Alginate Improves the Chondrogenic Capacity of 3D PCL Scaffolds In Vitro: A Histological Approach.

Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic properties of the two biomaterials. Porous PCL scaffolds were manufactured using a modified salt-leaching method and embedded in a culture medium or alginate in the presence or absence of chondrocytes. The chondrogenic capacity was studied in vitro. Type II collagen and aggrecan were measured by immunofluorescence, cell morphology by F-actin fluorescence staining and gene expression of COL1A1, COL2A1, ACAN, COL10A1, VEGF, RUNX1 and SOX6 by reverse transcription polymerase chain reaction (RT-PCR). The biocompatibility of the scaffolds was determined in vivo using athymic nude mice and assessed by histopathological and morphometric analysis. Alginate improved the chondrogenic potential of PCL in vitro by increasing the expression of type II collagen and aggrecan, as well as other markers related to chondrogenesis. All scaffolds showed good biocompatibility in the in vivo model. The presence of cells in the scaffolds induced an increase in vascularization of the PCL/alginate scaffolds. The results presented here reinforce the benefits of the combined use of PCL and alginate for the regeneration of articular cartilage.

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression.

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell-cell contact.

Morphological Characterization of Human Lung Cancer Organoids Cultured in Type I Collagen Hydrogels: A Histological Approach.

The malignity of lung cancer is conditioned by the tumor microenvironment (TME), in which cancer-associated fibroblasts (CAFs) are relevant. In this work, we generated organoids by combining A549 cells with CAFs and normal fibroblasts (NF) isolated from adenocarcinoma tumors. We optimized the conditions for their manufacture in a short time. We evaluated the morphology of organoids using confocal microscopy analysis of F-actin, vimentin and pankeratin. We determined the ultrastructure of the cells in the organoids via transmission electron microscopy and the expression of CDH1, CDH2 and VIM via RT-PCR. The addition of stromal cells induces the self-organization of the organoids, which acquired a bowl morphology, as well as their growth and the generation of cell processes. They also influenced the expression of genes related to epithelial mesenchymal transition (EMT). CAFs potentiated these changes. All cells acquired a characteristic secretory phenotype, with cohesive cells appearing inside the organoids. In the periphery, many cells acquired a migratory phenotype, especially in organoids that incorporated CAFs. The deposit of abundant extracellular matrix could also be observed. The results presented here reinforce the role of CAFs in the progression of lung tumors and could lay the foundation for a useful in vitro pharmacological model.

Patient journey of individuals tested for HCV in Spain: LiverTAI, a retrospective analysis of EHRs through natural language processing.

OBJECTIVES: Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals. PATIENTS AND METHODS: LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia. RESULTS: From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p<.001). CONCLUSIONS: Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care.

Human Dental Pulp Stem Cells Differentiate into Cementoid-Like-Secreting Cells on Decellularized Teeth Scaffolds.

Periodontitis is a common inflammatory disease that in some cases can cause tooth loss. Cementum is a mineralized tissue that forms part of the insertion periodontium and serves to fix the teeth to the alveolar bone. In addition, it acts as a reservoir of different growth and differentiation factors, which regulate the biology of the teeth. Cementogenesis is a complex process that is still under investigation and involves different factors, including dentin sialophosphoprotein (DSPP). In this work we studied the role of surface microtopography in the differentiation of human dental pulp stem cells (hDPSCs) into cementoid-like secreting cells. We cultured hDPSCs on decellularized dental scaffolds on either dentin or cementum surfaces. Cell morphology was evaluated by light and electron microscopy. We also evaluated the DSPP expression by immunohistochemistry. The hDPSCs that was cultured on surfaces with accessible dentinal tubules acquired an odontoblastic phenotype and emitted characteristic processes within the dentinal tubules. These cells synthesized the matrix components of a characteristic reticular connective tissue, with fine collagen fibers and DSPP deposits. The hDPSCs that was cultured on cementum surfaces generated a well-organized tissue consisting of layers of secretory cells and dense fibrous connective tissue with thick bundles of collagen fibers perpendicular to the scaffold surface. Intra- and intercellular deposits of DSPP were also observed. The results presented here reinforce the potential for hDPSCs to differentiate in vitro into cells that secrete a cementoid-like matrix in response to the physical stimuli related to the microtopography of contact surfaces. We also highlight the role of DSPP as a component of the newly formed matrix.

