Individuals with diabetes are at a significantly greater risk of developing cardioymyopathy and heart failure despite adjusting for concomitant risks such as coronary artery disease or hypertension. This has led to the increased recognition of a distinct disease process termed as "diabetic cardiomyopathy." In this article, we perform an extensive review of the pathogenesis and treatment of this disease. From a clinical perspective, physicians should be aware of this entity, and early screening should be considered because physical evidence of early diabetic cardiomyopathy could be difficult to detect. Early detection of the disease should prompt intensification of glycemic control, concomitant risk factors, use of pharmacologic agents such as β-blockers and renin-angiotensin-aldosterone system antagosists. From a research perspective, more studies on myocardial tissue from diabetic patients are needed. Clinical trials to evaluate the development of diabetic cardiomyopathy and fibrosis in early stages of the disease, as well as clinical trials of pharmacologic intervention in patients specifically with diabetic cardiomyopathy, need to be conducted.
Pyogenic liver abscess secondary to dissemination from Sigmoid Diverticulitis is rare. Streptococcus Anginosus has been linked to abscesses but has been rarely reported from a Sigmoid Diverticulitis source. We report a case of liver abscess in which the source was confounding but eventually was traced to Sigmoid Diverticulitis on laparotomy.
Context
A newly-recognized pathogenic mechanism underlying light chain amyloidosis (AL) involves endothelial dysfunction and cell injury caused by misfolded light chain proteins (LC). Nanoliposomes (NL) are artificial phospholipid vesicles that could attach to misfolded proteins and reduce tissue injury.
Objective
To test whether co-treatment with NL reduce LC-induced endothelial dysfunction and cell death.
Methods
Abdominal subcutaneous adipose arterioles from 14 non-AL subjects were cannulated; dilator response to acetylcholine and papaverine were measured at baseline and following 1-hour exposure to LC (20 μg/mL, 2 purified from AL subjects’ urine, 1 from human recombinant LC [AL-09]) ± NL (phosphatidylcholine/cholesterol/phosphatidic acid 70/25/5 molar ratio) or NL alone. Human aortic artery endothelial cells (HAEC) were exposed to Oregon Green-labeled LC±NL for 24 hours and intracellular LC and apoptosis (Hoechst stain) were measured. Circular dichroism spectroscopy was performed on AL-09 LC±NL to follow changes in secondary structure and protein thermal stability.
Results
LC caused impaired dilation to acetylcholine that was restored by NL (control-94.0±1.8%, LC-65.0±7.1%, LC+NL-95.3±1.8%, p≤0.001 LC vs. control or LC+NL). NL protection was inhibited by L-NG-nitroarginine methyl ester. NL increased the beta sheet structure of LC, reduced endothelial cell internalization of LC and protected against LC-induced endothelial cell death.
Conclusions
LC induced human adipose arteriole endothelial dysfunction and endothelial cell death, which were reversed by co-treatment with NL. This protection may partly be due to enhancing LC protein structure and reducing LC internalization. Nanoliposomes represent a promising new class of agents to ameliorate tissue injury from protein misfolding diseases such as AL.
For patients with need for an Impella device, regardless of the indication, early implantation is associated with better in-hospital and 1-year outcomes as compared to when the device is implanted late as a bailout.
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