The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.</p> <p>Methods</p> <p>To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.</p> <p>Results</p> <p>Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.</p> <p>Conclusion</p> <p>These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.</p

Multi-year interlaboratory exercises for the analysis of illicit drugs and metabolites in wastewater:development of a quality control system

This study presents the development of a worldwide inter-laboratory testing scheme for the analysis of seven illicit drug residues in different matrices (standard solutions, tap- and wastewater). By repeating this exercise for six years with participation of 37 laboratories from 25 countries, the testing scheme was substantially improved based on experiences gained across the years (e.g. matrix type, sample conditions, spiking levels). From the exercises (pre-)analytical issues (e.g. pH adjustment, filtration), were revealed for some analytes which resulted in formulation of best-practice protocols, both for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the inter-laboratory testing scheme in assessing laboratory performance in the framework of illicit drug analysis in wastewater. The exercise proved that measurements of laboratories were of high quality (&gt;80% satisfactory results for 6 out of 7 analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results

P451Optimizing the EP lab workflow in atrial fibrillation ablation - The use of Z stitch for groin access closure

Abstract Introduction As catheter ablation became the standard therapy for atrial fibrillation (AF), the number of AF procedures has risen exponentially. Therefore, workflow optimization is crucial in order to meet the rising demands for EP interventions. Recently, instead of standard groin compression we have started using the "Z stitch" for introducers’ removal. This novel method does not necessitate protamine administration and often lengthy manual compression. Purpose We aim to demonstrate utilization of "Z stitch" for groin access closure in cryoballoon (CB) ablation and its impact on EP lab workflow. Methods We have analyzed all patients having undergone CB ablation utilizing the "Z stitch" (Z group) and the last 50 consecutive CB patients who received standard groin compression (non-Z group). Procedures were performed under conscious sedation. Both femoral veins were punctured and a single introducer was placed in each vein. A single transeptal puncture was preformed guided by intracardial ultrasound and a 28 mm cryoballoon was used. A single 180 seconds freeze strategy was employed. In the past, protamine was slowly administered after ablation and at least 15 minute manual groin compression was applied until no visual bleeding could be detected. Elastic bandage was placed around both groins. Later on, the "Z stitch" was used around both introducers without the need for protamine administration, manual compression and bandage placement (Picture). The stitches were removed next morning. Results A total of 100 consecutive patients (79% male, 61.2 ± 10.6 years old) were evaluated, 50 in both groups. There was no difference in the mean procedure duration ("skin to skin") between two groups. However, a total lab time was significantly longer in non-Z group. There was no differences in complication rates, which consisted solely of phrenic nerve palsy and groin complications. There was no AV fistula or pseudoaneurysms detected in our cohort (Table). Conclusion Utilization of Z stitches for introduces’ removal seems safe and effective way to achieve hemostasis after cryoballoon ablation. It abolishes the need for protamine administration which can cause serious advert events. Manual compression is no longer required. Consequently, EP lab workflow is improved, since the total lab time utilization per patient is significantly shortened. Results non-Z group Z group p Procedure duration (min) 69.4 ± 20.4 73.4 ± 24.8 0.380 Lab time (min) 129.9 ± 35.3 109.1 ± 30.6 0.002 Complications (N) 5 (2 hematoma) 4 (2 hematoma) NS Abstract Figure. Z stich </jats:sec

P420Improved real time recordings using the third generation cryoballoon technology - detection of dual fascicle electrograms

Abstract Introduction The third-generation cryoballoon has been designed with a 40% shortened tip length compared with the former second-generation CB device. Ideally, a shorter tip could result with an improved visualization of real-time (RT) recordings in the pulmonary vein (PV) due to a more proximal positioning of the inner lumen mapping catheter. Beside the high incidence of RT recordings, for the first time, we observed dual fascicle electrograms with different isolation time for each fascicle, when using the new device. Purpose We sought to analyze the rate of visualization of RT recordings and dual fascicle electrograms in our first series of patients with the third generation cryoballoon device. Methods All consecutive patients having undergone CB ablation using the third generation technology were analyzed. Procedures were performed under conscious sedation. A single transeptal puncture was preformed guided by intracardial ultrasound and a 28 mm cryoballoon was used. A single 180 seconds freeze strategy was employed. Results A total of 80 consecutive patients (77.5% male, 60.3 ± 10.8 years) were evaluated. Real-time recordings were detected in 275 of 320 PVs (85.9%). Specifically, RT recordings could be visualized in 68 left superior PVs (85%), 69 left inferior PVs (86.2%), 73 right superior PVs (91.2%), and 65 right inferior PVs (81.2%). Furthermore, in 14 of 320 PVs (4.3%) two different fascicles electrograms were detected. A distinctive isolation time for each fascicle could be observed both in sinus rhythm and in atrial fibrillation (Picture). Most commonly, dual fascicles were observed in left superior PV (7.5%) and right inferior PV (6.3%). In the rest of the veins this phenomenon was not so frequent. In 2.5% of right superior PV and in only 1.2% of left inferior PV dual fascicles could be observed. Conclusion The rate of visualization of RT recordings is significantly high during third generation CB ablation. Real-time recordings can be visualized in 85.9% of veins with this novel cryoballoon. Furthermore, for the first time, isolation of two different fascicles during a single cryoballoon lesion could be observed. Other that more proximal mapping catheter position, there is second possible explanation for the visualization of dual fascicles with this novel balloon. Shorter tip could result with poorer cryoballoon stability and weaker contact with the atrium wall, hence non-uniform freezing and isolation of different fascicles in different times. Abstract Figure. </jats:sec

His pacing program: a 2-year single-centre experience

Abstract Funding Acknowledgements Type of funding sources: None. Background His bundle pacing (HBP) physiologically activates the ventricles by a direct stimulation of the His-Purkinje cardiac conduction system. It was first described in the 1970s, and the initial feasibility studies were reported in the early 2000s. Later on, technological advances led to its widespread adoption and growing evidence base.  Purpose This retrospective study aimed to assess implant success rate, feasibility and safety of the His-bundle lead implantation program in our centre. Methods All patients who underwent His-bundle lead implantation in our centre from the start of the HBP program in November 2018 until November 2020 were analyzed. Data were collected from existing hospital electronic medical records. Results A total of 125 patients (64.8 % male, 65.1 ± 13.9 years) were included in the study. Nearly half of patients (47.2 %) had chronic heart failure and 39.2 % had atrial fibrillation. Indications for pacing included antibradycardia pacing (68.8 %) and cardiac resynchronization therapy (31.2 %). His-bundle lead was successfully implanted in 114 patients (91.2 % acute success), while the rest of the procedures were converted into right ventricle lead placement. 32.8 % of all patients had native narrow QRS complexes. Among patients who received HBP for cardiac resynchronization therapy, QRS duration was reduced from 177.5 ± 26.4 at baseline to 145.8 ± 23.9 after HBP (p &amp;lt; 0.001). However, QRS duration slightly prolonged in the antibradycardia group from 118.8 ± 31.9 at baseline to 130.4 ± 25.3 after HBP (p = 0.011). Seven (8.6 %) patients in the antibradycardia group had late lead disfunction/dislodgement and therefore underwent reoperation with the conventional right ventricle lead placement. Two patients (4.7 %) from the resynchronization group had inappropriate resynchronization response and underwent the conventional coronary sinus lead implantation. Only one patient (0.8 %) had a device-associated infection.  Conclusion Our data suggest that HBP is a feasible strategy of physiological pacing and resynchronization with an acceptable success and low complication rates. Our His-bundle implantation program results are similar to data available in the current literature. </jats:sec