Now You See It, Now You Don't: Point-of-Care Ultrasound Identification of Left Ventricular Thrombus-in-Transit.

BACKGROUND: Left-sided intracardiac thrombi are most commonly seen in conditions with decreased cardiac flow, such as myocardial infarction or atrial fibrillation. They can be propagated into the systemic circulation, leading to a cerebrovascular accident. Identification of thrombus-in-transit via point-of-care ultrasound (POCUS) has the potential to change patient management given its association with high patient morbidity and mortality. CASE REPORT: An intubated 60-year-old man was transferred to our emergency department for management of altered mental status and seizure-like activity. The patient was markedly hypotensive on arrival, and cardiac POCUS was performed to identify potential causes of hypotension. A left ventricular thrombus-in-transit was identified. The thrombus was notably absent on a repeat POCUS examination < 10 min later, which led to concern for thrombus propagation. Furthermore, the patient's vasopressor requirements had significantly increased in that time period. Subsequent emergent neuroimaging revealed a large ischemic stroke in the left internal carotid and middle cerebral artery distribution. The patient was, unfortunately, deemed to not be a candidate for either thrombectomy or thrombolysis and ultimately expired in the hospital. Why Should an Emergency Physician Be Aware of This? Serial POCUS examinations identified the propagation of this patient's thrombus-in-transit, leading the physician to change the initial presumptive diagnosis and treatment course, and pursue further imaging and workup for ischemic stroke. Identification of a thrombus-in-transit is a clue to potentially underlying critical pathology and should be followed with serial POCUS examinations to assess for treatment efficacy and thrombus propagation.

Ocular and eyelid involvement in collagen vascular diseases. Part I. Sjögren syndrome and systemic lupus erythematosus.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. Part I of our series will discuss the ocular manifestations, their diagnosis, and therapeutic options in Sjögren syndrome and systemic lupus erythematosus.

Ocular and eyelid involvement in collagen vascular diseases. Part II. Dermatomyositis, scleroderma, and sarcoidosis.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can also be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. In part II of our series, we discuss the ocular manifestations, diagnosis, and therapeutic options of dermatomyositis, scleroderma, and sarcoidosis.

Cow's milk polar lipids reduce atherogenic lipoprotein cholesterol, modulate gut microbiota and attenuate atherosclerosis development in LDL-receptor knockout mice fed a Western-type diet.

Milk sphingomyelin (SM), a polar lipid (PL) component of milk fat globule membranes, is protective against dyslipidemia. However, it is unclear whether ingestion of milk PLs protect against atherosclerosis. To determine this, male LDLr-/- mice (age 6 weeks) were fed ad libitum either a high-fat, added-cholesterol diet (CTL; 45% kcal from fat, 0.2% cholesterol by weight; n=15) or the same diet supplemented with 1% milk PL (1% MPL; n=15) or 2% milk PL (2% MPL; n=15) added by weight from butter serum. After 14 weeks on diets, mice fed 2% MPL had significantly lower serum cholesterol (-51%) compared to CTL (P<.01), with dose-dependent effects in lowering VLDL- and LDL-cholesterol. Mice fed 2% MPL displayed lower inflammatory markers in the serum, liver, adipose and aorta. Notably, milk PLs reduced atherosclerosis development in both the thoracic aorta and the aortic root, with 2% MPL-fed mice having significantly lower neutral lipid plaque size by 59% (P<.01) and 71% (P<.02) compared to CTL, respectively. Additionally, the 2% MPL-fed mice had greater relative abundance of Bacteroidetes, Actinobacteria and Bifidobacterium, and lower Firmicutes in cecal feces compared to CTL. Milk PL feeding resulted in significantly different microbial communities as demonstrated by altered beta diversity indices. In summary, 2% MPL strongly reduced atherogenic lipoprotein cholesterol, modulated gut microbiota, lowered inflammation and attenuated atherosclerosis development. Thus, milk PL content may be important to consider when choosing dairy products as foods for cardiovascular disease prevention.

Long-Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E-Knockout Mice.

SCOPE: HDL particles are protective against atherosclerosis, but may become dysfunctional during inflammation and chronic disease progression. Anthocyanin-rich foods, such as the black elderberry, may improve HDL function and prevent disease development via antioxidant and/or anti-inflammatory effects. This study investigates the long-term consumption of black elderberry extract (BEE) on HDL function and atherosclerosis in apolipoprotein (apo) E-/- mice. METHODS AND RESULTS: ApoE-/- mice (n = 12/group) are fed a low-fat diet, supplemented with 0, 0.25%, or 1% (by weight) BEE (≈37.5-150 mg anthocyanins per kg body weight) for 24 weeks. Feeding 1% BEE increases total serum cholesterol (+31%) and non-HDL cholesterol (+32%) compared with the control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increase with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increase HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose-dependently lowers serum liver enzymes and hepatic inflammatory gene expression. Although there is no change in neutral lipid accumulation in atherosclerotic lesions, BEE promotes connective tissue deposition in the aortic root. CONCLUSIONS: Chronic BEE supplementation in apoE-/- mice dose-dependently improves HDL function. Despite BEE promoting hyperlipidemia, which likely offsets HDL effects, BEE increases connective tissue content, suggesting improved atherosclerotic plaque stability.

Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice.

Western-type diets can induce obesity and related conditions such as dyslipidemia, insulin resistance and hepatic steatosis. We evaluated the effects of milk sphingomyelin (SM) and egg SM on diet-induced obesity, the development of hepatic steatosis and adipose inflammation in C57BL/6J mice fed a high-fat, cholesterol-enriched diet for 10 weeks. Mice were fed a low-fat diet (10% kcal from fat) (n=10), a high-fat diet (60% kcal from fat) (HFD, n=14) or a high-fat diet modified to contain either 0.1% (w/w) milk SM (n=14) or 0.1% (w/w) egg SM (n=14). After 10 weeks, egg SM ameliorated weight gain, hypercholesterolemia and hyperglycemia induced by HFD. Both egg SM and milk SM attenuated hepatic steatosis development, with significantly lower hepatic triglycerides (TGs) and cholesterol relative to HFD. This reduction in hepatic steatosis was stronger with egg SM supplementation relative to milk SM. Reductions in hepatic TGs observed with dietary SM were associated with lower hepatic mRNA expression of PPARγ-related genes: Scd1 and Pparg2 in both SM groups, and Cd36 and Fabp4 with egg SM. Egg SM and, to a lesser extent, milk SM reduced inflammation and markers of macrophage infiltration in adipose tissue. Egg SM also reduced skeletal muscle TG content compared to HFD. Overall, the current study provides evidence of dietary SM improving metabolic complications associated with diet-induced obesity in mice. Further research is warranted to understand the differences in bioactivity observed between egg and milk SM.

Milk sphingomyelin improves lipid metabolism and alters gut microbiota in high fat diet-fed mice.

High dietary fat intake can cause elevated serum and hepatic lipids, as well as contribute to gut dysbiosis, intestinal barrier dysfunction and increased circulating lipopolysaccharide (LPS). Dietary milk sphingomyelin (SM) has been shown to inhibit lipid absorption in rodents. We evaluated the effects of milk SM on lipid metabolism and LPS levels in C57BL/6J mice fed a high-fat diet for 4weeks and compared it with egg SM. Mice were fed a high-fat diet (45%kcal from fat) (CTL, n=10) or the same diet modified to contain 0.25% (wt/wt) milk SM (MSM, n=10) or 0.25% (wt/wt) egg SM (ESM, n=10). After 4weeks, MSM had gained significantly less weight and had reduced serum cholesterol compared to CTL. ESM had increases in serum cholesterol, triglycerides, phospholipids and SM compared to CTL. MSM significantly decreased, while ESM increased, hepatic triglycerides. This may have been related to induction of hepatic stearoyl-CoA desaturase-1 mRNA observed in ESM. MSM displayed intestinal and hepatic gene expression changes consistent with cholesterol depletion. MSM had significantly lower serum LPS compared to CTL, which may have been due to altered distal gut microbiota. Fecal Gram-negative bacteria were significantly lower, while fecal Bifidobacterium were higher, in MSM. These results suggest that milk SM is more effective than egg SM at combating the detrimental effects of a high-fat diet in mice. Additionally, distal gut microbiota is altered with milk SM and this may have contributed to the lower serum LPS observed.

Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice.

Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate obesity-related complications. Black elderberry is one of the richest sources of anthocyanins. We investigated the metabolic effects of anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J mouse model. Mice were fed either a low-fat diet (n 8), high-fat lard-based diet (HFD; n 16), HFD+0·25 % (w/w) BEE (0·25 %-BEE; n 16) or HFD+1·25 % BEE (1·25 %-BEE; n 16) for 16 weeks. The 0·25 % BEE (0·034 % anthocyanin, w/w) and 1·25 % BEE (0·17 % anthocyanin, w/w) diets corresponded to estimated anthocyanin doses of 20-40 mg and 100-200 mg per kg of body weight, respectively. After 16 weeks, both BEE groups had significantly lower liver weights, serum TAG, homoeostasis model assessment and serum monocyte chemoattractant protein-1 compared with HFD. The 0·25 %-BEE also had lower serum insulin and TNFα compared with HFD. Hepatic fatty acid synthase mRNA was lower in both BEE groups, whereas PPARγ2 mRNA and liver cholesterol were lower in 1·25 %-BEE, suggesting decreased hepatic lipid synthesis. Higher adipose PPARγ mRNA, transforming growth factor ß mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was less inflammatory in 1·25 %-BEE. Skeletal muscle mRNA expression of the myokine IL-6 was higher in 0·25 %-BEE relative to HFD. These results suggest that BEE may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum TAG, inflammatory markers and insulin resistance.