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Objectives: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia managed in emergency departments, and the already high prevalence of this arrhythmia is increasing in Spain. This serious condition associated with increased mortality and morbidity has a negative impact on patient quality of life and the functioning of the health care system. The management of AF requires consideration of diverse clinical variables and a large number of possible therapeutic approaches, justifying action plans to coordinate the work of several medical specialties in the interest of providing appropriate care and optimizing resources. This consensus statement brings together recommendations for emergency department management of AF based on available evidence adapted to special circumstances. The statement was drafted by a multidisciplinary team of specialists from the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Cardiology (SEC), and the Spanish Society of Thrombosis and Hemostasis (SETH). Strategies for stroke prophylaxis, measures to bring heart rate and heart rhythm under control, and related diagnostic and logistic issues are discussed in detail.

Background: Freezing rate of second-generation cryoballoon (CB) is a biophysical parameter that could assist pulmonary vein isolation. The aim of this study is to assess freezing rate (time to reach -30°C ([TT-30C]) as an early predictor of acute pulmonary vein isolation using the CB., Methods: Biophysical data from CB freeze applications within a multicenter, nation-wide CB ablation registry were gathered. Successful application (SA), was defined as achieving durable intraprocedural vein isolation. And SA with time to isolation under 60 s (SA-TTI<60) as achieving durable vein isolation in under 60 s. Logistic regressions were performed and predictive models were built for the data set., Results: 12,488 CB applications from 1,733 atrial fibrillation (AF) ablation procedures were included within 27 centers from a Spanish CB AF ablation registry. SA was achieved in 6,349 of 9,178 (69.2%) total freeze applications, and SA-TTI<60 was obtained in 2,673 of 4,784 (55.9%) freezes where electrogram monitoring was present. TT-30C was shorter in the SA group (33.4 ± 9.2 vs 39.3 ± 12.1 s; p < 0.001) and SA-TTI<60 group (31.8 ± 7.6 vs. 38.5 ± 11.5 s; p < 0.001). Also, a 10 s increase in TT-30C was associated with a 41% reduction in the odds for an SA (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.56-0.63) and a 57% reduction in the odds for achieving SA-TTI<60 (OR 0.43; 95% CI 0.39-0.49), when corrected for electrogram visualization, vein position, and application order., Conclusions: Time to reach -30°C is an early predictor of the quality of a CB application and can be used to guide the ablation procedure even in the absence of electrogram monitoring.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5 - and Cd6 -deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002 CC ) and requirement of biological therapies (rs2241002 C -rs2229177 T haplotype), and with poor UC prognosis (rs2241002 T -rs2229177 T haplotype). Regarding CD6 , association was observed with CD ileal location (rs17824933 G ) and poor prognosis (rs12360861 G ), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933 G ). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders., Competing Interests: FL is founder and ad-honorem scientific advisor of Sepsia Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Casadó-Llombart, Velasco-de Andrés, Català, Leyton-Pereira, Gutiérrez-Cózar, Suárez, Armiger, Carreras, Esteller, Ricart, Ordás, Gisbert, Chaparro, Esteve, Márquez, Busquets, Iglesias, García-Planella, Martín-Arranz, Lohmann, Ayata, Niess, Engel, Panés, Salas, Domènech, Lozano and ENEIDA Project of GETECCU.)

CD6 is a lymphocyte-specific scavenger receptor expressed on adaptive (T) and innate (B1a, NK) immune cells, which is involved in both fine-tuning of lymphocyte activation/differentiation and recognition of bacterial-associated molecular patterns (i.e., lipopolysaccharide). However, evidence on CD6's role in the physiological response to bacterial infection was missing. Our results show that induction of monobacterial and polymicrobial sepsis in Cd6 -/- mice results in lower survival rates and increased bacterial loads and pro-inflammatory cytokine levels. Steady state analyses of Cd6 -/- mice show decreased levels of natural polyreactive antibodies, concomitant with decreased cell counts of spleen B1a and marginal zone B cells. Adoptive transfer of wild-type B cells and mouse serum, as well as a polyreactive monoclonal antibody improve Cd6 -/- mouse survival rates post-sepsis. These findings support a nonredundant role for CD6 in the early response against bacterial infection, through homeostatic expansion and functionality of innate-related immune cells., Competing Interests: F.L. and M.I. are founders and ad-honorem scientific advisors of Sepsia Therapeutics S.L. F.L. is the inventor of patents WO2008119851A1, WO2018091679A1, and WO2019/175261A1. The rest of the authors have no additional financial interests., (© 2022 The Authors.)

