McDonald, Jennifer S.

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) outcomes are unclear in patients with pre-stroke dementia or cognitive impairment. Although these individuals make up ~12% of acute stroke patients, they are often excluded from both stroke trials and routine care. This systematic review and meta-analysis explored reperfusion therapy outcomes in this population. Methods: Using the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, this systematic review investigated studies on acute ischemic stroke patients with dementia or cognitive impairment treated with either IVT or EVT. Primary outcome was defined as favorable 90-day outcome (modified Rankin Scale (mRS) score 0-2). Secondary outcomes included 90-day mortality, radiographic intracranial hemorrhage (ICH) and symptomatic ICH (SICH). Results: 9 articles were included from 825 screened. 5 observational studies of IVT use in patients with (n=1078) and without dementia (n=2805) were selected for a meta-analysis. There were no significant differences in favourable 90-day mRS (adjusted OR 0.61, 95% CI 0.24 to 1.59), 90-day mortality (unadjusted OR of 1.19, 95% CI 0.86 to 1.64), ICH (unadjusted OR 1.32, 95% CI 0.79 to 2.19) and SICH (unadjusted OR of 0.94, 95% CI 0.70 to 1.25). EVT in dementia patients in one study found only increased odds of ICH (adjusted OR 1.57 95%CI 1.03 to 2.40). For patients with cognitive impairment, no significant association was found with assessed outcomes in a pooled analysis of 3 IVT studies and one EVT study found poorer 90-day mRS outcomes. Conclusions: This systematic review and meta-analysis suggests no considerable safety concerns for IVT or EVT use in patients with pre-existing dementia or cognitive impairment, compared to those without. Uncertainty remains in the efficacy of these therapies for these individuals. Rigorous, patient-caregiver informed design, and a more nuanced outcome approach are warranted for future studies. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

AbstractPurposeDental amalgam contains mercury and is commonly used in dental restorations. The impact of MRI on mercury excretion from dental amalgam is not well understood across clinical field strengths, especially 7T. We investigated the effects of MRI exposure on mercury excretion using fresh, lab‐created dental amalgam restorations and in extracted teeth with old, pre‐existing restorations.MethodsDonated, unfilled human teeth (n = 120) were restored with amalgam before being stored in saline, artificial saliva, or a dry box prior to MRI scanning. The teeth were placed in individual tubes of fresh artificial saliva and scanned at 1.5T, 3T, or 7T or left unscanned as controls. Mercury concentrations were measured 24–30 h later. Donated teeth with pre‐existing restorations (n = 40) were stored in artificial saliva, scanned at 7T or left unscanned as controls, and mercury concentration tested.ResultsFor teeth extracted and restored in a laboratory, no significant difference was found (F = 2.42, P = 0.072) between mean mercury concentrations of unscanned teeth (13.72 μg/L) and teeth scanned at 1.5T (10.88 μg/L), 3T (12.65 μg/L), or 7T (8.88 μg/L). For teeth extracted with previously placed restorations, no significant difference (P = 0.288) was found between unscanned controls (4.28 μg/L) and teeth scanned at 7T (6.63 μg/L).ConclusionMRI of dental amalgam does not significantly increase mercury excretion at 1.5T, 3T, or 7T compared to unscanned teeth. This holds true for controlled laboratory restorations as well as for those placed and lived with prior to extraction and scanning, demonstrating no added risk to the clinical patient or research subject.

PURPOSE:High-dose methotrexate (HDMTX; > 500 mg/m2) is an important component of lymphoma therapy. Serum MTX monitoring at 48 hours is the standard approach to identify those at increased risk of developing MTX toxicity. Our aim was to characterize the incidence of complications and their association with MTX levels.METHODS:A retrospective review of our institutional electronic medical record was conducted to identify patients with lymphoma who received HDMTX between January 1, 2002, and December 31, 2018. We characterized the incidence of acute kidney injury (AKI), intensive care unit (ICU) admission, length of hospital stay (LOS), and 30-day mortality across 48-hour MTX levels. To establish an association between 48-hour MTX levels and the complications listed, we performed chi-square analysis for dichotomous variables and Kruskal-Wallis for nonparametric data. Receiver operator characteristic curve analysis was performed to identify the MTX level where AKI grade ≥ 2 was more likely. Multivariate logistic regression analysis was performed to identify risk factors for this MTX level.RESULTS:We identified 642 patients with 2,804 cycles of HDMTX. The incidence of AKI was 19.1% with AKI grade ≥ 2 making up 21% of cases. Rates of AKI, ICU admission, and 30-day mortality are associated with elevated 48-hour MTX levels. There was a significant increase in median LOS with elevated MTX levels ( P < .001). Receiver operator characteristic curve analysis for AKI grade ≥ 2 demonstrated a 48-hour MTX level threshold of 1.28 μmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher MTX dose, monotherapy, and first cycle as independent factors.CONCLUSION:Elevated MTX levels are associated with a significant increased rate of AKI, ICU admission, prolonged LOS, and 30-day mortality. Elevated 48-hour MTX levels, particularly > 1.28 μmol/L, should alert clinicians for complications and to initiate measures to reduce MTX levels.