No abstract

The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial would not have been completed in a timely fashion without subjects enrolled by surrogate consent. Furthermore, exclusion of subjects who could not provide their own consent would have severely limited the generalizability and value of trial results.

Central sympathetic activation relates to clinical severity and female gender. No definitive associations were found for age, hemorrhage amount, or aneurysm location.

Objective: Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. Methods: Observational study of consecutive SAH grade 3–5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. Results: For the 102 patients included, mean age was 58, and 73% were female – 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01–1.17)], H/H grade [9.52 (1.19–77)], infarction [10.87 (1.22–100)], ICP elevation [32.26 (2–500)], EPI [1.06 (1.01–1.10)], and (inversely) DHPG [0.99 (0.99–1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62–83)], ICP elevation [18.52 (1.93–166)], and EPI [1.05 (1.02–1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003–1.08)], H/H grade [6.9 (1.54–31.25)], NC [4.31 (1.5–12.35)], and EPI [1.032 (1.009–1.054)] independently predicted early mortality. Conclusions: CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH.

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Recently multiple new therapeutic options have been introduced which was able to improve overall survival but ultimately patient become refractory specifically in patients with poor cytogenetics. Therefore, novel therapeutic options like immunotherapy are needed to improve outcomes. Chimeric antigen receptor (CAR) T-cell therapy is immunotherapy in which T cell are genetically engineered against a tumor-specific antigen and transfused back to the patient to mount major histocompatibility complex-independent cancer-specific immune response. The success of CAR T-cell therapy in lymphoid malignancies encouraged its development in MM. Most of the clinical studies target B-cell maturation antigen in relapsed refractory MM and relapse is the major issue. In this article, we will present the basics of CAR T-cell therapy, the most recent clinical and preclinical data, and we will discuss the future therapeutic realm of CAR T cells in MM.