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Aims: Stem cells are a promising therapy for various medical conditions. The literature regarding their adoption for the clinical care of cardiovascular diseases (CVD) is still conflicting. Therefore, our aim is to assess the strength and credibility of the evidence on clinical outcomes and application of stem cells derived from systematic reviews and meta-analyses of intervention studies in CVD., Methods and Results: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For meta-analyses of RCTs, outcomes with a random-effect p-value <0.05, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment was used, classifying the evidence from very low to high. From 184 abstracts initially identified, 11 meta-analyses (for a total of 34 outcomes) were included. Half of the outcomes were statistically significant (p < 0.05), indicating that stem cells are more useful than placebo. High certainty of evidence supports the associations of the use of stem cells with a better left ventricular end systolic volume and left ventricular ejection fraction (LVEF) in acute myocardial infarction; improved exercise time in refractory angina; a significant lower risk of amputation rate in critical limb ischemia; a higher successful rate in complete healing in case of lower extremities ulcer; and better values of LVEF in systolic heart failure, as compared to placebo., Conclusion and Relevance: The adoption of stem cells in clinical practice is supported by a high certainty of strength in different CVD, with the highest strength in acute myocardial infarction and refractory angina., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Few reports have been published on the correlation between plasma concentrations of rivaroxaban and clinical outcome in patients who have experienced venous thromboembolism. This article describes the case of a 44-year-old woman who experienced deep vein thrombosis during anticoagulation therapy with rivaroxaban, with evidence of repeated low plasma levels of the drug. We postulate that the determination of plasma rivaroxaban anti-Xa activity can be useful in the evaluation of anticoagulation therapy in selected cases., Learning Points: Some patients with deep vein thrombosis do not respond to rivaroxaban therapy.Accurate determination of rivaroxaban plasma concentrations is important in clinical practice.The clinical value of rivaroxaban plasma concentrations might be limited by intra- and inter-individual variations., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Aims: The European Lead Extraction ConTRolled Registry (ELECTRa), is a prospective registry of consecutive transvenous lead extraction (TLE) procedures conducted by the European Heart Rhythm Association (EHRA) in order to identify the safety and efficacy of the current practice of TLE., Methods and Results: European centres performing TLE, invited by the organizing committee on behalf of EHRA, prospectively recruited all consecutive patients undergoing TLE at their institution. The primary endpoint was TLE safety defined by pre-discharge major procedure-related complications including death. Secondary endpoints included clinical and radiological success and overall complication rates. Outcomes were compared between Low Volume (LoV) vs. High Volume (HiV) centers (LoV < 30 and HiV ≥ 30 procedures/year). A total of 3555 consecutive patients (pts) of whom 3510 underwent TLE at 73 centres in 19 European countries were enrolled between November 2012 and May 2014. The primary endpoint of in-hospital procedure-related major complication rate was 1.7% [95% CI 1.3-2.1%] (58/3510 pts) including a mortality of 0.5% [95% CI 0.3-0.8%] (17/3510 pts). Approximately two-thirds (37/58) of these complications occurred during the procedure and one-third (21/58) in the post-operative period. The most common procedure related complications were those requiring pericardiocentesis or chest tube and/or surgical repair (1.4% [95% CI 1.0-1.8%]). Complete clinical and radiological success rates were 96.7% [95% CI 96.1-97.3%] and 95.7% [95% CI 95.2-96.2%], respectively. The all cause in-hospital major complications and deaths were significantly lower in HiV centres vs. LoV centres (2.4% [95% CI 1.9-3.0%] vs. 4.1% [95% CI 2.7-6.0%], P = 0.0146; and 1.2% [95% CI 0.8-1.6%] vs. 2.5% [95% CI 1.5-4.1%] P = 0.0088), although those related to the procedure did not reach statistical significance. Radiological and clinical successes were more frequent in HiV vs. LoV centres., Conclusion: The ELECTRa study is the largest prospective registry on TLE and confirmed the safety and efficacy of the current practice of TLE. Lead extraction was associated with a higher success rate with lower all cause complication and mortality rates in high volume compared with low volume centres., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: The real-time and continuous assessment of left ventricular (LV) myocardial contractility through an implanted device is a clinically relevant goal. Transvalvular impedance (TVI) is an impedentiometric signal detected in the right cardiac chambers that changes during stroke volume fluctuations in patients. However, the relationship between TVI signals and LV contractility has not been proven. We investigated whether TVI signals predict changes of LV inotropic state during clinically relevant loading and inotropic conditions in swine normal heart., Methods: The assessment of RVTVI signals was performed in anesthetized adult healthy anesthetized pigs (n = 6) instrumented for measurement of aortic and LV pressure, dP/dtmax and LV volumes. Myocardial contractility was assessed with the slope (Ees) of the LV end systolic pressure-volume relationship. Effective arterial elastance (Ea) and stroke work (SW) were determined from the LV pressure-volume loops. Pigs were studied at rest (baseline), after transient mechanical preload reduction and afterload increase, after 10-min of low dose dobutamine infusion (LDDS, 10 ug/kg/min, i.v), and esmolol administration (ESMO, bolus of 500 µg and continuous infusion of 100 µg·kg-1·min-1)., Results: We detected a significant relationship between ESTVI and dP/dtmax during LDDS and ESMO administration. In addition, the fluctuations of ESTVI were significantly related to changes of the Ees during afterload increase, LDDS and ESMO infusion., Conclusions: ESTVI signal detected in right cardiac chamber is significantly affected by acute changes in cardiac mechanical activity and is able to predict acute changes of LV inotropic state in normal heart.

