Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3\u2009cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3\u2009cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT

WARM UP LUBE SYSTEM (WULS) RELATION BETWEEN A NEW APPROACH TO LUBRICATION DURING START-UP PHASES AND THE THERMAL SHOCK ON THE DIE SURFACE AND SCRAP REDUCTION

The continuous research for efficiency, associated with higher and higher quality standards in the different industrial production processes, has led, in the last few years, to further and more exhaustive analysis of the various machine cycle phases in the light alloy diecasting sector. The result of these studies was the development of new interdisciplinary technologies, which have firstly highlighted, and then solved “chronic” inefficiencies during the start-up phases. Today, the WULS system is able to optimize the Warm Up phase, being based on the die surface temperature value (thanks to the C.T.C. - acquisition module) and retroacting on the lubrication equipment. In this paper the authors present the WULS technology and highlight the existing relation between the Warm Up phase and the thermal shock generated on the die surface, emphasizing its high level of influence. It has been well shown by means of several tests in an Italian foundry that WULS technology, together with a specific warm-up phase lubricant, ensure: - decreasing thermal shock (approx. 66% of reduction in temperature drop) - reduction of scrap pieces during production starting (approx. - 50%)

Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed

DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness

Relationship between low Ankle-Brachial Index and rapid renal function decline in patients with atrial fibrillation: A prospective multicentre cohort study

OBJECTIVE: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). DESIGN: Observational prospective multicentre cohort study. SETTING:Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. PARTICIPANTS: 897 AF patients on treatment with vitamin K antagonists. MAIN OUTCOME MEASURES: The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. RESULTS: Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). CONCLUSIONS: In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p &lt;0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p &lt;0.0001), age (OR 1.03 per year, p &lt;0.001), hypertension (OR 2.30, p &lt;0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

PRODUZIONE E CARATTERIZZAZIONE DI COMPOSITI A MATRICE IN LEGA DI ALLUMINIO RINFORZATI CON SCHIUMA CERAMICA

La ricerca di materiali e tecniche produttive sufficientemente economiche è diventato un aspetto essenziale per l’estensione delle potenzialità applicative dei compositi a matrice di alluminio. In questo lavoro viene illustrata la produzione, con la tecnica dell’infiltrazione sotto pressione di gas inerte, di materiali compositi a matrice in lega Al-Si, rinforzati con una schiuma ceramica (SiC) di facile reperibilità. La caratterizzazione dei materiali così ottenuti ha consentito di verificare la formazione di una buona interfaccia tra matrice e rinforzo e l’assenza di porosità. Le caratteristiche di microdurezza della matrice sono risultate influenzate dalla tipologia di schiuma impiegata, per effetto delle differenti condizioni di solidificazione

SOBRE ESTUDIOS PARA ESTABLECER UN PROCEDIMIENTO INDUSTRIAL PARA PRODUCIR PIEZAS MEDIANTE COLADA A PRESION (DIE-CASTING) FUNDIENDO MATERIAL COMPUESTO DE MATRIZ METALICA

Los materiales compuestos de matriz met\ue1lica (Metal Matrix Composites, MMC), es decir, aleaciones conteniendo en su interior refuerzo de part\uedculas o fibras, han sido poco utilizados como material para ser colado a presi\uf3n, tal como se hace con otras aleaciones en la producci\uf3n industrial de piezas. El motivo puede encontrarse, por un lado, en la dificultad de obtener una pieza final con las buenas caracter\uedsticas que pose\ueda el material de partida (morfolog\ueda, dimensi\uf3n y distribuci\uf3n del refuerzo; interfase matriz-refuerzo), y por otro, en la necesidad de introducir algunos cambios en el sistema de colada a presi\uf3n. Esto \ufaltimo puede involucrar modificaciones del molde, del crisol y material fundido, as\ued como optimizaci\uf3n de los par\ue1metros de m\ue1quina. En este trabajo se estudian defectos caracter\uedsticos observados en piezas coladas a presi\uf3n con aleaci\uf3n de Al conteniendo part\uedculas de SiC, mediante metalograf\ueda y radiograf\ueda, en funci\uf3n de par\ue1metros de producci\uf3n. Se discute sobre las condiciones m\ue1s favorables del proceso de colada, y se muestra que mediante la "personalizaci\uf3n" de cada caso (selecci\uf3n del tipo de matriz y refuerzo, geometr\ueda de la pieza, eventuales modificaciones del molde sugeridas por un "modelling" de fundici\uf3n, etc.) la producci\uf3n industrial es viable