L' agoaspirato tiroideo sotto guida elastosonografica: studio prospettico randomizzato e revisione della Letteratura

L' agoaspirato ecoguidato (FNA) rappresenta ad oggi il gold standard per la diagnosi della patologia nodulare tiroidea. L’esame è caratterizzato da un basso tasso di complicanze e da una buona tollerabilità da parte del paziente. Nonostante l’agoaspirato presenti una elevata sensibilità e specificità, è tuttavia gravato da una certa percentuale di campioni non diagnostici che si attesta a seconda delle varie casistiche tra il 10 ed il 30%. Un prelievo non diagnostico può portare a procedure ripetute, aumentando la morbilità del paziente, i costi, nla probabilità di complicanze ed il ritardo nella diagnosi. Un altro importante limite dell'esame citologico è rappresentato dai prelievi "indeterminati", classificati come TIR 3, per i quali i soli criteri citologici non sono sufficienti a definire la benignità o malignità della lesione. I noduli tiroidei TIR 3 risultano infatti maligni all'istologia in una percentuale compresa tra il 10 e il 30% a seconda delle diverse casistiche. Le linee guida della Società Italiana di Anatomia Patologica e Citologia Diagnostica sulla classificazione citologica dell’agoaspirato tiroideo suddividono questa categoria in due sottocategorie, TIR 3A, con un rischio di malignità atteso del 5-10%, e la categoria TIR 3B con un rischio del 15-30%. Le linee guida indicano la chirurgia come trattamento di scelta solo per la categoria TIR 3B, mentre per la categoria a rischio minore è consigliabile il follow-up clinico e l’eventuale ripetizione dell’esame a distanza. Tuttavia, nonostante lo sforzo classificativo, la categoria TIR3 rischia spesso di configurarsi, sia per il patologo che per il clinico, come una vera e propria "zona grigia". Recentemente l’elastosonografia ha attirato notevole interesse per la sua capacità di differenziare la patologia nodulare tiroidea benigna da quella maligna, in base alle caratteristiche di elasticità dei tessuti. Dal momento che tale metodica è in grado di definire, anche all’interno dello stesso nodulo, aree con maggiore o minore ‘rigidità’, abbiamo ipotizzato che ottenere una mappa della lesione nodulare potesse ‘guidare’ il prelievo citologico sulla zona ottimale da campionare. Dopo aver analizzato sistematicamente le più recenti evidenze scientifiche inerenti l'elastosonografia e la citoaspirazione tiroidea, è stato condotto uno studio prospettico randomizzato sull' applicazione della tecnologia elastosonografica all' esame citoaspirativo tirodeo. Lo studio ha compreso un totale di 62 pazienti (50 F, 12 M, età media 40,1 ± 5,2 anni, range: 28-68 anni) randomizzati in due gruppi: Gruppo A (31 pazienti) con nodulo tiroideo sottoposto a FNA convenzionale (ecoguidato), Gruppo B (31 pazienti) con nodulo tiroideo sottoposto a FNA con selezione dell'area da campionare mediante esame elastosonografico. Il campionamento effettuato sotto guida elastosonografica delle aree caratterizzate da maggior rigidità (colore blu) ha prodotto una percentuale di prelievi non diagnostici pari al 6.4 % (2 TIR1) mentre la percentuale di agoaspirati non diagnostici eseguiti sotto guida ecografica (9 TIR 1) è stata del 29 % (p=0.02). La distribuzione nei Gruppi A e B delle altre categorie diagnostiche non ha presentato differenze statisticamente significative (p >0.05). La sensibilità e la specificità delle due diverse metodiche citoaspirative sono risultate sostanzialmente sovrapponibili. L’ applicazione della metodica elastosonografica ha determinato una riduzione degli agoaspirati non diagnostici (TIR 1) del 22,6%, supportando l'ipotesi che una mappa elastosonografica della formazione nodulare possa efficacemente guidare il prelievo citologico sulla zona ottimale da campionare, riducendo i costi, le complicanze e soprattutto il disconfort per il paziente derivante dalla reiterazione dell' esame. Sebbene tali risultati siano supportati da una ridotta numerosità campionaria, aprono nuove prospettive nella ricerca e nello sviluppo di metodiche innovative, capaci di incrementare l'accuratezza diagnostica dell'agoaspirato tiroideo

