We have checked levels of leukotriene(LT) C4, one of the arachidonic acid(AA) metabolites, in the lumbar, cisternal and ventricular cerebrospinal fluid(CSF) of 37 patients admitted with diagnosis of aneurysmal subarachnoid hemorrhage(SAH) and in lumbar CSF of 10 patients without aneurysmal SAH as the control group. We compared the levels of LTC4 in the CSF of the patients with aneurysmal SAH with those of the control group. We observed the changes of levels of LTC4 periodically after the onset of SAH. We devided the data of patients with aneurysmal SAH into 3 groups according to sampling days(respectively 1-4, 5-11, 12-24 days after SAH) and the clinical spasm group was compared with that of the non-spasm group. We also looked for the differences in the sampling sites and the correlation between the white blood cell counts and the levels of LTC4 in the CSF. The results of this study showed that the mean level of CSF LTC4(+/- standard deviation) of the SAH group was significantly higher than that of the control group(215.59+/-94.95 vs. 98.44+/-31.72pg/ml, respectively : P<0.001). The level of the CSF LTC4 progressively increased upto 7-8 days after SAH and decreased thereafter in the spasm group. The level of the CSF LTC4 of the spasm group was significantly higher than that of the non-spasm group(239.03+/-49.94 vs. 163.06+/-64.39pg/ml, respectively : P<0.05) in the first 4 days after SAH. There was no significant difference in the level of CSF LTC4 in the ventricular, cisternal, and lumbar CSF statistically(196.25+/-61.15 vs. 222.51+/-101.50 vs. 233.40+/-100.85pg/ml, respectively : P>0.05) even though we expected the level in the cisternal CSF to be higher than the lumbar CSF. There was no correlation between the white blood cell counts and the levels of LTC4 in the CSF(correlation coefficient=0.1240). From this study it is concluded that : 1) the AA metabolism via the lipoxygenase pathway is enhanced after SAH ; 2) the LTC4 may play a role in the pathogenesis of cerebral vasospasm, especially in the early days after SAH ; 3) the extraction of CSF via the external ventricular or cisternal drainage may decrease substances such as LTC4 which was thought to be vasoconstrictor material ; and 4) the granulocyte production of the LTC4 accounts for only a small part.
Aneurysm* ; Arachidonic Acid ; Cerebrospinal Fluid* ; Diagnosis ; Drainage ; Granulocytes ; Humans ; Leukocyte Count ; Leukotriene C4* ; Lipoxygenase ; Metabolism ; Spasm ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*