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Background Brugada syndrome is a major cause of sudden cardiac death in young people with a distinctive electrocardiogram (ECG) feature. We aimed to develop a deep learning-enabled ECG model for automatic screening Brugada syndrome to identify these patients at an early time, thus allowing for life-saving therapy. Methods A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was further validated in the independent ECG dataset, collected from the hospitals in Taiwan and Japan. Results The diagnoses by the deep learning model (AUC: 0.96, sensitivity: 88.4%, specificity: 89.1%) were highly consistent with the standard diagnoses (Kappa coefficient: 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity: 86.0%, specificity: 90.0%). Conclusions We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivaling trained physicians.

Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24–3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

BACKGROUND Extramedullary plasmacytoma (EMP), a variant form of myeloma, is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3% of all plasma cell tumors. EMP can affect various tissues and organs, about 90% of which is found in the head and neck. However, EMP in the reproductive organs is rare, and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings. CASE SUMMARY Herein, we report a case with coexistence of EMP and squamous cell carcinoma in the cervix. The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP. Both ultrasound and pelvic enhanced magnetic resonance imaging (MRI) indicated that there was a tumor in the cervix. Thus, another cervical biopsy and pathological examination were performed, which indicated EMP combined with squamous cell carcinoma. Then, the patient underwent extensive total hysterectomy (type C1) + systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery. During 2-year follow-up, no recurrence was reported. CONCLUSION In conclusion, EMP involving the reproductive system is relatively rare. In this case, MRI, B-ultrasound, and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma. The patient had improved prognosis after appropriate treatments.

Background Choriocarcinoma is a highly malignant trophoblastic tumor. However, the awareness surrounding its atypical clinical presentation is insufficient. The presence of a solitary lung lesion without uterine lesions often leads to misdiagnosis or missed diagnosis, which in turn causes delayed treatment or even multiple metastases throughout the body. Case presentation We present the case of a 36-year-old female patient who was misdiagnosed with a lung abscess and received suboptimal anti-infective treatment. She then underwent left upper lobectomy and was misdiagnosed with lung cancer by abscess incision and drainage in thoracic surgery, however, the results after pleural effusion removal were suboptimal. During this time a breast nodule was found, and a large segment of the right breast was excised and misdiagnosed as breast cancer but was finally diagnosed as choriocarcinoma with multiple metastases of lung and breast. Multiple metastases were also detected in the head, liver, kidney, and bones. The patient underwent multiple adjuvant chemotherapies. The blood β-hCG level gradually declined to normal. When we reported this case, that is, seven months after the diagnosis, the patient was still alive, and the disease was stable without progress. Conclusion Choriocarcinoma with a solitary lung lesion as the first presentation and no lesions in the uterus is clinically rare. This may lead to a delay in diagnosis due to poor awareness of the disease and the appearance of multiple metastases throughout the body. Clinicians should be more aware of choriocarcinoma with an atypical presentation to reduce misdiagnosis and missed diagnosis.

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end‐stage renal disease (ESRD) (eGFR

BACKGROUND A recent study suggested to develop and implement more interacted material for preprocedural education to decrease patients' anxiety about the atrial fibrillation (AF) ablation. This study compared the effectiveness of using either newly developed virtual reality (VR) materials (VR group) or paper-based materials (paper group) on giving AF preprocedural education. METHODS This study consequentially enrolled 33 AF patients preparing for ablation from November 2019 to October 2020. After enrollment, patients were randomized as either paper (n = 22) or VR (n = 11) groups. RESULTS In comparison with the baseline stage, at the posteducation stage, the degree of improvement in patients' self-assessed self-efficacy on AF ablation knowledge was higher among VR group patients than those in the paper group. At the posteducation stage, the patients' satisfaction to preprocedural education and used materials were higher among the VR group than that among the paper group. In addition to meet their needs and give accurate medical information, VR group patients reported that VR materials increased the effectiveness of education, increased their preparedness for AF catheter ablation, achieved paperless purposes, and willing to recommend VR materials to others. Operators subjectively reported that the periprocedure cooperation was increased both among paper and VR group patients after preprocedural education for the details of procedure. Better preparedness of VR group patients was supported by less periprocedure pain, anxiety, and impatience than those among paper group patients. CONCLUSION Interactive VR-based materials are superior to the paper-based materials to provide patients immerse and imagine the journey and detail knowledge of AF catheter ablation before the procedure and better prepared patients for the procedure.

Introduction The efficacy of stereotactic body radiation therapy (SBRT) as an alternative treatment for recurrent ventricular tachycardia (VT) is still unclear. This study aimed to report the outcome of SBRT in VT patients with nonischemic cardiomyopathy (NICM). Methods The determination of the target substrate for radiation was based on the combination of CMR results and electroanatomical mapping merged with the real-time CT scan image. Radiation therapy was performed by Flattening-filter-free (Truebeam™) system, and afterward, patients were followed-up for 13.5±2.8 months. We analyzed the outcome of death, incidence of recurrent VT, ICD shocks, anti-tachycardia pacing (ATP) sequences, and possible irradiation side-effects. Results A total of 3 cases of NICM patients with anteroseptal scar detected by CMR. SBRT was successfully performed in all patients. During the follow-up, we found that VT recurrences occurred in all patients. In one patient, it happened during a 6-week blanking period, while the others happened afterward. Re-hospitalization due to VT only appeared in one patient. Through ICD interrogation, we found that all patients have reduced VT burden and ATP therapies. All of the patients died during the follow-up period. Radiotherapy-related adverse events did not occur in all patients. Conclusions SBRT therapy reduces the number of VT burden and ATP sequence therapy in NICM patients with VT, which had a failed previous catheter ablation. However, the efficacy and safety aspects, especially in NICM cases, remained unclear. This article is protected by copyright. All rights reserved.

Objectives This study aimed to assess the comparative efficacy of 4 ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3-year follow-up in patients with persistent AF. Background The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear. Methods Patients with persistent AF were enrolled consecutively to undergo each of 4 ablation strategies: (a) Group 1 (Gp 1, n=69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n=75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n=42), PVI plus elimination of complex fractionated atrial electrograms; (d) Gp 4 (n=67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model. Results Baseline characteristics were similar across the 4 groups. At a follow-up period of 34.9±38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other 3 groups (p=0.002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p=0.006). Independent predictors of recurrence of AF were the ablation strategy (p=0.002) and left atrial diameter (LAD) (p=0.01). Conclusion In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared to the other strategies. Both ablation strategy and baseline LAD predicted the 3-year outcomes of freedom from AT/AF This article is protected by copyright. All rights reserved.

To evaluate the performance of low b-value diffusion-weighted imaging (DWI) for detection of inflamed vessels in active Takayasu arteritis (TA).Forty patients with active TA involving the thoracic aorta and its super-aortic branches underwent low b-value (50 s/mmThe overall image quality of DEI, DWI, and T2WI was scored 7.97 ± 1.15, 7.32 ± 1.73, and 6.51 ± 1.69 respectively. The score of DEI and DWI was higher than that of T2WI (p0.001). The quality of blood suppression was rated higher in DWI than T2WI and DEI (p0.001). Both the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the diseased vessel walls measured on DEI and DWI were significantly higher than those on T2WI (p0.001). However, there was no significant difference in SNR and CNR between DEI and DWI (p = 0.283 and 0.063). In detection of mural inflammation, significant advantage was observed when comparing the findings from DEI/DWI to those from T2WI (p0.001). But no significant difference was found between the findings of DWI and DEI (p0.99).Low b-value DWI may be used as a promising alternative to DEI for detecting inflamed vessels in active TA.• Currently, the most widely used imaging modality in detection of mural inflammation is contrast-enhanced MRI. • Low b-value DWI is shown comparable to contrast-enhanced MRI and superior to T2WI in identifying mural inflammation in patients with active Takayasu arteritis. • Low b-value DWI is a fast and unenhanced MRI technique which may potentially replace contrast-enhanced MRI in identifying disease activity of Takayasu arteritis.

Introduction A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of ECG features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown. Methods Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0-51.0] years; 25 men], including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada-like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12-lead ECGs recorded from the 2nd , 3rd , and 4th intercostal spaces (ICS) before and at 1, 6, 12, 18, 24 hours after DPT (oral flecainide 400 mg) were analyzed. Results The total amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT was significantly lower in patients with history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT than in those without unstable VAs (0.28[0.18-0.41] mV vs. 0.08[0.01-0.15] mV, p=0.01). A multivariate analysis revealed that the amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT and the ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT were associated with history of unstable VA. Conclusion Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification. This article is protected by copyright. All rights reserved.

Objective To investigate the influences of non–vitamin K antagonist oral anticoagulants (NOACs) on rates of initiations of oral anticoagulants (OACs) and outcomes among elderly patients with atrial fibrillation (AF). Methods From January 1, 2009, to December 31, 2015, 33,539 newly-diagnosed AF patients older than 85 years old who survived more than 180 days after AF diagnosis were studied. Temporal trends regarding OAC initiation rates after incident AF were analyzed. The 1-year risks of ischemic stroke, intracranial hemorrhage, and mortality of incident AF patients diagnosed each year were compared with that of the year 2009. Results Initiation rates of OACs after AF was newly diagnosed in the elderly significantly increased from 9.5% to 34.3%, mainly due to the introduction of NOACs (from 0% to 26.2%). Several clinical factors were associated with OACs underuse, including chronic obstructive pulmonary disease, abnormal renal function, anemia, and history of bleeding. Compared with year 2009 (incidence rate, 5.55%/year), the 1-year risk of ischemic stroke after AF diagnosis decreased in the era of NOACs (incidence rate, 4.20%/year; adjusted hazard ratio [aHR], 0.748 in year 2012; 4.39%/year, aHR, 0.789 in 2014; 2.75%/year; aHR, 0.513 in year 2015; all P Conclusion Initiation rates of OACs after AF was newly diagnosed in the elderly significantly increased following the introduction of NOACs. A lower risk of ischemic stroke, mortality, and composite adverse events was observed, which was temporally associated with the increasing prescription rates of OACs.

Background A discordant biological clock could potentially induce sudden cardiac death (SCD). We aimed to evaluate the circadian change of heart rate variability (HRV) and its relationship to the risks of ventricular arrhythmia (VA) and near syncope in patients with chronic kidney disease (CKD). Methods In this retrospective study, non-CKD and CKD patients were enrolled and underwent a 24-hour Holter examination for linear and nonlinear HRV analyses. The multiscale entropy (MSE) method was selected for nonlinear HRV analyses. The documented VAs or episodes of near syncope were classified as high-risk SCD group (n = 8) and others as low-risk SCD group (n = 21). Results In linear analyses, time and frequency domains revealed no significant difference between groups. In nonlinear analyses with MSE, MSE5, MSE6–20, and MSEslope 5 were significantly lower (p = 0.002, p Conclusions Nonlinear analysis with MSE demonstrated the loss of circadian change in CKD patients and was associated with a higher risk for VAs and near syncope. The MSE method demonstrated the diurnal change of rhythm dynamics which identifies potential autonomic dysfunction leading to poor prognosis.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P

Purpose Our research aimed to investigate the expression level of circ_0002232, which is transcribed from PTEN, and find out the association of circ_0002232/miR-92a-3p/PTEN network in acute myeloid leukemia (AML). Methods Circ_0002232 expression in 115 AML patients and 48 controls was detected by using real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of circ_0002232 for overall survival. Associated network of circ_0002232 was predicted by using interaction prediction websites. Results Compared with controls, circ_0002232 was notably low-expressed in AML (P

Reports concerning clinical characteristics of cor triatriatum and approaches for catheter ablation of complex atrial tachyarrhythmias remain limited. Here, we describe successful catheter ablation treatments for complex atrial tachyarrhythmias in patients with cor triatriatum and address the clinical caveats. Demographic characteristics, electrophysiologic findings, and ablation results in four patients with cor triatriatum were described. Catheter ablation was performed in four patients with cor triatriatum (three sinister and one dexter) and complex atrial arrhythmias (three with persistent atrial fibrillation (AF) and one with atypical left atrial flutter). A transseptal puncture was selectively directed into the accessory compartment containing the pulmonary veins. A comprehensive preview involving transthoracic echocardiography, transesophageal echocardiography, and computed tomography of the pulmonary veins was critical for proper positioning of ablation catheters. The pulmonary veins remain the major triggers or initiators for AF, and four pulmonary vein isolation procedures were sufficient to achieve successful results with negative inducibility test in the patients with AF. Heterogeneous conduction and complex fractionated signals were observed on the fibromuscular membrane. Atypical flutter was terminated during ablation over the connection between membrane and left atrial roof. The procedure was successfully performed on all patients without complications. No acute recurrences of atrial tachyarrhythmias were observed in any of the patients during short-term follow-up. Catheter ablation is a feasible and efficient therapeutic strategy for treating complex atrial tachyarrhythmias in patients with cor triatriatum. Atrial remodeling due to anatomical obstruction or heterogeneous conduction of the fibromuscular membrane may serve as an arrhythmic substrate.

The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.

This study aimed to investigate the electromechanical function detected by acoustic cardiography before and after radiofrequency ablation therapy (RFA) in paroxysmal AF (PAF) patients with preserved left ventricular ejection fraction (LVEF). Seventy-five symptomatic PAF patients and 69 patients without arrhythmia were enrolled. Thirty-seven PAF patients received RFA therapy. Acoustic cardiographic exam was performed to check S3 and S4 heart sound, electromechanical activation time (EMAT), LV systolic time percentage (LVST), and systolic dysfunction index (SDI) in all participants. Furthermore, 37 PAF patients also received follow-up acoustic cardiography postRFA. PAF had impaired electromechanical systolic function compared with health participants (%EMAT 14.69 ± 3.62 vs. 10.84 ± 2.62; %LVST 40.83 ± 5.14 vs. 36.70 ± 3.87; SDI 4.75 ± 1.61 vs. 3.26 ± 0.96 all p

Commonly used tools to assess the probability of obstructive-coronary artery disease (CAD) were derived based on Caucasian cohorts, with their performance in China is still unknown. Furthermore, most were established based on non-laboratory variables, contributing to the limited predictive ability to some extent. Thus, we developed and internally validated a laboratory-based model with data from a Chinese cohort of 8963 inpatients, with suspected stable chest pain, referred to catheter-based coronary angiography (CAG) from September 2007 to April 2019, and then compared the present model's performance with the four most commonly used prediction tools, Coronary Artery Disease Consortium 1/2 Score (CAD1/2), Duke clinical score (DCS), and Diamond-Forrester score (DF). The final model was developed by random forest method, including 8 predictors derived from 70 variables. Five-fold cross-validation was performed to evaluate the model's prediction accuracy. In the external validation set, the present model showed a superior area under the receiver-operating curve (0.816), followed by DCS (0.66), CAD2 (0.61), CAD1 (0.59) and at last DF (0.58), respectively. Furthermore, the present model correctly classified 74.4% of obstructive-CAD patients as high-risk, and correctly classified more than one third of non-obstructive-CAD patients as low-risk. The present model's net reclassification improvement (NRI) showed a significant positive reclassification over CAD1 (NRI = 0.60, P < 0.001), DF (NRI = 0.59, P < 0.001), CAD2 (NRI = 0.57, P < 0.001), and DCS (NRI = 0.43, P < 0.001). Decision curve analysis demonstrated that the present model provided a larger net benefit compared with CAD1/2, DCS, and DF. In conclusion, the novel model, using 8 laboratory and non-laboratory variables, performed well in risk stratifying patients with suspected chest pain regarding the presence of obstructive-CAD in the present Chinese cohort.

Resistin is an adipocytokine that is abundantly secreted from lipid cells and is related to the inflammatory process and cardiometabolic diseases. This study aimed to examine the role of resistin on inflammation and its effect on the clinical outcome of patients with atrial fibrillation (AF) following catheter ablation.A total of 108 patients (56.9 ± 12.0 years, 76.8% male) with symptomatic and drug-refractory AF undergoing catheter ablation were enrolled. Inflammatory biomarkers and epicardial fat volume by contrast computed tomography (CT) images were assessed in all patients before the procedure. Baseline resistin correlated with epicardial fat volume, tumor necrosis factor-α (TNF-α), and left atrial (LA) scar area. After the index procedure, the univariate analysis revealed that hypertension, persistent AF, LA diameter, and plasma resistin level were related to recurrent atrial arrhythmia. Multivariate regression analysis revealed that persistent AF, LA diameter, and plasma resistin level all independently predicted recurrent atrial arrhythmia after ablation. Plasma resistin with a level higher than 777 (pg/mL) could predict recurrence following catheter ablation of AF.High plasma resistin level is associated with poor left atrial substrate, high epicardial fat volume, and elevated TNF-α level in patients with AF. Plasma resistin may predict the recurrence of atrial arrhythmia after ablation.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and serious disorder among children. Video games have shown potential for aiding in child healthcare. Video games could contribute to the assessment and management of ADHD, but there are no previous reviews on this topic. Here, we systematically review the evidence about video game-based assessment tools and interventions for children diagnosed with ADHD. This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The review protocol was registered in PROSPERO database. We searched four databases-PubMed, PsycInfo, Embase and clinicaltrials.gov-to identify original studies exploring either video game-based interventions or video game-based assessment tools in children with ADHD. After initial screening, full text revision and study selection, 22 articles were finally included in the review. Most studies used PC as platform, with a minority using a video console, pad, or 3D device. Video game-based assessment tools were generally effective in discriminating ADHD cases from controls, and in discriminating between ADHD subtypes. Video game-based therapeutic interventions were well accepted and generally effective in improving cognitive areas and decreasing ADHD symptoms. Gamification and cognitive training could be the main mechanisms underlying the usefulness and effectiveness of video game-based assessment tools and interventions. Software optimization and greater collaboration between developers and healthcare professionals are some of the priorities for future research in this area.