In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer.

There is evidence that demonstrates the effect of cannabinoid agonists inhibiting relevant aspects in lung cancer, such as proliferation or epithelial-to-mesenchymal transition (EMT). Most of these studies are based on evidence observed in in vitro models developed on cancer cell lines. These studies do not consider the complexity of the tumor microenvironment (TME). One of the main components of the TME is cancer-associated fibroblasts (CAFs), cells that are relevant in the control of proliferation and metastasis in lung cancer. In this work, we evaluated the direct effects of two cannabinoid agonists, tetrahydrocannabinol (THC) and cannabidiol (CBD), used alone or in combination, on CAFs and non-tumor normal fibroblasts (NFs) isolated from adenocarcinoma or from healthy lung tissue from the same patients. We observed that these compounds decrease cell density in vitro and inhibit the increase in the relative expression of type 1 collagen (COL1A1) and fibroblast-specific protein 1 (FSP1) induced by transforming growth factor beta (TGFß). On the other hand, we studied whether THC and CBD could modulate the interactions between CAFs or NFs and cancer cells. We conditioned the culture medium with stromal cells treated or not with THC and/or CBD and cultured A549 cells with them. We found that culture media conditioned with CAFs or NFs increased cell density, induced morphological changes consistent with EMT, inhibited cadherin-1 (CDH1) gene expression, and induced an increase in the relative expression of cadherin-2 (CDH2) and vimentin (VIM) genes in A549 cells. These changes were inhibited or decreased by THC and CBD administered alone or in combination. In another series of experiments, we conditioned culture media with A549 cells treated or not with THC and/or CBD, in the presence or absence of TGFß. We observed that culture media conditioned with A549 in the presence of TGFß induced an increase in the expression of COL1A1 and VIM, both in CAFs and in non-tumor NFs. Both THC and CBD ameliorated these effects. In summary, the results presented here reinforce the usefulness of cannabinoid agonists for the treatment of some relevant aspects of lung cancer pathology, and demonstrate in a novel way their possible effects on CAFs as a result of their relationship with cancer cells. Likewise, the results reinforce the usefulness of the combined use of THC and CBD, which has important advantages in relation to the possibility of using lower doses, thus minimizing the psychoactive effects of THC.

Ertapenem neurotoxicity in liver transplantation.

Carbapenems are antibiotics of the cephalosporin family with a good penetrance into the central nervous system. Neurotoxicity is a rare adverse effect, most often associated with imipenem (0.4-10 %) and unusual with ertapenem. It usually presents as seizures, although encephalopathy or hallucinations may develop. However, a recent large study (n = 544) found neurotoxicity associated to the use of ertapenem with an incidence of 4.6 %. There were associated factors such as advanced age or renal dysfunction (ertapenem has a renal metabolism level of 80 %).

Influence of baseline inducibility and activation mapping on ablation outcomes in patients with structural heart disease and ventricular tachycardia.

INTRODUCTION: Stand-alone substrate ablation has become a standard ventricular tachycardia (VT) ablation strategy. We sought to evaluate the influence of baseline VT inducibility and activation mapping on ablation outcomes in patients with structural heart disease (SHD) undergoing VT ablation. METHODS: Single center, observational and retrospective study including consecutive patients with SHD and documented VT undergoing ablation. Baseline VT induction was attempted before ablation in all patients and VT activation mapping performed when possible. Ablation was guided by activation mapping for mappable VTs plus substrate ablation for all patients. Ablation outcomes and complications were evaluated. RESULTS: One hundred and sixty patients were included and were classified in three groups according to baseline VT inducibility:group 1 (non inducible, n = 18), group 2 (1 VT morphology induced, n = 53), and group 3 (>1 VT morphology induced, n = 89). VT activation mapping was possible in 35%. After a median follow-up of 38.5 months, baseline inducibility of greater than 1 VT morphology was associated with a significant incidence of VT recurrence (42% for group 3 vs. 15.1% for group 2% and 5.6% for group 1, Log-rank p < .0001) and activation mapping with a lower rate of VT recurrence (24% vs. 36.3%, Log-rank p = .035). Baseline inducibility of greater than 1 VT morphology (hazards ratio [HR]: 12.05, 95% confidence interval [CI]: 1.60-90.79, p = .016) was an independent predictor of VT recurrence while left ventricular ejection fraction less than 30% (HR: 1.93, 95% CI: 1.13-3.25, p = .014) and advanced heart failure (HR: 4.69, 95% CI: 2.75-8.01, p < .0001) were predictors of mortality or heart transplantation. Complications occurred in 11.2% (5.6% hemodynamic decompensation). CONCLUSION: Baseline VT inducibility and activation mapping may add significant prognostic information during VT ablation procedures.

