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Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)( P <0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction( P >0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P =0.476; major bleeding-free survival comparison, P =0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism( HR =1.21, 95% CI : 0.42-3.50, P =0.720) and major bleeding( HR =1.50, 95% CI : 0.27-8.41, P =0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.

Rare, biallelic loss-of-function mutations in DOCK8 result in a combined immune deficiency characterized by severe and recurrent cutaneous infections, eczema, allergies, and susceptibility to malignancy, as well as impaired humoral and cellular immunity and hyper-IgE. The advent of next-generation sequencing technologies has enabled the rapid molecular diagnosis of rare monogenic diseases, including inborn errors of immunity. These advances have resulted in the implementation of gene-guided treatments, such as hematopoietic stem cell transplant for DOCK8 deficiency. However, putative disease-causing variants revealed by next-generation sequencing need rigorous validation to demonstrate pathogenicity. Here, we report the eventual diagnosis of DOCK8 deficiency in a consanguineous family due to a novel homozygous intronic deletion variant that caused aberrant exon splicing and subsequent loss of expression of DOCK8 protein. Remarkably, the causative variant was not initially detected by clinical whole-genome sequencing but was subsequently identified and validated by combining advanced genomic analysis, RNA-seq, and flow cytometry. This case highlights the need to adopt multipronged confirmatory approaches to definitively solve complex genetic cases that result from variants outside protein-coding exons and conventional splice sites., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The adherence of oral anticoagulant (OAC) therapy among nonvalvular atrial fibrillation (NVAF) patients with acute ischemic stroke (AIS) in China during recent years was unclear, and the possible factors that influenced the initiation and persistent use of OAC were needed to be explored., Methods: A total of 1085 NVAF patients, who experienced new-onset and nonfatal AIS from August 2011 to December 2020 during follow-ups in the China Atrial Fibrillation Registry (China-AF), were enrolled. Information including patients' demographic characteristics, medical history, medication usage, which were collected before and after the index stroke, were used in the analysis., Results: OAC was initiated in 40% (434/1085) NVAF patients within 3 months after new-onset AIS. High-reimbursement-rate insurance coverage (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.03-2.22, p = .036), 3-month-peri-stroke AF episodes (OR: 2.63, 95% CI: 1.88-3.69, p < .001), and pre-stroke OAC usage (OR: 8.92, 95% CI: 6.01-13.23, p < .001), were positively associated with initiation of OAC within 3 months after new-onset AIS, while age (OR: 0.98, 95% CI: 0.96-1.00, p = .024), female (OR: 0.63, 95% CI: 0.44-0.90, p = .012) and higher modified HASBLED score (OR: 0.45, 95% CI: 0.37-0.55, p < .001) were negatively associated with it. Among 3-month-post-stroke OAC users, history of radiofrequency ablation (hazard ratio: 1.65, 95% CI: 1.16-2.35; p = .006) was positively associated with non-persistence of OAC usage., Conclusions: In China, the proportion of NVAF patients who initiated OAC therapy since new-onset AIS was still low. More efforts are needed on improving patients' adherence to anticoagulant therapy., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Frailty is prevalent in elderly patients with cardiovascular diseases. However, the association between frailty and in-hospital outcomes for elderly patients with heart failure and reduced ejection (HFrEF) remains unknown., Aim: To evaluate the predictive efficacy of frailty, compared with pre-frailty, for adverse events in these patients., Methods: Elderly patients (≥ 60 years) with HFrEF were assessed. Frailty was evaluated with the Fried phenotype criteria, and physical performance was evaluated based on handgrip strength and the short physical performance battery (SPPB). The composite incidence of adverse events, including all-cause death, multiple organ failure, cardiac shock, and malignant arrhythmia, during hospitalization was recorded., Results: Overall, 252 elderly individuals with HFrEF [mean age: 69.4 ± 6.7 years, male: 169 (67.0%)] were included. One hundred and thirty-five (53.6%) patients were frail and 93 (36.9%) were pre-frail. Frail patients were older, more likely to be female, to have a lower blood pressure, and to present with left ventricular thrombosis ( P all < 0.05). Frail patients with HFrEF had a higher incidence of in-hospital mortality (11.9% vs 4.3%, P = 0.048). Multivariate analyses showed that female gender (OR = 0.422), aging (OR = 1.090), poor cardiac functional class (OR = 2.167), frailty (OR = 2.379), and lower handgrip strength (OR = 1.106) were independent predictors of in-hospital adverse events ( P all < 0.05)., Conclusion: Frailty may be associated with poor in-hospital outcomes for elderly patients with HFrEF. The influence of frailty on long-term prognosis in these patients deserves further investigation., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Dronedarone, a class Ⅲ antiarrhythmic drug, is a deiodinated benzofuran derivative of amiodarone. It has similar antiarrhythmic effects with amiodarone, but much lesser adverse effects than amiodarone, particularly in those outside the heart. It is suggested to use dronedarone for the rhythm control of atrial fibrillation/flutter, for it has been shown to prevent the recurrence of atrial fibrillation/flutter and reduce rehospitalization in patients with paroxysmal or persistent atrial fibrillation/flutter. Dronedarone is not recommended for the rhythm control in patients with long-term persistent atrial fibrillation or permanent atrial fibrillation, and atrial flutter or atrial fibrillation patients with reduced ejection fraction. Liver function, electrolyte tests and an electrocardiogram should be performed before and after the drug initiation. Potential interactions with other kinds of drugs have to be taken into consideration as well.

Background: Chronic kidney disease (CKD) is highly prevalent in patients with atrial fibrillation (AF). However, the association between CKD and clinical consequences in AF patients is still under debate., Methods: We included 19,079 nonvalvular AF patients with available estimated glomerular filtration rate (eGFR) values in the Chinese Atrial Fibrillation Registry from 2011 to 2018. Patients were classified into no CKD (eGFR ≥ 90 mL/min per 1.73 m 2 ), mild CKD (60 ≤ eGFR < 90 mL/min per 1.73 m 2 ), moderate CKD (30 ≤ eGFR < 60 mL/min per 1.73 m 2 ), and severe CKD (eGFR < 30 mL/min per 1.73 m 2 ) groups. The risks of thromboembolism, major bleeding, and cardiovascular mortality were estimated with Fine-Gray regression analysis according to CKD status. Cox regression was performed to assess the risk of all-cause mortality associated with CKD., Results: Over a mean follow-up of 4.1 ± 1.9 years, there were 985 thromboembolic events, 414 major bleeding events, 956 cardiovascular deaths, and 1,786 all-cause deaths. After multivariate adjustment, CKD was not an independent risk factor of thromboembolic events. As compared to patients with no CKD, those with mild CKD, moderate CKD, and severe CKD had a 45%, 47%, and 133% higher risk of major bleeding, respectively. There was a graded increased risk of cardiovascular mortality associated with CKD status compared with no CKD group: adjusted hazard ratio [HR] was 1.34 (95% CI: 1.07-1.68, P = 0.011) for mild CKD group, 2.17 (95% CI: 1.67-2.81, P < 0.0001) for moderate CKD group, and 2.95 (95% CI: 1.97-4.41, P < 0.0001) for severe CKD group, respectively. Risk of all-cause mortality also increased among patients with moderate or severe CKD., Conclusions: CKD status was independently associated with progressively higher risks of major bleeding and mortality, but didn't seem to be an independent predictor of thromboembolism in AF patients., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Background: "Atrial fibrillation Better Care" (ABC) pathway has been proposed to improve the management of patients suffered from atrial fibrillation (AF). This integrated or holistic management approach comprise of three aspects, including "A" Avoid stroke or Anticoagulation; "B" Better symptom control with rate or rhythm control strategies; "C" Cardiovascular risk factor and Concomitant diseases management. We aimed to confirm the beneficial evidence of ABC pathway compliance in a Chinese AF cohort. Method and Results: From the Chinese Atrial Fibrillation registry (CAFR) dataset, a total of 19,187 non-valvular AF patients were enrolled, of which 4.365 (22.8%) were ABC pathway compliant (ABC compliance group). During a median follow-up of 4.1 ± 1.8 years, The incident rate of all-cause death in ABC compliance group and non-ABC compliance group is 2.7 and 1.1 per 100 person-year ( p < 0.001), the incident rate of ischemic stroke is 1.3 and 0.8% per 100 person-year ( p < 0.001), the incident rate of composite outcome, which consist of all-cause death, ischemic stroke and intracranial hemorrhage, is 3.8 and 1.9 per 100 person-year ( p < 0.001). On Cox multivariable analysis, ABC pathway shows an independently association with reduction of all-cause death [hazard ratio (HR) = 0.82; 95% confidence interval (CI) = 0.70-0.95] and the composite outcome (HR 0.86, 95% CI 0.76-0.96). The increasingly components of ABC integrated care compliance is associated with lower risk of all-cause death and composite events. Conclusion: In a large cohort of Chinese AF patients, ABC pathway compliance shows an independently association with reduction of all-cause death and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. Better compliance of ABC integrated care contributes to lower HR for adverse events., Competing Interests: C-SM has received honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer-Ingelheim, and Bayer for giving lectures. J-ZD has received honoraria from Johnson & Johnson for giving lectures. GL has served as a Consultant and Speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. 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 Wang, Jiang, He, Du, Sang, Long, Tang, Dong, Lip and Ma.)

Purpose: Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2. Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are available on the phenotype and function of leukocytes from DADA2 patients. The aim of this study was to perform in-depth immunophenotyping and functional analysis of the impact of DADA2 on human lymphocytes., Methods: In-depth immunophenotyping and functional analyses were performed on ten patients with confirmed DADA2 and compared to heterozygous carriers of pathogenic ADA2 mutations and normal healthy controls., Results: The median age of the patients was 10 years (mean 20.7 years, range 1-44 years). Four out of ten patients were on treatment with steroids and/or etanercept or other immunosuppressives. We confirmed a defect in terminal B cell differentiation in DADA2 and reveal a block in B cell development in the bone marrow at the pro-B to pre-B cell stage. We also show impaired differentiation of CD4 + and CD8 + memory T cells, accelerated exhaustion/senescence, and impaired survival and granzyme production by ADA2 deficient CD8 + T cells. Unconventional T cells (i.e. iNKT, MAIT, Vδ2 + γδT) were diminished whereas pro-inflammatory monocytes and CD56 brigh t immature NK cells were increased. Expression of the IFN-induced lectin SIGLEC1 was increased on all monocyte subsets in DADA2 patients compared to healthy donors. Interestingly, the phenotype and function of lymphocytes from healthy heterozygous carriers were often intermediate to that of healthy donors and ADA2-deficient patients., Conclusion: Extended immunophenotyping in DADA2 patients shows a complex immunophenotype. Our findings provide insight into the cellular mechanisms underlying some of the complex and heterogenous clinical features of DADA2. More research is needed to design targeted therapy to prevent viral infections in these patients with excessive inflammation as the overarching phenotype., (© 2021. The Author(s).)

Objective: To investigate theoptimal idarucizumab (dabigatran antagonist) usage strategy for patients with acute pericardial tamponade receiving uninterrupted dabigatran during catheter ablation for atrial fibrillation (AF)., Methods: Ten patients presenting acute pericardial tamponade while receiving uninterrupted dabigatran during catheter ablation for AF in Beijing Anzhen Hospital from January 2019 to July 2020 were enrolled and retrospectively analyzed. A "wait and see" strategy of idarucizumab was carried out for all patients; in brief, idarucizumab was applied following pericardiocentesis, comprehensive evaluation of bleeding and hemostasis., Results: There were five males, five paroxysmal AF, and the average age of the patients was 64.0 ± 9.8 years. Among the 10 patients, four were treated with dabigatran 110 mg, six were treated with dabigatran 150 mg, and one was simultaneously given clopidogrel. The average time from pericardial tamponade to the last dose of dabigatran was 8.2 ± 3.4 h. All patients underwent pericardiocentesis successfully, and the average drainage volume was 322.5 ml (220.0 ± 935.0 ml). For reversal anticoagulation, six patients received protamine, and five patients received idarucizumab. Of the five patients who were treated with idarucizumab, four presented exact hemostasis, except for one patient who underwent continuous drainage and finally received surgery repair. The average time to restart anticoagulation was 1.1 ± 0.3 days after the procedure, and no rebleeding, embolism or deaths were observed., Conclusion: The "wait and see" strategy of idarucizumab for acute pericardial tamponade during the perioperative period of catheter ablation for AF may be safe and feasible., (© 2021 Wiley Periodicals LLC.)

Accumulation of human CD21 low B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21 low B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-bet high CD21 low B cells. Investigating essential signals for generating these cells in vitro established that B cell receptor (BCR)/interferon-γ receptor (IFNγR) costimulation induced the highest levels of T-bet expression and enabled their differentiation during cell cultures with Toll-like receptor (TLR) ligand or CD40L/interleukin-21 (IL-21) stimulation. Low proportions of CD21 low B cells in peripheral blood from patients with defined inborn errors of immunity (IEI), because of mutations affecting canonical NF-κB, CD40, and IL-21 receptor or IL-12/IFNγ/IFNγ receptor/signal transducer and activator of transcription 1 (STAT1) signaling, substantiated the essential roles of BCR- and certain T cell–derived signals in the in vivo expansion of T-bet high CD21 low B cells. Disturbed TLR signaling due to MyD88 or IRAK4 deficiency was not associated with reduced CD21 low B cell proportions. The expansion of human T-bet high CD21 low B cells correlated with an expansion of circulating T follicular helper 1 (cTfh1) and T peripheral helper (Tph) cells, identifying potential sources of CD40L, IL-21, and IFNγ signals. Thus, we identified important pathways to target autoreactive T-bet high CD21 low B cells in human autoimmune conditions, where these cells are linked to pathogenesis and disease progression.

Acquired resistance represents a bottleneck to molecularly targeted therapies such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. A deeper understanding of resistance mechanisms can provide insights into this phenomenon and help to develop additional therapeutic strategies to overcome or delay resistance. Here, we identified a pharmacologically targetable metabolic mechanism that drives resistance to EGFR TKIs in lung cancer cell lines and patient-derived xenograft mice. We demonstrated that aldo-keto reductase family 1 member B1 (AKR1B1) interacts with and activates signal transducer and activator of transcription 3 (STAT3) to up-regulate the cystine transporter solute carrier family 7 member 11 (SLC7A11). This leads to enhanced cystine uptake and flux to glutathione de novo synthesis, reactive oxygen species (ROS) scavenging, protection from cell death, and EGFR TKI drug resistance in lung cancer cell lines and xenograft mouse models. Suppression of AKR1B1 with selective inhibitors, including the clinically approved antidiabetic drug epalrestat, restored the sensitivity of resistant cell lines to EGFR TKIs and delayed resistance in lung cancer patient-derived xenograft mice. Our findings suggest a metabolic mechanism for resistance to a molecularly targeted therapy and provide a potential therapeutic target for overcoming resistance to EGFR TKIs, including the third-generation inhibitor osimertinib.

The production of high-affinity antibodies is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. However, dysregulated production of antibodies can cause immune pathologies, such as autoimmunity and immune deficiency. Long-lived humoral immunity depends on B-cell help provided by T follicular helper (Tfh) cells, which support the differentiation of antigen (Ag)-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4 + T cells following the receipt of inputs from various cell surface receptors, and can undergo further differentiation into subsets with specialised effector functions to induce and maintain serological memory. While genetically modified mice have provided great understanding of the requirements for generating Tfh cells, it is critical that requirements for human Tfh cell generation and function are also established. Key insights into the molecular requirements for human Tfh cells have been elucidated from the systematic analysis of humans with monogenic germline variants that cause inborn errors of immunity characterised by impaired humoral immunity following infection or vaccination or immune dysregulation and autoimmunity. In this review we will discuss how studying rare 'experiments of nature' has enabled discovery of non-redundant molecules and pathways necessary for Tfh cell generation, differentiation, regulation and function in humans, and how these findings inform us about basic and clinical immunology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist., Hypothesis: To investigate the prognosis of catheter ablation versus drug therapy in patients with AF and SCAD., Methods: In total, 25 512 patients with AF in the Chinese AF Registry between 2011 and 2019 were screened for SCAD. 815 patients with AF and SCAD underwent catheter ablation therapy were matched with patients by drug therapy in a 1:1 ratio. Primary end point was composite of thromboembolism, coronary events, major bleeding, and all-cause death. The secondary endpoints were each component of the primary endpoint and AF recurrence., Results: Over a median follow-up of 45 ± 23 months, the patients in the catheter ablation group had a higher AF recurrence-free rate (53.50% vs. 18.41%, p < .01). In multivariate analysis, there was no significant difference between the strategy of catheter ablation and drug therapy in primary composite end point (adjusted HR 074, 95%CI 0.54-1.002, p = .0519). However, catheter ablation was associated with fewer all-cause death independently (adjusted HR 0.36, 95%CI 0.22-0.59, p < .01). In subgroup analysis, catheter ablation was an independent risk factor for all-cause death in the high-stroke risk group (adjusted HR 0.39, 95%CI 0.23-0.64, p < .01), not in the low-medium risk group (adjusted HR 0.17, 95%CI 0.01-2.04, p = .17)., Conclusions: In the patients with AF and SCAD, catheter ablation was not independently associated with the primary composite endpoint compared with drug therapy. However, catheter ablation was an independent protective factor of all-cause death., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To evaluate the safety and effectiveness of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis. Methods: Six patients with AF and end-stage renal disease(ESRD)on long term hemodialysis who underwent LAAO from March 2017 to March 2021 in Beijing Anzhen Hospital were enrolled. Baseline characteristics such as age, sex, types of arrhythmia, stroke and bleeding score, and continuous dialysis time were collected. Four patients underwent LAAO, two patients underwent the combined procedure of catheter ablation and LAAO. Perioperative treatment and serious complications were recorded. Transesophageal echocardiography was repeated at 45 days and 60 days after the procedure. Telephone follow-up was conducted at 3, 6 and 12 months after the procedure, and every 6 months thereafter. Thromboembolism and major bleeding events and survival were evaluated. Results: The average age was (66.7±17.0) years old, and 5 were male (5/6). There were 4 patients with paroxysmal AF (4/6), and 2 patients with persistent AF (2/6). The mean CHA 2 DS 2 -VASc score was (4.8±1.5), and the HAS-BLED score was (3.5±1.4). The duration of hemodialysis was 2.6 (1.1, 8.3) years. Successfully Watchman implantation was achieved in all patients. There were no severe perioperative complications, and no device related thrombosis or leaks were observed by transesophageal echocardiography. During a mean of 22.0 (12.0, 32.0) months follow-up, there was no thromboembolism or major bleeding events. A total of 2 patients died, one from sudden cardiac death, and another one from heart failure. Conclusions: LAAO may be a safe and effective therapeutic option for prevention of thromboembolism in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis, further studies with larger patient cohort are needed to confirm our results.

Climate change has the potential to change the distribution of pests globally and their resistance to pesticides, thereby threatening global food security in the 21st century. However, predicting where these changes occur and how they will influence current pest control efforts is a challenge. Using experimentally parameterised and field-tested models, we show that climate change over the past 50 years increased the overwintering range of a global agricultural insect pest, the diamondback moth (Plutella xylostella), by ~2.4 million km 2 worldwide. Our analysis of global data sets revealed that pesticide resistance levels are linked to the species' overwintering range: mean pesticide resistance was 158 times higher in overwintering sites compared to sites with only seasonal occurrence. By facilitating local persistence all year round, climate change can promote and expand pesticide resistance of this destructive species globally. These ecological and evolutionary changes would severely impede effectiveness of current pest control efforts and potentially cause large economic losses., (© 2021. The Author(s).)

We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for a loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid and myeloid cells. The patient had low frequencies of NK, effector memory cells reexpressing CD45RA (Temra) CD8+ T cells, memory CD4+ T cells, including Th1 and Th1*, Tregs, and memory B cells, whereas the counts and proportions of other leukocyte subsets were normal. Functional deficits of myeloid cells included the abolition of IL-12 and IL-23 production by conventional DC1s (cDC1s) and monocytes, but not cDC2s. c-Rel was also required for induction of CD86 expression on, and thus antigen-presenting cell function of, cDCs. Functional deficits of lymphoid cells included reduced IL-2 production by naive T cells, correlating with low proliferation and survival rates and poor production of Th1, Th2, and Th17 cytokines by memory CD4+ T cells. In naive CD4+ T cells, c-Rel is dispensable for early IL2 induction but contributes to later phases of IL2 expression. The patient's naive B cells displayed impaired MYC and BCL2L1 induction, compromising B cell survival and proliferation and preventing their differentiation into Ig-secreting plasmablasts. Inherited c-Rel deficiency disrupts the development and function of multiple myeloid and lymphoid cells, compromising innate and adaptive immunity to multiple infectious agents.

Objective: To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF). Methods: This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality. Results: The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR =1.28, 95% CI 1.01-1.61, P =0.038), cardiovascular mortality ( H R=1.48,95% CI 1.10-2.00, P =0.010), cardiovascular hospitalization ( HR =1.67,95% CI 1.35-2.07, P =0.008) and the composite endpoints ( HR =2.02,95% CI 1.71-2.38, P <0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR =1.44,95% CI 1.05-1.98, P =0.025), cardiovascular hospitalization ( HR =1.44,95% CI 1.09-1.90, P =0.010) and the composite endpoints ( HR =1.37, 95% CI 1.01-1.70, P =0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR =2.56,95% CI 1.44-4.54, P =0.001). Conclusion: Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

Background: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures., Method: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy., Results: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%)., Conclusions: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings., (Copyright © 2021. Published by Elsevier B.V.)

To evaluate the efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over 75 years. A total of 82 patients with AF who underwent LAAO successfully in Beijing Anzhen Hospital from March 2014 to March 2019 were divided into two groups according to age: the elderly group (aged>75 years) and the young group (aged ≤75 years). Risk of perioperative complications and incidence of ischemic stroke and major bleeding during follow-up were retrospectively analyzed. The results showed that there were no significant differences in procedure-related ischemic stroke(0 vs.1.6%, P =0.768) and major bleeding (0 vs.1.6%, P =0.768) during perioperative period between the two groups. No complications as death or pericardial tamponade occurred in the two group. During a (25.9±15.9) months period of followed up, ischemic stroke event rate was 3.6/100 person-years in the elderly group and 4.9/100 person-years in the young group, respectively. Major bleeding event rate was 2.5/100 person-years in the elderly group and 0/100 person-years in the young group, respectively. Compared with the expected ones, the relative risk reduction (RRR) of stroke in the elderly group was more profound than that in the young group (32.0% vs. 25.0%), while the risk of major bleeding in the young group was significantly lower than that in the elderly group (RRR 100% vs. 56.9%). Therefore, LAAO might be suitable for stroke prevention in the elderly AF patients.

The pathophysiology of adverse events following programmed cell death protein 1 (PD-1) blockade, including tuberculosis (TB) and autoimmunity, remains poorly characterized. We studied a patient with inherited PD-1 deficiency and TB who died of pulmonary autoimmunity. The patient's leukocytes did not express PD-1 or respond to PD-1-mediated suppression. The patient's lymphocytes produced only small amounts of interferon (IFN)-γ upon mycobacterial stimuli, similarly to patients with inborn errors of IFN-γ production who are vulnerable to TB. This phenotype resulted from a combined depletion of Vδ2 + γδ T, mucosal-associated invariant T and CD56 bright natural killer lymphocytes and dysfunction of other T lymphocyte subsets. Moreover, the patient displayed hepatosplenomegaly and an expansion of total, activated and RORγT + CD4 - CD8 - double-negative αβ T cells, similar to patients with STAT3 gain-of-function mutations who display lymphoproliferative autoimmunity. This phenotype resulted from excessive amounts of STAT3-activating cytokines interleukin (IL)-6 and IL-23 produced by activated T lymphocytes and monocytes, and the STAT3-dependent expression of RORγT by activated T lymphocytes. Our work highlights the indispensable role of human PD-1 in governing both antimycobacterial immunity and self-tolerance, while identifying potentially actionable molecular targets for the diagnostic and therapeutic management of TB and autoimmunity in patients on PD-1 blockade., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: The effect of renin-angiotensin system inhibitors (RASIs) in patients with heart failure (HF) and atrial fibrillation (AF) remains unclear. This study aimed to investigate associations between RASI use and all-cause mortality and cardiovascular outcomes in patients with AF and HF., Methods: Using data from the China Atrial Fibrillation Registry study, we included 938 patients with AF and HF with a left ventricular ejection fraction <50%. Cox regression models for RASIs vs. non-RASIs with all-cause mortality as the primary outcome were fitted in a 1:1 propensity score-matched cohort. A sensitivity analysis was performed by using a multivariable time-dependent Cox regression model. As an internal control, we assessed the relation between β-blocker use and all-cause mortality., Results: During a mean follow-up of 35 months, the risk of all-cause mortality was similar in RASI users compared with non-users (hazard ratio: 0.92; 95% confidence interval: 0.67-1.26). Similar results were obtained in the sensitivity analysis. In contrast, β-blocker use was associated with significantly lower all-cause mortality in the same population., Conclusions: RASI use was not associated with better outcomes in patients with AF and HF in this prospective cohort, which raises questions about their value in this specific subset.Trail Registration: ChiCTR-OCH-13003729.

We have described a child suffering from Mendelian susceptibility to mycobacterial disease (MSMD) due to autosomal recessive, complete T-bet deficiency, which impairs IFN-γ production by innate and innate-like adaptive, but not mycobacterial-reactive purely adaptive, lymphocytes. Here, we explore the persistent upper airway inflammation (UAI) and blood eosinophilia of this patient. Unlike wild-type (WT) T-bet, the mutant form of T-bet from this patient did not inhibit the production of Th2 cytokines, including IL-4, IL-5, IL-9, and IL-13, when overexpressed in T helper 2 (Th2) cells. Moreover, Herpesvirus saimiri-immortalized T cells from the patient produced abnormally large amounts of Th2 cytokines, and the patient had markedly high plasma IL-5 and IL-13 concentrations. Finally, the patient's CD4+ αβ T cells produced most of the Th2 cytokines in response to chronic stimulation, regardless of their antigen specificities, a phenotype reversed by the expression of WT T-bet. T-bet deficiency thus underlies the excessive production of Th2 cytokines, particularly IL-5 and IL-13, by CD4+ αβ T cells, causing blood eosinophilia and UAI. The MSMD of this patient results from defective IFN-γ production by innate and innate-like adaptive lymphocytes, whereas the UAI and eosinophilia result from excessive Th2 cytokine production by adaptive CD4+ αβ T lymphocytes., Competing Interests: Disclosures: L.H. Glimcher reports "other" from GlaxoSmith Kline, Analog Devices, Bristol-Myers Squibb, and Waters Corporation; and personal fees from Repare Therapeutics, Kaleido Therapeutics, and Abpro Therapeutics outside the submitted work. No other disclosures were reported., (© 2021 Yang et al.)

T follicular helper (Tfh) cells cognately guide differentiation of antigen-primed B cells in secondary lymphoid tissues. 'Tfh-like' populations not expressing the canonical Tfh cell transcription factor BCL6 have also been described, which can aid particular aspects of B cell differentiation. Tfh and Tfh-like cells are essential for protective and pathological humoral immunity. These CD4 + T cells that help B cells are polarized to produce diverse combinations of cytokines and chemokine receptors and can be grouped into distinct subsets that promote antibodies of different isotype, affinity, and duration, according to the nature of immune challenge. However, unified nomenclature to describe the distinct functional Tfh and Tfh-like cells does not exist. While explicitly acknowledging cellular plasticity, we propose categorizing these cell states into three groups based on phenotype and function, paired with their anatomical site of action., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) recurrence is common in the 3-month blanking-period after catheter ablation, during which electrical cardioversion (ECV) is usually performed to restore sinus rhythm. Whether ECV can affect the clinical outcome of post-ablation AF patients is inconsistent, however. We aimed to explore the 1-year effect of ECV on AF recurrence and rehospitalization in patients experienced recurrence within 3-month after AF catheter ablation., Methods: Patients who experienced recurrence within 3-month after AF catheter ablation procedure were enrolled from the China Atrial Fibrillation Registry (China-AF). A 1:3 Propensity score matching (PSM) method was applying to adjust the confounders between patients who had been treated by ECV or not. Logistic regression models were conducted to evaluate the association of ECV with 1-year AF recurrence and rehospitalization., Results: In this study, 2961 patients experienced AF recurrence within 3-month after the procedure, and 282 of them underwent successful ECV, 2155 patients did not undergo ECV. One-year AF recurrence rates were 56.4% in ECV group versus 65.4% in non-ECV group (p = .003), and were 55.9% versus 65.9%, respectively, after PSM (adjusted odds ratio [OR] 0.66; 95% confidence interval (CI): 0.49-0.88, p = .005). However, the difference of 1-year rehospitalization rates between two groups were not statistically significant before (ECV group: 23.7% vs. non-ECV group: 22.3%, p = .595) and after PSM (ECV group: 24.4% vs. non-ECV group: 21.6%, adjusted OR1.14; 95% CI 0.81-1.62, p = .451)., Conclusions: Successful ECV was associated with lower rate of one-year recurrence in patients with early recurrent AF after catheter ablation., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections. While eight IL-21R-deficient patients have been reported previously, the natural course, immune characteristics of disease, and response to hematopoietic stem cell transplantation (HSCT) remain to be comprehensively examined. In our study, we have collected clinical histories of 13 patients with IL-21R deficiency from eight families across seven centers worldwide, including five novel patients identified by exome or NGS panel sequencing. Eight unique mutations in IL21R were identified in these patients, including two novel mutations. Median age at disease onset was 2.5 years (0.5-7 years). The main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients. Overall survival following HSCT (6 patients, mean follow-up 1.8 year) was 33.3%, with pre-existing organ damage constituting a negative prognostic factor. Mortality of non-transplanted patients (n = 7) was 57.1%. Our detailed analysis of the largest cohort of IL-21R-deficient patients to date provides in-depth clinical, immunological and immunophenotypic features of these patients, thereby establishing critical non-redundant functions of IL-21/IL-21R signaling in lymphocyte differentiation, humoral immunity and host defense against infection, and mechanisms of disease pathogenesis due to IL-21R deficiency. Outcome following HSCT depends on prior chronic infections and organ damage, which should thus be considered as early as possible following molecular diagnosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Catheter ablation is widely used in atrial fibrillation (AF) management. In this study, we are aimed to investigate the incidence of postprocedural cognitive decline in a larger population undergoing AF ablation under local anesthesia, and to evaluate the associated risk factors., Methods: This study included 287 patients with normal cognitive functions, with 190 ablated AF patients (study group) and 97 AF patients who are awaiting ablation (practice group). We assessed the neuropsychological function of each patient for twice (study group: 24 h prior to ablation and 48 h post ablation; practice group: on the day of inclusion and 72 h later but before ablation). The reliable change index was used to analyze the neuropsychological testing scores and to identify postoperative cognitive dysfunction (POCD) at 48 h post procedure. Patients in the study group accepting a 6-month follow up were given an extra cognitive assessment., Results: Among the ablated AF patients, 13.7% (26/190) had POCD at 48 h after the ablation procedure. Multivariable analysis revealed that, a minimum intraoperative activated clotting time (ACT) < 300 s (OR 3.82, 95% CI 1.48-9.96, P = 0.006) and not taking oral anticoagulants within one month prior to ablation(OR 10.35, 95% CI 3.54-30.27, P < 0.001) were significantly related to POCD at 48 h post-ablation. In 172 patients of the study group accepting a 6-month follow up, there were 23 patients with POCD at 48 h post-ablation and 149 patients without POCD. The global cognitive scores were decreased in 48 h post-operation tests (0 ± 1 vs - 0.15 ± 1.10, P < 0.001) and improved significantly at 6 months post-operation (0 ± 1 vs 0.43 ± 0.92, P < 0.001). In the 23 patients with POCD at 48 h after the procedure, global cognitive performance at 6 months was not significantly different compared with that at baseline (- 0.05 ± 1.25 vs - 0.19 ± 1.33, P = 0.32), while 13 of them had higher scores than baseline level., Conclusions: Incident of POCD after ablation procedures is high in the short term. Inadequate periprocedural anticoagulation are possible risk factors. However, most POCD are reversible at 6 months, and a general improvement was observed in cognitive function at 6 months after ablation., (© 2021. The Author(s).)

Designing photo-responsive host-guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo-responsive macrocyclic hosts, modulated by light-driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first-generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown-ether-like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host-guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi-state light-driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli-responsive host-guest systems and dynamic materials., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Prescribing patterns for stroke prevention in atrial fibrillation (AF) patients evolved with approval of non-Vitamin K antagonist oral anticoagulants (NOACs) over time., Objectives: To assess changes in anticoagulant prescription patterns in various geographical regions upon first approval of a NOAC and to analyze the evolution of oral anticoagulants (OACs) use over time in relation to CHA 2 DS 2 -VASc and HAS-BLED risk profiles., Methods: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation ( GLORIA-AF) Phases II and III reported data on antithrombotic therapy for patients with newly diagnosed AF and ≥1 stroke risk factor. We focused on sites enrolling patients in both phases and reported treatment patterns for the first 4 years after initial NOAC approval., Results: From GLORIA-AF Phases II and III, 27 432 patients were eligible for this analysis. When contrasting the first year with the fourth year of enrolment, the proportion of NOAC prescriptions increased in Asia from 29.2% to 60.8%, in Europe from 53.4% to 75.8%, in North America from 49.0% to 73.9% and in Latin America from 55.7% to 71.1%. The proportion of Vitamin K antagonists (VKAs) use decreased across all regions over time, in Asia from 26.0% to 9.8%, in Europe from 35.5% to 16.8%, in North America from 28.9% to 12.1%, and in Latin America from 32.4% to 17.8%. In the multivariable analysis, factors associated with NOAC prescription were as follows: enrolment year, type of site, region, stroke and bleeding risk scores, and type and categorization of AF., Conclusions: During 4 years after the approval of the first NOAC, NOAC use increased, while VKA use decreased, across all regions., Competing Interests: Dr Kozieł and Professor Rothman declare they have no conflict of interest. Dr Bayer, Gurusamy, and Dr Teutsch are employees of Boehringer Ingelheim. Dr Lu was employee of Boehringer Ingelheim at time of manuscript writing. Dr Diener has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, Bayer Vital, Bristol‐Myers Squibb (BMS), Boehringer Ingelheim, Daiichi‐Sankyo, Medtronic, Pfizer, Portola, Sanofi‐Aventis, and WebMD Global. Financial support for research projects was provided by Boehringer Ingelheim. Dr Diener chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. Professor Halperin has engaged in consulting activities with Boehringer Ingelheim, for advisory activities involving anticoagulants, and he is a member of the Executive Steering Committee of the GLORIA‐AF Registry. Professor Ma has received honoraria for lectures from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, BMS, Johnson & Johnson, and Pfizer. Professor Huisman reports grants from ZonMW Dutch Healthcare Fund, grants and personal fees from Boehringer Ingelheim, Pfizer‐BMS, Bayer HealthCare, Aspen, Daiichi‐Sankyo, outside the submitted work. Professor Lip: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi‐Sankyo. No fees are received personally., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent of revertant memory CD4 + T cells. T cell development is barely affected, and T cells respond to CD3 and CD2, but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactive CD4 + T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity., Competing Interests: Declaration of interests L.D.N. receives compensation as Chief Editor of Frontiers in Immunology. T.W. serves on advisory boards for MSD (Merck Sharp and Dohme). J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics. All other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Rapid, accurate identification of patients with acute myocardial infarction (AMI) at high risk of in-hospital major adverse cardiac events (MACE) is critical for risk stratification and prompt management. This study aimed to develop a simple, accessible tool for predicting in-hospital MACE in Chinese patients with AMI., Design: Retrospective review of deidentified medical records., Setting: 38 urban and rural hospitals across diverse economic and geographic areas in China (Beijing, Henan Province and Jilin Province)., Participants: 15 009 patients discharged from hospital with a diagnosis of AMI., Main Outcome Measure: The primary outcome was MACE occurrence during index hospitalisation. A multivariate logistic regression model (China AMI Risk Model, CHARM) derived using patient data from Beijing (n=7329) and validated with data from Henan (n=4247) and Jilin (n=3433) was constructed to predict the primary outcome using variables of age, white cell count (WCC) and Killip class. C-statistics evaluated discrimination in the derivation and validation cohorts, with goodness-of-fit assessed using Hosmer-Lemeshow statistics., Results: The CHARM model included age (OR: 1.06 per 1-year increment, 95% CI 1.05 to 1.07, p<0.001), WCC (OR per 10 9 /L increment: 1.10 (95% CI 1.07 to 1.13), p<0.001) and Killip class (class II vs class I: OR 1.34 (95% CI 0.99 to 1.83), p=0.06; class III vs class I: OR 2.74 (95% CI 1.86 to 3.97), p<0.001; class IV vs class I: OR 14.12 (95% CI 10.35 to 19.29), p<0.001). C-statistics were similar between the derivation and validation datasets. CHARM had a higher true positive rate than the Thrombolysis In Myocardial Infarction score and similar to the Global Registry of Acute Coronary Events (GRACE). Hosmer-Lemeshow statistics were 5.5 (p=0.703) for derivation, 41.1 (p<0.001) for Henan, and 103.2 for Jilin (p<0.001) validation sets with CHARM, compared with 119.6, 34.0 and 459.1 with GRACE (all p<0.001)., Conclusions: The CHARM model provides an inexpensive, accurate and readily accessible tool for predicting in-hospital MACE in Chinese patients with AMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In the last decade, unexpected high temperatures have been frequent in spring and early summer. Numerous studies have shown that such thermal stress has substantial effects on life-history traits that influence fitness of insects, but few have examined expression dynamics of heat shock proteins (Hsps) across developmental stages, especially as regards potential carry-over effects at the transcriptional level across metamorphosis. We exposed pupae of the oriental fruit moth ("OFM," Grapholita molesta Busck) to mild heat stress (38°C, 6 h) and then quantified expression patterns of six Hsps (Hsp90, 70, 60, 40, 21, and 11) from pupal through adult stages. Almost all Hsps showed a higher expression immediately after pupae were heat-stressed, but later dropped to normal levels after metamorphosis. Although upregulation of Hsps is transient and the effects carry over longer to early adult stage, upregulation will nonetheless have positive effects on adult fitness. The fitness of some insects may benefit from higher expression of chaperon genes after mild stress, in the form of higher fecundity and longer lifespan, as a carry-over effect. These results suggest that mild thermal stress can change genetic expression that later boosts adult fitness through a cascade effect., (© 2021 Wiley Periodicals LLC.)

Purpose of Review: Stroke is an uncommon cause of amnesia. We describe in detail 3 cases of anterograde amnesia and confabulation secondary to acute ischemic stroke and review the available literature., Recent Findings: In our case series, all 3 patients presented with anterograde amnesia and 2 of 3 copresented with prominent confabulation. These symptoms were recognized in delayed fashion, and no patients received IV tissue plasminogen activator (tPA). Although stroke infarct topology was variable, all 3 patients had infarction of the fornix. Long-term follow-up was obtained in 2 of 3 patients: both had persistent memory impairment and were no longer functionally independent., Summary: Acute onset anterograde amnesia and confabulation may uncommonly represent acute ischemic stroke. Delays in this diagnosis typically exclude patients from emergent stroke treatment or timely diagnostic stroke evaluation. Clinicians should maintain a high degree of suspicion for ischemic stroke in this setting, especially in patients with comorbid vascular risk factors. Memory impairment secondary to ischemic stroke can produce considerable long-term disability., (© 2021 American Academy of Neurology.)

Background: Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients., Methods: From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score)., Results: Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%)., Conclusion: In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making., Trial Registration: www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729)., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n =123), ASP under X-ray alone (X-ray group, n =118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA 2 DS 2 -VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% ( n =138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% ( n =135), and the ratio of repeat ablation was 17.8% ( n =43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P =0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P <0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P <0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P =0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P =0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.

Diabetes is the most important comorbidity of cardiovascular disease, and cardiovascular disease is the main cause of mortality and disability of patients with type 2 diabetes. In order to standardize the diagnosis and treatment of patients with diabetes and cardiovascular disease, the National Health Commission Capacity Building and Continuing Education Center organized the experts from the field of cardiology and endocrinology systematically reviewing the research progresses and expert experiences of relevant disciplines from home and abroad, and formulated this consensus. This consensus covers the diagnosis, drug treatment, and risk factor management for patients with diabetes and cardiovascular disease (including atherosclerotic cardiovascular disease and heart failure) from the perspective of cardiovascular disease and diabetes management aiming to strengthen the comprehensive management of patients and ultimately to improve the prognosis of patients. The management of cardiovascular diseases mainly includes the management of blood pressure, blood lipids, anti-thrombosis, anti-myocardial ischemia, anti-ventricular remodeling and so on. Diabetes management mainly includes lifestyle intervention (including diet, exercise, weight loss, etc.), anti-hyperglycemia therapy (including drugs and insulin), blood glucose monitoring, and hypoglycemic prevention. In addition, specific clinical recommendations are given to patients with special health care needs such as diabetic nephropathy, elderly (>75 years), and cardiovascular critical illness.

Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The quality of care presented to AF cases in tertiary and non-tertiary hospitals in China remains obscure and needs further investigation. Therefore, we examined the compliance with quality measures (QMs) and clinical performance measures (PMs) that were proposed by the ACC/AHA in 2016 in a Chinese adult population with nonvalvular atrial fibrillation (AF). We also investigated the changes in patients' characteristics, treatment plans, and quality of provided care at different time-points [2011-2016]., Methods: We used the datasets from two registry-based studies in Beijing, including the Chinese Atrial Fibrillation Registry (CHINA-AF) investigation. From August 2011 to July 2016, an overall number of 13,439 nonvalvular AF cases were included. Our primary outcome was to determine the compliance rate with two PMs [oral anticoagulant (OAC) use and prothrombin time international normalized ratio (INR)] and six QMs (beta-blocker, ACEI-ARB, and the inappropriate prescription of antiarrhythmic drugs, Sotalol, antiplatelet and OAC, and non-dihydropyridine calcium channel antagonist) over a period of 5 years [2011-2016]. Also, the difference in compliance between tertiary and non-tertiary hospitals was investigated., Results: The compliance with PMs and QMs was variable between tertiary and non-tertiary hospitals. In tertiary hospitals, the total number of inpatient beds was >500, and each bed was equipped with >1.03 health technical personnel and >0.4 nurses. In non-tertiary hospitals, the available beds capacity was <500, and each bed corresponded with 0.7-0.88 health technical personnel and >0.4 nurses. The compliance rates with OAC use steadily increased from 2011-2015 in tertiary hospitals (35%, 35.9%, 37.9%, 45%, and 49%, P<0.001). In non-tertiary hospitals, INR follow-up of warfarin use increased significantly over the years, with rates of 36.2%, 60.5%, 71.6%, 64.3%, and 81.5% (P=0.04), respectively. In terms of QMs, the compliance with the six measure sets was quite similar among tertiary and non-tertiary hospitals avoiding any significant difference over the years (P>0.05)., Conclusions: We noted an improvement in medical quality regarding the use of OAC, especially in tertiary hospitals. Meanwhile, the compliance rates of INR follow-up improved in non-tertiary hospitals. However, the compliance rates of other performance and QMs are still low, which are in need of improvement.

Although climate warming can increase both mean temperature and its variability, it is often the effects of climate warming on short periods of extreme temperatures that are expected to have particularly large physiological and ecological consequences. Understanding the vulnerability of organisms at various latitudes to climate extremes is thus critical for understanding warming effects on regional biodiversity conservation and ecosystem management. While previous studies have shown that thermal responses depend on temperature regimes that organisms have previously experienced, this issue has not been considered much when comparing the effects of temperature extremes at different latitudes. To fill this gap, here we manipulated different combinations of amplitude and duration of daily high temperature extremes to simulate conditions at different latitudes. We tested the effects of those regimes on life-history traits and fitness of a globally-distributed aphid species, Rhopalosiphum padi. We compared our results with previous studies to better understand the extent to which these regimes affect conclusions based on comparisons under different mean temperatures. As a consequence of asymmetrical thermal performance curves, we hypothesized that the temperature regimes with higher daily maximum temperatures at higher latitudes would cause strong negative effects. Our results showed that these regimes with thermal extremes caused substantial decreases in life-history traits and fitness relative to the predictions from different mean temperatures. Specifically, the regime with higher daily maximum temperature reflecting a higher mid-latitude location had larger impacts on development, reproduction and population fitness than the regime representing a lower mid-latitude location. These findings have implications for understanding the vulnerability of organisms across latitudes to increasingly frequent extreme heat events under ongoing climate warming., (Copyright © 2021. Published by Elsevier Ltd.)

Up to 15% of individuals with a clinical phenotype of type 1 diabetes (T1D) do not have evidence of seropositivity for pancreatic islet autoantibodies. On this basis, they are classified as nonimmune or idiopathic, and remain an understudied population, as they are excluded from T1D immunomodulatory trials. Our limited understanding of the disease aetiopathogenesis in autoantibody-negative T1D hinders our ability to improve diagnostic pathways and discover novel therapeutic agents; particularly as we progress towards an era of precision medicine. This review summarises the current understanding and challenges in studying autoantibody-negative T1D. We review the literature regarding T1D classification, and the role of autoimmunity and defects in the immunogenic pathway that may distinguish autoantibody-positive and -negative T1D., Competing Interests: Declaration of Interests There are no interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To investigate the causes of death and predictors in patients with nonvalvular atrial fibrillation (AF) undergoing anticoagulation therapy. Methods: Consecutive anticoagulated nonvalvular AF patients were recruited from the China Atrial Fibrillation Registry (China-AF) Study from August 2011 to December 2018. After exclusion of patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, or loss of follow-up within 1 year, 2 248 patients were included in this analysis. Enrolled patients were followed up were followed up for 3 and 6 months, and then every 6 months. The primary endpoint was death, including cardiovascular death, non-cardiovascular death and undetermined death. The patients were divided into survival group and death group according to the survival status after follow-up. Clinical information such as age and sex was collected. Cox proportional hazards regression was performed to identify associated risk factors for all-cause mortality, and Fine-Gray competing risk model was used to identify associated risk factors for cardiovascular mortality. Results: A total of 2 248 patients with atrial fibrillation receiving anticoagulant therapy died over a mean follow-up of (42±24) months, mean age was (67±10) years old and 41.1% (923/2 248) patients were female. The mortality rate was 2.8 deaths per 100 patient-years. The most common cause of death was cardiovascular deaths, accounted for 55.0% (120/218). Worsening heart failure was the most common cause of cardiovascular deaths (18.3% (40/218)), followed by bleeding events (12.9% (28/218)) and ischemic stroke (8.7% (19/218)). Multivariate Cox regression analysis showed that age ( HR = 1.05, 95% CI 1.04-1.07, P <0.001), anemia ( HR = 1.81, 95% CI 1.02-3.18, P = 0.041), heart failure ( HR =2.40, 95% CI 1.75-3.30, P <0.001), ischemic stroke/transient ischemic attack (TIA)( HR = 1.59, 95% CI 1.21-2.13, P = 0.001) and myocardial infarction ( HR = 2.93, 95% CI 1.79-4.81, P <0.001) were independently associated with all-cause death. Fine-Gray competing risk model showed that age ( HR =1.05, 95% CI 1.02-1.08, P <0.001), heart failure ( HR =2.81, 95% CI 1.79-4.39, P <0.001), ischemic stroke/TIA ( HR =1.50, 95% CI 1.02-2.22, P =0.041) and myocardial infarction ( HR =3.31, 95% CI 1.72-6.37, P <0.001) were independently associated with cardiovascular death. Conclusions: In anticoagulated nonvalvular AF patients, ischemic stroke represents only a small subset of deaths, whereas worsening heart failure is the most common cause of cardiovascular deaths. Heart failure, ischemic stroke/TIA, and myocardial infarction are associated with increased mortality.

Background: Patients with AF often have multimorbidity (the presence of ≥2 concomitant chronic conditions)., Objective: To describe baseline characteristics, patterns of antithrombotic therapy, and factors associated with oral anticoagulant (OAC) prescription in patients with AF and ≥2 concomitant, chronic, comorbid conditions., Methods: Phase III of the GLORIA-AF Registry enrolled consecutive patients from January 2014 through December 2016 with recently diagnosed AF and CHA2DS2-VASc score ≥1 to assess the safety and effectiveness of antithrombotic treatment., Results: Of 21,241 eligible patients, 15,119 (71.2%) had ≥2 concomitant, chronic, comorbid conditions. The proportions of patients with multimorbidity receiving non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKA) were 60.2% and 23.6%, respectively. The proportion with paroxysmal AF was 57.0% in the NOAC group and 45.4% in the VKA group. Multivariable log-binomial regression analysis found the following factors were associated with no OAC prescription: pattern of AF (paroxysmal, persistent, or permanent), coronary artery disease, myocardial infarction, prior bleeding, smoking status, and region (Asia, North America, or Europe). Factors associated with OAC prescriptions were age, body mass index, renal function, hypertension, history of cerebral ischemic symptoms, and AF ablation., Conclusion: Multimorbid AF patients prescribed NOACs have fewer comorbidities than those prescribed VKAs. Age, AF pattern, comorbidities, and renal function are associated with OAC prescription., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Dr. Teutsch, Sabrina Marler, and Venkatesh K. Gurusamy are paid employees of Boehringer Ingelheim. Dr. Lu was a paid employee of Boehringer Ingelheim at the time that the manuscript was written. Professor Halperin has engaged in consulting activities for Boehringer Ingelheim and advisory activities involving anticoagulants, and he is a member of the Executive Steering Committee of the GLORIA-AF Registry. Over the past 3 years, Professor Diener received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from: Abbott, Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Pfizer, Portola, Sanofi-Aventis, and WebMD Global. Financial support for research projects was provided by Boehringer Ingelheim. He received research grants from the German Research Council (DFG), German Ministry of Education and Research (BMBF), European Union, NIH, Bertelsmann Foundation, and Heinz-Nixdorf Foundation. Professor Ma received honoraria from Bristol-Myers Squibb, Pfizer, Johnson & Johnson, Boehringer Ingelheim, Bayer, and AstraZeneca for giving lectures. Professor Huisman reports grants from ZonMW Dutch Healthcare Fund, grants and personal fees from Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, Bayer Health Care, Aspen, Daiichi Sankyo, outside the submitted work. Professor Lip has been a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi Sankyo. He has been a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi Sankyo. No fees directly received personally. These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. Dr Kozieł and Professor Rothman declare no competing interests.

Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta-analysis was to investigate the association between anti-HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random-effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta-analysis. Among those, four studies reported on any CVD between anti-HCV-treated and anti-HCV-untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50-0.83), CAD (HR = 0.73, 95% CI: 0.55-0.96) and stroke (HR = 0.74, 95% CI: 0.64-0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non-SVR (HR = 0.74, 95% CI: 0.60-0.92). In conclusion, this meta-analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR., (© 2021 John Wiley & Sons Ltd.)

Objective: The aim of this study was to explore the relationship between arrhythmia-associated or electrocardiogram (ECG)-associated common variants and PR interval, QRS duration, QT corrected , and heart rate in a Chinese cohort., Methods: We studied the association between 26 single-nucleotide polymorphisms (SNPs) and digital ECG data from 379 unrelated Han Chinese individuals collected in an epidemiological survey in Beijing. All subjects were 45 years of age or older and were free of cardiovascular diseases and diabetes. The SNPs were genotyped in a multiplex panel using the Sequenom MassARRAY platform., Results: Missense variant T66A (Thr66Ala, rs4074536) of the CASQ2 gene, which was previously reported to be associated with QRS complex in European populations, was significantly associated with PR interval prolongation in our sample (p adjusted  = 0.006, beta adjusted  = 3.983 ms). A two-tailed t test showed that the CC genotype (n = 86) had a significantly longer PR interval (162.9 ± 19.4 ms) than the non-CC genotypes (n = 288, PR interval: 154.6 ± 20.9 ms), with a remarkable difference of 8.2 ms between the groups (p = 0.001). Interestingly, this association between T66A of CASQ2 and PR interval was more evident in females (p adjusted  = 0.007, beta adjusted  = 5.723 ms) than in males (p adjusted  = 0.177, beta adjusted  = 2.725 ms). In addition, rs3822714 in the HAND1 locus might be associated with QRS duration (p adjusted  = 0.034, beta adjusted  = -2.268 ms)., Conclusion: We identified a novel signal of an association between the CC genotype of T66A in CASQ2 and PR interval prolongation in a Chinese population, particularly in females. This association deserves further exploration given its possible effects on calcium handling in cardiac electrophysiology.

Aims: This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing., Methods and Results: This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in-hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra-hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65-80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61-79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of β-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10-3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02-2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63-3.52, P = 0.368)., Conclusions: Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved satisfactory clinical effects in the therapy of non-small cell lung cancer (NSCLC), but acquired resistance limits their clinical application. NRF2 has been shown to enhance the resistance to apoptosis induced by radiotherapy and some chemotherapy. In this study, we investigated the role of NRF2 in resistance to EGFR-TKIs. We showed that NRF2 protein levels were markedly increased in a panel of EGFR-TKI-resistant NSCLC cell lines due to slow degradation of NRF2 protein. NRF2 knockdown overcame the resistance to EGFR-TKIs in HCC827ER and HCC827GR cells. Furthermore, we demonstrated that NRF2 imparted EGFR-TKIs resistance in HCC827 cells via upregulation of GPX4 and SOD2, and suppression of GPX4 and SOD2 reversed resistance to EGFR-TKIs. Thus, we conclude that targeting NRF2-GPX4/SOD2 pathway is a potential strategy for overcoming resistance to EGFR-TKIs.

Objective: To define the current status and analyze the medical quality of interventional therapy for patients with atrial fibrillation (AF) in China. Methods: This survey was performed in all seven large regions of China, one to three regional major medical centers were selected from each region. Medical records of patients underwent interventional therapy for AF in the year 2017 were randomly inspected. CHA 2 DS 2 -VASc score, prescribed anticoagulant after ablation, indication of left atrial appendage occlusion (LAAO), and complications in the medical records were analyzed. Results: A total of 10 800 AF catheter ablations and 447 LAAOs were performed in 17 regional medical centers in 2017. There were 10/17 centers performing AF catheter ablation<500 cases and 7/17 centers performing LAAO<20 cases. A total of 1 347 cases of catheter ablation and 160 cases of LAAO were selected for further analysis. Among all selected cases, 15.8% (238/1 505) non-valvar AF cases recorded CHA 2 DS 2 -VASc scores. The anticoagulation rate after AF catheter ablation was 98.6% (1 328/1 347), anticoagulation rate was higher than 90% in 16 out of 17 centers. The complication and severe complication rates of AF catheter ablation were 0.9% (12/1 347) and 0.4% (5/1 347), respectively. The differences of complication and severe complication rates in AF catheter ablation were similar between centers performing<500 cases and centers performing ≥500 cases (0.5% (2/413) vs. 1.1% (10/934), P >0.05; 0.5% (2/413) vs. 0.3% (3/934), P >0.05). The coincidence rate of LAAO indication was 81.3% (130/160), and the rate was higher in center performing ≥20 cases than in centers performing<20 cases (84.8% (106/125) vs. 68.6% (24/35), P <0.05). The complication and severe complication rates of LAAO were 3.1% (5/160) and 1.9% (3/160). The rate of complications in LAAO was higher in center performing<20 cases than in centers performing ≥20 cases (8.6% (3/35) vs. 1.6% (2/125), P <0.05), and there was no significant difference in severe complication rate (5.7% (2/35) vs. 0.8% (1/125), P >0.05). Conclusions: Interventional therapy for AF in China is generally standardized and safe. The overall incidence of complications post AF interventional ablation is low, the anticoagulation rate after AF catheter ablation is high, and the adherence rate of LAAO indication is fair. The indicators mentioned above vary widely among centers.