Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Abstract Background Serum uric acid (SUA) is a simple and independent marker of morbidity and mortality in a variety of cardiovascular diseases. In this study we aimed to investigate SUA and the risk ...of left atrial (LA) thrombus in patients with nonvalvular atrial fibrillation (AF). Methods In this retrospective study, 1359 consecutive patients undergoing transesophageal echocardiography before catheter ablation of AF were enrolled. Sixty-one of the 1359 patients (4.5%) had LA thrombus. Results SUA levels in patients with LA thrombus were significantly greater (413.5 ± 98.8 μmol/L vs 366.7 ± 94.3 μmol/L; P < 0.001). Hyperuricemia was defined as SUA ≥ 359.8 μmol/L in women and ≥ 445.6 μmol/L in men determined according to receiver operating characteristic curve. The incidence of LA thrombus was significantly greater in patients with hyperuricemia than in those with a normal SUA level in women (12.1% vs 1.9%; P < 0.001) and in men (8.5% vs 2.8%; P < 0.001). Hyperuricemia had a negative predictive value of 98.1% in women and 97.1% in men for identifying LA thrombus. Hyperuricemia was associated with significantly greater risk of LA thrombus among Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2 DS2 -VASc) score = 0, 1, and ≥ 2 groups with odds ratios of 7.19, 4.05, and 3.25, respectively. In multivariable analysis, SUA was an independent risk factor of LA thrombus (odds ratio, 1.004; 95% confidence interval, 1.000-1.008; P = 0.028). Conclusions Hyperuricemia was a modest risk factor for LA thrombus, which might refine stratification of LA thrombus in patients with nonvalvular AF.
Verification of bidirectional block is important for mitral isthmus (MI) ablation. However, recurrent perimitral reentry exists despite apparently MI block.
The purpose of this study was to identify ...and investigate the characteristics of the ridge breakthrough despite apparent bidirectional MI block and related reentry.
In 60 patients undergoing MI ablation and achieving the criteria of bidirectional block when assessed on the line, the pattern under differential pacing was reassessed at the ridge away from the line to check whether a breakthrough existed. Also, activation and entrainment mapping was performed in 7 patients with ridge-related reentry (RRR) to investigate its possible mechanism.
A ridge breakthrough was found in 7 of 60 patients (11.7%) apparently fulfilling the criteria of bidirectional block. The delay from pacing artifact during distal coronary sinus pacing was shorter at the ridge than on the line (95.6 ± 11.7 ms vs 130.9 ± 15.3 ms; P < .001). In 7 patients with RRR, the left atrial endocardial activation time accounted for 58.5% ± 3.2% of the tachycardia cycle length (TCL) and wide double potential could be recorded on the line. The post-pacing interval (PPI) - TCL after entrainment at the ridge was shorter than that on the line (11.4 ± 3.9 ms vs 34.3 ± 6.6 ms; P < .001), and in 2 patients in whom entrainment from the coronary sinus was possible, the PPI - TCL was 15 and 18 ms, respectively.
Apparent bidirectional MI block despite a ridge breakthrough is not uncommon and may lead to RRR, while the line is not part of the reentry.
Abstract Background Rheumatoid arthritis (RA) is associated with an increased incidence of atrial fibrillation (AF). This study evaluated the safety and efficacy of catheter ablation (CA) in the ...treatment of AF in patients with RA, which has not been previously reported. Methods A total of 15 RA patients with AF who underwent CA were enrolled. For each RA patient, we selected 4 individuals (control group, 60 patients in total) who presented for AF ablation in the absence of structural heart or systemic disease and matched the RA patients with same gender, age (±2 years), type of AF, and procedure date. Results Patients with RA had a significantly higher C-reactive protein level (1.81 ± 2.35 mg/dl vs. 4.14 ± 2.30 mg/dl, p = 0.0320), white blood cell count (5632 ± 1200 mm3 vs. 6361 ± 1567 mm3 , p = 0.0482), and neutrophil count (3308 ± 973 mm3 vs. 3949 ± 1461 mm3 , p = 0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa) recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control group (31.7%, 19/60; p = 0.579) after single procedure. In all the five patients from the RA group who developed recurrence, ATa relapsed within 90 days following index procedure (median recurrence time 18 days vs. 92 days in control group; p = 0.0373). Multivariate Cox regression analysis showed that hypertension and left atrial diameter but not RA, C-reactive protein, white blood cell count, and neutrophil count were independent predictors of ATa recurrence. Conclusions Catheter ablation of AF can be safely performed in patients with RA, with a success rate comparable to that of patients without RA. RA patients tend to develop early ATa recurrence after AF ablation.
