic stochastic method that invokes a generalized route generation function combined with an adaptive large neighborhood search heuristic. The heuristic is composed of destroying and repairing operators. The generalized route generation function takes advantage of sampled-scenarios, which are solved with the heuristic, to determine which decisions should be taken at any instant. Results obtained on different benchmark instances prove the effectiveness of the proposed method in comparison with a consensus function from the literature, with an average decrease of 10.7%, in terms of solution cost, and 24.5%, in terms of runtime

Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy

Objectives: Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy Material and method: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. Results: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn't find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn't find mDCs in urine during monthly instillation. Conclusions: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation

le polmoniti nei pazienti provenienti da residenze sanitarie assistenziali e necessaria una strategia terapeutica dedicata

Summary Background: Nursing home-acquired pneumonia (NHAP) was described in 1978, but only in 2005 it has been proposed as part of a new category (health care-associated pneumonia) distinct from community- or hospital-acquired infections. However, limited clinical data exist to validate this proposal. Aim of the study: To compare characteristics and outcome of patients hospitalised for pneumonia and coming from private residence or nursing home. Methods: Post-hoc analysis of the prospective phase of the FASTCAP study, performed to evaluate the impact of the Recommendations issued by the Italian Federation of Internal Medicine (FADOI) in 2002 on the management of hospitalised community-acquired pneumonia (CAP)

The influence of physical activity performed at 20-40 years of age on cardiovascular outcomes in medical patients aged 65-75

Summary Introduction Several studies show that physical activity can reduce the risk of cardiovascular disease, but the vast majority of these focus on the short- to intermediate-term benefits or refer to very specific populations. This observational study was conducted to determine whether physical activity performed during the third or fourth decade of life influences the occurrence of cardiovascular events in patients aged 65-75 years. Materials and methods We studied a cohort of 2191 unselected patients admitted to Internal Medicine Departments. Data were collected on the patients' medical history and their physical activity level when they were 20 to 40 years old. For the latter purpose, we used a specific questionnaire to assess the levels of physical activity related to the patients' job, daily life, leisure time, and sports. Results Almost half (44.2%) of the patients we evaluated reported moderate-intense physical activity when they were 20-40 years old. Around one third (35.8%) of the patients had experienced at least one major cardiovascular event, and there was a slight trend towards fewer cardiovascular events in patients with histories of physical activity (mean risk reduction: 4%, multivariate analysis). More evident benefits were observed in the subgroup of patients with diabetes, where cardiovascular outcomes were much better in patients who had been physically active than in those with sedentary life-styles (mean risk reduction: 24%). Conclusions Given its design, our study may have underestimated the cardiovascular benefits of physical activity. Nonetheless, our results suggest that moderate-intense exercise during young adulthood may have limited beneficial effects on cardiovascular disease in old age, except in specific high-risk populations (diabetic patients). More evident benefits are probably associated with regular physical activity throughout life

Longevity of Replaced ICD/CRT-D

Longevity of Replaced ICD/CRT-D Introduction The longevity of defibrillators (ICD) is extremely important from both a clinical and economic perspective. We studied the reasons for device replacement, the longevity of removed ICD, and the existence of possible factors associated with shorter service life. Methods and Results Consecutive patients who underwent ICD replacement from March 2013 to May 2015 in 36 Italian centers were included in this analysis. Data on replaced devices were collected. A total of 953 patients were included in this analysis. In 813 (85%) patients the reason for replacement was battery depletion, while 88 (9%) devices were removed for clinical reasons and the remaining 52 because of system failure (i.e., lead or ICD generator failure or a safety advisory indication). The median service life was 5.9 years (25th–75th percentile, 4.9–6.9) for single- and dual-chamber ICD and 4.9 years (25th–75th percentile, 4.0–5.7) for CRT-D. On multivariate analysis, the factors CRT-D device, SC/DC ICD generator from Biotronik, percentage of ventricular pacing, and the occurrence of a system failure were positively associated with a replacement procedure. By contrast, the device from Boston Scientific was an independent protective factor against replacement. Considerable differences were seen in battery duration in both ICD and CRT-D. Specifically, Biotronik devices showed the shortest longevity among ICD and Boston Scientific showed the longest longevity among CRT-D (log-rank test, P < 0.001 for pairwise comparisons). Conclusion Several factors were associated with shorter service life of ICD devices: CRT-D, occurrence of system failure and percentage of ventricular pacing. Our results confirmed significant differences among manufacturers

Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen.

The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas. The conditioning regimen consisted of thiotepa, cyclophosphamide, fludarabine, and rituximab (500\u2009mg/m2). Rabbit antithymocyte globulin was administered only in case of unrelated donors. Sixty-seven (55%) and 54 (45%) patients received grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of nonrelapse mortality (NRM) was 21% at 3 years. The CCIs of chronic graft-verus-host disease (GVHD) at 3 years were 54% and 31% in recipients of matched sibling and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-year progression-free and overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite endpoint of GVHD-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a prospective trial of lymphoma patients: the 1-year and 3-year GRFS were 40% and 34%, respectively. AlloSCT can cure a fraction of patients with rather low NRM and an encouraging PFS and GRFS