To evaluate the value of interleukin-6 (IL-6) in predicting long-term disease prognosis for Takayasu arteritis (TA).Sixty-seven TA patients, who had IL-6 levels detected at the first visit and had a regular follow-up of at least 2 years, were enrolled. Data recorded up to March 31, 2019, including clinical presentations, laboratory indices, treatments, and radiological images were collected and used for analysis. The value of IL-6 in predicting disease relapse and imaging progression was analyzed.IL-6 levels were positively related with disease activity index, including Kerr scores, C-reactive protein (CRP) levels. Patients were divided into three groups according to baseline serum IL-6 levels: low group ( 5.4 pg/mL, n = 29), medium group (5.4-11.5 pg/mL, n = 20), and high group ( 11.5 ng/mL, n = 18). Patients in the medium and high group had higher disease activity than those in the low group (p 0.01). Baseline IL-6 levels were correlated with luminal stenosis (p 0.05), although no significant correlations with long-term imaging progression were observed. Patients with more than 2 episodes of disease relapses were most commonly seen in the medium group (p 0.05). Multivariate Cox proportional hazard regression analysis indicated that medium and high IL-6 levels were positive predictors for disease relapse (HR 4.3, 95%CI 1.3-18.7 p = 0.07 for medium group; HR 2.1, 95% CI 0.7-48.9, p = 0.19 for high group) with disease status and treatment adjusted.IL-6 may be a valuable predictor of TA disease relapse during long-term follow-up. Treatments targeted at IL-6 pathways might reduce disease relapse and have better prognostic effects for TA. Key Points • Positive relationships between IL-6 levels and disease activity index, including Kerr scores, C-reactive protein (CRP) levels, etc. were indicated. • Medium and high baseline IL-6 levels were valuable for predicting disease relapse during the 2-year follow-up. • Baseline IL-6 levels were positively correlated with luminal stenosis on imaging.

The purpose of this study was to identify which stage of intraplaque hemorrhage (IPH) is an independent risk factor for ipsilateral new ischemic lesions (NILs) after carotid artery stenting (CAS).In 268 patients treated with CAS, the association between postoperative ipsilateral NILs on diffusion-weighted imaging (DWI) and patient demographics, intraoperative factors, and plaque characteristics on multicontrast atherosclerosis characterization sequence was retrospectively analyzed.A total of 268 patients were enrolled in the study. Ipsilateral NILs on DWI were detected in 32.8% of patients. Univariate analysis showed that the stage of IPH (along with lipid-rich necrotic core [LRNC]) (P0.001) in the carotid plaque, predilation (P = 0.012), stent type (P = 0.002), and aortic arch ulcer (P = 0.009) were associated with postoperative ipsilateral NILs, whereas other patient-related factors (P0.05), type of embolic protection device (P = 0.072), postdilation (P = 0.388), calcification (P = 0.140), and LRNC (without IPH) (P = 0.086) were not. Multivariate logistic regression analysis showed that the acute and recent IPH (along with LRNC) (odds ratio [OR], 3.78, P = 0.011 and OR, 16.73, P0.001, respectively), aortic arch ulcer (OR, 2.46; P = 0.006), predilation (OR, 4.78; P = 0.015), and open cell stent (OR, 4.19; P0.001) were significantly associated with postoperative ipsilateral NILs on DWI.Screening for recent IPH in carotid plaques using multicontrast atherosclerosis characterization sequence may identify plaques at a higher risk for cerebral embolism during CAS.

INTRODUCTION Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval

Aims This study aimed to explore whether pearl could help prevent cognitional morbidity and improve the metabolic processes of hippocampus. Methods Rats were divided into group of control (CTL), sleep deprivation (SD) and pearl powder (PP). The sleeplessness was introduced to all rats except control. Before and after administration with vehicle or pearl powder, cognition was evaluated by Morris water maze (MWM). The protein expression in hippocampus among all groups was examined using iTRAQ‐based global proteomic analysis. Results Morris water maze tests revealed improvements of insomnia‐induced cognitive deficit in both PP‐ and ES‐treated rats, as compared to SD rats. However, proteomic analysis indicates that the pharmacological impact on gene expression of these two medicines is quite different: pearl is more capable of correcting aberrant gene expression caused by SD than estazolam. Therefore, pearl is more suitable for treatment of insomnia. These data, together with protein‐protein interaction analysis, indicate that several pathways, affected by sleep deprivation, may be rescued by pearl powder: retrograde endocannabinoid signalling pathway, and the protein interaction or network enrich in oxidative phosphorylation Parkinson's disease and Huntington disease, etc Conclusions Sleep deprivation can mimic cognition decline caused by insomnia with altered protein expression in the hippocampus; such behavioural and pathological changes can be significantly ameliorated by pearl powder.

Background and aims Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. Methods We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. Results During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78–3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53–3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52–16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32–5.05), and total major CV events (HR: 2.72, 95% CI: 2.09–3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36–1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38–1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13–1.82), CV death (HR: 1.77, 95% CI: 1.50–2.11), HF (HR: 1.43, 95% CI: 1.29–1.58), and total major CV events (HR: 1.46, 95% CI: 1.34–1.58). Conclusions High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

Tumor necrosis factor inhibitors (anti-TNF) have become the standard treatment for rheumatoid arthritis (RA). However, evidence is inconsistent as to whether RA patients with anti-TNF are associated with an increased risk of non-melanoma skin cancer (NMSC) compared with those without anti-TNF. We performed a systematic review and meta-analysis to evaluate the risk of NMSC in patients with anti-TNF drugs compared with those without anti-TNF.We did a systematic literature search with PubMed, EMBASE, and the Cochrane Library from inception to April 1, 2019. Prospective observational studies were eligible for inclusion if they included any of the approved anti-TNF drugs and reported the risk estimates and 95% confidence interval (95% CI) of NMSC associated with anti-TNF in RA patients. Pooled relative risks (RRs) and 95% CIs were calculated using a fixed-effects model. To assess the heterogeneity and risk of publication bias, we respectively conducted the subgroup and sensitivity analysis, funnel plot, Begg's and Egger's test.The present meta-analysis included six studies with 123,031 patients. Compared with RA patients without anti-TNF, patients with anti-TNF drugs were associated with an increased risk of NMSC (RR 1.28, 95% CI 1.19 to 1.38; IThese results suggest that RA patients treated with anti-TNF are at an increased risk of NMSC, especially SCC. However, this association in RA urgently needs the more clinical studies and basic researches to further validate.Key Points• Rheumatoid arthritis patients treated with tumor necrosis factor inhibitors are associated with a higher risk of non-melanoma skin cancer compared to those patients treated without tumor necrosis factor inhibitors. Hence, tumor necrosis factor inhibitors may be avoided in rheumatoid arthritis patients who are at high risk of non-melanoma skin cancer.• Of note, rheumatoid arthritis patients who were treated for tumor necrosis factor inhibitors compared with patients who were not treated for tumor necrosis factor inhibitors were at significantly increased risk of squamous cell skin cancer, but were not at increased risk of basal cell skin cancer. Therefore, use of tumor necrosis factor inhibitors in rheumatoid arthritis patients should be paid attention to the occurrence of squamous cell skin cancer.

Accumulating studies have proved EZH2 dysregulation mediated by mutation and expression in diverse human cancers including AML. However, the expression pattern of EZH2 remains controversial in acute myeloid leukaemia (AML). EZH1/2 expression and mutation were analysed in 200 patients with AML. EZH2 expression was significantly decreased in AML patients compared with normal controls but not for EZH1 expression. EZH2 mutation was identified three of the 200 AML patients (1.5%, 3/200), whereas none of the patients harboured EZH1 mutation (0%, 0/200). EZH2 expression and mutation were significantly associated with −7/del(7) karyotypes. Moreover, lower EZH2 expression was associated with older age, higher white blood cells, NPM1 mutation, CEBPA wild‐type and WT1 wild‐type. Patients with EZH2 mutation showed shorter overall survival (OS) and leukaemia‐free survival (LFS) than patients without EHZ2 mutation after receiving autologous or allogeneic haematopoietic stem cell transplantation (HSCT). However, EZH2 expression has no effect on OS and LFS of AML patients. Notably, in EZH2 low group, patients undergone HSCT had significantly better OS and LFS compared with patients only received chemotherapy, whereas no significant difference was found in OS and LFS between chemotherapy and HSCT patients in EZH2 high group. Collectively, EZH2 dysregulation caused by mutation and under‐expression identifies specific subtypes of AML EZH2 dysregulation may be acted as potential biomarkers predicting prognosis and guiding the treatment choice between transplantation and chemotherapy.

IntroductionPhosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. Methods 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization(HHF). The key secondary outcome was MACE. ResultsThere was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE+HHF (HR:1.12, 95% CI:1.05-1.21): CV death (HR: 1.37,95% CI: 1.22-1.55) and HHF (HR: 1.12, 95% CI: 1.02-1.23). Subgroup analyses showed more prominent association between phosphate and MACE+HHF in male, age > 65, bare-metal stents (BMSs), LVEF< 50%, eGFR 70 mg/dL, and emergent PCI.ConclusionPhosphate has a J-curve association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Background Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. Methods Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25–30 W, force–time integral = 400 g s, n = 40) or with HPSD (power control: 40–50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. Results 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). Conclusion Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL.Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence.Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence.Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Background Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. Methods Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. Results In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. Conclusions The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Background: The clinical significance and outcomes of ventricular tachyarrhythmias (VTa) in patients undergoing valve replacement have rarely been reported.Objective: This study aimed to investigate the incidence and outcome of VTa after surgical valve replacement.Methods: We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,212 patients were selected after 1:1 propensity-score matching based on the type of prosthetic valve used (mechanical vs. bioprosthetic). Various outcomes during long-term follow-up were analyzed.Results: After a median follow-up period of 59.6 months, the crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased after surgery. Furthermore, the occurrences of VTa after valve replacement significantly increased the risk of cardiovascular (CV) death (P < 0.001, HR 1.67, 95% CI 1.41–1.96), stroke- (P < 0.001, HR 1.66, 95% CI 1.37–2.01), atrial fibrillation- (P < 0.001, HR 2.80, 95% CI 2.42–3.24), and congestive heart failure-related hospitalization (P < 0.001, HR 2.61, 95% CI 2.30–2.95). Among patients with VTa, all-cause mortality (P = 0.001, HR 0.49, 95% CI 0.32–0.75) and CV death (P = 0.047, HR 0.58, 95% CI 0.34–0.99) in those with implantable cardioverter-defibrillator (ICD) implantation were lower than those without.Conclusion: The crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased during follow-up. The presence of VTa after surgical valve replacement increases hospitalization and CV death, while ICD implantation reduced the mortality rate in these patients.

BACKGROUND: The relationship between plaque calcification and new ischemic brain lesions after carotid artery stenting (CAS) remains controversial. The purpose of this study was to determine if the circumferential degree of carotid calcification is associated with new ischemic brain lesions on diffusion-weighted imaging (DWI) after CAS. METHODS: A total of 96 patients with carotid stenosis of ≥50% who underwent CAS were enrolled in the study. All patients underwent preoperative carotid computed tomography (CT), and preoperative and postoperative brain MRI. The brain MRI sequences included T1WI, T2WI, T2-fluid-attenuated inversion recovery (FLAIR), and DWI. The location, circumferential degree, volume, percentage volume, maximum density, mean density, Agatston score of carotid calcification, and total plaque volume were assessed and compared between patients with and without new ischemic brain lesions after CAS. Univariate and multivariate analyses were performed to evaluate predictors of new ischemic brain lesions. RESULTS: All of the 96 patients (67.8±6.8 years of age, 83.3% men) were included in the analysis. New ischemic brain lesions on DWI were observed in 40 patients (41.7%). Patients with new ischemic brain lesions after CAS had a larger circumferential degree of calcification than those without new ischemic brain lesions (P

Aim: This prospective, Phase III study assessed the pharmacokinetics (PK), safety and tolerability of immune globulin subcutaneous, human – klhw 20% solution (IGSC-C 20%) in participants with primary humoral immunodeficiency (PI), compared with immune globulin injection (human), 10% caprylate/chromatography purified (IGIV-C 10%). Patients & methods: About 53 participants enrolled. Total 44 received IGIV-C 10% in the run-in phase and then entered the IV phase (with an additional nine who were already receiving IGIV-C 10% and entered the IV phase directly) for steady-state IV PK assessments. Total 49 entered the SC phase (weekly doses of IGSC-C 20% for ∼24 weeks). The PK profiles of IGIV-C 10% and IGSC-C 20% and their safety and tolerability parameters were compared. Results: At a dose adjustment factor of 1.37, IGSC-C 20% provided comparable (noninferior and bioequivalent) overall total immunoglobulin G exposure to IGIV-C 10% over an equal time interval. About 33 participants reported 79 adverse events during run-in + IV phases; 41 participants reported 141 adverse events during the SC phase, with most being local infusion site reactions. The majority of infusion site reactions were mild to moderate in severity. Conclusion: IGSC-C 20% was bioequivalent to IGIV-C 10% and was well tolerated, with a safety profile comparable with IGIV-C 10%, in this study. Trial registration: ClinicalTrials.gov identifier: NCT02604810

New formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed. In a pivotal, confirmatory, controlled, prospective, single-blinded, randomized, multicenter phase III clinical trial, the efficacy and safety of FS Grifols during vascular surgeries were evaluated.Patients undergoing a nonemergency, open, peripheral vascular surgical procedure with moderate arterial bleeding were recruited. In an initial preliminary part of the study, all patients were treated with FS Grifols. In a subsequent primary part, patients were randomized (2:1) to FS Grifols or manual compression (MC). The primary efficacy end point was the proportion of the primary part patients achieving hemostasis by 4 minutes after the start of treatment. Cumulative proportion and time to hemostasis were secondary efficacy end points. Safety end points (in pooled preliminary and primary parts) included adverse events (AEs), vital signs, physical assessments, clinical laboratory tests, viral markers, and immunogenicity.The primary efficacy end point was met by 76.1% of patients (83/109) for the FS Grifols group versus 22.8% of patients (13/57) for the MC group (P .001). The cumulative proportion of patients at 5, 7, and 10 minutes was 80.7%, 84.4%, and 88.1%, respectively, in the FS Grifols treatment group, and 28.1%, 35.1%, and 45.6% in the MC treatment group (P .001). The median time to hemostasis was shorter in the FS Grifols group (4 minutes vs ≥10 minutes in the MC group; P .001). The nature of AEs reported were those expected in the study patient profile. The percentage of patients experiencing treatment-emergent AEs were similar in both the FS Grifols (pooled n = 59 + 109) and MC groups (81.0% and 77.2%, respectively), most recurrent being procedural pain (34.5% and 36.8%, respectively) and pyrexia (11.3% and 10.5%, respectively).FS Grifols was superior in efficacy and similar in safety to MC as an adjunct local hemostatic agent in patients undergoing open vascular surgeries.

Background: Contrast-induced nephropathy (CIN) is a frequent cause of hospital-acquired acute kidney injury. Previous animal models developed to explore the pathogenesis of CIN were based primarily on surgery or indomethacin treatment. Thus, we sought to explore a novel CIN rat model comparable to the human CIN. Methods and results: Both serum creatinine and tubular injury score were used to assess the successful establishment of the present model. In our study, dehydration duration and the iohexol dosage were found to be the two most important factors to develop a rat CIN model. And, dehydration for 3 days plus furosemide (10 mL/kg) injection before iohexol (15 mL/kg) administration was demonstrated the optimal strategy. Renal injury induced by 15 mL/kg iohexol was almost twice more severe than 10 mL/kg. Moreover, significant renal function decrease, morphological damage and mitochondrial dysfunction occurred as early as 6 h after iohexol injection, not 24 h as previous studies reported. Unexpectedly, we firstly discovered that dehydration after iohexol administration did not increase the extent of renal damage, indicating that hydration after contrast media exposure may be ineffective. Conclusions: A novel CIN rat model based on dehydration and iohexol exposure was established and validated to assist in understanding and preventing CIN. Keywords: Contrast-induced nephropathy, Iohexol, Rat model, Dose-related, Hydration

Background and Purpose— In the daily practice, low-dose nonvitamin K antagonist oral anticoagulants are commonly used among Asian patients with atrial fibrillation (AF). The aim of the present study was to compare the risks of ischemic stroke, intracranial hemorrhage, and net clinical benefit of Asian patients with AF treated with off-label low-dose and on-label dosing rivaroxaban. Methods— A total of 2214 patients with AF aged ≥20 years treated with rivaroxaban at a tertiary medical center in Taiwan were studied. Patients were categorized into 2 groups: (1) on-label dose (n=1630): ROCKET-AF or J-ROCKET dosage criteria; and (2) off-label low-dose (10 mg/d for patients with an estimated glomerulus filtration rate >50 mL/min, n=584). The risks of ischemic stroke and intracranial hemorrhage were compared between 2 groups. Results— Compared with the on-label dose group, off-label low-dose rivaroxaban was associated with an increased risk of ischemic stroke with an adjusted hazard ratio of 2.75; 95% CI =1.62–4.69; P P =0.213). Compared with off-label low-dose group, on-label dosing rivaroxaban was associated with a positive net clinical benefit in different weighted models. The results were consistent among the propensity-matched cohort. Conclusions— Off-label low-dosing rivaroxaban should be avoided for Asian patients with AF giving the higher risk of ischemic stroke without risk reduction in intracranial hemorrhage compared with on-label dosing.