Summary Background The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016–17 prompted concerns that the epidemiology of the virus might ...have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016–17 epidemic compared with previous epidemics. Methods In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques. Findings Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013–14, 219 in 2014–15, 114 in 2015–16, and 447 in 2016–17. The 2016–17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016–17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015–16 and 2016–17 epidemics (63% 72 of 114 and 61% 274 of 447, respectively) were higher than those in the first three epidemics (39% 52 of 134, 55% 169 of 306, and 56% 122 of 219, respectively). The clinical severity of individuals admitted to hospital in the 2016–17 epidemic was similar to that in the previous epidemics. Interpretation Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus. Funding The National Science Fund for Distinguished Young Scholars.
Objectives This study sought to evaluate the prognostic value of coronary artery calcium score (CACS) and coronary computed tomography angiography (CTA) for major adverse cardiac events (MACE). ...Background The prognostic value of CACS has been well described. Few studies use the rich information of coronary CTA to predict future clinical outcomes and compare CACS with coronary CTA. Methods We followed up 5,007 outpatients who were suspected of having coronary artery disease (CAD) and who underwent cardiac CTA. Cardiac CT was assessed for CACS and the extent, the location, the stenosis severity, and the composition of the plaque in coronary CTA. The endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. Results Follow-up was completed in 4,425 patients (88.4%), with a median follow-up period of 1,081 days. At the end of the follow-up period, 363 (8.2%) patients had experienced MACE. Cumulative probability of 3-year MACE increased across CT strata for CACS (CACS 0, 2.1%; CACS 1 to 100, 12.9%; CACS 101 to 400, 16.3%; and CACS >400, 33.8%; log-rank p < 0.001); for coronary CTA (no plaque 0.8%, nonobstructive disease 3.7%, 1-vessel disease 27.6%, 2-vessel disease 35.5%, and 3-vessel disease 57.7%; log-rank p < 0.001); and for characteristics of the plaques (5.5% for calcified plaque, 22.7% for noncalcified plaque, and 37.7% for mixed plaque; log-rank p < 0.001). The area under the receiver-operating characteristic curves showed the incremental value of CACS and coronary CTA for predicting MACE: 0.71 for clinical risk factors, which improved to 0.82 by adding CACS and further improved to 0.93 by adding coronary CTA (both p < 0.001). Conclusions The CACS and coronary CTA findings have prognostic value and have incremental value over routine risk factors for MACE, and coronary CTA is superior to CACS. Cardiac CT seems to be a promising noninvasive modality with significant prognostic value.
Abstract Purpose Patients with head-and-neck cancer (HNC) may experience xerostomia after radiation therapy (RT), which leads to compromised quality of life. The purpose of this study is to explore ...how the spatial pattern of radiation dose (radiomorphology) in the major salivary glands influences xerostomia in patients with HNC. Methods and materials A data-driven approach using spatially explicit dosimetric predictors, voxel dose (ie, actual radiation dose in voxels in parotid glands PG and submandibular glands SMG) was used to predict whether patients would develop xerostomia 3 months after RT. Using planned radiation dose data and other nondose covariates including baseline xerostomia grade of 427 patients with HNC in our database, the machine learning methods were used to investigate the influence of dose patterns across subvolumes in PG and SMG on xerostomia. Results Of the 3 supervised learning methods studied, ridge logistic regression yielded the best predictive performance. Ridge logistic regression was also preferred to evaluate the influence pattern of highly correlated dose on xerostomia, which showed a discriminative pattern of influence of doses in the PG and SMG on xerostomia. Moreover, the superior–anterior portion of the contralateral PG and medial portion of the ipsilateral PG were determined to be the most influential regions regarding dose effect on xerostomia. The area under the receiver operating characteristic curve from a 10-fold cross-validation was 0.70 ± 0.04. Conclusions Radiomorphology, combined with machine learning methods, is able to suggest patterns of dose in PG and SMG that are the most influential on xerostomia. The influence pattern identified by this data-driven approach and machine learning methods may help improve RT treatment planning and reduce xerostomia after treatment.