Safety and feasibility of conduction system pacing in patients with congenital heart disease.

INTRODUCTION: Conduction system pacing (CSP) has emerged as an ideal physiologic pacing strategy for patients with permanent pacing indications. We sought to evaluate the safety and feasibility of CSP in a consecutive series of unselected patients with congenital heart disease (CHD). METHODS: Consecutive patients with CHD in which CSP was attempted were included. Safety and feasibility, implant tools and electrical parameters at implant and at follow-up were evaluated. RESULTS: A total of 20 patients were included (10 with a previous device). A total of 10 patients had complex forms of CHD, 9 moderate defects and 1 a simple defect. CSP was achieved in 75% of cases (10 His bundle pacing, 5 left bundle branch pacing) with left ventricular septal pacing in the remaining 5 patients. Procedure times and fluoroscopy times were prolongued (126 ± 82 min and 27 ± 30 min, respectively). Ventricular lead implant times widely varied ranging from 4 to 115 min, (mean 31 ± 28 min) and the use of multiple delivery sheaths was frequent (50%). The QRS width was reduced from 145 ± 36 ms at baseline to 116 ± 18 ms with CSP. Implant electrical parameters included: CSP pacing threshold 0.95 ± 0.65 V; R wave amplitude 9.2 ± 8.8 mV and pacing impedance 632 ± 183 Ohms, and remained stable at a median follow-up of 478 days (interquartile range: 225-567). Systemic ventricle systolic function and NYHA class (1.50 ± 0.51 vs. 1.10 ± 0.31; p = .008) significantly improved at follow-up. Lead revision was required in one patient at Day 4. CONCLUSIONS: Permanent CSP is safe and feasible in patients with CHD although implant technique is complex.

Decellularized tracheal prelamination implant: A proposed bilateral double organ technique.

In tracheal replacement transplantation, prelamination is a critical stage. Nowadays, the most widely used prelamination technique is the prethoracic fascia flap with lateral thoracic artery. We propose a flap based on the internal thoracic artery, which allows a relatively non-aggressive double organ implant, and we have tested its efficacy in decellularized tracheas. Tracheas of albino New Zealand rabbits were decellularized following a protocol that uses detergents and cryogenization, sterilized with 1kGy gamma radiation, and tutorized with a stent. Bilateral pedicled flaps made of pectoral fascia and a muscular component were harvested through a longitudinal 3-cm central thoracic incision, wrapping the tracheas with them in 16 rabbits, remaining them implanted for 2, 4, 8, and 12 weeks. The tracheas were then studied histologically using standard stainings plus immunohistochemistry (CD31). The models were adjusted with Bayesian statistics using ordinal regression; results as odds ratios and credibility intervals. All analysis were performed using R software. Acute inflammatory cell invasion was observed at 2 weeks, which almost disappeared at week 8 after implant. Only macrophages and giant cells increased between Weeks 8 and 12 (OR 10.487, CI [1.603-97.327]). The cartilage maintained its structure, with slight signs of ischemia in a few cases. New CD31-positive vessels were observed from Week 2 and increasing thereafter, reaching a maximum peak at Week 8. We propose a bilateral implant technique that is viable and effective as a prelamination option for two concurrent tracheas, achieving perfect vascularization and integration of the organ with hardly any inflammatory response in the medium or long term.

