A thrombus (blood clot) is formed in injured vessels to maintain the integrity of vasculature. However, obstruction of blood vessels by thrombosis slows blood flow, leading to death of tissues fed by the artery and is the main culprit of various life-threatening cardiovascular diseases. Herein, we report a rationally designed nanomedicine that could specifically image obstructed vessels and inhibit thrombus formation. On the basis of the physicochemical and biological characteristics of thrombi such as an abundance of fibrin and an elevated level of hydrogen peroxide (HO), we developed a fibrin-targeted imaging and antithrombotic nanomedicine, termed FTIAN, as a theranostic system for obstructive thrombosis. FTIAN inhibited the generation of HO and suppressed the expression of tumor necrosis factor-alpha (TNF-α) and soluble CD40 ligand (sCD40L) in activated platelets, demonstrating its intrinsic antioxidant, anti-inflammatory, and antiplatelet activity. In a mouse model of ferric chloride (FeCl)-induced carotid thrombosis, FTIAN specifically targeted the obstructive thrombus and significantly enhanced the fluorescence/photoacoustic signal. When loaded with the antiplatelet drug tirofiban, FTIAN remarkably suppressed thrombus formation. Given its thrombus-specific imaging along with excellent therapeutic activities, FTIAN offers tremendous translational potential as a nanotheranostic agent for obstructive thrombosis.

A thrombus (blood clot), composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and an elevated level of hydrogen peroxide (HO), we developed thrombus-specific theranostic (T-FBM) nanoparticles that could provide HO-triggered photoacoustic signal amplification and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by HO to generate CO bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a HO-triggered manner. T-FBM nanoparticles also exerted HO-activatable antioxidant, anti-inflammatory, and antiplatelet activities on endothelial cells. In mouse models of carotid arterial injury, T-FBM nanoparticles significantly enhanced the photoacoustic contrast specifically in thrombosed vessels and significantly suppressed thrombus formation. We anticipate that T-FBM nanoparticles hold great translational potential as nanotheranostics for HO-associated cardiovascular diseases.

The association between increased RDW and active IBD was evident in IBD patients with and without anemia.

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Background/Aims: Many patients with end-stage renal disease have additional comorbidities that are important to clinical study and impact the patient’s outcome. The Charlson Comorbidity Index (CCI) is a popular tool and a strong predictor of outcome in end-stage renal disease patients. We obtained comorbidity data from the hospital discharge database using the International Classification of Disease, 10th revision (ICD-10) and analyzed the mortality rate in incident patients undergoing maintenance hemodialysis (HD). Methods: We evaluated the medical records of a total of 456 patients on HD (58 ± 14 years of age, 56% males). We calculated CCI scores at the start of HD with information from the hospital discharge summary according to the ICD-10 code. We then analyzed patient mortality according to these CCI scores. Results: The percentages of patients that had diabetes with end-organ damage (51.1%), congestive heart failure (9.9%), coronary artery disease (8.1%) and stroke (6.8%) were identified. CCI scores were 5.09 ± 2.01 (range 2–11). Four comorbidity groups were established by quartile ranking of the CCI scores: low, moderate, high and very high. The mortality rates were: 0.83, 7.70, 14.09 and 18.69 deaths/100 patient-years, respectively (p = 0.001). Compared with the low comorbidity group, the hazard ratios for mortality were 9.22 (95% CI 3.29–25.84) for the moderate group, 16.77 (95% CI 5.97–47.11) for the high group, and 22.37 (95% CI 8.08–61.93) for the very high group. Conclusions: The CCI scores using the ICD-10 database information were significant predictors of mortality in incident patients undergoing maintenance HD.

Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use.

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