The square antiprism/twisted square antiprism ratio in LnDOTA-tetraamide chelates is a critical parameter in governing water-exchange kinetics and ultimately the utility of a chelate as a PARACEST MRI contrast agent. In LnDOTA-tetraamide chelates with tertiary amides, this ratio and the rate of interconversion between these two structural isomers are found to be dramatically dependent upon the solvent and possibly other local environmental factors.The realization that Ln 3+ chelates with slowly exchanging inner-sphere water molecules could induce magnetic resonance imaging (MRI) contrast through a paramagnetic chemical exchange saturation transfer (PARACEST) mechanism has given rise to a recent upsurge in interest in LnDOTA-tetraamide chelates. 1,2 The large paramagnetic hyperfine chemical shifts induced by anisotropic 4f electrons effectively shift the resonance of the inner-sphere water far from that of solvent water. However, because unchelated Ln 3+ ions are toxic, suitable chelating ligands must be employed that both eliminate the toxic effects 3 of these ions and appropriately slow water exchange. 1,2,4,5 Ligands derived from cyclen have been widely accepted in the development of MRI contrast agents, 3 and the related DOTAtetraamide ligands (Chart 1) are now widely studied as PARACEST agents. Although DOTA-tetraamide chelates are kinetically inert, retaining the Ln 3+ ion throughout the in vivo residence of the chelate, 6,7 the use of DOTA-tetraamide ligands in vivo can be problematic. It has been shown that only when the cationic nature of these chelates is offset by anionic substituents, such as carboxylates, can the severe toxic effects intrinsic to cationic chelates be avoided at the relatively high dosing levels required for MRI. 6 A chelate incorporating four glycinateamide substituents has been shown to be safe for in vivo use. 6,7 The unique water-exchange characteristics of these chelates make them attractive as MRI sensors of various biological species such as glucose, Zn 2+ , or protons (pH), [8][9][10][11] species. In such situations, it may be desirable to incorporate the offsetting negative charges as tertiary amide substituents, leaving the sensing secondary amide substituents in place.However, DOTA-tetraamides with tertiary amide pendant arms have not been widely studied as PARACEST agents. Of particular relevance is the coordination chemistry of these chelates. LnDOTA-tetraamide chelates can adopt both a monocapped square antiprismatic (SAP) and a monocapped twisted square antiprismatic (TSAP) coordination geometry, 4,5 and it has been shown that water exchange in complexes that form a TSAP isomer is 1-2 orders of magnitude faster than that in complexes that form a SAP isomer. 4,5,12 Given the requirement for slow exchange kinetics in putative PARACEST agents, it is clearly preferable for the SAP coordination geometry to predominate. Indeed, to our knowledge, the rate of exchange observed in the TSAP isomers of these complexes is so fast that CEST arising from this species has not...

Despite overall strong positive correlations between paired NBP and IAP readings of MAP and SBP, clinically relevant differences in blood pressure are frequent. When treating with vasoactive infusions targeted to a specific BP goal, it is important to keep in mind that NBP and IAP values are not interchangeable.

Background and Purpose: Cerebral microbleeds (CMB) are reported to be frequent in moyamoya disease (MMD) and moyamoya syndrome (MMS) in the Asian population. It is associated with an increased risk of intracerebral hemorrhage. The significance of CMB in MMD/MMS in non-Asian populations has not been well established. Our study aimed to investigate the prevalence of CMB in MMD/MMS in a moymoya cohort with a majority of non-Asians and to identify risk factors for developing a CMB and its predictive value for subsequent vascular events. Methods: The moyamoya database was compiled by screening for MMD/MMS among patients admitted to the Zale-Lipshy University Hospital at the University of Texas Southwestern Medical Center. We identified and analyzed data of 67 patients with MMD or MMS. Patients were characterized as CMB+ or CMB– based on MRI findings. In CMB+ patients, the total number and location of CMB were identified. Univariate and multivariate logistic regression were used to identify risk factors for developing CMB and whether CMB are associated with the development of subsequent vascular events. Results: Out of a total of 67 patients, 11 (16%) had CMB. Males had significantly higher odds of having CMB as compared to females (OR 1.76; 95% CI 1.40–24.3, p = 0.021). The incidence of CMB was also associated with age at diagnosis (mean age of CMB+ patients vs. CMB– patients: 44 vs. 34 years, respectively, p = 0.024), smoking (p = 0.006), and hemorrhagic stroke at presentation (p = 0.034). Logistic regression with multivariate analysis found that gender and age at diagnosis remained statistically significant. New ischemic events occurred in 2 (20%) out of 10 CMB+ patients and 13 (23%) out of 55 CMB– patients, respectively (p = 0.79). While 2 (3%) CMB– patients had a new cerebral hemorrhage during follow-up, none of the CMB+ patients did. Conclusions: CMB are less prevalent in MMD/MMS in the USA than in Asia. An older age at diagnosis and male gender were associated with CMB. The presence of CMB was not associated with an increased risk of a subsequent ischemic or hemorrhagic stroke.

Background The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. The Adam Williams Initiative is a program established to provide education and resources to encourage hospitals across the United States to incorporate the guidelines into practice. Objective To explore the relationship in hospitals between participation in the Adam Williams Initiative and adherence to the Brain Trauma Foundation guidelines for patients with acute traumatic brain injury. Method Hospitals that participated in the Adam Williams Initiative entered data into an online tracking system of patients with traumatic brain injury for at least 2 years after the initial site training. Data included baseline hospital records and daily records on hospital care of patients with traumatic brain injury, including blood pressure, intracranial pressure, cerebral perfusion pressure, oxygenation, and other data relevant to the 15 key metrics in the Brain Trauma Foundation guidelines. Results The 16 hospitals funded by the Adam Williams Initiative had good overall adherence to the 15 key metrics of the recommendations detailed in the Brain Trauma Foundation guidelines. Variability in results was primarily due to data collection methods and analysis. Conclusions The Adam Williams Initiative helps promote adherence to the Brain Trauma Foundation guidelines for hospital care of patients with traumatic brain injury by providing a platform for developing and standardizing best practices. Participation in the initiative is associated with high adherence to clinical guidelines, a situation that may subsequently improve care and outcomes for patients with traumatic brain injury. (Critical Care Nurse. 2018;38[1]:e11-e20)

No abstract