Cerebral microvascular occlusion is a common phenomenon throughout life1,2 that could be an underappreciated mechanism of brain pathology. Failure to promptly recanalize microvessels may lead to disruption of brain circuits and significant functional deficits3. Hemodynamic forces and the fibrinolytic system4 are considered the principal mechanisms responsible for recanalization of occluded cerebral capillaries and terminal arterioles. However, using high resolution fixed tissue microscopy and two photon imaging in living mice we found that a large fraction of occluding microemboli failed to be lysed and washed out within 48 hours after internal carotid infusion. Surprisingly, emboli were instead found to translocate outside the vessel lumen within 2-7 days leading to complete re-establishment of blood flow and sparing of the vessel. Recanalization occurred by a previously unknown mechanism of microvascular plasticity involving the rapid envelopment of emboli by endothelial membrane projections which subsequently form a new vessel wall. This was followed by the formation of an endothelial opening through which emboli translocated into the perivascular parenchyma. The rate of embolus extravasation was significantly reduced by pharmacological inhibition of matrix metalloproteinase 2/9 activity. In aged mice, extravasation was markedly delayed, resulting in persistent tissue hypoxia, synaptic damage and cell death. Our study identifies a novel cellular mechanism that may be critical for recanalization of occluded microvessels. Alterations in the efficiency of this protective mechanism may have important implications in microvascular pathology, stroke recovery, and age-related cognitive decline.

Occlusion of the microvasculature by blood clots, atheromatous fragments, or circulating debris is a frequent phenomenon in most human organs. Emboli are cleared from the microvasculature by hemodynamic pressure and the fibrinolytic system. An alternative mechanism of clearance is angiophagy, in which emboli are engulfed by the endothelium and translocate through the microvascular wall. We report that endothelial lamellipodia surround emboli within hours of occlusion, markedly reducing hemodynamic washout and tissue plasminogen activator-mediated fibrinolysis in mice. Over the next few days, emboli are completely engulfed by the endothelium and extravasated into the perivascular space, leading to vessel recanalization and blood flow reestablishment. We find that this mechanism is not limited to the brain, as previously thought, but also occurs in the heart, retina, kidney, and lung. In the lung, emboli cross into the alveolar space where they are degraded by macrophages, whereas in the kidney, they enter the renal tubules, constituting potential routes for permanent removal of circulating debris. Retina photography and angiography in patients with embolic occlusions provide indirect evidence suggesting that angiophagy may also occur in humans. Thus, angiophagy appears to be a ubiquitous mechanism that could be a therapeutic target with broad implications in vascular occlusive disorders. Given its biphasic nature-initially causing embolus retention, and subsequently driving embolus extravasation-it is likely that different therapeutic strategies will be required during these distinct post-occlusion time windows.

Background Age-related loss of muscle mass and function (sarcopenia) is linked to poor outcomes after surgery and trauma. Here we evaluate CT measured psoas muscle density and area using quick and simple tools available to the beside clinician. We hypothesize these measures will predict poor outcomes after blunt traumatic injury. Methods We conducted a retrospective cohort study of patients ages ≥ 45 years in the Ohio State University Trauma Registry in 2008 that received a CT abdomen/pelvis with intravenous contrast. Psoas Index (PI) and Hounsfield Unit average calculation (HUAC) were measured at the L3 level. 90-day mortality, complication, length of stay ≥ 7 days, dependent discharge were compared to PI and HUAC. Results 151 patients met inclusion criteria. Patients were stratified into interquartile ranges based either on PI or HUAC values. After adjustment with sex-specific cutoffs, the lowest interquartile range of PI was associated with 90-day mortality (RR 5.95, p < 0.008) but did not reach significance in other outcomes. The lowest interquartile range of HUAC was associated with 90-day mortality (RR 5.95, p < 0.008) length of stay ≥ 7 days (RR 1.63, p = 0.048), complication risk (RR 2.30, p = 0.002), and dependent discharge 2.14, p = 0.015). Conclusion Psoas muscle density is a significant predictor of poor outcomes after traumatic injury. This objective, quick, and readily available measure of sarcopenia can identify patients requiring aggressive nutritional and physical therapy to improve prognosis, prevent recurrent traumatic injury, and aid in discharge planning.

Introduction Ultrasound guided thrombin injection (UGTI) is a well-established practice for treatment of femoral artery pseudoaneurysm. This procedure is highly successful but dependent on appropriate pseudoaneurysm anatomy and adequate ultrasound visualization. Morbid obesity can present a significant technical challenge due to increased groin adiposity, resulting in poor visualization of critical structures needed to safely perform the procedure. We aim to evaluate the safety and efficacy of UGTI to treat femoral artery pseudoaneurysm in the morbidly obese. Methods This is a retrospective cohort study in which all patients who underwent UGTI at The Ohio State University Ross Heart Hospital from 2009 to 2014 were analyzed for patient characteristics and stratified by body mass index (BMI). Patients with BMI ≥ 35 were considered morbidly obese and were compared to patients with a BMI < 35. Outcome was failed treatment resulting in residual pseudoaneurysm. Results Our cohort consisted of 54 patients who underwent thrombin injection. There were 41 non-morbidly obese, and 13 morbidly obese patients. Mean age was 64.5 years. The cohort was 44.4% male. There were 6 failures of which 1 underwent successful repeat injection, and 5 underwent open surgical repair. There was no statistically significant difference in failure between non-morbidly obese, and morbidly obese patients (9.8% vs. 15.4%, p=0.45). There were no embolic/thrombotic complications. Conclusion UGTI is a safe and effective therapy in the morbidly obese for the treatment of femoral artery pseudoaneurysm. In the hands of experienced sonographers and surgeons with adequate visualization of the pseudoaneurysm sac, ultrasound guided thrombin injection should remain standard therapy in the morbidly obese.

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