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. METHODS: The study was conducted on 111 patients who underwent surgery for VS between January 2017 and January 2020 at two different institutions. Patients fulfilled three questionnaires during follow-up: Glasgow Benefit Inventory, Depression Anxiety Stress Scales-21 and Penn Acoustic Neuroma Quality-Of-Life. The association between sex, age, date of surgery, tumor size, post-operative facial nerve (FN) function and QoL outcomes was assessed. RESULTS: An overall subjective impairment was demonstrated in all groups. Age, Koos staging and FN functions were associated to distinct QoL outcomes. CONCLUSIONS: QoL decreases in patients surgically treated for VS. The TTS may allow improved scores in many domains, confirming to be a subjectively well-tolerated technique.

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. There is a requirement for an alternative approach, and to this aim, we evaluated the feasibility of muscle electro gene transfer (EGT) performed in the IDS-knockout (IDS-ko) mouse model. EGT is a highly efficient method of delivering exogenous molecules into different tissues. More recently, pre-treatment with bovine hyaluronidase has shown to further improve transfection efficiency of muscle EGT. We here show that, by applying such procedure, IDS was very efficiently produced inside the muscle. However, no induced IDS activity was measured in the IDS-ko mice plasma, in contrast to matched healthy controls. In the same samples, an anticipated and rapidly increasing immune response against the recombinant protein was observed in the IDS-ko vs control mice, although reaching the same levels at 5 weeks post-injection. Additional experiments performed on healthy mice showed a significant contribution of hyaluronidase pre-treatment in increasing the immune response.

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. To overcome CD4+ T-cell tolerance, we explored the effect of adjuvants inducing in vivo dendritic cell maturation. Two different Toll-like receptor ligands, monophosphoryl lipid A (MPL) and CpG motif-containing oligodeoxynucleotides (CpG-ODN), were tested. CD4+-mediated IFN-gamma production was induced in the CEA-transgenic mice only when the genetic immunization was performed in the presence of these adjuvants. Moreover, CpG-ODN had a greater effect than MPL in inducing CD4+ T-cell response and enabling anti-CEA antibody production.