Clinical Utility of a Biomarker to Detect Contrast-Induced Acute Kidney Injury during Percutaneous Cardiovascular Procedures

<b><i>Introduction:</i></b> Contrast-induced acute kidney injury (CI-AKI) is a major clinical complication of percutaneous cardiovascular procedures requiring iodinated contrast. Despite its relative frequency, practicing physicians are unlikely to identify or treat this condition. <b><i>Methods:</i></b> In a 2-round clinical trial of simulated patients, we examined the clinical utility of a urine-based assay that measures liver-type fatty acid-binding protein (L-FABP), a novel marker of CI-AKI. We sought to determine if interventional cardiologists’ ability to diagnose and treat potential CI-AKI improved using the biomarker assay for 3 different patient types: pre-procedure, peri-procedure, and post-procedure patients. <b><i>Results:</i></b> 154 participating cardiologists were randomly divided into either control or intervention. At baseline, we found no difference in the demographics or how they identified and treated potential complications of AKI, with both groups providing less than half the necessary care to their patients (46.4% for control vs. 47.6% for intervention, <i>p</i> = 0.250). The introduction of L-FABP into patient care resulted in a statistically significant improvement of 4.6% (<i>p</i> = 0.001). Compared to controls, physicians receiving L-FABP results were 2.9 times more likely to correctly identify their patients’ risk for AKI (95% CI 2.1–4.0) and were more than twice as likely to treat for AKI by providing volume expansion and withholding nephrotoxic medications. We found the greatest clinical utility in the pre-procedure and peri-procedure settings but limited value in the post-procedure setting. <b><i>Conclusion:</i></b> This study suggests L-FABP as a clinical marker for assessing the risk of potential CI-AKI, has clinical utility, and can lead to more accurate diagnosis and treatment.

Correlation between Serum Fatty Acid Binding Protein 4 (FABP4) Levels and Cardiac Function in Patients with Thalassemia Major

Background. Patients with thalassemia major may suffer from complications due to iron overload. It has been suggested that several adipokines may play a potential role in the development of complications in thalassemia. Fatty acid-binding protein 4 (FABP4) is one of the adipokines, bridging several aspects of metabolic and inflammatory pathways. Little is known about the relationship between this adipokine and cardiac and liver function, especially in patients with thalassemia major. Aims. This study is aimed at determining serum FABP4 levels in patients with thalassemia major and whether its concentration correlated with serum ferritin levels, as well as cardiac and liver function. Methods. Thalassemia major outpatients ( n = 48 ) completed laboratory examination, echocardiography, and electrocardiography. Results. The mean age was 21.9 ± 8.0 years. A negative and weak correlation between serum ferritin and FABP4 was observed ( r = − 0.291 , p < 0.05 ). In addition, there was moderate and positive correlation between left atrial volume index (LAVI) and FABP4 ( r = 0.316 , p < 0.05 ). Conclusions. Serum FABP4 correlated with serum ferritin and cardiac function in patients with thalassemia major. FABP4 may be a potential clinical biomarker for cardiac dysfunction via metabolic and inflammatory pathways due to iron accumulation and toxicity in patients with thalassemia major.

Recombinant Fasciola hepatica Fatty Acid Binding Protein as a Novel Anti-Inflammatory Biotherapeutic Drug in an Acute Gram-Negative Nonhuman Primate Sepsis Model

Sepsis caused by Gram-negative bacteria affects 1.7 million adults annually in the United States and is one of the most important causes of death at intensive care units. Although the effective use of antibiotics has resulted in improved prognosis of sepsis, the pathological and deathly effects have been attributed to the persistent inflammatory cascade.

Histone H3 deacetylation promotes host cell viability for efficient infection by Listeria monocytogenes

For many intracellular bacterial pathogens manipulating host cell survival is essential for maintaining their replicative niche, and is a common strategy used to promote infection. The bacterial pathogen Listeria monocytogenes is well known to hijack host machinery for its own benefit, such as targeting the host histone H3 for modification by SIRT2. However, by what means this modification benefits infection, as well as the molecular players involved, were unknown. Here we show that SIRT2 activity supports Listeria intracellular survival by maintaining genome integrity and host cell viability. This protective effect is dependent on H3K18 deacetylation, which safeguards the host genome by counteracting infection-induced DNA damage. Mechanistically, infection causes SIRT2 to interact with the nucleic acid binding protein TDP-43 and localise to genomic R-loops, where H3K18 deacetylation occurs. This work highlights novel functions of TDP-43 and R-loops during bacterial infection and identifies the mechanism through which L. monocytogenes co-opts SIRT2 to allow efficient infection.