Catheter ablation provides a therapeutic option for decreasing episodes of ventricular tachycardia in patients with coronary artery disease. Clinical studies show improvement with catheter ablation in reducing arrhythmia recurrence and therapy from implantable defibrillators, but not in decreasing mortality. Ablation can be an important tool for patients with electrical storm. Overall, complication rates of catheter ablation are acceptable, but recurrence rates are still significant. Advances in mapping and ablation technologies could be expected to improve the success rates and reduce the mortality.

The relationship between carotid blood flow and carotid intraplaque haemorrhage (IPH) is not fully understood. This study was to investigate the relationship between local haemodynamics and carotid plaques with IPH associated with severe artery stenosis. Fifty-nine patients with carotid atherosclerosis were enrolled in this study and underwent magnetic resonance imaging (MRI) measurement. IPH and non-IPH compositions were differentiated based on plaque sequences. Haemodynamic simulations were performed by using computational fluid dynamics (CFD). All the carotids were categorised into IPH and non-IPH groups. In each group, the artery stenosis was divided into mild (50%), moderate (50-70%) and severe (70%) subgroups. Maximum wall shear stress (mWSS) was calculated and comparisons made between IPH and non-IPH groups using independent t-test. Furthermore, the relationship between mWSS and IPH volume was examined using Pearson's correlation. The mWSS result calculated from the IPH group was significantly higher than that of the non-IPH group; at mild stenosis (P = 0.001) and moderate stenosis (P = 0.002) respectively. However, there was no significant difference in cases of severe stenosis (P = 0.42). Furthermore, the results showed a positive correlation between mWSS and IPH volume (r = 0.763, P 0.001) in the cases of stenosis of less than 70%. mWSS was found to be significantly associated with IPH for carotids with stenosis of less than 70%. This highlights that mWSS is a potential quantitative parameter for the risk diagnosis of the carotid atherosclerosis.

AIM A modified repair technique for traumatic cloaca caused by obstetric anal sphincter injury was evaluated, and its feasibility and functional outcome were investigated. METHODS A retrospective review of 23 consecutively enrolled patients diagnosed with traumatic cloaca who underwent the modified repair technique between September 2010 and August 2018 was performed. Demographic, clinical feature, operative and follow-up data were recorded. RESULTS The patients diagnosed with traumatic cloaca who underwent surgical repair after obstetric anal sphincter injury had a median time from obstetric injury of 24 (12-35) years. The median preoperative Wexner faecal incontinence score was 16 (14-17). The postoperative hospital stay was 6 (6-7) days. The median postoperative Wexner faecal incontinence score decreased to 2 (2-3). The anal resting pressure increased from 9.00 (5.25-11.50) mmHg to 56.00 (55.00-65.75) mmHg (P

Mesenchymal stem cell therapy brings hope for regenerating damaged periodontal tissues. The present study aimed to investigate the therapeutic role of local bone marrow stem cell (BMSC) injection in ligation-induced periodontitis and the underlying mechanisms. Alveolar bone lesion was induced by placing ligatures subgingivally around the bilateral maxillary second molars for 28 days. The alveolar bone lesion was confirmed by micro-CT analysis and bone histomorphometry. Allogeneic BMSC transplantation was carried out at 28 day after ligation. The survival state of the transplanted BMSC was observed by bioluminescent imaging. The implantation of the BMSC into the gingival tissues and periodontal ligament was confirmed by green fluorescent protein (GFP) immunohistochemical staining. The expression level of pro-inflammatory, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues were evaluated by immunohistochemical staining and real-time PCR. Significant reverse of alveolar bone lesion was observed after BMSC transplantation. The expression of TNF-α and IL-1β was down-regulated by BMSC transplantation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the periodontal ligament was reduced, and the increased RANKL expression and decreased OPG expression were also reversed after BMSC transplantation. It is concluded that allogeneic BMSC local injection could inhibit the inflammation of the periodontitis tissue and promote periodontal tissue regeneration.

Background Our previous study has reported that aberrant SOX30 methylation was associated with poor prognosis in AML, and it correlated with disease progression in MDS. Herein, we further determined SOX30 methylation and its clinical significance in the other myeloid malignance - chronic myeloid leukemia (CML). Methods SOX30 methylation was examined by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR, whereas SOX30 expression was detected by real-time quantitative PCR. Results SOX30 methylation was identified in 11% (10/95) CML patients. SOX30 methylation was associated with lower hemoglobin and platelets (P=0.006 and 0.032, respectively). Importantly, significant differences were observed in the distributions of clinical stages and cytogenetics (P=0.006 and 0.002, respectively). The frequency of SOX30 methylation in chronic phase (CP) stage occurred with lowest frequency (4/74, 5%), higher in accelerated phase (AP) stage (1/7, 14%), and the highest in blast crisis (BC) stage (12/31, 39%). In addition, SOX30 methylated patients tended to have a higher level of BCR-ABL transcript than SOX30 non-methylated patients (P=0.063). In two paired CML patients, SOX30 methylation showed lower density in CP stage (19% and 17%, respectively), and was significantly increased in BC stage (89% and 69%, respectively) during disease progression. Additionally, SOX30 methylated CML patients presented a lower SOX30 transcript level than SOX30 non-methylated CML patients (P=0.046). Conclusion Our study revealed that SOX30 methylation correlated with disease progression in chronic myeloid leukemia.

Introduction We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with nonparoxysmal atrial fibrillation (AF). Methods and results Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug-refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity-matched analysis (N = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95% confidence interval [95% CI], 1.63-10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09-3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16-5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08-0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17-0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups. Conclusion Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia.

