Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

Predictors of first pass isolation of the pulmonary veins in real world ablations: An analysis of 2671 patients from the REAL-AF registry.

INTRODUCTION: During atrial fibrillation ablation (AFA), achievement of first pass isolation (FPI) reflects effective lesion formation and predicts long-term freedom from arrhythmia recurrence. We aim to determine the clinical and procedural predictors of pulmonary vein FPI. METHODS: We reviewed AFA procedures in a multicenter prospective registry of AFA (REAL-AF). A multivariate ordinal logistic regression, weighted by inverse proceduralist volume, was used to determine predictors of FPI. RESULTS: A total of 2671 patients were included with 1806 achieving FPI in both vein sides, 702 achieving FPI in one, and 163 having no FPI. Individually, age, left atrial (LA) scar, higher power usage (50 W), greater posterior contact force, ablation index >350 posteriorly, Vizigo™ sheath utilization, nonstandard ventilation, and high operator volume (>6 monthly cases) were all related to improved odds of FPI. Conversely sleep apnea, elevated body mass index (BMI), diabetes mellitus, LA enlargement, antiarrhythmic drug use, and center's higher fluoroscopy use were related to reduced odds of FPI. Multivariate analysis showed that BMI > 30 (OR 0.78 [0.64-0.96]) and LA volume (OR per mL increase = 1.00 [0.99-1.00]) predicted lower odds of achieving FPI, whereas significant left atrial scarring (>20%) was related to higher rates of FPI. Procedurally, the use of high power (50 W) (OR 1.32 [1.05-1.65]), increasing force posteriorly (OR 2.03 [1.19-3.46]), and nonstandard ventilation (OR 1.26 [1.00-1.59]) predicted higher FPI rates. At a site level, high procedural volume (OR 1.89 [1.48-2.41]) and low fluoroscopy centers (OR 0.72 [0.61-0.84]) had higher rates of FPI. CONCLUSION: FPI rates are affected by operator experience, patient comorbidities, and procedural strategies. These factors may be postulated to impact acute lesion formation.

Hyperparasitism in bat flies (Diptera: Streblidae): new records and interaction networks in the Neotropics.

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.

Food insecurity and sociodemographic factors in Latin America during the COVID-19 pandemic.

Objective: To understand the association of food insecurity with sociodemographic factors in a sample population in Latin America during the COVID-19 pandemic. Methods: This was a multicenter cross-sectional study conducted in 10 countries in Latin America using an online survey through various digital platforms from October 14, 2020 to February 15, 2021. Statistical analysis of data was performed by applying descriptive statistics, chi-square test, and logistic regression analysis. Results: Of a total of 6 357 surveys, 58.2% of respondents experienced food security, 29.3% were slightly food insecure, 9.2% were moderately food insecure, and 3.3% were severely food insecure. Concerning the association food insecurity and sociodemographic variables, there is a significant association in the variables studied, including area of residence, education level, occupation, number of persons in the household, household with children younger than 10 years of age, and socioeconomic level. Conclusions: These findings indicate that sociodemographic factors associated with food insecurity during the COVID-19 pandemic in Latin America were rural residence; complete and incomplete basic and secondary schooling; occupation (homemaker, unemployed, and self-employed); low, medium-low, and medium socioeconomic level; household with more than four persons; and household with children younger than 10 years of age.

Paroxysmal atrial fibrillation ablation with a novel temperature-controlled CF-sensing catheter: Q-FFICIENCY clinical and healthcare utilization benefits.

INTRODUCTION: The prospective, nonrandomized, multicenter Q-FFICIENCY study demonstrated the safety and 12-month efficacy of paroxysmal atrial fibrillation (AF) ablation with the novel QDOT MICRO temperature-controlled, contact force-sensing, radiofrequency (RF) catheter. Participants underwent pulmonary vein isolation with very high-power short-duration (vHPSD) mode (90 W, ≤4 s) alone or combined with conventional-power temperature-controlled (CPTC) mode (25-50 W). This study aimed to assess quality-of-life (QOL) and healthcare utilization (HCU) benefits experienced by Q-FFICIENCY study participants. METHODS: Besides evaluating procedural efficiency, QOL and HCU were assessed through 12 months postablation via Atrial Fibrillation Effect on Quality-of-Life Tool (AFEQT) score, antiarrhythmic drug (AAD) use, and incidence of cardioversion and cardiovascular hospitalization. RESULTS: Of 191 participants enrolled, 166 were ablated with the new catheter. Compared to baseline, statistically significant, clinically meaningful improvements in composite and subcategories of AFEQT scores were observed at 3 months and sustained through 12 months (12-month increase, 29.3-44.2 points). Class I/III AAD use decreased from 97.6% (162/166) at baseline to 19.6% (31/158) during Months 6-12, representing a significant 79.9% reduction. The cardioversion rate significantly declined by 93.9% from 31.3% (12 months preablation) to 1.9% (evaluation period). One-year Kaplan-Meier estimates of freedom from all-cause and cardiovascular hospitalization were 80.9% (95% confidence interval [CI], 74.8%-86.9%) and 88.8% (95% CI, 84.0%-93.7%), respectively. CONCLUSIONS: Paroxysmal AF ablation with the novel temperature-controlled RF catheter in vHPSD mode, alone or with CPTC mode, led to clinically meaningful improvement in QOL and significant reduction in AAD use, cardioversion, and cardiovascular hospitalization.

