ABSTRACT
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
ABSTRACT
<p><b>OBJECTIVE</b>To detect the influencing factors for posttraumatic hydrocephalus in patients with severe traumatic brain injuries and provide theoretical reference for clinical treatment.</p><p><b>METHODS</b>Retrospective study was made on 139 patients with severe traumatic brain injuries in our hospital. The patients were divided into two groups: hydrocephalus group and non-hydrocephalus group. Single factor analysis and multiple factor analysis were used to determine the related factors and hydrocephalus. Multiple factor analysis was conducted with logistic regression.</p><p><b>RESULTS</b>Posttraumatic hydrocephalus was found in 19.42% of patients. Age(OR equal to 1.050, 95%CI: 1.012-1.090), decompressive craniectomy (OR equal to 4.312, 95%CI: 1.127-16.503), subarachnoid hemorrhage(OR equal to 43.421, 95%CI: 7.835-240.652) and continuous lumbar drainage of cerebrospinal fluid (OR equal to 0.045, 95%CI: 0.011-0.175) were screened out from nine factors as the influencing factors for posttraumatic hydrocephalus.</p><p><b>CONCLUSIONS</b>Risk factors for PTH are as follows: age, decompressive craniectomy and subarachnoid hemorrhage (SAH). Continuous lumbar drainage of cerebrospinal fluid can greatly reduce posttraumatic hydrocephalus.</p>
