Project description:Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.
Project description:Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 μm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10-20 μm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities-IVUS and OCT-and discuss the expected potential of the novel hybrid IVUS-OCT catheter system in the clinical field.
Project description:Hypertension is one of the most prevalent chronic diseases worldwide and the incidence of resistant hypertension is increasing. Catheter-based renal denervation (RDN) offers a new approach to reaching blood pressure goals by targeting the renal nerves. The technique has demonstrated significant and sustained reductions in blood pressure (BP) in the Symplicity HTN-1 and Symplicity HTN-2 clinical trials. The Global SYMPLICITY Registry aims to demonstrate safety and effectiveness in a 'real-world' patient population. Real-world RDN experience has emphasised that patient selection is crucial to successful outcomes; a multidisciplinary referral network is recommended to increase awareness of the procedure and identify patients who are likely to respond best to RDN. Further advances in catheter technology have led to the development of the multi-electrode Symplicity Spyral™ multi-electrode catheter; preliminary data from the feasibility study using the Symplicity Spyral catheter indicate clinical efficacy and procedural safety with reduced procedure times. The Symplicity Spyral catheter is not yet commercially available. The indications of RDN may also expand beyond resistant hypertension - encouraging data have been seen in patients with moderate treatment resistant hypertension. Furthermore, RDN may be beneficial in other clinical states characterised by sympathetic nervous system overactivation including heart failure and chronic kidney disease. Additional data are needed to evaluate the efficacy of RDN in these disease states.
Project description:BackgroundDespite the optimal angiographic result of percutaneous coronary intervention (PCI), residual disease at the site of the culprit lesion can lead to major adverse cardiac events. Post-PCI physiological assessment can identify residual stenosis. This meta-analysis aims to investigate data of studies examining post-PCI physiological assessment in relation to long-term outcomes.MethodsStudies were included in the meta-analysis after performing a systematic literature search on July 1, 2022. The primary end point was the incidence of major adverse cardiac events, vessel-orientated cardiac events, or target vessel failure.ResultsLow post-PCI fractional flow reserve, reported in 7 studies with fractional flow reserve cutoff values between 0.84 and 0.90, including 4017 patients, was associated with an increased rate of the primary end point (hazard ratio [HR], 2.06; 95% CI, 1.37-3.08). One study reported about impaired post-PCI instantaneous wave-free ratio with instantaneous wave-free ratio cutoff value of 0.95 in relation to major adverse cardiac events, showing a significant association (HR, 3.38; 95% CI, 0.99-11.6; P = .04). Low post-PCI quantitative flow ratio, reported in 3 studies with quantitative flow ratio cutoff value between 0.89 and 0.91, including 1181 patients, was associated with an increased rate of vessel-orientated cardiac events (HR, 3.01; 95% CI, 2.10-4.32). Combining data of all modalities, impaired physiological assessment showed an increased rate of the primary end point (HR, 2.32; 95% CI, 1.71-3.16) and secondary end points, including death (HR, 1.41; 95% CI, 1.04-1.89), myocardial infarction (HR, 2.70; 95% CI, 1.34-5.42) and target vessel revascularization (HR, 2.88; 95% CI, 1.91-4.35).ConclusionsImpaired post-PCI physiological assessment is associated with increased adverse cardiac events and individual end points, including death, myocardial infarction, and target vessel revascularization. Therefore, prospective studies are awaited on whether physiology-based optimization of PCI results in better clinical outcomes.
Project description:BackgroundCoronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA).AimsThis study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment.MethodsWe analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis.ResultsOn average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98).ConclusionsIn patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.
Project description:For several decades, coronary artery bypass grafting has been regarded as the standard choice of revascularization for significant left main coronary artery (LMCA) disease. However, in conjunction with remarkable advancement of device technology and adjunctive pharmacology, percutaneous coronary intervention (PCI) offers a more expeditious approach with rapid recovery and is a safe and effective alternative in appropriately selected patients with LMCA disease. Several landmark randomized clinical trials showed that PCI with drug-eluting stents for LMCA disease is a safe option with similar long-term survival rates to coronary artery bypass grafting surgery, especially in those with low and intermediate anatomic risk. Although it is expected that the updated evidence from recent randomized clinical trials will determine the next guidelines for the foreseeable future, there are still unresolved and unmet issues of LMCA revascularization and PCI strategy. This paper provides a comprehensive review on the evolution and an update on the management of LMCA disease.
Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.
Project description:Current approaches for cancer detection and characterization are based on radiological procedures coupled with tissue biopsies, despite relevant limitations in terms of overall accuracy and feasibility, including relevant patients' discomfort. Liquid biopsies enable the minimally invasive collection and analysis of circulating biomarkers released from cancer cells and stroma, representing therefore a promising candidate for the substitution or integration in the current standard of care. Despite the potential, the current clinical applications of liquid biopsies are limited to a few specific purposes. The lack of standardized procedures for the pre-analytical management of body fluids samples and the detection of circulating biomarkers is one of the main factors impacting the effective advancement in the applicability of liquid biopsies to clinical practice. The aim of this work, besides depicting current methods for samples collection, storage, quality check and biomarker extraction, is to review the current techniques aimed at analyzing one of the main circulating biomarkers assessed through liquid biopsy, namely cell-free nucleic acids, with particular regard to circulating tumor DNA (ctDNA). ctDNA current and potential applications are reviewed as well.
Project description:Cangrelor is the only currently available intravenous platelet P2Y12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real-world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real-world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.
Project description:The surface roughness of the coronary artery is associated with the onset of atherosclerosis. The study applies, for the first time, the micro-scale variation of the artery surface to a 3D coronary model, investigating the impact on haemodynamic parameters which are indicators for atherosclerosis. The surface roughness of porcine coronary arteries have been detailed based on optical microscopy and implemented into a cylindrical section of coronary artery. Several approaches to rheology are compared to determine the benefits/limitations of both single and multiphase models for multi-scale geometry. Haemodynamic parameters averaged over the rough/smooth sections are similar; however, the rough surface experiences a much wider range, with maximum wall shear stress greater than 6 Pa compared to the approximately 3 Pa on the smooth segment. This suggests the smooth-walled assumption may neglect important near-wall haemodynamics. While rheological models lack sufficient definition to truly encompass the micro-scale effects occurring over the rough surface, single-phase models (Newtonian and non-Newtonian) provide numerically stable and comparable results to other coronary simulations. Multiphase models allow for phase interactions between plasma and red blood cells which is more suited to such multi-scale models. These models require additional physical laws to govern advection/aggregation of particulates in the near-wall region.