Microglial activation in Parkinson’s disease using [18F]-FEPPA

BACKGROUND: Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson’s disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo. METHODS: Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [(18)F]-FEPPA between PD patients and HC. FEPPA total distribution volume (V (T)) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function. RESULTS: Our results revealed a significant main effect of genotype on [(18)F]-FEPPA V (T) in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA V (T) between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21). CONCLUSIONS: Future investigations are needed to determine the significance of [(18)F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD

PET Imaging of Pathological Tau in Progressive Supranuclear Palsy

PSP is a neurodegenerative movement disorder that is characterized by the pathological accumulation of tau aggregates in the brain. PSP differs neuropathologically from other movement disorders such as PD and MSA, which are classified as synucleinopathies. PSP patients would benefit from a clinically approved tau imaging agent for diagnostic and prognostic purposes. Previous testing of the tau radiotracer [18F]AV-1451 in AD, another tauopathy, suggested that it was capable of distinguishing AD from MCI and healthy controls. The aim of this investigation was to test whether [18F]AV-1451 was able to distinguish PSP patients from PD patients and healthy controls. There were no significant increases in [18F]AV-1451 retention in PSP patients compared to the other two subject groups. These findings may indicate that [18F]AV-1451 is not an effective radiotracer for imaging tau in PSP, or perhaps the method of measuring [18F]AV-1451 retention used in this study was not appropriate.M.Sc

Barriers and facilitators of following perioperative internal medicine recommendations by surgical teams: a sequential, explanatory mixed-methods study

Abstract Background Preoperative medical consultations add expense and burden for patients and the impact of these consults on patient outcomes is conflicting. Previous work suggests that 10–40% of preoperative medical consult recommendations are not followed. This limits measurement of the effect of perioperative medical consultation on patient outcomes and represents a quality gap, given the patient time and healthcare cost associated with consultation. We aimed to measure, characterize, and understand reasons for missed recommendations from preoperative medical consultation. Methods This explanatory, sequential mixed-methods study used chart audits followed by semi-structured interviews. Chart audit of consecutive patients seen in preoperative medical clinic were reviewed to measure the proportion and characterize the type of recommendations that were not completed (“missed”). This phase informed the interview participants and questions. The interview guide was developed using the Consolidated Framework for Implementation Research and the Theoretical Domains Framework. Template analysis was used to understand drivers and barriers of missed recommendations Results Chart audit included 255 patients (n=161, 63.1% female) seen in preadmission clinic between April 1 and April 30, 2019. 55.7% of patients had all recommendations followed (n=142). Postoperative anticoagulation management and postoperative cardiac biomarker surveillance recommendations were least commonly followed (50.0%, n=28, and 68.9%, n=82, respectively). Eighteen surgical team members were interviewed. Missed recommendations were both unintentional and intentional, and the key drivers differed by these categories. Unintentionally missed recommendations occurred due to individual-level factors (drivers: knowledge of the consultation note, lack of routine for reviewing the consultation note, and competing demands on time) and systems-level factors (driver: lack of role clarity). Intentionally missed recommendations occurred due to user error due (drivers: lack of knowledge of guidelines or evidence) and appropriate modifications (driver: need to adapt a preoperative plan for a complicated postoperative course). Conclusions Only 55.7% of consult notes had all recommendations followed, suggesting a quality gap in perioperative medical care. Qualitative data suggests multiple drivers of missed recommendations that should be targeted to improve the efficiency of care for these patients

Microglial activation in Parkinson’s disease using [18F]-FEPPA

Abstract Background Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson’s disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo. Methods Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [18F]-FEPPA between PD patients and HC. FEPPA total distribution volume (V T) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function. Results Our results revealed a significant main effect of genotype on [18F]-FEPPA V T in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA V T between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21). Conclusions Future investigations are needed to determine the significance of [18F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD