Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation

IntroductionThere are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long‐term recurrence of AF after catheter ablation, depending on AF type.MethodsAF patients who underwent point‐by‐point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni‐ and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence.ResultsIn total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence‐free time of 22.7 (9.3–43.1) months. Patients with persistent AF had significantly higher body surface area‐indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38–3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01–1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF.ConclusionThe current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.     

Microstructure and Mechanical Properties of Ti-25Nb-4Ta-8Sn Alloy Prepared by Spark Plasma Sintering

As the commercially most-used Ti-6Al-4V alloy has a different modulus of elasticity compared to the modulus of elasticity of bone and contains allergenic elements, β-Ti alloy could be a suitable substitution in orthopedics. The spark plasma sintering (SPS) method is feasible for the preparation of materials, with very low porosity and fine-grained structure, leading to higher mechanical properties. In this study, we prepared quaternary Ti-25Nb-4Ta-8Sn alloy using the spark plasma sintering method. The material was also heat-treated in order to homogenize the structure and compare the microstructure and properties in as-sintered and annealed states. The SPS sample had a modulus of elasticity of about 63 ± 1 GPa, which, after annealing, increased to the value of 73 ± 1 GPa. The tensile yield strength (TYS) of the SPS sample was 730 ± 52 MPa, ultimate tensile strength (UTS) 764 ± 10 MPa, and ductility 22 ± 9%. Annealed samples reached higher values of TYS and UTS (831 ± 60 MPa and 954 ± 48 MPa), but the ductility decreased to the value of 3 ± 1%. The obtained results are discussed considering the observed microstructure of the alloy.     

Accelerated recovery of 5-fluorouracil-damaged bone marrow after rosiglitazone treatment

Our preliminary data indicate that rosiglitazone may be myeloprotective. We investigated whether it can modify bone marrow recovery. Five-day pre-treatment with rosiglitazone significantly accelerated recovery of 5-fluorouracil-damaged bone marrow in mice. Frequency and femoral content of granulocyte-macrophage progenitors reached mean baseline faster in pre-treated groups than in 5-fluorouracil-treated controls. Consequently, neutropenia was milder. Five-day insulin pre-treatment had similar effects in vivo. Insulin supports in vitro hematopoiesis. The observed myeloprotection demonstrated the importance of insulin in vivo. Clinical use of insulin to moderate myelotoxicity is impractical but rosiglitazone, an insulin sensitizer, could offer hope. Although rosiglitazone tends to increase plasma insulin levels, the significant myeloprotection was partly due to direct effects on progenitors. In vitro rosiglitazone enhanced the survival of both murine progenitor and human mobilized blood stem cells in the presence of 5-fluorouracil, the effect of which was neutralized by a peroxisome-proliferator-activated receptor-gamma antagonist.     

Gesundheit und Frühe Hilfen: Die intersektorale Kooperation im Blick der Forschung

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Frühe Hilfen sind Angebote für Familien mit Kindern bis zum Alter von 3&nbsp;Jahren. Sie leisten einen Beitrag zur...     

The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non‐HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre‐transplant regimens.     

Midline anterior neck inclusion cyst: A novel superficial congenital developmental anomaly of the neck

Background/Objectives

A variety of congenital developmental anomalies arise on the neck because of the many fusion planes and complex embryologic structures in this region. We describe a series of seven patients with a novel type of superficial midline congenital anomaly.

Methods

Retrospective case series. Clinical and histopathologic features were compared and used to describe this entity.

Results

Seven patients with nearly identical clinical findings were identified. In all cases, a small superficial cyst resembling a giant milium was observed at birth. There were no significant changes during infancy and no evidence of underlying abnormalities. The histopathologic findings were identical to those of an infundibular follicular cyst.

Conclusion

We have termed this entity midline anterior neck inclusion cyst. We believe it is a superficial developmental anomaly, probably a forme fruste of a midline fusion developmental defect, which has not to our knowledge, previously been described.     

Two distinct non-T helper type 2 interleukin-4 cell subsets in mice as revealed by single-cell cytokine analysis

We have previously defined four murine CD4⁺ peripheral T cell subsets, fractions (Fr.) I – IV, based on expression of the 6C10 and 3G11 determinants (Hayakawa, K. and Hardy, R. R., J. Exp. Med. 1988. 168: 1825). These subsets also show distinctive levels of other cell surface markers: the two minor subsets, Fr. III and Fr. IV, are both CD45RB^low/-, L-selectin (Mel-14)^? and CD44^hi, characteristic of secondary T cells. The patterns and levels of cytokine production by individual cells in each subset were determined by bioassay for interleukin (IL)-2/IL-4 or IL-4/interferon (IFN)-γ production after anti-CD3 stimulation. Our data revealed that these four phenotypically defined subsets largely coincide with clusters of cells showing uniform distinctive cytokine profiles, i.e. IL-2⁺/IFN-γ^?/IL-4^? (Fr. I and Fr. II, L-selectin⁺), IL-2⁺/IFN-γ⁺/IL-4⁺ (Fr. III, L-selectin^?), and IL-2^?/IFN-γ^low/-/IL-4⁺ (Fr. IV, L-selectin^?). Besides these subsets, an L-selectin-negative cell subfraction within Fr. II appears to represent a transitional population between the IL-2⁺/IFN-γ^?/IL-4^? stage and the IL-2⁺/IFN-γ⁺/IL-4⁺ stage. Taken together, these results demonstrate the presence of two IL-4⁺ secondary T cell subsets with distinct cytokine production patterns, and show that the majority of IL-4⁺ cells found in healthy adult laboratory mice co-produce IFN-γ, and thus are not typical T helper type 2 cells.     

High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n = 23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p < 0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.