With the growing recognition of the clinical need and wider indications for cardiovascular implantable electronic devices (CIED), the number of implant procedures has increased considerably. Consequently, the rate of complications related to these devices has also increased. Transvenous lead extraction (TLE) is the gold standard in the treatment of CIED-related infective complications and is often required in the management of lead malfunction. An increasing number of centers currently perform TLE procedures. The ELECTRa (European Lead Extraction ConTRolled) Registry is the first large prospective multicenter registry of consecutive patients undergoing TLE in Europe, conducted by the European Heart Rhythm Association (EHRA) and managed by the European Society of Cardiology (ESC) EURObservational Research Department. The primary objective of the registry is to evaluate the acute and long-term safety of TLE; the secondary objective is to describe the characteristics of the patients, the leads, the indications for TLE, and the tools and techniques currently used for TLE. About 100 centers will be enrolled on a voluntary basis from European countries; they are anonymous and stratified on the basis of their volume of activity into high-volume centers (>30 patients/year) and low-volume centers: (≤30 patients/year). Each participating center will have to enroll and follow up for 1 year consecutively assessed patients undergoing TLE from November 2012 to January 2014. The target is to achieve a sample size of at least 3,500 patients for statistical analysis. Data will be collected using a Web-based system and will be audited at randomly selected centers. The official start was on 6 November. Eighty-nine centers have joined so far, 65 centers are currently active, those who have already obtained the approval of their own ethics committee, and 1,099 patients were enrolled at the end of June 2013. The independence of the registry, the consecutiveness of the patient enrolment, and the monitoring of the study are characteristics of this registry that will contribute to the scientific validity of the objectives to be achieved.

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation.

Objective: Although specifically designed aortic clamps are mainstay of minimally invasive cardiac surgery, so far, no comparative reports about their mechanical properties and interaction with the aortic wall have been reported. In this study, the generated force in the clamps' jaws and the biological response of the aorta after clamping are evaluated., Methods: The jaw force of five commercially available clamps [Geister, Cygnet, Cardiovision (CV) 195.10, CV 195.40, and CV 195.83] was assessed by clamping a 2.2-mm compression load cell with a dedicated computer universal serial bus interface at the proximal, the middle, and the distal site from the fulcrum. Biological response of the aortic wall was assessed in five minipigs (weight, 38-40 kg) that underwent thoracic aorta clamping and leakage point test. Immunohistochemistry and morphometric analysis were carried out for each aortic segment tested., Results: Force generation pattern is peculiar of each clamp, being higher in the proximal and the middle portion and lower in the distal part. One clamp (Cygnet) exhibited homogeneous maximal force generation at all three sites. All clamps exhibited peculiar crushing artifacts. A variable degree of endothelial layer disruption occurred in all clamping tests; three clamps (CV 195.10, Cygnet, and Geister) had the lower amount of intact endothelium. The clamping force was not associated with the degree of endothelial disruption (P value was not significant)., Conclusions: The choice of a clamp that is not only minimally invasive in design but also least traumatic will help avoid complications of aortic manipulation.

Scleractinian corals, which include the architects of coral reefs, are found throughout the world's oceans and have left a rich fossil record over their 240 million year history. Their classification has been marked by confusion but recently developed molecular and morphological tools are now leading to a better understanding of the evolutionary history of this important group. Although morphological characters have been the basis of traditional classification in the group, they are relatively few in number. In addition, our current understanding of skeletal growth and homology is limited, and homoplasy is rampant, limiting the usefulness of morphological phylogenetics. Molecular phylogenetic hypotheses for the order, which have been primarily focused on reef-building corals, differ significantly from traditional classification. They suggest that the group is represented by two major lineages and do not support the monophyly of traditional suborders and most traditional families. It appears that once a substantial number of azooxanthellate taxa are included in molecular phylogenetic analyses, basal relationships within the group will be clearly defined. Understanding of relationships at lower taxonomic levels will be best clarified by combined analyses of morphological and molecular characters. Molecular phylogenies are being used to inform our understanding of the evolution of morphological characters in the Scleractinia. Better understanding of the evolution of these characters will help to integrate the systematics of fossil and extant taxa. We demonstrate how the combined use of morphological and molecular tools holds great promise for ending confusion in scleractinian systematics., (© The Author 2010. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.)

The combination of coloniality and symbiosis in Scleractinia is thought to confer competitive advantage over other benthic invertebrates, and it is likely the key factor for the dominance of corals in tropical reefs. However, the extant Scleractinia are evenly split between zooxanthellate and azooxanthellate species. Most azooxanthellate species are solitary and nearly absent from reefs, but have much wider geographic and bathymetric distributions than reef corals. Molecular phylogenetic analyses have repeatedly recovered clades formed by colonial/zooxanthellate and solitary/azooxanthellate taxa, suggesting that coloniality and symbiosis were repeatedly acquired and/or lost throughout the history of the Scleractinia. Using Bayesian ancestral state reconstruction, we found that symbiosis was lost at least three times and coloniality lost at least six times, and at least two instances in which both characters were lost. All of the azooxanthellate lineages originated from ancestors that were reconstructed as symbiotic, corroborating the onshore-offshore diversification trend recorded in marine taxa. Symbiotic sister taxa of two of these descendant lineages are extant in Caribbean reefs but disappeared from the Mediterranean before the end of the Miocene, whereas extant azooxanthellate lineages have trans-Atlantic distributions. Thus, the phyletic link between reef and nonreef communities may have played an important role in the dynamics of extinction and recovery that marks the evolutionary history of scleractinians, and some reef lineages may have escaped local extinction by diversifying into offshore environments. However, this macroevolutionary mechanism offers no hope of mitigating the effects of climate change on coral reefs in the next century.

Mitochondrial genes have been used extensively in population genetic and phylogeographical analyses, in part due to a high rate of nucleotide substitution in animal mitochondrial DNA (mtDNA). Nucleotide sequences of anthozoan mitochondrial genes, however, are virtually invariant among conspecifics, even at third codon positions of protein-coding sequences. Hence, mtDNA markers are of limited use for population-level studies in these organisms. Mitochondrial gene sequence divergence among anthozoan species is also low relative to that exhibited in other animals, although higher level relationships can be resolved with these markers. Substitution rates in anthozoan nuclear genes are much higher than in mitochondrial genes, whereas nuclear genes in other metazoans usually evolve more slowly than, or similar to, mitochondrial genes. Although several mechanisms accounting for a slow rate of sequence evolution have been proposed, there is not yet a definitive explanation for this observation. Slow evolution and unique characteristics may be common in primitive metazoans, suggesting that patterns of mtDNA evolution in these organisms differ from that in other animal systems.

Relationships among families and suborders of scleractinian corals are poorly understood because of difficulties 1) in making inferences about the evolution of the morphological characters used in coral taxonomy and 2) in interpreting their 240-million-year fossil record. Here we describe patterns of molecular evolution in a segment of the mitochondrial (mt) 16S ribosomal gene from taxa of 14 families of corals and the use of this gene segment in a phylogenetic analysis of relationships within the order. We show that sequences obtained from scleractinians are homologous to other metazoan 16S ribosomal sequences and fall into-two distinct clades defined by size of the amplified gene product. Comparisons of sequences from the two clades demonstrate that both sets of sequences are evolving under similar evolutionary constraints: they do not differ in nucleotide composition, numbers of transition and transversion substitutions, spatial patterns of substitutions, or in rates of divergence. The characteristics and patterns observed in these sequences as well as the secondary structures, are similar to those observed in mt 16S ribosomal DNA sequences from other taxa. Phylogenetic analysis of these sequences shows that they are useful for evaluating relationships within the order. The hypothesis generated from this analysis differs from traditional hypotheses for evolutionary relationships among the Scleractinia and suggests that a reevaluation of evolutionary affinities in the order is needed.

The response of cultured CHO cells to U.V.L. irradiation during treatment with anisotonic solutions shows that treatment with hypotonic sucrose, NaCl or KCl solutions causes an increase in the cellular U.V.L. sensitivity, while exposure to hypertonic solutions causes a large decrease in U.V.L. sensitivity. Cells exposed to 1.8 M sucrose, NaCl or KCl solutions and given a U.V.L. dose of 252 erg/mm2 towards the end of the 20 min solution exposure time have survival levels which are respectively 228,26, and 23 times higher than the controls, i.e. cells irradiated in phosphate buffered saline. Cell volume data obtained using a Coulter counter, and nuclear area data of attached cells obtained using an optical microscope with a micrometer reticle, show that cell and nuclear size are related to U.V.L. sensitivity. That is, as cells shrink and the nuclear area decreases, the cells become more U.V.L.-resistant. During hypotonic treatment with 0.1 M NaCl, the cell volume, nuclear area and U.V.L. sensitivity increased in the first 2 to 4 min of exposure time, but at longer exposure times (greater than 3 to 4 min), cell volume, nuclear area and cellular U.V.L. sensitivity decreased. For 0.1 M KCl treatment the cells initially displayed a rapid increase in volume, nuclear area and U.V.L. sensitivity, but at the longer exposure times no decrease in cell and nuclear size were observed, and a slight increase in U.V.L. sensitivity occurred. Changes in U.V.L. sensitivity were related to changes in nuclear size and cell volume; however, calculations showed that during hypertonic treatment there is an ionic effect as well as an osmotic effect. That is, the cellular U.V.L. survival in equal hypertonic concentrations of NaCl or KCl was lower than in the same concentration of sucrose.