Utility of high density multielectrode mapping during ablation of scar-related ventricular tachycardia.

INTRODUCTION: Multielectrode mapping catheters (MEMC) allow the performance of high resolution and density maps but the utility of these catheters in ventricular tachycardia (VT) ablation procedures has not been yet widely described. We sought to evaluate the utility of a MEMC during scar-related VT ablation procedures. METHODS: Eighty-five consecutive scar-related VT ablation procedures were performed in 81 patients. In the first 26 procedures, a standard 3.5-mm tip linear catheter was employed for endocardial/epicardial mapping (control group). In the following 59 procedures mapping was performed with a MEMC (study group). Procedural time, LV endocardial and epicardial mapping time, complications and ablation outcomes were compared. RESULTS: The use of the MEMC resulted in a significant shortening of the endocardial and epicardial mapping times (38 ± 15 minutes vs. 56 ± 24 minutes for endocardial LV mapping in the study and control group, respectively, P = 0.001; and 28 ± 9 minutes vs 41 ± 16 minutes, for epicardial mapping, P = 0.011) as well as the total procedural time (177 ± 53 minutes vs. 206 ± 50 minutes, respectively, P = 0.02). The mapping density was also significantly increased in the study group (mean endocardial LV points: 2,143 ± 1,419 vs. 485 ± 174, for the study and control group, respectively, P < 0.0001), specially within the scar area (49.6 ± 34 points/cm2 vs. 8.4 ± 4.6 points/cm2 , P < 0.001). No differences in acute and long-term follow-up outcomes were observed. CONCLUSIONS: High-density multielectrode mapping is associated with a significant reduction of procedural and mapping times and a significant increase of mapping density without affecting outcomes in patients with scar-related VT.

Incidence and predictors of clinically relevant cardiac perforation associated with systematic implantation of active-fixation pacing and defibrillation leads: a single-centre experience with over 3800 implanted leads.

AIMS: Active-fixation leads have been associated with higher incidence of cardiac perforation. Large series specifically evaluating this complication are lacking. We sought to evaluate the incidence and predictors of clinically relevant cardiac perforation in a consecutive series of patients implanted with active-fixation pacing and defibrillation leads. METHODS AND RESULTS: We conducted a retrospective observational study including all consecutive patients implanted with an active-fixation pacing/defibrillation lead at our institution from July 2008 to July 2015. The incidence of clinically relevant cardiac perforation and cardiac tamponade was evaluated. Univariate and multivariate analyses were used to identify predictors of cardiac perforation. Acute and long-term management of these patients was also investigated. A total of 3822 active-fixation pacing (n = 3035) and defibrillation (n = 787) leads were implanted in 2200 patients. Seventeen patients (0.8%) had clinically relevant cardiac perforation (13 acute and 4 subacute perforations), and 13 (0.5%) had cardiac tamponade resolved with pericardiocentesis. None of the patients with cardiac perforation required surgical treatment. In multivariate analysis, an age >80 years (OR 3.84, 95% CI 1.14-12.87, P = 0.029), female sex (OR 3.14, 95% CI 1.07-9.22, P = 0.037), and an apical position of the right ventricular lead (OR 3.37, 95% CI 1.17-9.67, P = 0.024) were independent predictors of cardiac perforation. CONCLUSIONS: Implantation of active-fixation leads is associated with a low incidence of clinically relevant cardiac perforation. Older and female patients have a higher risk of perforation as well as those patients receiving the ventricular lead in an apical position.

The Role of Conventional and Right-Sided ECG Screening for Subcutaneous ICD in a Tetralogy of Fallot Population.

