Endoscopic transcanal approach to geniculate ganglion hemangioma and simultaneous facial nerve reinnervation: A case report

Hemangioma of the facial nerve (FN) is a very rare benign tumor whose origin is the vascular plexi that surround the nerve. The transpetrous, retrosigmoid, and middle cranial fossa (MCF) routes are the traditional and most widely used approaches to reach these lateral skull base neoformations. However, this very complex region can be reached through an exclusive transcanal endoscopic procedure in selected cases. One of these was a 42-year-old patient who had been presenting a worsening left FN paralysis (grade VI according to the House-Brackmann scale at the time of visit) for 22 months without a history of trauma or infection. Radiological studies showed a lesion in the region of the geniculate ganglion. A suprageniculate endoscopic approach was performed to remove the lesion, with the sacrifice of the FN and a simultaneous hypoglossal-facial anastomosis. The aim of this minimally invasive surgery is the complete excision of the disease, maintaining the hearing function intact and restoration of facial function, whenever possible, avoiding more invasive approaches

Phytocoenotic diversity of the N-Adriatic coastal sand dunes - The herbaceous communities of the fixed dunes and the vegetation of the interdunal wetlands

The hemicryptophytic, chamaephytic and therophytic communities which inhabit the fixed sand dunes of the N-Adriatic coast, along with those of the interdunal wetlands, have been studied from the phytosociological point of view. The floristic-sociological analysis focuses on the syntaxonomic discussion of the xerophilous communities; in this context, the following new syntaxa have been described: Syntrichio ruraliformis-Lomelosion argenteae, Tortulo-Scabiosetum typicum and Sileno conicae-Avellinietum michelii. In regards to the dune slack vegetation, the study points out the occurrence in the coastal area of two rare inland microtherm communities (Plantagini altissimae-Molinietum caeruleae and Erucastro-Schoenetum nigricantis). As already stated in previous papers, the originality of this sector of the Mediterranean basin is highlighted as a result of both bioclimatic and phytogeographic factors, which confer to this area a unique character in the European context

Tracheostomy in the COVID-19 pandemic

Purpose: The role of tracheostomy in COVID-19-related ARDS is unknown. Nowadays, there is no clear indication regarding the timing of tracheostomy in these patients. Methods: We describe our synergic experience between ENT and ICU Departments at University Hospital of Modena underlining some controversial aspects that would be worth discussing tracheostomies in these patients. During the last 2 weeks, we performed 28 tracheostomies on patients with ARDS due to COVID-19 infection who were treated with IMV. Results: No differences between percutaneous and surgical tracheostomy in terms of timing and no case of team virus infection. Conclusion: In our experience, tracheostomy should be performed only in selected patients within 7- and 14-day orotracheal intubation

Valutazione della qualità e dello stato di conservazione degli ambienti litoranei: l'esempio del pS.I.C. "Penisola del Cavallino: biotopi litoranei" (Venezia, NE-Italia)

Evaluation of quality and conservation status in coastal landscapes: the example of the Site of Community Importance “Penisola del Cavallino: biotopi litoranei”(Venice, NE Italy). Quality of coastal landscape has been estimated at two different scale: at the community level, we assessed a naturalistic value, by evaluating characteristics coming both from species (i.e. presence of endemic species) and from community itself (i.e. rarity). We also took into account the percentage of exotic and ruderal species on the total number of species of each community, as an indirect measure of alteration degree. At the landscape level, we tried to value structural and functional integrity by evaluating spatial connectivity and contrast among patches. As the plant communities of foredunes show a typical spatial zonation, the two indices have been calculated along 27 transects perpendicular to the seashore. On the basis of a digital map of the area, we measured the gamma connectivity index along each transect; we assessed both “total connectivity”, considering all the communities intersected by the transects, and “partial connectivity”, considering only the plant communitie s of foredunes, so describing spatial distribution model of coastal vegetation. Since on the backdune there is not a typical zonation of communiti es, we counted only the links between natural communities, considering anthropogenic communities as a break of natural landscape and of connectivity. I n addition, we measured the contrast index; this index evaluates the change in environmental conditions going from one community (or patch) to the neighbouring one. The different patches are included and surrounded by a matrix, consisting of “nonhabitat” at different degree of alteratio n, that may function as an impenetrable barrier for individuals or, on the contrary, may favour movements. Thus, the surrounding matrix may significant ly influence the effective isolation of habitat patches, rendering them more or less isolated than simple distance would indicate. For the contr ast computation, we utilized the naturalistic value assessed to each community on the basis of the phytosociological data. Both indices point to the extreme fragmentation of coastal landscape and to high vulnerability that characterizes all natural communities being they surrounded by a matrix hig hly contrasting. Conservation strategies should, then, concern natural habitat, their quality and their structural and functional integrity, but they should also consider the quality of surrounding matrix