Silent cerebral lesions following catheter ablation for atrial fibrillation: a state-of-the-art review.

Atrial fibrillation is associated with neurocognitive comorbidities such as stroke and dementia. Evidence suggests that rhythm control-especially if implemented early-may reduce the risk of cognitive decline. Catheter ablation is highly efficacious for restoring sinus rhythm in the setting of atrial fibrillation; however, ablation within the left atrium has been shown to result in MRI-detected silent cerebral lesions. In this state-of-the-art review article, we discuss the balance of risk between left atrial ablation and rhythm control. We highlight suggestions to lower the risk, as well as the evidence behind newer forms of ablation such as very high power short duration radiofrequency ablation and pulsed field ablation.

Real-world trends in atrial fibrillation ablation indicate increasing durability of pulmonary vein isolation at repeat ablation.

BACKGROUND: Durable electrical isolation of pulmonary veins (PVs) is associated with better outcomes after atrial fibrillation (AF) ablation, but previous studies of AF recurrence have reported high rates of reconnection despite successful acute isolation. This study aims to quantify historical trends in the durability of PV isolation (PVI) as radiofrequency (RF) ablation catheters, additional ablation technologies, and associated workflows have evolved. METHODS: The study population included adult patients receiving a first repeat ablation for AF between September 2013 and July 2019 at the study site. All index ablations were performed at the same site with an RF catheter and included PVI. Three generations of irrigated RF catheters based on the same technology platform were used by the site during the timeframe of this study. RESULTS: A total of 224 patients were included in the analysis. At repeat ablation, the mean number of patients with at least one reconnected PV dropped significantly with subsequent catheter generation, from 78.3% to 56.7% to 27.0% (p < .0001). Moreover, the mean number of reconnected PVs were significantly reduced from 1.48 to 0.92 to 0.47 (p < .0001), representing a 68.3% reduction across the 3 generations of devices. CONCLUSION: Significant improvement in durable PVI was seen with successive generations of RF catheter over a 6-year period. In addition to catheter technology, ancillary advances in ablation technologies, workflows, and operator experience likely contributed to these improvements.

Endoscopically Assisted LeFort I Osteotomy for Minimally Invasive Orthognathic Surgery: A Technical Note.

Minimally invasive surgery in orthognathic surgery has gained popularity in recent years. This is mainly due to the benefit to the patient of achieving a better postoperative period and a faster recovery. However, one of the main difficulties is the lack of direct vision, which is a concern for the surgeon. For this reason, this technical note aims to propose endoscopically assisted LeFort I osteotomy for MI orthognathic surgery.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Procedural and short-term results of electroanatomic-mapping-guided ganglionated plexus ablation by first-time operators: A multicenter study.

INTRODUCTION: Single-center observational studies have shown promising results with fragmented electrogram (FE)-guided ganglionated plexus (GP) ablation in patients with vagally mediated bradyarrhythmia (VMB). We aimed to compare the acute procedural characteristics during FE-guided GP ablation in patients with VMB performed by first-time operators and those of a single high-volume operator. METHODS AND RESULTS: This international multicenter cohort study included data collected over 2 years from 16 cardiac hospitals. The primary operators were classified according to their prior GP ablation experience: a single high-volume operator who had performed > 50 GP ablation procedures (Group 1), and operators performing their first GP ablation cases (Group 2). Acute procedural characteristics and syncope recurrence were compared between groups. Forty-seven consecutive patients with VMB who underwent FE-guided GP ablation were enrolled, n = 31 in Group 1 and n = 16 in Group 2. The mean number of ablation points in each GP was comparable between groups. The ratio of positive vagal response during ablation on the left superior GP was higher in Group 1 (90.3% vs. 62.5%, p = .022). Ablation of the right superior GP increased heart rate acutely without any vagal response in 45 (95.7%) cases. The procedure time was longer in group 2 (83.4 ± 21 vs. 118.0 ± 21 min, respectively, p < .001). Over a mean follow-up duration of 8.0 ± 3 months (range 2-24 months), none of the patients suffered from syncope. CONCLUSION: This multi-center pilot study shows for the first time the feasibility of FE-guided GP ablation across a large group of procedure-naïve operators.

Effect of conscious sedation and deep sedation on the vagal response characteristics during ganglionated plexus ablation.

INTRODUCTION: We aimed to determine the effects of conscious and deep sedation on vagal response (VR) characteristics during ganglionated plexus (GP) ablation. METHODS: Forty consecutive patients undergoing GP ablation for vasovagal syncope were divided to receive conscious sedation with midazolam (Group 1, n = 29) or deep sedation with the midazolam-propofol combination (Group 2, n = 11). VR was defined on three levels. R-R interval increase of >50% (Level 1); R-R interval increase of 20%-50% (Level 2); and R-R interval increase of <20% (Level 3). RESULTS: The ratio of Level 1 VR during ablation on left superior and inferior GPs was significantly lower in Group 2 (p < .0001 and p = .034, respectively). Once the cut-off for VR was decreased to Level 2, the ratio of (+) VR was similar between groups during ablation of left-sided GPs. Positive VR in any level was lower than 20% during ablation of right-sided GPs. CONCLUSIONS: The autonomic tone might be affected in different ways by the level or type of intravenous sedation. Awareness of anesthesia-related differences may be important if GP ablation will be performed by using VR characteristics during ablation.

Predictors of clinical success after paroxysmal atrial fibrillation catheter ablation.

INTRODUCTION: Contact force (CF) guided ablation of paroxysmal atrial fibrillation (PAF) with stable catheter-tissue contact optimizes clinical success and may increase an operator's ability to achieve pulmonary vein isolation (PVI) in a single encirclement. First pass PVI reduces procedure time but the relationship with long term clinical success is not well understood. This study evaluated patient characteristics and procedural details as predictors of 1-year clinical success after PAF ablation, including first pass isolation. METHODS: Consecutive de novo PAF ablations were performed with a porous tip CF catheter in 2017 and 2018. All ablations used wide-area circumferential ablation, with first pass isolation captured separately for the left and right pulmonary veins (PVs). CF was held between 10 and 20 g and the catheter was moved every 10-20 s. Radiofrequency energy was set at 40-45 W throughout the atrium. Patient characteristics and procedural details were tested for association with clinical success, defined as freedom from recurrent atrial tachyarrhythmia through 1 year. RESULTS: A total of 404 patients were included in the study. Clinical success at 1 year was 86.6%. Achieving first pass isolation on at least one ipsilateral PV pair was the most significant predictor of clinical success (p = .0126). After controlling for first pass isolation, only recurrence within the 90-day blanking period was independently predictive (p = .0015). First pass isolation was not associated with early recurrence (p = .2454). CONCLUSION: In a real-world setting, first pass isolation was highly predictive of 12-month clinical success after CF-guided ablation in a PAF population.

General anesthesia during atrial fibrillation ablation: Standardized protocol and experience.

BACKGROUND: Most atrial fibrillation (AF) ablations are performed with general anesthesia (GA). The ideal GA protocol is unknown, but it affects ablation outcomes and laboratory utilization. We sought to report a GA protocol used at a high-volume center, with special consideration on efficiency and optimization of mapping and ablation conditions. METHODS: Our protocol consists of propofol as sole anesthetic agent and analgesia with Fentanyl. IV fluids are minimized. After transseptal access, the right phrenic nerve is tagged, rocuronium is given, and redosing avoided. Ventilation is modulated to optimize mapping and ablation. After ablation, isoproterenol is infused for 20 min. After 10 min, propofol is gradually decreased and ventilation set to SIMV 8 breaths/min to promote spontaneous breathing, and then switched to pressure support and propofol stopped. Paralysis is reversed and furosemide given. Patient is extubated once meeting standard criteria. RESULTS: A total of 1286 patients underwent AF ablation from January 2017 to December 2018 using the protocol. Mean age was 66 years (41% paroxysmal AF, CHADS2Vasc 2.6). Total procedure time was 86 min. Median time to extubation was 9 min (first and third quartile 6-16) after procedure completed, with total anesthesia time of 116 min. On average 370 mL of fluids were given by anesthesia. Only one patient who had heart failure required reintubation with no other anesthesia-related complications seen. CONCLUSION: Our GA protocol was specifically designed for AF ablation. It was safe and led to efficient recovery and extubation times. It maximizes laboratory utilization time without compromising safety.

General anesthesia (GA) has been shown to improve outcomes of atrial fibrillation (AF) ablation. However, the ideal anesthetic protocol is unknown. We describe a GA protocol developed by the anesthesiology and electrophysiology team. It considers each phase of the ablation procedure separately in choosing drugs to be used and also careful modulation of ventilator settings to improve mapping and ablation conditions. This GA protocol was then utilized in 1286 patients undergoing AF ablation and it was safe and produced very efficient median time to extubation (9 min).

Acceptability by sensory and visual analyses of meat from Nellore heifers fed with natural additives and finished in feedlots.

BACKGROUND: This study evaluated the acceptability (by sensorial and visual analyses) of meat from 40 Nellore heifers (finished in feedlots for 73 days) fed with different diets supplemented with essential oils (EOs) and an active principle blend. The five diets tested were: CON - a diet without essential oil and active principle blend (eugenol, thymol, and vanillin); ROS - a diet supplemented with rosemary EO; BLE - supplemented with a blend; BCL - a diet with clove EO+ blend; and BRC - a diet with rosemary, clove EOs + blend. The acceptability of diet and aging time was evaluated by consumers. RESULTS: Diet affected consumer acceptability and visual analysis (meat color). The diets with EO and the blend showed better sensory acceptance by the consumers; meat aged for 7 days received higher scores than meat aged for 1 day. Meat from heifers that received both EOs + blend (BCL, BRC) obtained the highest scores in the visual evaluation. CONCLUSION: The use of natural compounds in ruminant diets improves the sensory characteristics of meat without damaging visual acceptability and may be an alternative to the conventional additive market. © 2020 Society of Chemical Industry.

Prediabetes is a risk factor for cardiovascular disease following renal transplantation.

Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.

Expression and function of TLR4- induced B1R bradykinin receptor on cardiac fibroblasts.

Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels. However, whether TLR4 activation regulates bradykinin receptor expression remains unknown. CF were isolated from human, neonatal rat and adult mouse heart. B1R mRNA expression was evaluated by qRT-PCR, whereas B1R, collagen, COX-2 and iNOS protein levels were evaluated by Western Blot. NO and PGI2 were evaluated by commercial kits. We report here that in CF, TLR4 activation increased B1R mRNA and protein levels, as well as COX-2 and iNOS levels. B1R mRNA levels were also induced by interleukin-1α via its cognate receptor IL-1R1. In LPS-pretreated CF the DAKD treatment induced higher responses with respect to those observed in non LPS-pretreated CF, increasing PGI2 secretion and NO production; and reducing collagen I protein levels in CF. In conclusion, no significant response to DAKD was observed (due to very low expression of B1R in CF) - but pre-activation of TLR4 in CF, conditions that significantly enhanced B1R expression, led to an additional response of DAKD.

Efficacy of New Measures Saving Time in Acute Stroke Management: A Quantified Analysis.

BACKGROUND: Time to treatment remains the most important factor in acute ischemic stroke prognosis. We quantified the effect of new interventions reducing in-hospital delays in acute stroke management and assessed its repercussion on door-to-imaging (DTI), imaging-to-needle (ITN), and door-to-needle (DTN) times. METHODS: Prospective registry of consecutive stroke patients who were candidates for reperfusion therapy attended in a tertiary care hospital from February 1 to December 31, 2014. A series of measures aimed at reducing in-hospital delays were implemented. We compared DTI, ITN, and DTN times between patients who underwent the interventions and those who did not. RESULTS: 231 patients. DTI time was lower when personal history was reviewed and tests were ordered before patient arrival (2.5 minutes saved, P = .016) and when electrocardiogram was not made (5.4 minutes saved, P < .001). Not performing a computed tomography angiography and not waiting for coagulation results from laboratory before intravenous thrombolysis (25.5%) reduced ITN time significantly (14 and 12 minutes saved, respectively, P < .001). These interventions remained as independent predictors of a shorter ITN and DTN time. Completing all steps resulted in the lowest DTI and ITN times (13 and 19 minutes, respectively). CONCLUSIONS: Every measure is an important part of a chain focused on saving time in acute stroke: the lowest DTI and ITN times were obtained when all steps were completed. Measures shortening ITN time produced a greater impact on DTN time reduction; therefore, ITN interventions should be considered a critical part of new protocols and guidelines.

