The α‐chemokine stromal‐derived factor (SDF)‐1 and the G‐protein–coupled seven‐span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. In this review, we present the ...concept that the SDF‐1–CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF‐1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSCs) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on nonhematopoietic tissue‐committed stem/progenitor cells (TCSCs); hence, the SDF‐1–CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, because most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF‐1–CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF‐1 (e.g., lymph nodes, lungs, liver, and bones). Hence, we postulate that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms, and we discuss here the common molecular mechanisms involved in these processes. Finally, the responsiveness of CXCR4+ normal and malignant stem cells to an SDF‐1 gradient may be regulated positively/primed by several small molecules related to inflammation which enhance incorporation of CXCR4 into membrane lipid rafts, or may be inhibited/blocked by small CXCR4 antagonist peptides. Consequently, strategies aimed at modulating the SDF‐1–CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.
Percutaneous device closure has become a valuable alternative to surgery in the management of paravalvular leaks. Consequently, imaging in these patients is currently not only meant to verify the ...hemodynamic significance of the lesion but also to assess the feasibility of transcatheter treatment. We present a methodology of comprehensive echocardiography assessment that allows for the selection of patients and plans the intervention. Next, procedure-oriented steps of echocardiography imaging, which are essential for eventual success, are reviewed.
Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment ...decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms.
The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters.
To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.
Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based ...decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients.
COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A.
COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied.
This study examined social disparities in cardiovascular mortality ...of people with and without cancer in the US population between 1999 and 2019.
Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting.
17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (−51.6% vs −38.3%); the greatest reductions were in colorectal (−68.4%), prostate (−60.0%), and breast (−58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer.
While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequalities and to promote equitable access to cardio-oncology services.
Illustrative overview of study findings, Central illustration footnote. AAMR: age adjusted mortality rate; CV: cardiovascular. Display omitted
Between December 2014 and March 2021, 144 patients with aortic (Ao) or mitral (Mi) paravalvular leaks (PVLs) were enrolled at 21 sites in 10 countries. Safety data were available for 137 patients, ...who were included in the safety analysis fraction (SAF), 93 patients with Mi PVLs and 44 patients with Ao PVLs. The full analysis set (FAS) comprised 112 patients with available stratum (aortic/mitral leak) as well as baseline (BL), 180-day or later assessments (2 years). Procedural success (implantation of the device with a proper closure of the PVL, defined as reduction in paravalvular regurgitation of ≥one grade as assessed by echocardiography post implantation) was achieved in 91.3% of FAS patients with Mi PVLs and in 90.0% of those with Ao PVLs. The proportion of patients suffering from significant or severe heart failure (HF), classified as New York Heart Association (NYHA) class III/IV, decreased from 80% at baseline to 14.1% at 2-year follow-up (FAS). The proportion of FAS patients needing hemolysis-related blood transfusion decreased from 35.5% to 3.8% and from 8.1% to 0% in Mi patients and Ao patients, respectively. In total, 35 serious adverse events (SAEs) were reported in 27 patients (19.7%) of the SAF population. The SAEs considered possibly or probably related to the device included device embolization (three patients), residual leak (two patients) and vascular complication (one patient). During follow-up, 12/137 (8.8%) patients died, but none of the deaths was considered to be device-related. Patients implanted with the Occlutech Paravalvular Leak Device (PLD) showed long-lasting improvements in clinical parameters, including NYHA class and a reduced dependency on hemolysis-related blood transfusions.
The two most common organisms found in infective endocarditis following transcatheter aortic valve implantation (TAVI-IE) are
(EC-IE) and
(SC-IE). We aimed to compare clinical characteristics and ...outcomes of patients with EC-IE and SC-IE.
TAVI-IE patients from 2007 to 2021 were included in this analysis. The 1-year mortality was the primary outcome measure of this retrospective multi-center analysis.
Out of 163 patients, 53 (32.5%) EC-IE and 69 (42.3%) SC-IE patients were included. Subjects were comparable with regard to age, sex, and clinically relevant baseline comorbidities. Symptoms at admission were not significantly different between groups, except for a lower risk for presenting with septic shock in EC-IE than SC-IE. Treatment was performed in 78% by antibiotics alone and in 22% of patients by surgery and antibiotics, with no significant differences between groups. The rate of any complication, in particular heart failure, renal failure, and septic shock during treatment for IE, was lower in EC-IE compared with SC-IE (
< 0.05). In-hospital (EC-IE: 36% vs. SC-IE: 56%,
= 0.035) and 1-year mortality (EC-IE: 51% vs. SC-IE: 70%,
= 0.009) were significantly lower in EC-IE compared with SC-IE.
EC-IE, compared with SC-IE, was associated with a lower morbidity and mortality. However, absolute numbers are high, a finding that should trigger further research in appropriate perioperative antibiotic management and improvement of early IE diagnosis in the case of clinical suspicion.
Recently we identified in bone marrow (BM) by employing chemotactic isolation to SDF-1 gradient combined with real time RT-PCR analysis a mobile population of CXCR4+ BM mononuclear cells that express ...mRNA for various markers of early tissue-committed stem cells (TCSCs). In this study we evaluated whether TCSCs respond to other motomorphogens, such as hepatocyte growth factor (HGF) and leukemia inhibitory factor (LIF).
We again employed chemotactic isolation combined with real-time RT-PCR analysis to assess whether murine and human BM contain TCSCs that respond to HGF and LIF gradients. We also evaluated expressions of HGF and LIF in damaged organs.
We noted that the number of TCSCs is highest in BM from young (1- to 2-month-old) mice and decreases in 1-year-old animals. Murine and human TCSCs 1) respond to HGF and LIF gradients in addition to an SDF-1 gradient, 2) reside in populations of BM-derived non-hematopoietic CD45-cells, and 3) are released (mobilized) from BM into the peripheral blood (PB) during tissue injury (e.g. after partial body irradiation).
These findings further support our theory of the BM as a "hideout" for TCSCs and we suggest that their presence in BM tissue should be considered before experimental evidence is interpreted simply as transdifferentiation/plasticity of hematopoietic stem cells. Since we demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the BM into the PB, from which they are subsequently chemoattracted to damaged organs, where they play a role in tissue repair/regeneration.
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