Salvage neck dissection for isolated neck recurrences in head and neck tumors: Intra and postoperative complications

Background and Objectives: The current evidence regarding complications after salvage neck dissection (ND) for isolated regional recurrences (IRRs) in head and neck cancers is poor. The aim of this study is to evaluate the incidence and differences in complication rates of salvage ND after primary surgery, radiotherapy, chemoradiotherapy, or combined treatments. Methods: This was a multicentric retrospective study on 64 patients who underwent salvage ND for IRR in three Italian institutes between 2008 and May 2020. Results: Complications were detected in 7 of the 34 patients (20.8%) and surgeons described difficult dissection in 20 patients (58.82%). Accidental vascular ligations or nervous injury during surgery were never detected. None of the variables analyzed were statistically significant in predicting the risk of complications, disease-free survival, or overall survival. Conclusions: IRR represents a rare entity among total relapses. The incidence of complications after salvage ND for IRR is higher than after primary surgery but at an acceptable rate in experienced hands. However, an adequate balance between functional and oncological outcomes is mandatory

PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation

Plasmacytoid predendritic cells (pDCs) are the main producers of type I interferon (IFN) in response to Toll-like receptor (TLR) stimulation. Phosphatidylinositol-3 kinase (PI3K) has been shown to be activated by TLR triggering in multiple cell types; however, its role in pDC function is not known. We show that PI3K is activated by TLR stimulation in primary human pDCs and demonstrate, using specific inhibitors, that PI3K is required for type I IFN production by pDCs, both at the transcriptional and protein levels. Importantly, PI3K was not involved in other proinflammatory responses of pDCs, including tumor necrosis factor α and interleukin 6 production and DC differentiation. pDCs preferentially expressed the PI3K δ subunit, which was specifically involved in the control of type I IFN production. Although uptake and endosomal trafficking of TLR ligands were not affected in the presence of PI3K inhibitors, there was a dramatic defect in the nuclear translocation of IFN regulatory factor (IRF) 7, whereas nuclear factor κB activation was preserved. Thus, PI3K selectively controls type I IFN production by regulating IRF-7 nuclear translocation in human pDCs and could serve as a novel target to inhibit pathogenic type I IFN in autoimmune diseases

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

Wound Healing Fluid Reflects the Inflammatory Nature and Aggressiveness of Breast Tumors

Wound healing fluid that originates from breast surgery increases the aggressiveness of cancer cells that remain after the surgery. We determined the effects of the extent of surgery and tumor-driven remodeling of the surrounding microenvironment on the ability of wound-healing to promote breast cancer progression. In our analysis of a panel of 34 cytokines, chemokines, and growth factors in wound healing fluid, obtained from 27 breast carcinoma patients after surgery, the levels of several small molecules were associated with the extent of cellular damage that was induced by surgery. In addition, the composition of the resulting wound healing fluid was associated with molecular features of the removed tumor. Specifically, IP-10, IL-6, G-CSF, osteopontin, MIP-1a, MIP-1b, and MCP1-MCAF were higher in more aggressive tumors. Altogether, our findings indicate that the release of factors that are induced by removal of the primary tumor and subsequent wound healing is influenced by the extent of damage due to surgery and the reactive stroma that is derived from the continuously evolving network of interactions between neoplastic cells and the microenvironment, based on the molecular characteristics of breast carcinoma cells

The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Background: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. Methods: The expression of CDCP1, PDGFR\u3b2 and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFR\u3b2 was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFR\u3b2 in TNBC clinical samples. Results: We discovered that PDGF-BB-mediated activation of PDGFR\u3b2 increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock-down of PDGFR\u3b2 in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFR\u3b2 immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFR\u3b2 axis in the modulation of CDCP1 expression. Conclusion: We have identified PDGF-BB/PDGFR\u3b2-mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFR\u3b2 and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs