ABSTRACT
Background: The dose of anaesthetic and opioid drugs must be continuously adjusted after the induction of general anaesthesia to maintain an adequate depth of anaesthesia. The TI.VA algorithm is a multiple-input/multiple-output algorithm designed to optimise the balance between anaesthetic and opioid concentrations during general anaesthesia. It applies vector analysis to a two-dimensional matrix to quantify any inadequacy of the depth of anaesthesia at any given moment and determine any drug dose adjustments required to achieve an adequate depth of anaesthesia. This study aimed to capture preliminary data on the performance and safety of the TI.VA algorithm during total i.v. anaesthesia in patients. Methods: This prospective study enrolled nine patients with breast cancer scheduled to undergo surgery. General anaesthesia was induced under manual control using propofol and remifentanil. Anaesthesia was guided using the TI.VA algorithm from skin incision until surgical resection was completed. The quality of anaesthesia was assessed through an analysis of performance errors. A bispectral index global score (GSBIS) <50 was considered an acceptable target for algorithm performance. Results: All nine procedures were completed without any adverse events and none of the patients recalled any intraoperative event. Overall, we analysed 3417 monitoring points corresponding to 285 min of surgery. All patients presented a GSBIS below the cut-off value of 50. Conclusions: The TI.VA algorithm provides adequate control of clinical anaesthesia. A more sophisticated prototype needs to be developed before the trial is expanded to include larger patient populations. Clinical trial registration: NCT05199883.
ABSTRACT
The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage given with GM-CSF and IFN-alpha in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days -1, 0 and +1, while IFN-alpha (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-alpha is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with those recorded in a previous study investigating HSPPC-96 monotherapy.
