instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged ≥90 years.', 'We analyzed data from the Get With The Guidelines-Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged ≥90 and 3 younger age groups (18-64, 65-79, and 80-89 years).', 'Among 35\u2009708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were ≥90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged ≥90 years (67.4% versus 84.1% in 18-89-year olds; P<0.0001). Discharge outcomes among individuals aged ≥90 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged ≥90 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds.\Question: Do use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients ≥90 Years of Age?
answer:
The use of intravenous tPA among those aged ≥90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower.


question:
Context: HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.', 'MVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs.\Question: Do glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity?
answer:
These findings support MVs as a potential pathway/mechanism of excessive glutamate generation and neurotoxicity in HAND and therefore MVs may serve as a novel therapeutic target.


question:
Context: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT).', 'Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out.', 'Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival.\Question: Does postmastectomy radiotherapy reduce locoregional recurrence in elderly women with high-risk breast cancer?
answer:

In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.