Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy.

OBJECTIVE: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. METHODS: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. RESULTS: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death (p < 0.001). CONCLUSION: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S.

Massive hemorrhage protocol survey: Marked variability and absent in one-third of hospitals in Ontario, Canada.

BACKGROUND: Massive hemorrhage protocols (MHP) are critical to standardized delivery of timely, safe, and resource-effective coordinated care for patients with life-threatening bleeding. METHODS: A standardized MHP survey was sent to all hospitals (n = 150) in Ontario with a transfusion service. This study aim was to determine the proportion of hospitals with an MHP and assess for variability. RESULTS: The overall survey completion rate was 133 of 150 hospitals (89%) (remaining 17 providing negative affirmation that they did not have an MHP). An MHP was in place at 97 of 150 (65%) hospitals (60% of small (<5000 red cell units/year) vs. 91% of medium/large). A total of 10 different names of protocols were reported, with "Massive Transfusion Protocol" (68%) predominating. Activation criteria were present in 82 of 97 (85%); commonly activated based on volume of blood loss (70%). Blood work was drawn at the discretion of the physician (37%) or at predefined intervals (31%; majority every 60 min). Common routine laboratory tests performed were CBC (87%) and INR (84%). Fibrinogen testing was available at 88 (66%) of 133 reporting hospitals and part of the standard testing at 73 of 97 (75%) hospitals with an MHP. Median targets of hemostatic resuscitations, stated in the protocol at 49% of hospitals with an MHP, were: platelets >50 × 109/L, INR < 1.8, fibrinogen >1.5 g/L, and hemoglobin >70 g/L. Protocol required patient temperature monitoring in 65% and specified a reversal plan for patients on anticoagulants in 59%. At 36% of sites all patients are initially managed with O RhD negative blood. Overall, 61% of sites issue blood in predefined packs (vs. on demand). Hemostatic agents in protocols included: tranexamic acid (70%), prothombin complex concentrate (14%), fibrinogen concentrate (13%), and recombinant FVIIa (4%). Quality metrics were tracked in 32% of hospitals. CONCLUSIONS: A third of hospitals lack formal MHPs, with the majority lacking in smaller hospitals. The survey results indicate that there is marked variability in all key aspects of the reported MHPs. This may be due to differences in hospital resources and personnel, lack of supporting evidence to dictate requirements, and differences in knowledge base of the individuals involved in protocol setting.

A regional massive hemorrhage protocol developed through a modified Delphi technique.

BACKGROUND: A massive hemorrhage protocol (MHP) enables rapid delivery of blood components in a patient who is exsanguinating pending definitive hemorrhage control, but there is variability in MHP implementation rates, content and compliance owing to challenges presented by infrequent activation, variable team performance and patient acuity. The goal of this project was to identify the key evidence-based principles and quality indicators required to develop a standardized regional MHP. METHODS: A modified Delphi consensus technique was performed in the spring and summer of 2018. Panellists used survey links to independently review and rate (on a 7-point Likert scale) 43 statements and 8 quality indicators drafted by a steering committee composed of transfusion medicine specialists and technologists, and trauma physicians. External stakeholder input from all hospitals in Ontario was sought. RESULTS: Three rounds were held with 36 experts from diverse clinical backgrounds. Consensus was reached for 42 statements and 8 quality indicators. Additional modifications from external stakeholders were incorporated to form the foundation for the proposed MHP. INTERPRETATION: This MHP template will provide the basis for the design of an MHP toolkit, including specific recommendations for pediatric and obstetrical patients, and for hospitals with limited availability of blood components or means to achieve definitive hemorrhage control. We believe that harmonization of MHPs in our region will simplify training, increase uptake of evidence-based interventions, enhance communication, improve patient comfort and safety, and, ultimately, improve patient outcomes.