Introduction: Cryoballoon ablation (CBA) has become a standard treatment for paroxysmal atrial fibrillation (PaAF) but limited data is available for outcomes in patients with persistent atrial fibrillation (PeAF). Methods: We analyzed the first 944 patients included in the Spanish Prospective Multi-center Observation Post-market Registry to compare characteristics and outcomes of patients undergoing CBA for PeAF versus PaAF. Results: A total of 944 patients (57.8 ± 10.4 years; 70.1% male) with AF (27.9% persistent) were prospectively included from 25 centers. PeAF patients were more likely to have structural heart disease (67.7 vs. 11.4%; p < 0.001) and left atrium dilation (72.6 vs. 43.3%; p < 0.001). CBA of PeAF was less likely to be performed under general anesthesia (10.7 vs. 22.2%; p < 0.001), with an arterial line (32.2 vs. 44.6%; p < 0.001) and assisted transeptal puncture (11.9 vs. 17.9%; p = 0.025). During an application, PeAF patients had a longer time to −30 °C (35.91 ± 14.20 vs. 34.93 ± 12.87 s; p = 0.021) and a colder balloon nadir temperature during vein isolation (−35.04 ± 9.58 vs. −33.61 ± 10.32 °C; p = 0.004), but received fewer bonus freeze applications (30.7 vs. 41.1%; p < 0.001). There were no differences in acute pulmonary vein isolation and procedure-related complications. Overall, 76.7% of patients were free from AF recurrences at 15-month follow-up (78.9% in PaAF vs. 70.9% in PeAF; p = 0.09). Conclusions: Patients with PeAF have a more diseased substrate, and CBA procedures performed in such patients were more simplified, although longer/colder freeze applications were often applied. The acute efficacy/safety profile of CBA was similar between PaAF and PeAF patients, but long-term results were better in PaAF patients.

Cryoablation is safe and effective for the treatment of atrial fibrillation (AF) in controlled clinical trials, but contemporary real-world usage and outcomes are limited. The Report of the Spanish Cryoballoon Ablation Registry (RECABA) was designed to evaluate acute and 12-month outcomes of cryoballoon ablation for the treatment of AF in Spain. Patients from 27 Spanish centers were prospectively enrolled. Patients were treated with cryoballoon ablation and managed according to standard of care protocols at each center. The primary endpoint was ≥ 30 s freedom from AF at 12-month after a 3-month blanking period. Secondary endpoints included a description of patient characteristics, cryoablation procedural strategy and safety, and predictors of efficacy. In total, 1742 patients (71.4% PAF, 68.8% male, mean age 58.02 ± 10.40 years, 76.1% overweight or obese, CHA 2 DS 2 -VASc index 1.40 ± 1.28) were enrolled. Patients received 7.2 ± 2.67 cryo-applications. PV potentials could be detected in 61% of the PVs during ablation, with a mean time to block of 52.9 ± 37.02 s. Acute PVI was observed in 97% of PVs with 75.8% isolated with the first cryo-application. Mean procedural time was 113 ± 41 min. Acute complications occurred in 4.4% of the cases. With follow-up in 1628 patients, AF-free survival was 78.5% (PAF: 80.6% vs PersAF 73.3%; p < 0.001). Left atrium enlargement, female sex, non-PAF, and early recurrence were independent predictors of AF recurrence (p < 0.05). RECABA provides detailed insight into current dosing practices and demonstrates cryoablation is safe and effective in real-world use.ClinicalTrials.gov number: NCT02785991., (© 2021. The Author(s).)

In genetically prone individuals, chronic immune activation may lead to expansion of autoreactive lymphocyte clones that can induce organ damage developing autoimmune disorders. Sjögren's Syndrome (SjS) is a systemic chronic autoimmune disease that primarily affects exocrine glands. Despite the accumulated evidences of profound B-cell alterations of humoral immunity, the repertoire and development of B-cell autoreactivity in SjS remains to be determined. We hypothesize that SjS mice will have an increased frequency of self-reactive B cells with a progressive evolution to antigen-driven oligoclonality. Here, we study the B cell repertoire of NOD.H-2 h4 mice, a mouse model of spontaneous autoimmunity mimicking SjS without developing diabetes. A library of 168 hybridomas from NOD.H-2 h4 mice and 186 C57BL/6J splenocytes at different ages was created. The presence of mono or polyreactive autoantibodies to several antigens was evaluated by ELISA, and their staining patterns and cellular reactivity were tested by IFA and FACS. We observed a higher frequency of autoreactivity among B-cell clones from NOD.H-2 h4 mice as compared to wild-type mice. The presence of polyreactive and autoreactive IgG clones increased with mice age. Strikingly, all anti-Ro52 autoantibodies were polyreactive. No loss of polyreactivity was observed upon antibody class switching to IgG. There was a progression to oligoclonality in IgG B cells with mice aging. Our results indicate that in the NOD.H-2 h4 mouse model of SjS, IgG+ B cells are mainly polyreactive and might expand following an unknown antigen-driven positive selection process., Competing Interests: JB is CEO and cofounder and JC is CSO and cofounder of AlbaJuna Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sáez Moya, Gutiérrez-Cózar, Puñet-Ortiz, Rodríguez de la Concepción, Blanco, Carrillo and Engel.)

Introduction and Objectives: This report presents the findings of the 2019 Spanish Catheter Ablation Registry., Methods: Data collection was retrospective. A standardized questionnaire was filled by each of the participant centers., Results: Data sent by 102 centers were analyzed, with a total number of ablation procedures performed of 18549 (the highest historically reported in this registry) for a mean of 181.9±137.0 and a median of 144.5 procedures per center. The ablation targets most frequently treated were atrial fibrillation (n=5164; 27.8%), cavotricuspid isthmus (n=3925; 21.1%) and atrioventricular nodal reentrant tachycardia (n=3768; 20.3%). A new peak is observed in the ablation of atrial fibrillation, increasing the distance from the other substrates. The overall success rate was again 91%. The rate of major complications was 1.9%, and the mortality rate was 0.03%. An electroanatomic mapping system was used in 44.5% of all procedures, with contact force-sensing irrigated catheters become the preferred for complex substrates, as atrial fibrillation (84.8%) or ventricular tachycardia (around 90%). 1.5% of the ablations were performed in pediatric patients., Conclusions: The Spanish Catheter Ablation Registry enrolls systematically and uninterruptedly the ablation procedures performed in Spain, showing a progressive increasing in the number of ablations over the years with a high success rate and low percentages of complications., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: This report presents the findings of the 2018 Spanish Catheter Ablation Registry., Methods: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers., Results: Data sent by 100 centers were analyzed, with a total number of 16566 ablation procedures performed (the highest historically reported in this registry) for a mean of 165.5±127.9 and a median of 119 procedures per center. The ablation targets most frequently treated were atrial fibrillation (n=4234; 25.6%), atrioventricular nodal re-entrant tachycardia (n=3525; 21.3%) and cavotricuspid isthmus (n=3425; 20.7%). A new peak was observed in the ablation of atrial fibrillation, increasing the distance from the other substrates. The overall success rate was 91%. The rate of major complications was 2.2%, and the mortality rate was 0.04%. A total of 2.1% of the ablations were performed in pediatric patients., Conclusions: The Spanish Catheter Ablation Registry enrolls systematically and continuously enrolls the ablation procedures performed in Spain, showing a progressive increasing in the number of ablations over the years, with a high success rate and low percentage of complications., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Unexplained cardiac arrest (UCA) can be caused by low-penetrance genetic disorders. The aim of this cross-sectional study is to assess the usefulness of a new diagnostic protocol: Thirty-five patients were recruited from 9 Spanish centers. Electrocardiogram, echocardiogram, and coronary catheterization were used to rule out electrical or structural heart disease in all subjects. Patients underwent pharmacologic tests with epinephrine and flecainide, followed by assessment of family members using electrocardiogram and echocardiogram, and next-generation genetic sequencing to analyze 126 genes if all the other test results were negative. A firm diagnosis of channelopathy required phenotypic proof of the condition in unmasking tests, the presence of a pathogenic variant consistent with the phenotype observed, and/or co-segregation of the mutation found in a family member's phenotype. A firm diagnosis was made in 18 cases. The diagnoses were 7 Brugada syndrome, 5 catecholaminergic polymorphic ventricular tachycardia, 3 long QT syndrome, 2 early repolarization syndrome, and 1 short QT syndrome. Pharmacologic testing was the most frequent method of diagnosis. In 5 cases, the diagnosis was made based on positive genetic testing without phenotypic alterations. In conclusion, this sequential diagnostic protocol allows diagnoses to be made in approximately half of the UCA cases. These diagnoses are low clinical penetrance channelopathies. If interpreted carefully, genetic tests can be a useful tool for diagnosing UCA without a phenotype., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction and Objectives: To summarize the findings of the Spanish Implantable Cardioverter-Defibrillator (ICD) Registry for 2008 compiled by the Spanish Society of Cardiology Working Group on Implantable Cardioverter-Defibrillators., Methods: Prospective data recorded voluntarily on single-page questionnaires were sent to the Spanish Society of Cardiology by each implantation team., Results: Overall, 3486 device implantations were reported, which is 84.7% of the estimated total number of implantations. The reported implantation rate was 76 per million population and the estimated total implantation rate was 90 per million. The proportion of first implantations was 78.1%. There continued to be substantial regional variations within Spain. The majority of ICD implantations took place in men (mean age 62+/-12 years) who had severe or moderate-to-severe ventricular dysfunction and were in New York Heart Association functional class II. Ischemic heart disease was the most frequent underlying cardiac condition, followed by dilated cardiomyopathy. The number of indications for primary prevention increased relative to the previous year, especially in patients with ischemic cardiomyopathy, and now account for 57% of first implantations. The types of ICD implanted were unchanged from 2007. Overall, 73.6% of ICDs were implanted by cardiac electrophysiologists., Conclusions: The 2008 Spanish ICD Registry includes data on almost 85% of all ICD implantations performed in Spain. Although the number has continued to increase, it still remains far from the European average. There was a significant increase in indications for primary prevention. Substantial regional variations continue to exist within Spain.

