Implementation of eunethta core model (R) in lombardia: the VTS Framework

Objectives: This study describes the health technology assessment (HTA) framework introduced by Regione Lombardia to regulate the introduction of new technologies. The study outlines the process and dimensions adopted to prioritize, assess and appraise the requests of new technologies. Methods: The HTA framework incorporates and adapts elements from the EUnetHTA Core Model and the EVIDEM framework. It includes dimensions, topics, and issues provided by EUnetHTA Core Model to collect data and process the assessment. Decision making is instead supported by the criteria and Multi-Criteria Decision Analysis technique from the EVIDEM consortium. Results: The HTA framework moves along three process stages: (i) prioritization of requests, (ii) assessment of prioritized technology, (iii) appraisal of technology in support of decision making. Requests received by Regione Lombardia are first prioritized according to their relevance along eight dimensions (e.g., costs, efficiency and efficacy, organizational impact, safety). Evidence about the impacts of the prioritized technologies is then collected following the issues and topics provided by EUnetHTA Core Model. Finally, the Multi-Criteria Decision Analysis technique is used to appraise the novel technology and support Regione Lombardia decision making. Conclusions: The VTS (Valutazione delle Tecnologie Sanitarie) framework has been successfully implemented at the end of 2011. From its inception, twenty-six technologies have been processed

Implementation of eunethta core model (R) in lombardia: the VTS Framework

Objectives: This study describes the health technology assessment (HTA) framework introduced by Regione Lombardia to regulate the introduction of new technologies. The study outlines the process and dimensions adopted to prioritize, assess and appraise the requests of new technologies. Methods: The HTA framework incorporates and adapts elements from the EUnetHTA Core Model and the EVIDEM framework. It includes dimensions, topics, and issues provided by EUnetHTA Core Model to collect data and process the assessment. Decision making is instead supported by the criteria and Multi-Criteria Decision Analysis technique from the EVIDEM consortium. Results: The HTA framework moves along three process stages: (i) prioritization of requests, (ii) assessment of prioritized technology, (iii) appraisal of technology in support of decision making. Requests received by Regione Lombardia are first prioritized according to their relevance along eight dimensions (e.g., costs, efficiency and efficacy, organizational impact, safety). Evidence about the impacts of the prioritized technologies is then collected following the issues and topics provided by EUnetHTA Core Model. Finally, the Multi-Criteria Decision Analysis technique is used to appraise the novel technology and support Regione Lombardia decision making. Conclusions: The VTS (Valutazione delle Tecnologie Sanitarie) framework has been successfully implemented at the end of 2011. From its inception, twenty-six technologies have been processed

Down regulation of membrane-bound Neu3 constitutes a new potential marker for childhood acute lymphoblastic leukemia and induces apoptosis suppression of of neoplastic cells

Membrane-linked sialidase Neu3 is a key enzyme for the extralysosomal catabolism of gangliosides. In this respect, it regulates pivotal cell surface events, including trans-membrane signaling, and plays an essential role in carcinogenesis. In this report, we demonstrated that acute lymphoblastic leukemia (ALL), lymphoblasts (primary cells from patients and cell lines) are characterized by a marked down-regulation of Neu3 in terms of both gene expression (-30 to 40%) and enzymatic activity toward ganglioside GD1a (-25.6 to 30.6%), when compared with cells from healthy controls. Induced overexpression of Neu3 in the ALL-cell line, MOLT-4, led to a significant increase of ceramide (+66%) and to a parallel decrease of lactosylceramide (-55%). These events strongly guided lymphoblasts to apoptosis, as we assessed by the decrease in Bcl2/Bax ratio, the accumulation of Neu3 transfected cells in the sub G0-G1 phase of the cell cycle, the enhanced annexin-V positivity, the higher cleavage of procaspase-3. Therefore, the reduced expression of Neu3 in ALL could help lymphoblasts to survive, maintaining the cellular content of ceramide below a critical level. Interestingly, we found that Neu3 activity varied in relation to disease progression, increasing in clinical remission after chemotherapy, and decreasing again in patients that relapsed. In addition, a negative correlation was observed between Neu3 expression and the percentage of the ALL marker 9-OAcGD3 positive cells. Consequently, Neu3 could represent a new potent biomarker in childhood ALL, to assess the efficacy of therapeutic protocols and to rapidly identify an eventual relapse

Acute lobar nephritis in children: Not so easy to recognize and manage

Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children

Computation of spatio-temporal parameters in level walking using a single inertial system in lean and obese adolescents