Clinical efficacy of single utility port video-assisted thoracoscopic surgery (VATS) and three-port VATS for patients with non-small cell lung cancer (NSCLC) was compared. A total of 156 patients with NSCLC who underwent VATS in Taizhou Hospital of Zhejiang Province from July 2015 to January 2017 were selected as subjects. They were randomly divided into group A (n=74) and group B (n=82), in which group A was treated with single utility port VATS and group B was treated with three-port VATS. Perioperative indicators such as operation time, intraoperative blood loss, postoperative drainage, removal of drainage tube, lymph node dissection, hospitalization time, postoperative complications, postoperative pain and postoperative quality of life were observed. Expression levels of CRP and IL-6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the operation time, postoperative drainage volume, drainage tube removal time and lymph node dissection between groups A and B (P>0.05). Blood loss and hospitalization time in group A were significantly lower than those in group B (P0.05). Overall quality of life scores of group A and B were significantly lower than the preoperative scores (P

Background: Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application. Purpose: Herein, we reported MCL-1 expression pattern in Chinese de novo acute myeloid leukemia (AML) and its impact on prognosis and may provide theoretical basis for AML patients using MCL-1 inhibitor in clinics. Real-time quantitative PCR was carried out to detect the transcript of MCL-1 in AML patients. Results: MCL-1 expression was significantly up-regulated in AML compared with controls (P=0.042). We divided the patients into two groups (higher and lower expression of MCL-1) based on the median level. Among both non-acute promyelocytic leukemia (APL) and cytogenetically normal AML (CN-AML), patients with higher expression of MCL-1 correlated with lower complete remission (CR) rate (P=0.031 and 0.004, respectively) and shorter overall survival (OS) time (P=0.008 and 0.004, respectively) compared with those with lower expression of MCL-1. Meanwhile, Cox regression analyses revealed that overexpression of MCL-1 acted as an independent risk factor for OS in non-APL patients and CN-AML patients (P=0.011 and 0.045, respectively). In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004). Conclusion: Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.

The risk of cerebral embolism after CAS in patients with carotid IPH is still controversial. This study was to further investigate the relationship between IPH and new ipsilateral ischemic lesion (NIIL) after CAS, and to perform a volumetric analysis of IPH for predicting the risk of NIIL following CAS. One hundred and seventeen patients with carotid stenosis undergoing CAS were prospectively enrolled. Preprocedural multi-contrast carotid MRI was performed. NIIL was evaluated by brain DWI before and after CAS. IPH volume, wall volume at the plaque (WVplaque) and relative IPH volume were calculated. Associations between IPH and postprocedural NIIL were studied. NIILs were shown in 52 patients. IPH were identified in 53 patients. NIILs were found more frequently in IPH-positive (33/53, 62.3%) than in IPH-negative patients (19/64, 29.7%, p

Background Premature ventricular contractions (PVCs) induced by subtle cardiac dysfunction are missed by echocardiography. We evaluated acoustic cardiography for detection of early electromechanical dysfunction in patients with idiopathic PVCs and normal left ventricular ejection fraction (LVEF), and investigated the impact of radiofrequency ablation (RFA) in reversing this adverse effect. Methods Eighty-six patients with PVCs and 33 normal controls having normal LVEF were studied. Fifty PVC patients were in the ablation group and 36 in the nonablation group. %Electromechanical activation time (%EMAT), %left ventricular systolic time (%LVST), third (S3) and fourth heart sound (S4), and systolic dysfunction index (SDI) during sinus rhythm (SR) were measured by acoustic cardiography (Audicor, Inovise Medical, Inc., Beaverton, OR, USA) pre- and postablation. In 28 patients, acoustic parameters were compared during SR without PVCs, and SR with single PVC, ≥ 2 PVCs, or ventricular tachycardia over 10-second Audicor recording in a single patient at different times. Twenty-four-hour acoustic cardiographic and acoustic cardiographic Holter recording were used to assess the impact of PVC burden on electromechanical function in 41 patients. Results %EMAT, S3, S4, and SDI showed significant worsening in the PVC versus control group. %EMAT and SDI were worsened with increasing PVC number in a 10-second strip. %EMAT showed significant linear increment with increasing PVC burden. There was a significant improvement in %EMAT, %LVST, S3, S4, and SDI postablation in patients with PVCs. Conclusion Acoustic cardiography can detect PVC-induced minor electromechanical dysfunction in patients with normal LVEF. RFA can reverse this adverse effect.

Background Oral anticoagulants (OACs) are not recommended for ‘low-risk’ patients with atrial fibrillation (AF). We investigated the incidences of new risk factors developing, and the temporal trends in the CHA2DS2-VASc score in initially ‘low-risk’ AF patients. Second, we propose a reasonable timing interval at which stroke risk should be reassessed for such AF patients. Methods We studied 14,606 AF patients who did not receive anti-platelet agents or OACs with a baseline CHA2DS2-VASc score of 0 (males) or 1 (females). The CHA2DS2-VASc scores of patients were followed up and updated until the occurrence of ischaemic stroke or mortality or 31 December 2011. The associations between the prescription of warfarin and risk of adverse events once patients' scores changed were analysed. Decile values of durations to incident co-morbidities and from the acquirement of new co-morbidities to ischaemic stroke were studied. Results During a mean follow-up of 4 years, 7,079 (48.5%) patients acquired at least one new stroke risk factor component(s) with annual risks of 6.35% for hypertension, 3.68% for age ≥ 65 years, 2.77% for heart failure, 1.99% for diabetes mellitus and 0.33% for vascular diseases. The incidence for CHA2DS2-VASc score increments was 12.1%/year. Initiation of warfarin was associated with a lower risk of adverse events (adjusted hazard ratio, 0.530; 95% confidence interval, 0.371–0.755). Among 6,188 patients who acquired new risk factors, 80% would acquire these co-morbidities after 4.2 months of AF diagnosis. The duration from the acquirement of incident co-morbidities to the occurrence of ischaemic stroke was longer than 4.4 months for 90% of the patients. Conclusion The CHA2DS2-VASc score increases in approximately 12% of initially ‘low-risk’ AF patients each year, and the initiation of warfarin once the score changed was associated with a better prognosis. Three to four months may be a reasonable timing interval at which stroke risk should be reassessed so that OACs could be prescribed in a timely manner for stroke prevention.