Summary Background Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and ...Nanjing—where most human cases of infection have occurred—live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus. Methods We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods. Findings 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93–100%) in Shanghai, by 99% (92–100%) in Hangzhou, by 97% (68–100%) in Huzhou, and by 97% (81–100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4–5·7). Interpretation LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health.
Objective: Thyroid nodules are a common medical problem in China and in other parts of the world. Many guidelines use ultrasound (US) as the first choice for evaluating thyroid nodules. A major ...limitation of US is operator dependency, resulting in a variety of discrepancies in diagnosing thyroid nodules in the literatures. Risk stratification of thyroid nodules is based on the patterns of US features in the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules. We hypothesize that special training targeting features recognition may increase the inter-observer agreement. Methods: The study was conducted on 52 participants from Peking Union Medical College Hospital (PUMCH) from March to May 2018.The participants were divided into two groups by their own decision for their convenience. Image featuresbased learning (IF-BL) was used to train the participants to learn special features including shape, margin, echo level, internal structure, calcification, vascularity through 10 standard images based on the 2015 ATA guideline. Group A (27 subjects) received IF-BL during the first month, and Group B (25 subjects) received IF-BL during the second month. All participants evaluated US features and risk stratification in 60 US images of 20 thyroid nodules before and after the training. The test results were graded by a teaching assistant according to the rule of 0.5 points assigned to every feature and 2 points assigned to risk stratification, with a total of 100 points. Inter-observer agreements of US features and risk stratification were assessed and compared before and after the training. Results: After the first month, Group A had better scores than Group B, the control group of the month (75.4±9.4 vs 68.7±8.4, p = 0.01). At the end of the second month during which both groups were trained, there was no difference of scores between Group A and Group B (74.5±10.4 vs 75.1±7.4, P = 0.78). Scores of all participants were significantly higher than the initial (74.8±9.0 vs 65.8±13.6, P < 0.01). After the training, the kappa values of US features improved from 0.28-0.43 to 0.43-0.75, and those of risk stratification improved from 0.13 to 0.55. Conclusion: IF-BL can effectively help trainees correctly recognize US features and evaluate the risk stratification of thyroid nodule and can improve the inter-observer agreement.
Abstract Background Congenital heart diseases (CHDs) are sometimes associated with coronary artery anomalies (CAAs). Accurate preoperative evaluation of coronary artery anatomy is essential for ...successful surgical repair of complex CHD. Objective The aim of this study was to evaluate the incidence of congenital CAAs in patients with complex CHD at dual-source CT. Methods Four hundred seventeen consecutive patients with complex CHD underwent contrast-enhanced cardiac CT angiography. The results were retrospectively analyzed, including the types and incidences of CAAs in various forms of complex CHD. Each patient was analyzed independently by 2 experienced cardiovascular radiologists. Image quality of coronary arteries was assessed on a 5-point scale with 2 or less being nondiagnostic. Results Thirty-five of 417 studies were nondiagnostic (8.39%). Sixty-three cases of CAA (15.11%) were detected by anomalous ostia and coronary arteries. CAA was involved in 6 of 108 patients with tetralogy of Fallot (5.56%), 18 of 84 patients with double outlet right ventricle (21.43%), 11 of 97 patients with pulmonary artery atresia (11.34%), 7 of 36 patients with transposition of the great arteries (22.22%), 15 of 41 patients with single ventricle (36.59%), 4 of 12 patients with truncus arteriosus/aortopulmonary window (33.33%), and 2 of 39 patients with interruption of the aortic arch/coarctation of the aorta (5.13%). Twenty of these were accompanied with an anomalous coronary course (31.74%). Conclusion Patients with complex CHD have a higher prevalence of CAAs, which should be considered before surgery. Dual-source CT is an effective technique to visualize and evaluate complex CHD.
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