Balancing Safety and Efficacy to Determine the Most Suitable Size of Imaging-Visible Embolic Microspheres for Bariatric Arterial Embolization in a Preclinical Model.

OBJECTIVES: To identify the most suitable size of imaging-visible embolic agents with balanced safety and efficacy for bariatric arterial embolization (BAE) in a preclinical model. MATERIALS AND METHODS: Twenty-seven pigs were divided into 3 cohorts. In Cohort I, 16 pigs were randomized to receive (n = 4 each) 40-100-µm microspheres in 1 or 2 fundal arteries, 70-340-µm radiopaque microspheres in 2 fundal arteries, or saline. In Cohort II, 3 pigs underwent renal arterial embolization with either custom-made 100-200-µm, 200-250-µm, 200-300-µm, or 300-400-µm radiopaque microspheres or Bead Block 300-500 µm with microsphere distribution assessed histologically. In Cohort III, 8 pigs underwent BAE in 2 fundal arteries with tailored 100-200-µm radiopaque microspheres (n = 5) or saline (n = 3). RESULTS: In Cohort I, no significant differences in weight or ghrelin expression were observed between BAE and control animals. Moderate-to-severe gastric ulcerations were noted in all BAE animals. In Cohort II, renal embolization with 100-200-µm microspheres occluded vessels with a mean diameter of 139 µm ± 31, which is within the lower range of actual diameters of Bead Block 300-500 µm. In Cohort III, BAE with 100-200-µm microspheres resulted in significantly lower weight gain (42.3% ± 5.7% vs 51.6% ± 2.9% at 8 weeks; P = .04), fundal ghrelin cell density (16.1 ± 6.7 vs 23.6 ± 12.6; P = .045), and plasma ghrelin levels (1,709 pg/mL ± 172 vs 4,343 pg/mL ± 1,555; P < .01) compared with controls and superficial gastric ulcers (5/5). CONCLUSIONS: In this preclinical model, tailored 100-200-µm microspheres were shown to be most suitable for BAE in terms of safety and efficacy.

Association Between Gut Hormones and Weight Change After Bariatric Arterial Embolization: Results from the BEAT Obesity Trial.

PURPOSE: To evaluate associations of ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY 3-36 (PYY3-36) with weight change after bariatric arterial embolization (BAE). MATERIALS AND METHODS: Subgroup analysis of data collected during the BEAT Obesity Trial involving 7 participants with BMI > 40 who were embolized with 300- to 500-µm Embosphere Microspheres. Three participants were characterized as "responders" (top tertile of weight loss at each visit) and 4 as "non-responders" (bottom tertile of weight loss at each visit). Mean ± standard deviation participant age was 44 ± 11 years, and 6 of 7 participants were women. Participants were evaluated at baseline, 2 weeks, and 1, 3, 6, and 12 months after BAE. After fasting, participants consumed a mixed meal test at each visit; blood samples were collected at 0, 15, 30, 60, 120, 180, and 240 min. Study outcome measures were changes in weight from baseline and plasma serum hormone levels. RESULTS: Percentage change in ghrelin decreased significantly in non-responders at 60 and 120 min at 1 and 12 months (estimated difference between 60 vs. 0 min at 1 month: 69% [95% CI - 126%, - 13%]; estimated difference between 120 vs. 0 min at 12 months: - 131% (95% CI - 239%, - 23%]). Responders had significantly lower ghrelin and greater weight loss than non-responders at 6 and 12 months. GLP-1 and PYY3-36 levels did not differ between groups. CONCLUSION: Participants with consistent weight loss throughout follow-up had lower ghrelin than non-responders, supporting decreased ghrelin as a mechanism underlying BAE-induced weight loss. LEVEL OF EVIDENCE I: High-quality randomized trial or prospective study; testing of previously developed diagnostic criteria on consecutive patients; sensible costs and alternatives; values obtained from many studies with multiway sensitivity analyses; systematic review of Level I RCTs and Level I studies.

Acute worsening of CADASIL in a patient with COVID-19 infection: illustrative case.

BACKGROUND: Reports of cerebrovascular ischemia and stroke occurring as predominant neurological sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), are increasingly evident within the literature. While various pathophysiological mechanisms have been postulated, including hypercoagulability, endothelial invasion, and systemic inflammation, discrete mechanisms for viral neurotropism remain unclear and controversial. OBSERVATIONS: The authors present a unique case study of a 64-year-old male with acute COVID-19 infection and acute worsening of previously stable cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare heritable arteriopathy due to mutation in the Notch3 gene, which is critical for vascular development and tone. Delayed cranial neuropathies, brainstem fluid-attenuated inversion recovery signal, and enhancement of olfactory and vagus nerves on magnetic resonance neurography in this patient further support viral neurotropism via cranial nerves in addition to cerebral vasculature. LESSONS: To the authors' knowledge, this is the first case in the literature that not only demonstrates the consequences of COVID-19 infection in a patient with altered cerebrovascular autoregulation such as CADASIL but also highlights the tropism of SARS-CoV-2 for (1) cranial nerves as a mode of entry to the central nervous system and (2) vessels as a cause of cerebrovascular ischemia.

Tentorial venous anatomy of mice and humans.

We recently described a transtentorial venous system (TTVS), which to our knowledge was previously unknown, connecting venous drainage throughout the brain in humans. Prior to this finding, it was believed that the embryologic tentorial plexus regresses, resulting in a largely avascular tentorium. Our finding contradicted this understanding and necessitated further investigation into the development of the TTVS. Herein, we sought to investigate mice as a model to study the development of this system. First, using vascular casting and ex vivo micro-CT, we demonstrated that this TTVS is conserved in adult mice. Next, using high-resolution MRI, we identified the primitive tentorial venous plexus in the murine embryo at day 14.5. We also found that, at this embryologic stage, the tentorial plexus drains the choroid plexus. Finally, using vascular casting and micro-CT, we found that the TTVS is the dominant venous drainage in the early postnatal period (P8). Herein, we demonstrated that the TTVS is conserved between mice and humans, and we present a longitudinal study of its development. In addition, our findings establish mice as a translational model for further study of this system and its relationship to intracranial physiology.

Reversing the effects of androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer.

OBJECTIVE: To investigate whether bipolar androgen therapy (BAT), involving rapid cyclic administration of high-dose testosterone, as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) promotes improvements in body composition and associated improvements in lipid profiles and quality of life. PATIENTS AND METHODS: Men from two completed trials with computed tomography imaging at baseline and after three cycles of BAT were included. Cross-sectional areas of psoas muscle, visceral and subcutaneous fat were measured at the L3 vertebral level. Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire and 36-item short-form health survey were used to assess quality of life. RESULTS: The 60 included patients lost a mean (sd) of 7.8 (8.2)% of subcutaneous fat, 9.8 (18.2)% of visceral fat, and gained 12.2 (6.7)% muscle mass. Changes in subcutaneous and visceral fat were positively correlated with each other (Spearman's correlation coefficient 0.58, 95% confidence interval 0.35-0.71) independent of the effects of age, body mass index, and duration of androgen-deprivation therapy. Energy, physical function, and measures of limitations due to physical health were all significantly improved at 3 months. The improvements in body composition were not correlated with decreases in lipid levels or observed improvements in quality of life. CONCLUSIONS: In the present study, BAT was associated with significant improvements in body composition, lipid parameters, and quality of life. This has promising implications for the long-term health of men with mCRPC.