cheilognatopalatoschisi sindromica: analisi della casistica nel Percorso Labiopalatoschisi di Pisa dal 2009 al 2015

Le cheilognatopalatoschisi (CGPS) sono una delle malformazioni congenite più frequenti. Questi disturbi sono causati da un’alterata, o mancata fusione di una o più strutture orofacciali durante la vita intrauterina. Rappresentano delle condizioni con un notevole impatto dal punto di vista delle spese sanitarie a breve e lungo termine e dal punto di vista sociale. I bambini affetti sono pazienti che necessitano dell’intervento di un team multidisciplinare. Le schisi possono essere classificate anatomicamente in: schisi del labbro con o senza schisi del palato (cleft lip with or without cleft palate CL/P) e schisi del solo palato (cleft palate only CPO). L’incidenza globale delle schisi orofacciali è di circa 1:700 nati vivi; lo studio dei dati epidemiologici delle differenti popolazioni ha mostrato che la prevalenza delle CPO è più bassa di quella delle CL/P. Le schisi orofacciali presentano un elevato tasso di ricorrenza familiare. Un’altra classificazione distingue le schisi orofacciali in forme sindromiche e forme isolate (o non sindromiche) in base alla presenza o meno di altre anomalie fisiche congenite e di sviluppo. Numerosi studi indicano che circa il 70% dei casi di CL/P e circa il 50% dei casi di CPO si presentano in assenza di altre anomalie e quindi in forme isolate. I casi restanti possono associarsi con una delle oltre 400 sindromi descritte. Presso la divisione di Chirurgia Plastica di Pisa è operante, dagli anni ’80, un gruppo interdisciplinare che segue i pazienti affetti da labiopalatoschisi durante tutte le fasi: diagnosi, trattamento, riabilitazione e follow-up. Nel 2014 è stato poi inaugurato il Percorso Labiopalatoschisi di Pisa costituito da un team di specialisti coordinati dal dr. Gian Luca Gatti, che seguono un protocollo di approccio multidisciplinare alla labiopalatoschisi. La notevole esperienza del team chirurgico del Percorso Labiopalatoschisi permette di trattare anche le malformazioni che possono associarsi alla CGPS nell’ambito dei pazienti sindromici. Tra queste malformazioni abbiamo: polidattilie, sindattilie, briglie aderenziali, anchiloglossia, deformità del padiglione auricolare, fistole labiali, schisi facciali rare e altre. Inoltre la presenza, nel team, del genetista, del neonatologo e del pediatra consente di diagnosticare rapidamente l’interessamento di altri organi e apparati. I pazienti sindromici trattati nell’Unità Operativa di Chirurgia Plastica dal 2009 al 2015 sono 51. Dall’analisi di questa casistica si deduce che per questi pazienti è fondamentale l’approccio multidisciplinare fin dalla diagnosi che può essere fatta durante la gravidanza mediante esami ecografici oppure direttamente alla nascita. Dal punto di vista del chirurgo plastico, gli interventi di riparazione delle schisi non risultano più complessi rispetto a quelli eseguiti su pazienti non sindromici. Le maggiori difficoltà stanno nella gestione del paziente durante i primi mesi di vita per assicurare un accrescimento staturo-ponderale adeguato, senza il quale il bambini non potrebbe essere sottoposti ad interventi chirurgici e nella programmazione di interventi aggiuntivi per la correzione delle malformazioni associate alla labiopalatoschisi

Embedding and Automating Conditional Logics in Classical Higher-Order Logic

A sound and complete embedding of conditional logics into classical higher-order logic is presented. This embedding enables the application of off-the-shelf higher-order automated theorem provers and model finders for reasoning within and about conditional logics.Comment: 15 pages, 1 Figure, 1 Tabl

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules

Adding Organizations and Roles as Primitives to the JADE Framework

The organization metaphor is often used in the design and implementation of multiagent systems. However, few agent programming languages provide facilities to define them. Several frameworks are proposed to coordinate MAS with organizations, but they are not programmable with general purpose languages. In this paper we extend the JADE framework with primitives to program in Java organizations structured in roles and to enable agents to play roles in organizations. Roles facilitate the coordination of agents inside an organization and give new abilities in the context of organizations, called powers, to the agents which satisfy the requirements necessary to play the roles. As primitives to program organizations and roles we provide classes and protocols which enable an agent to enact a new role in an organization and to interact with the role by invoking the execution of powers, and to receive new goals to be fulfilled. Roles have state and behaviour, thus, they are instances of classes and are strictly connected with the organization offering them. Since roles and organizations can be on a different platform with respect to the role player, the communication with them happens via protocols. Moreover, since, besides using protocols, roles and organizations can have complex behaviours, they are implemented by extending the JADE agent class

Post-surgical Thyroid Bed Pyoderma Gangrenosum Mimicking Recurrent Papillary Thyroid Carcinoma

Background: Pyoderma gangrenosum (PG) is a rare inflammatory disease presenting with chronic-recurrent cutaneous ulcers histopathologically hallmarked by neutrophilic infiltrates, which may occur more frequently at sites of surgical traumas. The disease is habitually limited to the skin, but it can virtually involve any organ. Nevertheless, no prior cases of PG involving the thyroid bed have ever been reported.Case Report: A bilateral PG of the breast was diagnosed in a 51-year-old woman and treated with intravenous methylprednisolone pulse-therapy and cyclosporine, with partial improvement. During the hospitalization, cytological examination of two hypoechoic thyroid nodules by fine-needle aspiration (FNA) was consistent with thyroid carcinoma. After total thyroidectomy, histopathology confirmed a papillary thyroid cancer (PTC), and radioactive iodine ablation was performed. At 12-month ultrasonographic follow-up, two hypoechoic avascular areas localized in the empty thyroid bed raised the suspect of PTC recurrence. However, (i) undetectable levels of thyroglobulin without anti-thyroglobulin antibodies, (ii) neutrophilia and increased inflammatory marker levels, and (iii) cytological examination of FNA showing numerous neutrophils induced to suspect thyroid bed PG infiltration. An ex juvantibus approach with high-dose methylprednisolone led to dimensional reduction of the hypoechoic areas on ultrasonography, thus confirming the hypothesis of thyroid bed PG.Conclusion: This case of thyroid bed PG supports the idea that PG reflects a cutaneous phenotype encompassed in the spectrum of systemic neutrophilic diseases. Endocrinologists should be aware that thyroid bed PG involvement is an albeit rare differential diagnosis to consider in patients who had undergone thyroid surgery, especially with a history of PG

Robot-assisted pancreaticoduodenectomy with vascular resection: technical details and results from a high-volume center

Background: Pancreaticoduodenectomy with vein resection (PD-VR) is widely accepted as a standard procedure to achieve a higher rate of R0 resections in borderline resectable pancreatic tumors. Thanks to the availability of newer technologies, such as the da Vinci Surgical System, several high-volume centers are reporting small series of minimally invasive PD-VR. Methods: A retrospective review of a prospectively maintained database was performed to identify patients who underwent robot-assisted PD-VR (RAPD-VR) between May 2011 and December 2019. The following factors were specifically analyzed: intraoperative results, post-operative complications, mortality at 90 days, patency of vascular reconstructions, overall survival (OS) and disease-free survival (DFS). Results: During the study period 184 patients underwent RAPD, including 22 who received a RAPDVR (12.0%). The superior mesenteric vein was resected in 9 patients (40.9%), the portal vein in 3 patients (13.6%) and the spleno-mesenteric junction in 10 patients (45.5%). Based on the classification provided by the International Study Group on Pancreatic Surgery these procedures were classified as follows: 1 type I (4.5%), 3 type II (13.6%), 10 type III (45.5%) and 8 type IV (36.4%). In no patient the splenic vein was ligated and left behind. The splenic vein was always reimplanted either on the porto-mesenteric axis or in the inferior vena cava. All but one procedure, were completed under robotic assistance (conversion rate 1/22; 4.5%) after a mean operative time of 610.0±83.5 minutes. Median estimated blood loss was 899.7 mL (719.4–1,430.2 mL), with 2 patients (9.1%) receiving intraoperative blood transfusions. Sixteen patients developed post-operative complications (72.7%), graded ≥III (according to Clavien-Dindo) in 5 patients (22.7%). Two patients died within 90 days, accounting for a postoperative mortality of 9.1%. Interestingly, post-operative pancreatic fistula (grade B) occurred in only 1 patient (4.5%). Repeat surgery was required in 4 patients (18.2%) and hospital readmission in 1 patient (4.5%). At the longest available follow-up, vein reconstruction was patent in 19 patients (86.4%). Eighteen patients had a final diagnosis of pancreatic ductal adenocarcinoma (81.8%). After circumferential study of resection margins, microscopic tumor residual ≤1 mm was found in 11 patients (50.0%). The mean number of examined lymph nodes was 42.2 (±16.3), and vascular infiltration was confirmed in 13 patients (59.1%). Median OS was 39.7 (27.5–not available) and DFS 32.9 (11.5–45.8). Tumor recurrence was identified in 6 patients (27.3%). One patient (4.5%) developed isolated local recurrence. Conclusions: We have shown the feasibility of RAPD-VR. The results reported herein need to be confirmed in larger series and their generalizability remains to be established