Classical vs. Retrograde Endoscopic Dacryocystorhinostomy: Analyses and Comparison of the Results.

In endoscopic dacryocystorhinostomy (DCR), surgical landmarks such as the maxillary line (ML) and the axilla of the middle turbinate (MT) guide the surgeon in identifying the lacrimal sac. The primary surgical risk associated with the classical technique, which involves directly opening the lacrimal sac, is the height of the bone drilling on the projection of the lateral wall of the nasal fossa. This poses a significant risk of damaging the orbit, the floor of the frontal sinus, and the anterior skull base.

Patterns and timing of recovery from facial nerve palsy after nerve-sparing parotid surgery: the role of neuromuscular retraining.

Objectives: Among the complications of parotid surgery, facial palsy is frequent and burdened by high functional and social impact for the patient. There are few data on the efficacy of facial neuromuscular retraining (FNR) in patients with facial palsy after parotid surgery, and no data exist on its impact in timing and extent of recovery.

Material And Methods: A retrospective study was conducted on patients undergoing FN sparing parotid surgery and suffering from postoperative facial palsy.

Pericranial Flap-Based Multilayer Reconstruction of Endoscopic Transcribriform Craniectomy for Sinonasal Malignancies.

Objective: Diffusion of endoscopic techniques for the resection of ethmoid bone malignancies through a transcribriform approach (TA) has raised new challenges regarding reconstruction options to reduce post-operative complications. Although there is consensus on the advantages of vascularized flaps over free grafts for large defects, no standard protocol exists on reconstruction procedures. In addition, although the pedicled nasoseptal flap has been extensively discussed, few studies have been published on extranasal pedicled flaps.

Prognostic role of EAONO/JOS, STAMCO, and ChOLE Staging for Exclusive Endoscopic and Endoscopic-Microscopic Tympanoplasty.

Objective: The aim of the study is to evaluate cholesteatoma's surgical outcomes in patients treated with endoscopic ear surgery (EES) or a combined endoscopic-microscopic approach (cEMA) according to STAM, STAMCO, ChOLE, and EAONO/JOS system (EJS) classifications and staging.

Study Design: Retrospective study.

Setting: Monocentric study in a tertiary referral center.

Vestibular schwannoma removal through expanded transcanal transpromontorial approach: a multicentric experience.

Purpose: Expanded Transcanal Transpromontorial Approach (ExpTTA) is an endomicroscopic technique that allow surgical excision of small and symptomatic neuromas limited to the internal auditory canal (IAC) or minimally invasive the cerebellopontine angle (CPA). ExpTTA is a safer alternative to the exclusive endoscopic technique as it allows a wider surgical field and better management of the auditory porus and CPA.

Methods: We report a retrospective case series of 34 patients who underwent ExpTTA between 2017 and 2022 at the ENT Departments of the University Hospital of Modena, Bologna and Verona.

Technique for Foreign-Body Removal with the Use of Transnasal Endoscopic Prelacrimal Approach - A Case Report.

The Rationale: Foreign body (FB) in the nasal cavities is a frequent cause of otolaryngology emergency consultation that sometimes requires surgical treatment. When there is involvement of the posterolateral wall of the maxillary sinus (MS) and of the pterygopalatine fossa (PPF), conventional techniques such as antrostomy and medial endoscopic maxillectomy may not allow sufficient domination of the surgical field.

Patient Concerns: We report the case of a woman who suffered from intranasal trauma with epistaxis and pain.

Quality of life in vestibular schwannoma: a comparison of three surgical techniques.

Objective: Through years, interest in quality of life (QoL) among patients affected by vestibular schwannoma (VS) has increased. The expansion of the indications for endoscopic ear surgery allowed the development of the transcanal transpromontorial surgery (TTS) for VS removal. The objective of the present study was to assess QoL in a cohort of VS patients operated on by translabyrinthine (TL), retrosigmoid (RS) and TTS approach.

Can the AGE/RAGE/ERK signalling pathway and the epithelial-to-mesenchymal transition interact in the pathogenesis of chronic rhinosinusitis with nasal polyps?

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor β/Small mother against decapentaplegic (TGFβ/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls.

Anomalous aortic origin of the pulmonary arteries: Case series and literature review.

Anomalous origin of the pulmonary arteries from the ascending aorta is a rare, but severe clinical entity necessitating a scrupulous evaluation. Either the right or the left pulmonary arteries can arise directly from the ascending aorta while the other pulmonary artery retains its origin from the right ventricular outflow tract. Such a finding can be isolated or can coexist with several congenital heart lesions.

Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes.

Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors.

Coadministration of telomerase genetic vaccine and a novel TLR9 agonist in nonhuman primates.

The human telomerase reverse transcriptase (hTERT) is an attractive target for human cancer vaccination because its expression is reactivated in most human tumors. We have evaluated the ability of DNA electroporation (DNA-EP) and adenovirus serotype 6 (Ad6) to induce immune responses against hTERT in nonhuman primates (NHPs) (Macaca mulatta). Vaccination was effective in all treated animals, and the adaptive immune response remained detectable and long lasting without side effects.