In recent years, the availability of low-cost equipment capable of recording kinematic data during walking has facilitated the outdoor assessment of gait parameters, thus overcoming the limitations of three-dimensional instrumented gait analysis (3D-GA). The aim of this study is twofold: firstly, to investigate whether a single sensor on the lower trunk could provide valid spatio-temporal parameters in level walking in normal-weight and obese adolescents compared to instrumented gait analysis (GA); secondly, to investigate whether the inertial sensor is capable of capturing the spatio-temporal features of obese adolescent gait. These were assessed in 10 obese and 8 non-obese adolescents using both a single inertial sensor on the lower trunk and an optoelectronic system. The parameters obtained were not statistically different in either normal-weight or obese participants between the two methods. Obese adolescents walked with longer stance and double support phase compared to normal-weight participants. The results showed that the inertial system is a valid means of evaluating spatio-temporal parameters in obese individuals

Performance measures for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound: A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a short list of key performance measures for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). We recommend that endoscopy services across Europe adopt the following seven key and one minor performance measures for EUS and ERCP, for measurement and evaluation in daily practice at centre and endoscopist level: 1 Adequate antibiotic prophylaxis before ERCP (key performance measure, at least 90%); 2 antibiotic prophylaxis before EUS-guided puncture of cystic lesions (key performance measure, at least 95%); 3 bile duct cannulation rate (key performance measure, at least 90%); 4 tissue sampling during EUS (key performance measure, at least 85%); 5 appropriate stent placement in patients with biliary obstruction below the hilum (key performance measure, at least 95%); 6 bile duct stone extraction (key performance measure, at least 90%); 7 post-ERCP pancreatitis (key performance measure, less than 10%); and 8 adequate documentation of EUS landmarks (minor performance measure, at least 90%). This present list of quality performance measures for ERCP and EUS recommended by the ESGE should not be considered to be exhaustive; it might be extended in future to address further clinical and scientific issues

The Role of Sphingolipids in Cancer Immunotherapy

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets

Extracellular Sphingosine-1-Phosphate Downstream of EGFR Increases Human Glioblastoma Cell Survival

Sphingosine-1-phosphate (S1P) is a crucial mediator involved in the progression of different cancers, including glioblastoma multiforme (GBM), the most frequent and deadly human brain tumor, characterized by extensive invasiveness and rapid cell growth. Most of GBMs overexpress the epidermal growth factor receptor (EGFR), and we investigated the possible link between S1P and EGFR signaling pathways, focusing on its role in GBM survival, using the U87MG human cell line overexpressing EGFR (EGFR+). We previously demonstrated that EGFR+ cells have higher levels of extracellular S1P and increased sphingosine kinase-1 (SK1) activity than empty vector expressing cells. Notably, we demonstrated that EGFR+ cells are resistant to temozolomide (TMZ), the standard chemotherapeutic drug in GBM treatment, and the inhibition of SK1 or S1P receptors made EGFR+ cells sensitive to TMZ; moreover, exogenous S1P reverted this effect, thus involving extracellular S1P as a survival signal in TMZ resistance in GBM cells. In addition, both PI3K/AKT and MAPK inhibitors markedly reduced cell survival, suggesting that the enhanced resistance to TMZ of EGFR+ cells is dependent on the increased S1P secretion, downstream of the EGFR-ERK-SK1-S1P pathway. Altogether, our study provides evidence of a functional link between S1P and EGFR signaling pathways enhancing the survival properties of GBM cells

Characterization and Interaction with Biomembrane Model of Benzo[k,l]xanthene Lignan Loaded Solid Lipid Nanoparticles

Benzo[k,l]xanthene lignans are a group of rare natural products belonging to the class of polyphenols with promising biological activities and are studied as potential chemotherapeutic agents. The lipophilic character of a xanthene core makes these molecules difficult to be used in an aqueous medium, limiting their employment in studies for pharmaceutical applications. To overcome this problem, a drug-delivery system which is able to improve the stability and bioavailability of the compound can be used. In this study, a bioactive benzoxanthene lignan (BXL) has been included in SLN. Unloaded and BXL-loaded SLN have been prepared using the Phase Inversion Temperature method and characterized in terms of size, zeta potential, entrapment efficiency and stability. Differential scanning calorimetry was used to evaluate the thermotropic behavior and ability of SLN to act as carriers for BXL. A biomembrane model, represented by multilamellar vesicles, was used to simulate the interaction of the SLN with the cellular membrane. Unloaded and loaded SLN were incubated with the MLV, and their interactions were evaluated through variations in their calorimetric curves. The results obtained suggest that SLN could be used as a delivery system for BXL