BACKGROUND: Information regarding suitability for subcutaneous implantable cardioverter-defibrillator (S-ICD) implant in tetralogy of Fallot (ToF) population is scarce and needs to be further explored. THE AIMS OF OUR STUDY WERE: (1) to determine the proportion of patients with ToF eligible for S-ICD, (2) to identify the optimal sensing vector in ToF patients, (3) to test specifically the eligibility for S-ICD with right-sided screening, and (4) to compare with the proportion of eligible patients in a nonselected ICD population. METHODS: We recruited 60 consecutive patients with ToF and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left arm and right arm electrodes 1 cm right lateral to the xiphoid midline. The Boston Scientific electrocardiogram (ECG) screening tool was utilized. RESULTS: We found a higher proportion of patients with right-sided positive screening in comparison with standard screening (77 ± 0.4% vs. 67 ± 0.4%; P < 0.0001) and a trend to higher number of appropriate leads in right-sided screening (1.3 ± 1 vs. 1.1 ± 1 ms; P = 0.07). Patients who failed the screening had a longer QRS duration and longer QT interval. Standard and right-sided screening showed a higher percent of positive patients in the control group compared to ToF patients (P < 0.001). CONCLUSION: Right-sided screening was associated with a significant 10% increase in S-ICD eligibility in ToF patients. When comparing with an acquired cardiomyopathies group, ToF showed a lower eligibility for S-ICD. The most appropriate ECG vector was the alternate vector in contrast to what is observed in the general population.

Essential ECG clues in patients with congenital heart disease and arrhythmias.

The prevalence of adults with congenital heart disease has dramatically increased during the last decades due to significant advances in the surgical correction of these conditions. As a result, patient's survival has been prolonged and arrhythmias have become one of the principal causes of morbidity and mortality for these patients. The surface 12-lead ECG may play a critical role in the identification of the underlying heart disease of the patient, the recognition of the arrhythmia mechanism and may also help in the planification of the ablation procedure in this setting. Finally, important prognostic information can be also obtained from the ECG in these patients. The present review will offer an overview of the principal utilities of the surface ECG in the diagnosis and management of patients with CHD and arrhythmias.

Incidence of arrhythmias in a large cohort of patients with current implantable cardioverter-defibrillators in Spain: results from the UMBRELLA Registry.

AIMS: The benefit of implantable cardioverter-defibrillators (ICDs) in patients at risk of sudden death has been established in randomized clinical trials (RCTs) using the ICD models available at the time. However, observational large-scale data on the incidence of arrhythmias in up-to-date ICDs implanted according to the current guidelines are scarce. The aim was to assess the incidence of arrhythmias in a large, current ICD population based on a blinded peer review of the detected episodes. METHODS AND RESULTS: UMBRELLA is a multicentre, observational registry of ICD patients followed by remote monitoring. Stored episodes were classified by a blinded committee of experts. Subgroup analyses were based on clinical profiles established by previous pivotal RCTs of ICDs. Of 1514 enrolled patients, 605 (39.9%) patients had 5951 episodes after 26 ± 17 months follow-up, being 3353 of them (56.3%) sustained ventricular arrhythmias (SVA), and 13.2% of SVA were self-terminated. Appropriate and inappropriate shocks occurred in 11.6 and 5% of patients, respectively. The 3 years cumulative incidence of SVA was 25% (95% CI: 21-28%) in primary prevention patients and 41% (95% CI: 36-47%) in secondary prevention patients (P < 0.001). Male gender, secondary prevention, and atrial fibrillation as basal rhythm were significantly related to a higher incidence of SVA. CONCLUSION: This real-world analysis suggests that modern ICD patients have a low rate of appropriate and inappropriate shocks. The risk of SVA in secondary prevention patients is less than what has been reported in RCTs.

Initial Experience with a New Image Integration Module Designed for Reducing Radiation Exposure During Electrophysiological Ablation Procedures.

INTRODUCTION: Reduction of radiation exposure during cardiac arrhythmia ablation procedures is desirable. We sought to evaluate the utility of a new image integration module (CARTOUNIVU(TM) ) in reducing fluoroscopy times and dosages during left atrial arrhythmia (LAA) and ventricular tachycardia (VT) ablation procedures. METHODS AND RESULTS: Consecutive patients undergoing LAA (n = 28)/VT (n = 13) ablation using the CARTOUNIVU(TM) module were included. Total fluoroscopy time, radiation dose (total dose area product [tDAP], effective dose [ED]), and procedure duration were evaluated. A retrospective cohort of patients who underwent LAA (n = 16)/VT(n = 8) ablation without the new image integration module served as a control group. The use of the new image integration module significantly reduced mean fluoroscopy time (5.2 minutes [IQR 1.9;6.8] in the LAA ablation UNIVU group vs. 28.2 minutes [IQR 15.3;37.8] in the control group, P<0.001; 9.8 minutes [IQR 4.5;13.1] vs. 25.5 minutes [IQR 14.1;30.9] for VT ablation, P = 0.013), tDAP (2,088 cGy*cm(2) [IQR 664;2911] vs. 5,893 cGy*cm(2) [IQR 3088;8483], P< 0.001 for LAA ablation; 3,917 cGy*cm(2) [IQR 948;4217] vs. 12,377 cGy*cm(2) (IQR 3385;23157) for VT ablation patients, P = 0.025) and ED (4.1 mSv [IQR 1;5.8] vs. 11.8 mSv [IQR 6.2;16.9] for LAA ablation patients, P< 0.001; 7.8 mSv [IQR 1.9;8.4] vs. 24.7 mSv [IQR 6.8;46.3] for VT ablation patients, P = 0.025). Procedure duration did not significantly change (174 ± 45 minutes vs. 197 ± 36 minutes for LAA ablation, P = 0.083; 201 ± 51 minutes vs. 201 ± 63 minutes for VT ablation, P = 0.860). No serious adverse events related to the use of the CARTOUNIVU(TM) module occurred. CONCLUSIONS: The new image integration module significantly reduced total fluoroscopy time and mean radiation dose without influence in procedure duration during ablation of complex atrial and ventricular arrhythmias.

Systematic Implantation of Pacemaker/ICDs under Active Oral Anticoagulation Irrespective of Patient's Individual Preoperative Thromboembolic Risk.

BACKGROUND: A wide variability in the perioperative management of oral anticoagulation (OAC) has been documented in patients receiving cardiac rhythm management devices (CRMDs). We sought to evaluate the safety and feasibility of a new perioperative strategy consisting in systematically continuing OAC in all patients irrespective of their individual thromboembolic (TE) risk. METHODS: A total of 278 consecutive patients on chronic OAC receiving CRMDs were prospectively included. Patients were classified in high and low TE risk according to current guidelines for the perioperative management of antithrombotic therapy, but underwent implantation under active OAC (international normalized ratio 2-4) irrespective of their preoperative TE risk. Bleeding and TE complications were evaluated as well as other procedure-related complications, hospital stays, and the feasibility of outpatient implantations. RESULTS: A total of 117 patients were considered at high TE risk and 161 at low TE risk. Overall, the incidence of pocket hematoma was 2.9% with only three patients requiring pocket revision. Low TE risk patients had a very low incidence of pocket hematoma (1.9%) without needing pocket revision. The mean hospital stay was 1.17 ± 1.8 days and 169 patients (61%) received their CRMD in an outpatient basis, including 77 patients who were implanted with an implantable cardioverter defibrillator. No TE events were detected during the 30-day postimplant observation period in any patient. No other significant complications related with the implant (pneumothorax, hemothorax, cardiac tamponade) were registered. CONCLUSIONS: Systematic continuation of OAC in all patients undergoing implantation of CRMDs is safe and feasible, thus simplifying and standardizing the perioperative management in this setting.

The use of quadripolar left ventricular leads improves the hemodynamic response to cardiac resynchronization therapy.

BACKGROUND: The objective of the present study was to evaluate the usefulness of a left ventricle (LV) quadripolar lead in improving the hemodynamic response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We included 27 consecutive patients implanted with a CRT device with an LV quadripolar lead. Hemodynamic parameters were evaluated at 3-month follow-up by using impedance cardiography. We assessed the highest cardiac output and the highest stroke volume (SV) obtained after atrioventricular and interventricular optimization with pacing from each of the four electrodes of the LV lead. Each patient was evaluated according to three different pacing configurations: unipolar-simulated, bipolar, and quadripolar. Biventricular pacing improved hemodynamics in comparison to the nonpaced measurements: cardiac index (CI): 2.69 L/min/m(2) versus 2.17 L/min/m(2) (P = 0.001). The hemodynamic response was highest in the quadripolar in comparison to unipolar-simulated and bipolar configurations, with an increase of 29%, 23%, and 27%, respectively, in relation to the reference CI and with an increase of 22%, 11%, and 18%, respectively, in relation to the reference indexed SV (P < 0.05, for the comparison between unipolar-simulated and quadripolar configurations). Twelve patients (44%) showed the best hemodynamic response by pacing from any of the two distal electrodes and 15 patients (56%) by pacing from the two proximal electrodes. Finally, CRT responder rates were higher in quadripolar versus bipolar and unipolar-simulated configurations: 90%, 85%, and 75%, respectively. CONCLUSIONS: The quadripolar LV lead was associated with a better hemodynamic response and higher CRT responder rates when compared with unipolar-simulated and bipolar LV leads.

