OBJECTIVES The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent 18F-FDG–PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS 18F-FDG–PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively). DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS Noninvasive imaging with 18F-FDG–PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

Objectives We sought to determine the anti-atherosclerotic properties of pioglitazone using multi-modality non-invasive imaging techniques. Background Inflammation is an essential component of vulnerable or high risk atheromas. Pioglitazone, a peroxisome proliferator–activated receptor-gamma (PPAR-γ)agonist possesses potent anti-inflammatory properties. We aimed to non-invasively to quantify the anti-inflammatory effects of pioglitazone on atheroma using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT and dynamic contrast enhanced MRI (DCE-MRI). Methods Atherosclerotic plaques were induced in the aorta of fifteen New Zealand White (NZW) rabbits by a combination of hyperlipidemic diet and two balloon endothelial denudations. Nine rabbits continued the same diet whereas six received pioglitazone (10mg/kg orally) in addition to the diet. Twelve animals underwent 18F-FDG-PET/CT and fifteen animals underwent DCE-MRI at baseline, one and three months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed aortic histological analysis and correlation analysis was performed. Results 18F-FDG-PET/CT detected an increase in average standardized uptake value (SUV) in the control group (p<0.01), indicating progressive inflammation, while stable SUV values were observed in the treatment group, indicating no progression. DCE-MRI detected a significant decrease in area under the curve (AUC) for the pioglitazone group (p<0.01). Immunohistology of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p=0.04 and p=0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. A strong positive correlation between SUV and macrophage density and AUC and neovessels was detected ( r2=0.86, p<0.0001 and r2=0.66, p=0.004, respectively). Conclusions 18F-FDG-PET/CT and DCE-MRI demonstrate non-invasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging modalities appear suited to monitor inflammation in atherosclerosis.

Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations, native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Despite the long history of kratom use in Asia, it is only within the past 10–20 years that kratom has emerged as an important herbal agent in the United States, where it is being used for the self-treatment of pain, opioid withdrawal symptoms, and mood disorders. The increase in the use of kratom in the United States has coincided with the serious epidemic of opioid abuse and dependence. Since 2015, efforts to restrict access to prescription opioids have resulted in a marked increase in the use of “street” opioids such as heroin and illicit fentanyl. At the same time, many patients with chronic pain conditions or opioid use disorder have been denied access to appropriate medical help. The lack of access to care for patients with chronic pain and opioid use disorder has been magnified by the emergence of the COVID-19 pandemic. In this report, we highlight how these converging factors have led to a surge in interest in kratom as a potential harm reduction agent in the treatment of pain and opioid use disorder.

Various adverse outcomes related to the use of electrical weapons such as the stun gun or the Taser have been described in the literature over the years. Examples include cardiac arrhythmias, blunt and penetrating injuries, seizure activity, and altered mental status. Imaging findings related to electrical injuries have become more frequent with advancing imaging technologies, such as CT or MRI. However, imaging findings and pathophysiology of electrical injuries that result in significant neurological events remain largely unexplored. We report the case of a patient who developed an ischemic stroke following Taser discharge, raising the possibility of association between the electrical injury and the ischemic stroke.