Cardiac fibroblast cytokine profiles induced by proinflammatory or profibrotic stimuli promote monocyte recruitment and modulate macrophage M1/M2 balance in vitro.

Macrophage polarization plays an essential role in cardiac remodeling after injury, evolving from an initial accumulation of proinflammatory M1 macrophages to a greater balance of anti-inflammatory M2 macrophages. Whether cardiac fibroblasts themselves influence this process remains an intriguing question. In this work, we present evidence for a role of cardiac fibroblasts (CF) as regulators of macrophage recruitment and skewing. Adult rat CF, were treated with lipopolysaccharide (LPS) or TGF-ß1, to evaluate ICAM-1 and VCAM-1 expression using Western blot and proinflammatory/profibrotic cytokine secretion using LUMINEX. We performed in vitro migration and adhesion assays of rat spleen monocytes to layers of TGF-ß1- or LPS-pretreated CF. Finally, TGF-ß1- or LPS-pretreated CF were co-cultured with monocyte, to evaluate their effects on macrophage polarization, using flow cytometry and cytokine secretion. There was a significant increase in monocyte adhesion to LPS- or TGF-ß1-stimulated CF, associated with increased CF expression of ICAM-1 and VCAM-1. siRNA silencing of either ICAM-1 or VCAM-1 inhibited monocyte adhesion to LPS-pretreated CF; however, monocyte adhesion to TGF-ß1-treated CF was dependent on only VCAM-1 expression. Pretreatment of CF with LPS or TGF-ß1 increased monocyte migration to CF, and this effect was completely abolished with an MCP-1 antibody blockade. LPS-treated CF secreted elevated levels of TNF-α and MCP-1, and when co-cultured with monocyte, LPS-treated CF stimulated increased macrophage M1 polarization and secretion of proinflammatory cytokines (TNF-α, IL-12 and MCP-1). On the other hand, CF stimulated with TGF-ß1 produced an anti-inflammatory cytokine profile (high IL-10 and IL-5, low TNF-α). When co-cultured with monocytes, the TGF-ß1 stimulated fibroblasts skewed monocyte differentiation towards M2 macrophages accompanied by increased IL-10 and decreased IL-12 levels. Taken together, our results show for the first time that CF can recruit monocytes (via MCP-1-mediated chemotaxis and adhesion to ICAM-1/VCAM-1) and induce their differentiation to M1 or M2 macrophages (through the CF cytokine profile induced by proinflammatory or profibrotic stimuli).

Clinical evolution of post-transplant diabetes mellitus.

BACKGROUND: The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS: We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS: Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS: PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Tissue plasminogen activator for acute ischemic stroke: calculation of dose based on estimated patient weight can increase the risk of cerebral bleeding.

A dose of 0.9 mg/kg of intravenous tissue plasminogen activator (t-PA) has proven to be beneficial in the treatment of acute ischemic stroke (AIS). Dosing of t-PA based on estimated patient weight (PW) increases the likelihood of errors. Our objectives were to evaluate the accuracy of estimated PW and assess the effectiveness and safety of the actual applied dose (AAD) of t-PA. We performed a prospective single-center study of AIS patients treated with t-PA from May 2010 to December 2011. Dose was calculated according to estimated PW. Patients were weighed during the 24 h following treatment with t-PA. Estimation errors and AAD were calculated. Actual PW was measured in 97 of the 108 included patients. PW estimation errors were recorded in 22.7 % and were more frequent when weight was estimated by stroke unit staff (44 %). Only 11 % of patients misreported their own weight. Mean AAD was significantly higher in patients who had intracerebral hemorrhage (ICH) after t-PA than in patients who did not (0.96 vs. 0.92 mg/kg; p = 0.02). Multivariate analysis showed an increased risk of ICH for each 10 % increase in t-PA dose above the optimal dose of 0.90 mg/kg (OR 3.10; 95 % CI 1.14-8.39; p = 0.026). No effects of t-PA misdosing were observed on symptomatic ICH, functional outcome or mortality. Estimated PW is frequently inaccurate and leads to t-PA dosing errors. Increasing doses of t-PA above 0.90 mg/kg may increase the risk of ICH. Standardized weighing methods before t-PA is administered should be considered.