BMP-2 Enhances Osteogenic Differentiation of Human Adipose-Derived and Dental Pulp Stem Cells in 2D and 3D In Vitro Models.

Bone tissue provides support and protection to different organs and tissues. Aging and different diseases can cause a decrease in the rate of bone regeneration or incomplete healing; thus, tissue-engineered substitutes can be an acceptable alternative to traditional therapies. In the present work, we have developed an in vitro osteogenic differentiation model based on mesenchymal stem cells (MSCs), to first analyse the influence of the culture media and the origin of the cells on the efficiency of this process and secondly to extrapolate it to a 3D environment to evaluate its possible application in bone regeneration therapies. Two osteogenic culture media were used (one commercial from Stemcell Technologies and a second supplemented with dexamethasone, ascorbic acid, glycerol-2-phosphate, and BMP-2), with human cells of a mesenchymal phenotype from two different origins: adipose tissue (hADSCs) and dental pulp (hDPSCs). The expression of osteogenic markers in 2D cultures was evaluated in several culture periods by means of the immunofluorescence technique and real-time gene expression analysis, taking as reference MG-63 cells of osteogenic origin. The same strategy was extrapolated to a 3D environment of polylactic acid (PLA), with a 3% alginate hydrogel. The expression of osteogenic markers was detected in both hADSCs and hDPSCs, cultured in either 2D or 3D environments. However, the osteogenic differentiation of MSCs was obtained based on the culture medium and the cell origin used, since higher osteogenic marker levels were found when hADSCs were cultured with medium supplemented with BMP-2. Furthermore, the 3D culture used was suitable for cell survival and osteogenic induction.

Morbidity associated with three different antiplatelet regimens in patients undergoing implantation of cardiac rhythm management devices.

AIMS: Perioperative management of antiplatelet (AP) therapy in patients undergoing implantation of cardiac rhythm management devices (CRMD) remains an issue of concern that has not been prospectively evaluated in a large series. We sought to describe the morbidity associated with three different AP regimens in this setting. METHODS AND RESULTS: We conducted a prospective observational study including 849 consecutive patients who were classified in three groups according to the presence of any AP treatment: Group 1 (n= 220): single AP therapy; Group 2 (n= 60): dual AP therapy; and Group 3 (n= 40): oral anticoagulant (OAC) + enoxaparin 'bridging' + AP therapy. Two other groups served as controls: Group 4 (n= 375): no AP or OAC therapy; and Group 5 (n= 154): OAC + enoxaparin 'bridging'. The incidence of pocket haematoma, pocket revisions, hospital stays duration, and unscheduled follow-up visits due to pocket-related complications were compared. Patients on Groups 2, 3 and 5 had significantly higher incidences of pocket haematoma (13.3, 15, and 14.9%, respectively) when compared with Groups 1 and 4 (3.2 and 2.4%, respectively), as well as longer hospital stays and more unscheduled follow-up visits. Of note, only patients on enoxaparin 'bridging' required surgical revision of the pocket. Dual AP therapy (P< 0.001), enoxaparin 'bridging' (P< 0.001) and renal insufficiency (P= 0.02) were independent predictors of pocket haematoma in multivariate analysis. CONCLUSION: Dual AP therapy and OAC + AP therapy is strongly associated with a significant risk of pocket haematoma, longer hospital stays, and unscheduled follow-up visits. Importantly, surgical revision of the pocket was associated with enoxaparin 'bridging' strategy but was never necessary in patients taking exclusively antiaggregant agents.