Association Between Acute Kidney Injury and Long-Term Mortality in Patients With Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study

Background: Though acute kidney injury (AKI) in the context of aneurysmal subarachnoid hemorrhage (aSAH) worsens short-term outcomes, its impact on long-term survival is unknown. Aim: We aimed to evaluate the association between long-term mortality and AKI during hospitalization for aSAH. Methods: This was a retrospective study of patients who survived \u3e12 months after aSAH. All patients were evaluated at West China Hospital, Sichuan University, between December 2013 and June 2019. The minimum follow-up time was over 1 year. the maximum follow-up time was about 7.3 years. AKI was defined by the KDIGO (The Kidney Disease Improving Global Outcomes) guidelines, which stratifies patients into three stages of severity. The primary outcome was long-term mortality, which was analyzed with Kaplan-Meier curves and Cox proportional hazards models. Results: During this study period, 238 (9.2%) patients had AKI among 2,592 patients with aSAH. We confirmed that AKI during care for aSAH significantly increased long-term mortality (median 4.3 years of follow-up) and that risk increased with the severity of the kidney failure, with an adjusted hazard ratio (HR) of 2.08 (95% CI 1.49-2.89) for stage 1 AKI, 2.15 (95% CI 1.05-4.43) for stage 2 AKI, and 2.66 (95% CI 1.08-6.53) for stage 3 AKI compared with patients without AKI. Among patients with an AKI episode, those with renal recovery still had increased long-term mortality (HR 1.96; 95% CI 1.40-2.74) compared with patients without AKI but had better long-term outcomes than those without renal recovery (HR 0.51, 95% CI 0.27-0.97). Conclusions: Among 12-month survivors of aSAH, AKI during their initial hospitalization for aSAH was associated with increased long-term mortality, even for patients who had normal renal function at the time of hospital discharge. Longer, multidisciplinary post-discharge follow-up may be warranted for these patients

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

Background: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. Methods: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-γ Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines. © 2007 Okada et al; licensee BioMed Central Ltd