MELCOR-To-MELCOR Coupling Method in Severe Accident Analysis Involving Core and Spent Fuel Pool

A lot of effort has been spent to prevent the occurrence of SA in nuclear plant and to develop Severe Accidents (SA) Management to mitigate the consequences of a SA. Those consequences are mainly related to limit the release of fission product to the environment. The core in the vessel is not the only source of fission products as the Spent Fuel Pool (SFP) hosting the fuel removed by the core is, in some NPP, inside the containment and SA conditions can also occur. This is especially important in reactors having proximity between the RPV and SFP such as the VVER-1200. This close proximity implies that any SA occurring in the SFP potentially affects the RPV and vice-versa. This potential combination might cause unexpected evolution in the SA progression to whom the safety systems are not able to contain. MELCOR code is a widely used, flexible powerful SA code but it is incapable (due to the uniqueness of the COR package use inside the same input) to reproduce a situation in which both the fuel in vessel core and the fuel in the SFP, inside the same containment, are going to experience a severe accident scenario. The current study presents a MELCOR-to-MELCOR coupling method to simulate simultaneously scenarios with both, core and SFP, as sources capable of H2 generation, fuel damage and FP release in a VVER-1200 NPP. The coupling is performed by running two simulations in parallel and with the data exchange supervised and managed by a dedicated Python coupling supervising script developed at NINE

Spider surgical system versus multiport laparoscopic surgery. Performance comparison on a surgical simulator

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience

Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds

Recurrent differentiated thyroid cancer: to cut or burn

[No abstract available

Meta-analysis of thyroidectomy with ultrasonic dissector versus conventional clamp and tie

<p>Abstract</p> <p>Background</p> <p>We conducted a systematic review to evaluate the role of Ultrasonic dissector (UAS) versus conventional clamp and tie in thyroidectomy.</p> <p>Materials and methods</p> <p>We searched for all published RCT in into electronic databases. To be included in the analysis, the studies had to compare thyroidectomy with UAS versus conventional vessel ligation and tight (conventional technique = CT). The following outcomes were used to compare the total thyroidectomy group with UAS versus CT group: operative duration, operative blood loss, overall drainage volume during the first 24 hours, transiet laryngeal nerve palsy, permanent laryngeal nerve palsy, transiet hypocalcaemia and permanent hypocalcaemia.</p> <p>Results</p> <p>There are currently 7 RCT on this issue to compare thyroidectomy with UAS versus CT. From the analysis of these studies it was possible to confront 608 cases: 303 undergoing to thyroidectomy with UAS versus 305 that were treated with CT. Actually, it was shown a relevant advantage of cost-effectiveness in patients treated with UAS; there is a statistically significant reduction of the operative duration (weighted mean difference [WMD], -18.74 minutes; 95% confidence interval [CI], (-26.97 to -10.52 minutes) (P = 0.00001), intraoperative blood loss (WMD, -60.10 mL; 95% CI, -117.04 to 3.16 mL) (P = 0.04) and overall drainage volume (WMD, -35.30 mL; 95% CI, -49.24 to 21.36 mL) (P = 0.00001) in the patients underwent thyroidectomy with UAS. Although the analysis showed that the patients who were treated with USA presented more favourable results in incidence of post-operative complications (transient laryngeal nerve palsy: P = 0.11; permanent laryngeal nerve palsy: not estimable; transient hypocalcaemia: P = 0.24; permanent hypocalcaemia: P = 0.45), these data didn't present statistical relevance.</p> <p>Conclusion</p> <p>This meta-analysis shown a relevant advantage only in terms of cost-effectiveness in patients treated with UAS; it is subsequent to statistically significant reduction of operation duration, intraoperative blood loss and of overall drainage volume during the first 24 hours. Although the analysis showed that the patients who were treated with UAS presented more favourable results in incidence of post-operative complications (transiet laryngeal nerve palsy; transiet hypocalcaemia and permanent hypocalcaemia), these data didn't present statistical relevance.</p

Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold

Abstract: Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates, gave a new family of 1,4,5-trisubstitued triazole carboxylic acid derivatives that showed high affinity towards Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring, were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstitued triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18; SST0287CL1) was selected for further investigation as the most promising drug candidate