Modelling Pancreatic Neuroendocrine Cancer: From Bench Side to Clinic

Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease

Implant surfaces exposed to the oral cavity and treated with toothpaste containing oxygen releasing compound : a morphological controlled clinical trial

Aim of the present in vivo study is to assess if a toothpaste containing an oxygen releasing compound (AX) is able to reduce the biofilm formation on implants with rough surface compared to a control toothpaste, without affecting the microstructure of the tested surface. Methods: In this double blind, cross-over, controlled clinical trial, a total of fourteen healthy volunteers were recruited. For each subject, two mandibular splints (test and control) were created with one implant fixed on the right lingual side of the mandibular arch. The splint was continuously worn for 5 days and the daily hygiene was performed wearing the splint and using the test (AX) or control toothpaste. Implants were analyzed at scanning-electron-microscopy and at laser profilometer for the assessment of biofilm adhesion (% of areas free from biofilm-FA) and surface changes (morphology and roughness). Results: FA resulted significantly higher in test than in control implants. No differences were found between groups in term of biofilm organization, surface microstructure and roughness. Discussion: Daily use of toothpaste containing AX seems to reduce the amount of biofilm adherent to the rough implant surface without corrosion or degradation of the titanium surface

The effect of differential quality and differential zealotry in the best-of-n problem

© 2020 Owner/Author. In this paper, we study the interplay between differential option quality and differential quantity of individuals with fixed option (henceforth called zealots), in a best-of-n problem with n - 2 options. We study how the consensus equilibria change with respect to these two factors. We perform systematic computer simulations in an antagonistic scenario whereby one option has a higher quality but a minority of zealots compared to the other option

Heart rate variability in patients with cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Cirrhosis is associated with abnormal autonomic function and regulation of cardiac rhythm. Measurement of heart rate variability (HRV) provides an accurate and non-invasive measurement of autonomic function as well as liver disease severity currently calculated using the MELD, UKELD, or Child-Pugh scores. This review assesses the methods employed for the measurement of HRV, and evaluates the alteration of HRV indices in cirrhosis, as well as their value in prognosis. METHOD: We undertook a systematic review using Medline, Embase and Pubmed databases in July 2020. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias of included studies was assessed by a modified version of the Newcastle-Ottawa Scale. The studies descriptive were analysed and the standardized mean differences of HRV indices were pooled. RESULTS: Of the 247 studies generated from our search, 14 studies were included. One of the 14 studies was excluded from meta-analysis because it reported only median of HRV indices. The studies included have a low risk of bias, and include 583 patients with cirrhosis and 349 healthy controls. The HRV time and frequency domains were significantly lower in cirrhotic patients. Between-studies heterogeneity was high in most of the pooled studies (P<0.05). Further, HRV indices predict survival independent of the severity of liver disease as assessed by MELD. CONCLUSION: HRV is decreased in patients with cirrhosis compared with healthy matched controls. HRV correlated with severity of liver disease and independently predicted survival. There was considerable variation in the methods used for HRV analysis, and this impedes interpretation and clinical applicability. Based on the data analysed, SDNN (standard deviation of inter-beat intervals) and cSDNN (i.e. SDNN corrected for basal heart rate) are the most suitable indices for prognosis in patients with cirrhosis

Hypertrophic cardiomyopathy: two-dimensional echocardiographic score versus clinical and electrocardiographic findings.

The severity and site of hypertrophy is important in determining the clinical picture and the natural history of hypertrophic cardiomyopathy (HCM). We evaluated left ventricular hypertrophy by means of two-dimensional echocardiographic score and score index, and correlated these findings with symptoms, electrovector-cardiographic data, and ventricular arrhythmias. A total of 42 patients with HCM were studied by clinical examination, ECG, VCG, M-mode and 2D echocardiography, and 24-h Holter monitoring. The extent and severity of the hypertrophic process were calculated by a score system. The left ventricle was divided into 11 segments and a hypertrophic score (HS) was given to each segment. A hypertrophy score index (HSI) was also calculated by dividing the number of hypertrophied segments by 13. No correlation was found between symptoms and HS and HSI, nor ECG-VCG abnormalities and HS and HSI. A statistically significant relationship between the severity of ventricular arrhythmias and HS and HSI was found (p less than 0.01). The mechanism responsible for ventricular tachyarrhythmias in severe and diffuse hypertrophy might reside in the high intraventricular pressures which produce or worsen areas of myocardial ischemia

Il Percorso Diagnostico Terapeutico Assistenziale del paziente con melanoma metastatico presso l\u2019Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo come strumento applicativo della clinical governance

L\u2019evoluzione dello scenario internazionale relativo alla sanit\ue0 identifica cinque specifiche dimensioni come driver del cambiamento: il sistema, la finanza, le persone, i processi e la tecnologia. In linea con tali elementi, il patto per la salute 2014-2016 esplicita la necessit\ue0 di una rivisitazione a tutti i livelli del sistema salute, sia organizzativo che gestionale, con l\u2019intento di aumentare l\u2019efficienza e l\u2019efficacia, sviluppando nuovi modelli assistenziali, anche nella logica delle reti cliniche, dove tra gli \u201cstrumenti\u201d viene identificata l\u2019attivazione di Percorsi Diagnostico Terapeutico Assistenziali (PDTA). I percorsi condivisi e codificati per i vari stadi di patologia, con un sistema di raccolta dei dati clinici che possa generare gli indicatori di processo e di esito, sono ritenuti indispensabili per innescare il miglioramento della qualit\ue0 e valutare l\u2019efficacia e l\u2019efficienza. Tenendo conto di queste premesse, nell\u2019ambito dell\u2019Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo \ue8 stata sviluppata una progettualit\ue0 al fine di formalizzare e studiare il PDTA del paziente con melanoma metastatico, identificando il percorso ideale e descrivendo il percorso applicabile con le relative leve del cambiamento. Il progetto ha reso evidente come la gestione consapevole del \u201cprofondo cambiamento\u201d in essere nelle organizzazioni clinico assistenziali pu\uf2 essere \u201cgovernata\u201d grazie anche alla \u201cdocumentazione\u201d del proprio modo di operare in riferimento alle Linee Guida di riferimento e alle relative raccomandazioni. Il progetto ha reso evidente inoltre come la sostenibilit\ue0 dei percorsi passa anche attraverso la definizione di opportuni indicatori, correlati alle diverse fasi ed attivit\ue0 chiave, da poter monitorare nella \u201cvita corrente dell\u2019organizzazione\u201d

Dental treatment of a rare case of pyoderma gangrenosum with aggressive periodontal disease

Background and Overview: Pyoderma gangrenosum (PG) is a rare neutrophil-mediated autoinflammatory dermatosis that can involve the oral mucosa. Dental surgery is a potential triggering factor for the onset of PG lesions. The authors describe and discuss the dental management of a rare case of aggressive periodontitis in a patient with PG, from multiple tooth extractions to prosthetic rehabilitation, including administration of systemic steroid prophylaxis before surgery to prevent the potential onset of PG-related lesions. Case Description: A 22-year-old man who had a diagnosis of PG and who had aggressive periodontal disease underwent dental extractions, gingivoplastic surgery, and prosthetic rehabilitation. The patient received 8 milligrams of betamethasone intramuscularly 20 minutes before the oral surgery. The tissues healed perfectly, and no adverse effects were reported. Conclusions and Practical Implications: For minor oral surgery, prophylactic corticosteroids might help reduce the risk of developing PG-related lesions. The clinician should plan the prosthetic devices to be as atraumatic as possible

Beta-tricalcium phosphate ceramic triggers fast and robust bone formation by human mesenchymal stem cells

Due to their osteoconductive and inductive properties, a variety of calcium phosphate (CaP) scaffolds are commonly used in orthopaedics as graft material to heal bone defects. In this study, we have used two CaP scaffolds with different hydroxyapatite (HA) and \u3b2-tricalcium phosphate (\u3b2-TCP) ratios (MBCP\uae; 60/40 and MBCP+\uae; 20/80) to investigate their intrinsic capacity to favour human bone marrow stem cells (hBMSCs) osteogenic differentiation capacity. We report that MBCP+\uae showed in in vitro culture model a higher rate of calcium ion release in comparison with MBCP\uae. In two defined coculture systems, the hBMSC seeded onto MBCP+\uae presented an increased amount of VEGF secretion, resulting in an enhanced endothelial cell proliferation and capillary formation compared with hBMSC seeded onto MBCP\uae. When both ceramics combined with hBMSC were implanted in a nude mouse model, we observed a faster osteogenic differentiation and enhancement mature bone deposition sustained by the presence of a vast host vasculature within the MBCP+\uae ceramics. Bone formation was observed in samples highly positive to the activation of calcium sensing receptor protein (CaSr) on the surface of seeded hBMSC that also shown higher BMP-2 protein expression. With these data we provide valuable insights in the possible mechanisms of ossification and angiogenesis by hBMSC that we believe to be primed by calcium ions released from CaP scaffolds. Evidences could lead to an optimization of ceramic scaffolds to prime bone repair

Heart Rate Turbulence Predicts Survival Independently From Severity of Liver Dysfunction in Patients With Cirrhosis

Background: Reduced heart rate variability (HRV) is an independent predictor of mortality in patients with cirrhosis. However, conventional HRV indices can only be interpreted in individuals with normal sinus rhythm. In patients with recurrent premature ventricular complexes (PVCs), the predictive capacity of conventional HRV indices is compromised. Heart Rate Turbulence (HRT) represents the biphasic change of the heart rate after PVCs. This study was aimed to define whether HRT parameters could predict mortality in cirrhotic patients. Materials and Methods: 24 h electrocardiogram recordings were collected from 40 cirrhotic patients. Turbulence Onset was calculated as HRT indices. The enrolled patients were followed up for 12 months after the recruitment in relation to survival and/or transplantation. Results: During the follow-up period, 21 patients (52.5%) survived, 12 patients (30%) died and 7 patients (17.5%) had liver transplantation. Turbulence Onset was found to be strongly linked with mortality on Cox regression (Hazard ratio = 1.351, p < 0.05). Moreover, Turbulence Onset predicted mortality independently of MELD and Child-Pugh's Score. Conclusion: This study provides further evidence of autonomic dysfunction in cirrhosis and suggests that HRT is reliable alternative to HRV in patients with PVCs