Objectives: This study was designed to determine the effectiveness of a protocol for rapid intravenous hydration to prevent contrast-induced nephropathy (CIN) in patients undergoing emergency percutaneous coronary intervention (PCI)., Background: Contrast-induced nephropathy frequently complicates PCI, resulting in prolonged hospitalization and increased in-hospital and long-term morbidity and mortality. Little is known regarding prevention of CIN in patients undergoing urgent PCI., Methods: We conducted a prospective, controlled, randomized, single-center trial in 111 consecutive patients with acute coronary syndrome undergoing emergency PCI. As part of the hydration therapy, 56 patients (group A) received an infusion of sodium bicarbonate plus N-acetylcysteine (N-AC) started just before contrast injection and continued for 12 h after PCI. The remaining 55 patients (group B) received the standard hydration protocol consisting of intravenous isotonic saline for 12 h after PCI. In both groups, 2 doses of oral N-AC were administered the next day., Results: The 2 groups were similar with respect to age, gender, diabetes mellitus, and baseline serum creatinine. A serum creatinine concentration >0.5 mg/dl from baseline after emergency PCI was observed in 1 patient in group A (1.8%) and in 12 patients in group B (21.8%; p < 0.001). Acute anuric renal failure was observed in 1 patient (1.8%) in group A and in 7 patients (12.7%) in group B (p = 0.032)., Conclusions: Rapid intravenous hydration with sodium bicarbonate plus N-AC before contrast injection is effective and safe in the prevention of CIN in patients undergoing emergency PCI.

Introduction: In the last years, there has been a growing interest in the study of cognitive functioning, not only in schizophrenia but also in other psychoses and psychiatric disorders. Attention, memory and information processing deficits may have great relevance as predictors of social adjustment and quality of life., Objective and Methods: [corrected] We revised literature concerning comparative studies of neuropsychological performance in schizophrenia and affective disorders, mainly bipolar disorders., Results: Studies analyzed show contradictory results. Some authors report a more global dysfunction or a more limited and concrete dysfunction in schizophrenia. However, most of the studies, especially those with homogeneous samples of psychotic affective disorders do not find any difference in cognitive functioning between schizophrenic and bipolar patients., Discussion: Although some factors as sample selection, clinical state, course of the disorder, make difficult the interpretation of results, it would not exist specific deficits in any of the diagnostic groups studied.