ErbB2 genetic cancer vaccine in nonhuman primates: relevance of single nucleotide polymorphisms.

Aberrant Her2/neu expression is associated with the development of epithelial-derived human carcinomas and for this reason it is considered a good target for immunologic intervention. To define methods to circumvent immunologic tolerance and to elicit immunity against the Her2/neu tumor-associated antigen in a suitable animal model, we have isolated the cDNA encoding the rhesus monkey homolog of human Her2/neu (RhErbB2) to construct DNA plasmids and adenoviral vectors for the development of a cancer vaccine against this protein. To further increase the immunogenic potency of these vectors, a synthetic codon-optimized RhErbB2 cDNA (RhErbB2OPT) was constructed and characterized.

Gene therapy of Hunter syndrome: evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS).

Mucopolysaccharidosis type II (MPSII) is an inherited disorder due to a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The disease is characterized by a considerable deposition of heparan- and dermatan-sulfate, causing a general impairment of physiological functions. Most of the therapeutic protocols proposed so far are mainly based upon enzyme replacement therapy which is very expensive.

Immunogenicity and safety of a DNA prime/adenovirus boost vaccine against rhesus CEA in nonhuman primates.

Scaling up experimental protocols from rodents to humans is often not a straightforward procedure, and this particularly applies to cancer vaccines, where vaccination technology must be especially effective to overcome a variety of immune suppressive mechanisms. DNA electroporation (DNA-EP) and adenoviral vectors (Ad) have shown high potency and therapeutic efficacy for different antigens in several pre-clinical models. To evaluate the ability of DNA-EP and Ad to break tolerance to a self-antigen in large animals, we have cloned the CEA homologue (rhCEA) from rhesus monkeys (Macaca mulatta) colon tissue samples.

Genetic vaccines against Ep-CAM break tolerance to self in a limited subset of subjects: initial identification of predictive biomarkers.

The epithelial cell adhesion molecule, Ep-CAM, has been historically considered a target of passive immunotherapy using monoclonal antibodies, and more recently, of a first Pox-vector-based cancer vaccine Phase I trial in colorectal cancer patients. To shed further light on the use of this antigen, we isolated the mouse and rhesus homologues of human Ep-CAM and explored different genetic vaccination modalities based on the use of adenoviral vectors as well as DNA electroporation (DNA-EP). Immune responses to Ep-CAM were measured by IFN-gamma ELISPOT and intracellular staining assays using overlapping sets of peptides covering the entire coding regions.

CD8+ T-cell tolerance can be broken by an adenoviral vaccine while CD4+ T-cell tolerance is broken by additional co-administration of a Toll-like receptor ligand.

T-cell tolerance to tumor antigens is a considerable challenge to cancer immunotherapy. The existence of a murine model transgenic for human carcinoembryonic antigen (CEA) allows CEA vaccination efficacy to be studied in a physiologically tolerant context. Immunization of CEA-transgenic mice with an adenoviral vector coding for CEA induced a significant CD8+ T-cell response specific to CEA but failed to induce CEA-specific CD4+ T cells and antibodies.

Efficient induction of T-cell responses to carcinoembryonic antigen by a heterologous prime-boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA.

The immunogenic properties of plasmid DNA and recombinant adenovirus (Ad) encoding the carcinoembryonic antigen (CEA) were examined in mice by measuring both the amplitude and type of immune response, and the immunogenicity of codon usage optimized cDNA encoding CEA (CEAopt) was assessed both in C57Bl/6 and CEA transgenic mice. Vectors were injected into quadriceps muscle either alone or in combination, and plasmid DNA was electroporated to enhance gene expression efficiency and immunogenicity. Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4+ and CD8+ T-cell response to the target antigen, measured by both IFNgamma-ELIspot assay and intracellular staining.

Gene electro-transfer of an improved erythropoietin plasmid in mice and non-human primates.

Background: Anemia due to impaired erythropoietin (EPO) production is associated with kidney failure. Recombinant proteins are commonly administered to alleviate the symptoms of this dysfunction, whereas gene therapy approaches envisaging the delivery of EPO genes have been tried in animal models in order to achieve stable and long-lasting EPO protein production. Naked DNA intramuscular injection is a safe approach for gene delivery; however, transduction levels show high inter-individual variability in rodents and very poor efficiency in non-human primates.

Hyaluronidase increases electrogene transfer efficiency in skeletal muscle.

Electrogene transfer (EGT) of plasmid DNA into skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. We report here that preinjecting hyaluronidase (HYAse) significantly increases the gene transfer efficiency of muscle EGT. Three constructs encoding mouse erythropoietin (pCMV/mEPO), secreted alkaline phosphatase (pCMV/SeAP), and luciferase (pGGluc) were electroinjected intramuscularly in BALB/c mice and rabbits with and without HYAse pretreatment.