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Figure 1a

Yue Hu

and 10 more

Equine herpesvirus 1 (EHV-1) is prevalent in China, and this has had negative consequences for horse breeding. However, this is no date about the genome sequence and genetic characterization of the strains from China. This study aimed to determine the character of the strain that was isolated in China and to serve as a key reference for the development of specific assays for diagnosis and epidemiological research. EHV-1 YM2019 was isolated from the lung tissue of an aborted horse foetus in Xinjiang, China, and the YM2019 genome was sequenced and analysed. The amino acid sequences of 76 EHV-1, EHV-3, EHV-4, EHV-8 and EHV-9 proteins were compared and analysed, and the amino acid sequences of the ORF30 and ORF42 proteins were analysed through bioinformatics. The genome sequence (GenBank accession number: MT063054) is 150, 267 bp in length. It shared the highest similarity with Ab4 strain (92.26% nucleotide identity), which was isolated in the United Kingdom and belonged to the same monophyletic group. Amino acid analysis showed that the YM2019 strain is of the ORF30 A2254/N752 genotype. Multiple sequence alignments of the 76 proteins indicated that the ORF42 protein had the highest sequence identity and the ORF68 protein had the lowest identity. This could facilitate the tracking of EHV-1 in the outbreak situation and allow for the differentiation of the outbreak virus from the other EHV strains. In conclusions, this study provides the genome sequence for EHV-1 YM2019 in China and the strain shared high nucleotide homology with Ab4 strain. In addition, Analysis suggests that EHV-8 and EHV-9 are more closely related to EHV-1 than to EHV-3 and EHV-4, the prevalence of EHV-8 and EHV-9 in China and the potential threat to horse breeding deserve further investigation.

Huihui Zhang

and 8 more

Chao Ji

and 4 more

Abstract Objective To study the impacts of obstetric complications and anxiety among pregnant women in non-epizootic area which are caused by COVID-19. Design Retrospective cohort. Setting China. Population or sample the women who delivered in the third trimester of pregnancy in Qingdao Municipal hospital for the year the months March and April, 2019 and 2020. Method This paper is based on the clinical data from This paper makes a detailed analysis of the problems that can arise because of special circumstances related with delivery history, personal physical symptoms, anxiety index, adverse complications as well as neonatal birth weight. Result Comparing with the same period between 2019 and 2020, maternal age(32.12±5.32vs31.01±4.21, P<0.05) and the ratio of macrosomia(12.10%vs2.53%)are increasing steadily. Meanwhile, times of prenatal visits (10.49±2.15vs10.89±1.81, P<0.05) and score of PHQ-9(1.46±2.09vs4.96±1.38, P<0.05)are to fall significantly。 Conclusion It is helpful to relieve the negative emotion of fear and anxiousness for the pregnant women if they can be encouraged and soothed by social support. The leading cause why regular checkups are decreasing is due to the fear of the epidemic and the transport restrictions, which, in return, may result in a lack of effective management in fetal weight. The COVID-19 had no giant effect on the third trimester of pregnant women. Government as well as obstetric practitioners should strengthen the education of fetal weight management during the pregnancy. Keywords Pregnancy; COVID-19; obstetric complications; anxiety Tweetable abstract The COVID-19 had no giant effect on the third trimester of pregnant women in the non-epizootic area China.

Shan Gao

and 5 more

Peste des petits ruminants (PPR) is a highly infectious transboundary disease of small ruminants caused by peste-des-petits-ruminants virus. It is one of the most destructive diseases in sheep industry in Africa, Asia and the Middle East. In Pamir Plateau, India, Pakistan, Afghanistan, Tajikistan, Kazakhstan and other countries bordering Tibet and Xinjiang of China are all PPR epidemic areas. Within this region, there are many big population size wild small ruminants, moving freely across the border. The time-honored transboundary nomadic lifestyle results in transboundary migration of livestock too. China has experienced two national epidemics, which can be sourced back to Tibet and Xinjiang. In order to reach the China National Plan for the Eradication of Peste des Petits Ruminants and construct a national wide free zone without immunization in 2020, effective control of transboundary spreading and imported cases is an unavoidable choice. For the countries in the pan Pamir Plateau, the spatial risk distribution of PPR were predicted by a variety of eco-geographical, anthropoid and meteorological variants first time; by the resistance surface analysis, maximum available transboundary paths for PPR spreading by small ruminants were calculated. Finally, 5 paths were obtained, respectively from Kazakhstan, Tajikistan, Pakistan and Kashmir to enter Xinjiang and Tibet of China through different channels. This study not only confirmed the fact of transboundary communication of small ruminants for the first time, but also provided specific objectives for PPR prevention. This research can also provide new methods for the prevention and control of other transboundary infectious diseases.

Brij Bhushan

and 8 more

Kirolos Barssoum

and 15 more

Background This meta-analysis aims to evaluate the utility of speckle tracking echocardiography (STE) as a tool to evaluate for cardiac sarcoidosis (CS) early in its course. Electrocardiography and echocardiography have limited sensitivity in this role, while advanced imaging modalities such as cardiac magnetic resonance (CMR) and 18F-Fluorodeoxyglucose–Positron Emission Tomography (FDG-PET) are limited by cost and availability. Methods We compiled English language articles that reported left ventricular global longitudinal strain (LVGLS) or global circumferential strain (GCS) in patients with confirmed extra-cardiac sarcoidosis versus healthy controls. Studies that exclusively included patients with probable or definite CS were excluded. Continuous data were pooled as a standard mean difference (SMD) between the sarcoidosis group and controls. A random effect model was adopted in all analyses. Heterogeneity was assessed using Q and I2 statistics. Results Nine studies with 967 patients were included in our analysis. LVGLS was significantly lower in the extra-cardiac sarcoidosis group as compared to controls, SMD -3.98, 95% confidence interval (CI): -5.32, -2.64, p< 0.001, also was significantly lower in patients who suffered Major Cardiac Events(MCE), -3.89, 95% CI -6.14, -1.64, p< 0.001 . GCS was significantly lower in the extra-cardiac sarcoidosis group as compared to controls, SMD: -3.33, 95% CI -4.71, -1.95, p< 0.001 Conclusion LVGLS and GCS were significantly lower in extra-cardiac sarcoidosis patients despite not exhibiting any cardiac symptoms. LVGLS correlates with MCEs in CS. Further studies are required to investigate the role of STE in the early screening of CS.
Figure 1

Guozhi Xia

and 6 more

Aim: To assess effect of high-dose vitamin C on cardiac injury in coronavirus disease 2019 (COVID-19). Methods: The study was designed based on the severe and critically ill COVID-19 with cardiac injury. Demographics and baseline clinical characteristics were collected and analyzed in addition to laboratory examinations including inflammatory markers on admission and at 14 days after treatment from the electronic medical records. Participants were followed-up for 14 days after treatment with high-dose vitamin C in addition to conventional therapy. Result: The patients (n = 113) were categorized into the improved cardiac injury (ICI) group (n = 70) and the non-improved cardiac injury (NICI) group (n = 43). Overall, 51 (45.1%) patients were administrated with high-dose vitamin C, the percentages of patients treated with high-dose vitamin C were higher in the ICI group than that in the NICI group (52.8% vs 32.5%, P = 0.035). Further analysis showed that concentrations of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6 and IL-8 significantly decreased at 14 days after treatment in patients treated with high-dose vitamin C compared with those in patients administrated without high-dose vitamin C. Meanwhile, similar results were also observed regarding changes in inflammatory markers from baseline to 14 days after treatment in patients receiving high-dose vitamin C. Conclusion: High-dose vitamin C can improve cardiac injury through preventing hyper-inflammatory response in severe and critically ill COVID-19.
Background Pediatric patients represent approximately 2% of overall confirmed cases of COVID-19. Illness severity and symptoms differ from adults. Most cases in children are mild but various studies have reported severe and critical cases as well as fatal outcomes. Methods A systematic review and meta-analysis of the available literature was performed. Frequencies were used for reporting categorical variables. Meta-analyses were performed using the binary random effects model for symptoms frequencies in children and illness severity. Results We found 44 studies (n=6026), 38 were used for quantitative synthesis to estimate the frequency of symptoms in the pediatric population with Covid-19 and illness severity, 44 were used for qualitative synthesis. The most common symptoms were fever 64% (CI 95% 54-72%), cough 42% (CI 95% 37-48%) and gastrointestinal symptoms like vomit 31% (CI 95% 17-47%) and diarrhea 28% (CI 95% 17-40%). For illness severity 2% (CI 95%0-5%) were severe and 3% (CI 95% 1-6%) were critical. Children <1-year-old had the higher odds of severe/critical cases with an OR of 2.07 (IC95% 1.40-3.05). All patients were hospitalized, and a total of 10.34% children admitted to PICU. The mortality rate was 0.16% (8/487). A total of 141 patients developed PIMS-TS and only one died. Conclusions: Most cases in children were non-severe, nevertheless children less than 1 year had the higher risk of severe/critical cases. Symptoms frequencies encountered from major to minor were fever, cough and gastrointestinal symptoms. More testing in children should be done in order to understand transmission characteristics in the pediatric population.
Fig 1 genomic features of the p

Jianjian Lv

and 9 more

Portunus trituberculatus (Crustacea: Decapoda: Brachyura), commonly known as the swimming crab, is of major ecological importance, as well as being important to the fisheries industry. P. trituberculatus is also an important farmed species in China due to its rapid growth rate and high economic value. Here, we report the genome sequence of the swimming crab, which was assembled at the chromosome scale, covering ~1.2 Gb, with 79.99% of the scaffold sequences assembled into 53 chromosomes. The contig and scaffold N50 values were 108.7 kb and 15.6 Mb, respectively, with 19,981 protein-coding genes and a high proportion of simple sequence repeats (49.43%). Based on comparative genomic analyses of crabs and shrimps, the C2H2 zinc finger protein family was found to be the only gene family expanded in crab genomes, and its members were mainly expressed in early embryonic development and during the flea-like larval stage, suggested it was closely related to the evolution of crabs. Combined with transcriptome and Bulked Segregant Analysis (BSA) providing insights into the genetic basis of salinity adaptation in P. trituberculatus, strong immunity and rapid growth of the species were also observed. In addition, the specific region of the Y chromosome was located for the first time in the genome of P. trituberculatus, and Dmrt1 was identified as a key sex determination gene in this region. Decoding the swimming crab genome not only provides a valuable genomic resource for further biological and evolutionary studies, but is also useful for molecular breeding of swimming crabs.

Mohammad Ali

and 2 more

Background: Low back pain (LBP) is the top global cause of disability and physiotherapy interventions are used to manage it. However, the practice pattern of physiotherapists dealing with LBP patients in low-income countries are limited. Aim: The study aims to explore the LBP practice pattern of a low-income country’s ( i. e., Bangladeshi) physiotherapists by their demographic and professional factors. Methods: In a cross-sectional survey study, we have analyzed data from randomly selected 423 physiotherapists of Bangladesh who have invited to fill-up an online survey questionnaire about practice patterns. The first part of the questionnaire contained question demographic and professional background, second part included current intervention choices in the management of patients with LBP, the final part consisted of information on diagnosis, patient type and self-reported cure rate of LBP patients. Ethical approval: Clinical Trial Registry India: CTRI/2020/05/025313. Results: The Majority of the physiotherapists (54.8%) were non-government service holders and 87.7% worked in the town area. Regarding recommended interventions, only 12.3% frequently used those and 21.5% didn’t either offer or know about those interventions. For not recommended interventions, 69.3% occasionally, 13.5% frequently and 17.3% never used such interventions. The prevalence of good, moderate, and poor practice patterns was 14%, 62.4%, and 23.6% respectively. Participants‘ marital status (P = 0.003) and graduation institute category (P = 0.002) were significant factors for practice pattern variation. Conclusion: The study justified physiotherapy management status in a low-income country by comparing evidence-based practice guidelines. This finding set as a low-income country database to exhibit future research, clinical practice, and education for better LBP physiotherapy management adherence to evidence-based public health care.

Attaullah Shah

and 2 more

Fouad Atallah

and 1 more

Having lived through the havoc of COVID-19 in a hospital situated in one of the hardest hit zip codes in the United States, the thought that another wave could loom in the fall is bracing. Obstetricians at our institution have cared for well over 200 COVID-19-infected pregnant women, and are acutely aware of the herculean effort it took to reorganize the service to accommodate the needs of women infected with this new pathogen.1 Many institutions, including ours, modified the frequency of prenatal visits, among other measures, to minimize in-person contacts, in an effort to reduce the likelihood of viral spread. However, it is those changes, along with our prior experience of treating women unimmunized against influenza that leads to our concern that a singular focus on COVID-19 could leave pregnant women at risk from a more familiar threat.While COVID-19 is a threat to the health of individuals and society, its effect on pregnancy is less clear. Thus far, few COVID-19-infected pregnant women have required ICU care, and to date three maternal deaths has been reported in the United States.2-4 The toll of influenza in pregnancy is more clearly documented and is more severe.5Now that the first wave is ebbing in New York, we are seeing fewer and fewer cases but still diagnose about 15 infections per week in our hospital. That pattern is the converse of what is being seen in large swaths of the country. Despite the higher prevalence seen earlier in the epidemic in New York, and the fact that many of those women needed respiratory support, only two women in our hospital required admission to the intensive care unit (ICU), and only one needed ventilator support. Mercifully, none died. During the preceding influenza season, whose end overlapped with the start of the COVID-19 pandemic, we treated six women with influenza who required admission to the ICU, only one of whom had been vaccinated against influenza. As opposed to our COVID-19 cases (putting aside the more rigorous application of social distancing), there were clearly missed opportunities to have prevented some of the morbid events caused by influenza.Admittedly, the higher admission rate to the ICU may be misleading. It is certainly possible that criteria for admission to ICUs, like almost all other aspects of care, evolved during the COVID-19 crisis. There was such a rapid and dramatic increase in the need for ICU beds in our hospital (from a baseline of 40 mid-March, 2020 to a peak of 140 mid-April; 2020, internal data) that more stringent criteria for admission may have been applied and some of our COVID-19 patients that were cared for on the wards, may have been cared for in an ICU in less harrowing times. But even given that possibility, the fact that a similar number of women were extremely ill with influenza raises grave concerns going forward.In the first instance, co-infection with COVID-19 and influenza, as well as other viruses, has been reported.6 Co-infection events will make diagnosis of either entity more difficult, and could potentially increase morbidity. Thus, both because of the risks of co-infection, and the known risks of influenza in pregnancy, providers can’t afford to take their “eye off the ball,” and become less vigilant about vaccinating patients, even if some of the new protocols for fewer visits or telehealth visits remain in place. With fewer visits comes the risk of missing both the vaccination “window” and the opportunity to incorporate vaccination as an essential component of health maintenance. In addition, obstetricians’ performance as vaccinators has been less than ideal as only approximately half of pregnant women get influenza vaccines.7In addition to vaccination, obstetricians must remain vigilant in order to prevent progression of disease among those who get infected. Oseltamivir provides the opportunity for secondary prevention.8 It has been shown to reduce maternal ICU admission and mortality.9 Yet, as with vaccination, even before the COVID-19 epidemic, it was underutilized.10Beyond committing to better use of medical interventions for influenza, obstetricians have to assure that just because they have lived through COVID-19, and the world’s attention remains fixed on COVID-19, they don’t become so COVID-19-focused, that they fail to include influenza in the differential diagnosis of women reporting respiratory symptoms in the fall. Every fever and ache will not be COVID-19. If we delay consideration of the diagnosis of influenza, we will lose the opportunity to use Oseltamivir before the window of eligibility closes. In the post-pandemic world, it will be hard to avoid cognitive biases, such as the availability heuristic (a strategy for making judgments about likelihood of occurrence based on the salience of the information) and confirmation bias (the tendency to gather evidence that confirms preexisting expectations, typically by emphasizing or pursuing supporting evidence while dismissing or failing to seek contradictory evidence). These can result in physicians being hammers and every respiratory symptom, a COVID-19 nail; especially when rapid COVID-19 tests are not uniformly available and don’t yet have uniformly high quality. This is the reverse of one of the most cited examples of the availability heuristic, “In influenza season, it is tempting to consider all patients with fever and myalgias as having influenza.”11 An enhanced situational awareness, i.e., recognizing the influence of recent diagnoses on your diagnostic proclivities, will become an ever more crucial antidote to the hard earned reflex response to fevers and aches that developed during the first wave of COVID-19.We know from history that influenza recurs both in epidemic and pandemic forms, and that an initial wave can be a “herald wave” for the following one.12 Hence, it is our responsibility not to let the current COVID pandemic prevent us from properly dealing with the possibility of overlapping epidemics (seasonal influenza and COVID) in the fall. Vaccination, rapid recourse to antivirals (e.g., Oseltamivir), and community mitigation measures will be more important than ever. COVID-19 can kill, but so can influenza, and if we do our jobs, we can reduce that toll.
Supplement figure1

Yao Wang

and 10 more

Aspirin is essential in the primary and secondary prevention of hypertension. However, the effect of aspirin on blood pressure (bp) in hypertensive patients has been controversial. Therefore, we quantitatively evaluated the effect of aspirin on the bp in untreated hypertensive patients and antihypertensive patients. We searched the PubMed, Embase and Cochrane library electronic databases for articles published prior to June 2019. The overall effect of aspirin on changes in systolic and diastolic bp was estimated by using random-effects models according to the I2 statistic. A total of 15 randomized controlled trials (including 27 studies) met the criteria and were included in the review. For untreated patients with mild hypertension, taking aspirin significantly reduced systolic bp by 1.83 mm Hg (95% CI: -3.15~-0.5, P =0.007) and diastolic bp by 1.32 mm Hg (95% CI: -2.82~0.19, P =0.09). Other subgroup analyses suggest different effects on bp with different aspirin doses, duration and time of administration. Compared with taking aspirin in the morning, taking aspirin before bedtime significantly reduced systolic bp by 2.97 mm Hg (95% CI: -3.78~ -2.17, P <0.00001) and decreased diastolic bp by 2.16 mm Hg (95% CI: -2.87~ -1.44, P <0.00001). However, for patients on antihypertensive therapy, taking aspirin has no significant effect on bp and did not interfere with the antihypertensive drug treatment. Overall, for untreated hypertensive patients, aspirin can reduce bp, and may have a time-dependent effect. However, aspirin was not found to have an effect on bp in antihypertensive patients.
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Md Didarul Islam

and 2 more

Land use and land cover (LULC) change have significant consequences on habitat and environment. Scholars have developed several LULC models to identify the factors behind the changes and to simulate future LULC scenarios to assist in policymaking. Nevertheless, the accuracy of the models remains contentious and a matter of ongoing research agenda. Additionally, most of these studies used a training dataset to train the model and a validation dataset, which is a part of the original training dataset used to validate the model’s accuracy. However, to justify model’s actual predictive capability, we need to test the model on real-world dataset that was not used in modeling. So, we present XGBoost model to improve the accuracy of LULC prediction. Contrary to the typical studies, we use a separate test dataset to justify the model’s predictive capacity in real-world scenario. The result reveals that XGBoost model exhibits highest 84% kappa and 93% accuracy score compared to two benchmark model LR-CA (82% kappa and 92% accuracy score) and ANN-CA (82% kappa and 92% accuracy score). We also found that the built-up area increased by 48.7% in 2002 to 64% in 2010, while agricultural and vacant land declined by almost at the same magnitude over the period and the most important aspect of the LULC shift process in Khulna city was the proximity factors to major roads, industry and commercial establishments. The proposed model proved to increase the predictive accuracy making it much more reliable for analyzing and predicting urban LULC using spatial factors.

Roxana Farzanegan

and 9 more

Background: The pandemic caused by Coronavirus disease 2019, has caused great impact worldwide. Risk factors for severe outcomes have been identified, but asthma seems not to be one of them. Objectives: Our principal purpose is to analyze personal characteristics in severe asthma patients, in treatment with monoclonal antibody, belonging to the Health Department of Castellon, in order to see if these variables affect the probability of being infected by SARS-Cov-2. Methods: This is an observational study. Patients recruited had severe asthma in treatment with monoclonal antibody. A questionnaire was elaborated. Aspects evaluated were: COVID-19 symptoms, asthma control, exposition to the disease, and lifestyle before the pandemic. Serological tests were done by using total SARS-Cov-2 antibody test. Results: 108 patients were enrolled in the study, of whom 106 patients were included. 11 patients declared suggestive COVID-19 symptoms. A total of 21 patients had a serology test done, giving positive results 2 of them. 27 patients needed medical attention, being asthma exacerbation the most common symptom. 71,7% of patients had a normal or high level of social activity before the pandemic. Statistic significance was achieved for medical assistance, asthma control and contact with SARS-Cov-2 positive patients. Conclusion: Personal external factors in severe asthma patients do not influence the probability of being affected by the disease. We can hypothesize that these patients do not have an increased susceptibility for being infected by the virus. Bad asthma control was the main reason for medical assistance during the pandemic.

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Recently published in scholarly journals

Rand Ibrahim

and 1 more

Sudden Cardiac Death (SCD) remains a global threat.1The most common causes of SCD are ischemic heart diseases and structural cardiomyopathies in the elderly. Additional causes can be arrhythmogenic, respiratory, metabolic, or even toxigenic.2,3,4 Despite the novel diagnostic tools and our deeper understanding of pathologies and genetic associations, there remains a subset of patients for whom a trigger is not identifiable. When associated with a pattern of Ventricular Fibrillation, the diagnosis of exclusion is deemed Idiopathic Ventricular Fibrillation (IVF).2,5 IVF accounts for 5% of all SCDs6 – and up to 23% in the young male subgroup5 – and has a high range of recurrence rates (11-45%).7,8,9 There are still knowledge gaps in the initial assessment, follow-up approach, risk stratification and subsequent management for IVF.1,10,11 While subsets of IVF presentations have been better characterized into channelopathies, such as Brugada’s syndrome (BrS), Long QT Syndrome (LQTS), Early Repolarization Syndrome (ERS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), much remains to be discovered.12,13 Implantable Cardioverter Device (ICD) placement as secondary prevention for IVF is the standard of care. This is warranted in the setting of high recurrence rates of arrhythmias (11-43%). Multiple studies have shown potential complications from ICDs and a significant number of cases experiencing inappropriate shock after ICD placement.14In their article, Stampe et al. aim to further understand clinical presentation and assessment, and risk factors for recurrent ventricular arrhythmias in IVF patients. Using a single-centered retrospective study, they followed a total of 84 Danish patients who were initially diagnosed with IVF and received a secondary ICD placement between December 2007 and June 2019. Median follow-up time was 5.2 years (ICR=2-7.6). To ensure detection of many possible underlying etiologies ranging from structural, ischemic, arrhythmogenic, metabolic, or toxicologic, the researchers found that a wide array of diagnostic tools were necessary: standard electrocardiograms (ECGs), high-precordial leads ECGs, standing ECGs, Holter monitoring, sodium-channel blocker provocation tests, exercise stress tests, echocardiograms, cardiac magnetic resonance imaging, coronary angiograms, cardiac computed tomography, electrophysiological studies, histological assessment, blood tests, toxicology screens, and genetic analysis.The study by Stampe et al. highlights the importance of thorough and continuous follow-up with rigorous evaluation: Three (3.6%) patients initially diagnosed with IVF were later found to have underlying cardiac abnormalities (LQTS and Dilated Cardiomyopathy) that explained their SCA. Like other studies, the burden of arrhythmia was found to be high, but unlike reported data, the overall prognosis of IVF was good. Despite the initial pattern of ventricular fibrillation in those who experienced appropriate ICD placement (29.6%), ventricular tachycardia and ventricular fibrillation had a comparable predominance. As for patients with inappropriate ICD placements, atrial fibrillation was a commonly identified pathological rhythm (16.7%). Recurrent cardiac arrest at presentation (19.8%) was a risk factor for appropriate ICD therapy (HR=2.63, CI=1.08-6.40, p=0.033). However, in contrast to previous studies, early repolarization detected on baseline ECG (12.5%), was not found to be a risk factor (p=0.842).The study by Stampe et al. has few limitations. First, the study design, a retrospective cohort, precluded standardized follow-up frequencies and diagnostic testing. Second, while the study was included many of the cofounders tested in previous studies (baseline characteristics, baseline ECG patterns, comorbidities), medication use was not included. Third, the follow-up period may have been insufficient to detect effect from some of the confounding factors. Finally, the sample size was small and it was from a single center.There are several strengths of the Stampe et al. study. Firstly, the wide range of diagnostic tests used at index presentation and during the follow-up period ensured meticulous detection of most underlying etiologies. Secondly, appropriate and well-defined inclusion and exclusion criteria were used. Thirdly, funding by independent parties ensured no influence on study design, result evaluation, and interpretation. Finally, the study has succeeded in improving our understanding of IVF. Future studies should include though a larger population size and a more diverse population.References:1.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. J Am Coll Cardiol 2018;72:e91–e220.3. Refaat MM, Hotait M, London B: Genetics of Sudden Cardiac Death. Curr Cardiol Rep Jul 2015; 17(7): 6064. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932–1963.5. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36(41):2793-2867.6. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–2351.7. Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN. Long-term outcome of patients with idiopathic ventricular fibrillation: a meta-analysis. J Cardiovasc Electrophysiol 2015;26:1095–1104.8. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry. Circ Arrhythm Electrophysiol 2016;9:e003619.9. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E, Sattler S, et al.Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years. Europace 2016;18:718-25.10. Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.11. Gray B, Ackerman MJ, Semsarian C, Behr ER. Evaluation after sudden death in the young: a global approach. Circ Arrhythm Electrophysiol 2019;12: e007453.12. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Response to Letter Regarding Article, Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry”. Circ Arrhythm Electrophysiol 2016;9:e004012.13. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293–296.14. Baranchuk A, Refaat M, Patton KK, Chung M, Krishnan K, et al. What Should You Know About Cybersecurity For Cardiac Implantable Electronic Devices? ACC EP Council Perspective. J Am Coll Cardiol Mar 2018; 71(11):1284-1288.

Zengguo Cao

and 17 more

Ebolavirus (EBOV) is responsible for several EBOV disease (EVD) outbreaks in Africa, with a fatality rate of up to 90%. During 2014-2016, An epidemic of EVD spread throughout Sierra Leone, Guinea and Liberia, and killed over 11,000 people. EBOV began to circulate again in the Democratic Republic of Congo in 2018. Due to the need for a BSL-4 facility to manipulate this virus, the development and improvement of specific therapeutics has been hindered. As a result, it is imperative to perform reliable research on EBOV under lowered BSL restrictions. In this study, we developed a safe neutralization assay based on pseudotyped EBOV, which incorporates the glycoprotein of the 2014 EBOV epidemic strain into a lentivirus vector. Our results demonstrated that the tropism of pseudotyped EBOV was similar to that of authentic EBOV, but with only one infection cycle. And neutralizing activity of both authentic EBOV and pseudotyped EBOV were compared in neutralization assay using three different samples of antibody-based reagents against EBOV, similar results were obtained. In addition, an indirect ELISA was performed to show the relationship between IgG and neutralizing antibody against EBOV detected by our pseudotyped EBOV-based neutralization assay. As expected, the neutralizing antibody titers varied with the IgG titers detected by indirect ELISA, and a correlation between the results of the two assays was identified. By comparison with two different assays, the reliability of the results detected by the pseudotyped EBOV-based neutralization assay was confirmed. Collectively, in the absence of BSL-4 restrictions, pseudotyped EBOV production and neutralizing activity evaluation can be performed safely and in a manner that is neither labor- nor time-consuming, providing a simple and safe method for EBOV-neutralizing antibody detection and the assessment of immunogenicity of EBOV vaccines. All these remarkable advantages of the newly established assay highlight its potential to further application in assessment of immunogenicity of EBOV vaccine candidates.

Bachir Lakkis

and 1 more

Long QT syndrome (LQTS) is characterized by prolongation of the QT interval on the electrocardiogram (ECG). Clinically, LQTS is associated with the development of Torsades de Pointes (TdP), a well-defined polymorphic ventricular tachycardia and the development of sudden cardiac death (1). The most common type is the acquired form caused mainly by drugs, it is also known as the drug induced LQTS (diLQTS) (2-5). The diLQTS is caused by certain families of drugs which can markedly prolong the QT interval on the ECG most notably antiarrhythmic drugs (class IA, class III), anti-histamines, antipsychotics, antidepressants, antibiotics, antimalarial, and antifungals (2-5). Some of these agents including the antimalarial drug hydroxycholoquine and the antibiotic azithromycin which are being used in some countries as therapies for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(6,7). However, these drugs have been implicated in causing prolongation of the QT interval on the ECG (2-5).There is a solution for monitoring this large number of patients which consists of using mobile ECG devices instead of using the standard 12-lead ECG owing to the difficulty of using the 12-lead ECG due to its medical cost and increased risk of transmitting infection. These mobile ECG devices have been shown to be effective in interpreting the QT interval in patients who are using QT interval prolonging drugs (8, 9). However, the ECG mobile devices have been associated with decreased accuracy to interpret the QT interval at high heart rates (9). On the other hand, some of them have been linked with no accuracy to interpret the QT interval (10). This can put some patients at risk of TdP and sudden cardiac death.In this current issue of the Journal of Cardiovascular electrophysiology, Krisai P et al. reported that the limb leads underestimated the occurrence of diLQTS and subsequent TdP compared to the chest leads in the ECG device, this occurred in particular with the usage of mobile standard ECG devices which use limb leads only. To illuminate these findings, the authors have studied the ECGs of 84 patients who have met the requirements for this study, which are diLQTS and subsequent TdP. Furthermore, the patients in this study were also taking a QT interval prolonging drug. Krisai P et al. additionally reported the morphology of the T-wave in every ECG and classified them into flat, broad, notched, late peaked, biphasic and inverted. The authors showed that in 11.9% of these patients the ECG was non reliable in diagnosing diLQTS and subsequent Tdp using only limb leads due to T-wave flattening in these leads, in contrast to chest leads where the non- interpretability of the QT interval was never attributable to the T-wave morphology but to other causes. The authors further examined the QT interval duration in limb leads and chest leads and found that the QT interval in limb leads was shorter compared to that of the chest leads, but reported a high variability in these differences. Therefore, it should be taken into account when screening patients with diLQTS using only mobile ECG devices and these patients should be screened using both limb leads and chest leads. Moreover, the authors have highlighted the limitations of using ECG mobile devices as limb leads to interpret the QT interval especially in high heart rates (when Bazett’s equation overcorrects the QTc and overestimates the prevalence of the QT interval) and have advocated the usage of ECG mobile devices as chest leads instead of limb leads due to their superior ability to interpret the QT interval.The authors should be praised for their efforts in illustrating the difference in the QT interval interpretability between the chest leads and the limb leads in patients with diLQTS. The authors also pointed out the limitation of using mobile ECG devices as limb leads for the diagnosis of diLQTS and recommended their usage as chest leads by applying their leads onto the chest due to their better diagnostic accuracy for detecting the diLQTS. The study results are very relevant, it further expanded the contemporary knowledge about the limitation of the QT interval interpretability using ECG mobile device only (11). Future investigation is needed to elucidate the difference in chest and limb leads interpretability of the QT interval and to assess the ability of the mobile ECG devices to interpret the QT interval.ReferencesRefaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.Kannankeril P, Roden D, Darbar D. Drug-Induced Long QT Syndrome. Pharmacological Reviews. 2010;62(4):760-781.Nachimuthu S, Assar M, Schussler J. Drug-induced QT interval prolongation: mechanisms and clinical management. Therapeutic Advances in Drug Safety. 2012;3(5):241-253.Jankelson L, Karam G, Becker M, Chinitz L, Tsai M. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020 ; S1547-5271(20)30431-8.Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. P T . 2017;42(7):473-477.Singh A, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(3):241-246.Hashem A, Alghamdi B, Algaissi A, Alshehri F, Bukhari A, Alfaleh M et al. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Medicine and Infectious Disease. 2020; 35:101735.Chung E, Guise K. QTC intervals can be assessed with the AliveCor heart monitor in patients on dofetilide for atrial fibrillation. J Electrocardiol. 2015;48(1):8-9.Garabelli P, Stavrakis S, Albert M et al. Comparison of QT Interval Readings in Normal Sinus Rhythm Between a Smartphone Heart Monitor and a 12-Lead ECG for Healthy Volunteers and Inpatients Receiving Sotalol or Dofetilide. Journal Cardiovasc Electrophysiol. 2016;27(7):827-832.Bekker C, Noordergraaf F, Teerenstra S, Pop G, Bemt B. Diagnostic accuracy of a single‐lead portable ECG device for measuring QTc prolongation. Annals Noninvasive Electrocardiol. 2019;25(1): e12683.Malone D, Gallo T, Beck J, Clark D. Feasibility of measuring QT intervals with a portable device. American Journal of Health-System Pharmacy. 2017;74(22):1850-1851.
Figure 1

Volkan Sen

and 9 more

Objectives: There is no standardized and up-to-date education model for urology residents in our country. We aimed to describe our National E learning education model for urology residents. Methodology: The ERTP working group; consisting of urologists was established by Society of Urological Surgery to create E-learning model and curriculum at April 2018. Learning objectives were set up in order to determine and standardize the contents of the presentations. In accordance with the Bloom Taxonomy, 834 learning objectives were created for a total of 90 lectures (18 lectures for each PGY year). Totally 90 videos were shoot by specialized instructors and webcasts were prepared. Webcasts were posted at, which is the web library of Society of Urological Surgery. Satisfaction of residents and instructors was evaluated with feedbacks. An assessment of knowledge was measured with multiple-choice exam. Results: A total of 43 centers and 250 urology residents were included in ERTP during the academic year 2018/2019. There were 93/38/43/34/25 urology residents at 1st/2nd/3rd/4th and 5th year of residency, respectively. Majority of the residents (99.1%) completed the ERTP. The overall satisfaction rate of residents and instructors were 4,29 and 4,67(min:1 so bad, max:5 so good). An assessment exam was performed to urology residents at the end of the ERTP and the mean score was calculated as 57.99 points (min:20, max:82). Conclusion: Due to the Covid-19 pandemic, most of the educational programs had to move online platforms. We used this reliable and easily accessible e-learning platform for standardization of training in urology on national basis. We aim to share this model with international residency training programs.

Mohammad Ramadan

and 1 more

Atrial fibrillation (AF) is the most common cardiac arrhythmia and often occurs with heart failure (HF) [1]. AF prevalence increases with increasing severity of HF: for instance its prevalence ranges from 5 percent in patients with New York Heart Association (NYHA) functional class I HF to 40 percent in patients with NYHA class IV HF [2]. Its presence with HF plays a significant prognostic role and increases morbidity and mortality. Heart Failure with reduced ejection fraction (HFrEF) is associated with cardiac arrhythmias [3]. HFrEF is also one of the indications for Cardiac resynchronization therapy (CRT) placement [4]. Therefore, many patients undergoing CRT implantation will concomitantly have HF and AF. As the benefit from CRT in HF patients has been established, the data on patients with both HF and AF is limited, because patients with atrial arrhythmias were excluded from most of the major CRT trials, such as CARE-HF and COMPANION [5]. However, a number of observational studies and small randomized clinical trials suggest a benefit from CRT in AF and HF patients such as a CRT-mediated ejection fraction (EF) increase [6, 7]. Other studies showed a high non-response rate in patients with AF as compared to those in sinus rhythm (SR) [8]. Thus, it is important to determine whether CRT has a beneficial role in these patients to decide on adding an atrial lead at the time of CRT implantation especially in patients with longstanding-persistent AF.In their published study, Ziegelhoeffer et al. investigated the outcomes of CRT placement with an atrial lead in patients with HF and AF. This was done by conducting a retrospective analysis of all patients with AF who received CRT for HF at the Kerckhoff Heart Center since June 2004 and were observed until July 2018- completing a 5-year follow-up. The authors identified 328 patients and divided them into 3 subgroups: paroxysmal (px) AF, persistent (ps) AF, and longstanding-persistent (lp) AF, with all patients receiving the same standard operative management. During the observation period, the authors analyzed the rhythm course of the patients, cardiac parameters (NYHA class, MR, LVEF, left atrial diameter) and performed a subgroup analysis for patients who received an atrial lead. The study showed that all groups had a high rate of sinus rate (SR) conversion and rhythm maintenance at 1 and 5 years. Specifically, the patients who received an atrial lead among the lp AF group were shown to have a stable EF, less pronounced  left ventricular end-systolic diameter (LVESD) and  left ventricular end diastolic diameter (LVEDD) and lower mitral regurgitation (MR) rates at one year follow-up as compared to the group without atrial lead placement. Moreover, the results of the lp group were similar to the ps-AF group, although the latter had a lower number of participants (n=4) without initial implantation of the atrial lead. The authors attributed the improvement in cardiac function and SR conversion to CRT and the implantation of an additional atrial lead.Although some studies showed that CRT therapy reduced secondary MR in HF [9, 10], this study additionally suggests that CRT with an atrial lead was associated with improved myocardial function and improvement of interventricular conduction delay triggering cardiac remodeling in patients with HF and AF. Although the results showed better cardiac function in the subgroup analysis of the patients with an additional atrial lead, these results were reported as percentages with no level of significance specified, hence statistical significance of the difference in the described parameters (such as LVESD, LVEDD) could not be determined. Further investigation via prospective studies is needed with larger sample size in the future to further support the results of the study especially that it was done in a single center and had a relatively small sample size.References:1. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.2. Maisel, W.H. and L.W. Stevenson, Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol, 2003. 91 (6a): p. 2d-8d.3. AlJaroudi WA, Refaat MM, Habib RH, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.4. Yancy, C.W., et al., 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013. 62 (16): p. e147-239.5. Cleland, J.G., et al., The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med, 2005.352 (15): p. 1539-49.6. Leclercq, C., et al., Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J, 2002. 23 (22): p. 1780-7.7. Upadhyay, G.A., et al., Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2008. 52 (15): p. 1239-46.8. Wilton, S.B., et al., Outcomes of cardiac resynchronization therapy in patients with versus those without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm, 2011. 8 (7): p. 1088-94.9. van Bommel, R.J., et al., Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation, 2011.124 (8): p. 912-9.10. Breithardt, O.A., et al., Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol, 2003. 41 (5): p. 765-70.

Mohamad El Moheb

and 1 more

Idiopathic ventricular arrhythmias (VA) is defined as premature ventricular complexes (PVCs) or ventricular tachycardias (VT) that occur in the absence of structural heart disease. Endocardial radiofrequency (RF) ablation is often curative for idiopathic VA. The success of the procedure depends on the ability to localize the abnormal foci accurately. These arrhythmias typical originate from the right ventricular outflow tract (RVOT), specifically from the superior septal aspect, but can also originate from the left ventricular outflow tract (LVOT) and the coronary cusps.1 The QRS electrocardiogram (ECG) characteristics have been helpful in patients with VAs, patient with accessory pathways and patients who have pacemakers.2 VAs originating from the RVOT have typical ECG findings with a left bundle branch block (LBBB) morphology and an inferior axis.3In the current issue of the Journal of Cardiovascular Electrophysiology, Hisazaki et al. describe five patients with idiopathic VA suggestive of RVOT origin and who required ablation in the left-sided outflow tract (OT) in addition to the initial ablation in the RVOT for cure to be achieved. Patients exhibited monomorphic, LBBB QRS pattern with an inferior axis on ECG, consistent with the morphology of VAs originating from the RVOT. Interestingly, all patients had a common distinct ECG pattern: qs or rs (r ≤ 5 mm) pattern in lead I, Q wave ratio[aVL/aVR]>1, and dominant S-waves in leads V1 and V2. Mapping of the right ventricle demonstrated early local activation time during the VA in the posterior portion of the RVOT, matching the QRS morphology obtained during pacemapping. Despite RF energy delivery to the RV, the VAs recurred shortly after ablation in four patients and had no effect at all in one patient. A change in the QRS morphology was noted on the ECG that had never been observed before the procedure. The new patterns were suggestive of left-sided OT origin: the second VAs exhibited an increase in the Q wave ratio [aVL/aVR] and R wave amplitude in lead V1, decrease in the S wave amplitude in lead V1, and a counterclockwise rotation of the precordial R-wave transition. Early activation of the second VA could not be found in the RVOT, and the earliest activation time after mapping the LV was found to be relatively late. Real-time intracardiac echocardiography and 3D mapping systems were used to determine the location immediately contralateral to the initial ablation site in the RVOT. Energy was then delivered to that site which successfully eliminated the second VA. The authors postulated that the second VAs shared the same origins as the first VAs, and the change in QRS morphology is likely attributed to a change in the exit point or in the pathway from the origin to the exit point. The authors further explained that the VAs originated from an intramural area of the superior basal LV surrounded by the RVOT, LVOT and the transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV).A limitation of this study is that GCV-AIV ablation was not attempted; however, the authors’ approach is safer and was successful in eliminating VA. Another limitation is that left-sided OT mapping was not initially performed. Nevertheless, given the ECG characteristics, local activation time, and mapping, it was appropriate to attempt a RVOT site ablation.Overall, the authors should be commended for their effort to describe in detail patients with idiopathic VAs that required ablation in the left-sided OT following ablation in the RVOT. Although change in QRS morphology after ablation has been previously described, the authors were the first to describe the ECG patterns of these patients.4–7 The results of this study have important clinical implications. First, the authors have demonstrated the importance of anatomical approach from the left-sided OT for cure to be achieved. Second, insight into the location of the origin of the VA may be helpful to physicians managing patients with VAs from the RVOT. Finally, continuous monitoring of the ECG during ablation for a change in QRS morphology should be considered to identify patients who will require further ablation. We have summarized in Table 1 important ECG characteristics indicative VA of specific origins, based on the findings of this study and previous studies in the literature.3,8–15
Pulmonary Vein Isolation (PVI) remains the cornerstone for catheter ablation for atrial fibrillation (AF). Achieving durable PVI safely with Radiofrequency Catheter Ablation (RFCA) has proven challenging until recently, even with the use of Contact Force (CF) sensing catheters and electroanatomical mapping1. Ablation success rates improve markedly, including in persistent AF, when permanent PVI can be achieved1,2, which only underscores the critical role of the Pulmonary Veins (PV) in AF arrhythmogenesis.Historically, the only way to assess PVI durability has been through invasive electrophysiology study, with all its associated risk, inconvenience, and costs. This price appears particularly galling to pay if the PVs are found to be isolated at repeat study, as is now becoming increasingly common3. Multiple randomised studies have failed to show additional benefit from ablating extra-PV structures4,5, and the best outcomes following repeat AF ablation procedures are restricted to those where PV reconnection is identified and treated6. As such, there remains a pressing need for a non-invasive tool that can accurately assess PVI durability, and ideally, the size and location of residual gaps. As Magnetic Resonance Imaging (MRI) has increasingly been shown capable of delineating atrial scar, there is much anticipation that it may serve this important purpose7.RFCA and Cryoballoon ablation (CBA) are by far the most common modalities used for PVI, and there is remarkable equivalence in their clinical results8. However, the handling of the two technologies in the catheter laboratory is very different, and ultrahigh density mapping has shown important differences in the number and location of chronic gaps between the two9. The use of MRI in characterizing these differences has not been well described so far.In this issue of the journal, Kurose and colleagues present a small but elegant study10, in which 30 consecutive patients who underwent PVI (18 with CBA, 12 with RFCA) were assessed by LGE-MRI two months later, where lesion width and visual gap(s) around each vein were assessed. The RF applications were delivered using a CF sensing catheter, with a target lesion size index (LSI) of 5, and an inter-lesion distance of <6mm. They found that the mean lesion width on MRI was significantly wider in the CBA group (8.1±2.2 mm) as compared to the RFCA group (6.3±2.2 mm), p=0.032. However, there were more visual gaps seen in the CBA group, especially in the bottom segments of the two inferior veins. In the RFCA group, gaps were seen most often seen in the left posterior segments where the target LSI value could not be achieved because of esopheageal temperature rise. Furthermore, the number of gaps visualised on MRI was linked to freedom from AF at 12 months; receiver operating characteristic curve analysis suggested a cut off value of less than 5 visual gaps per patient as being predictive of a good outcome.The authors deserve to be congratulated for their study, which builds on their previous work where LGE-MRI was used to compare chronic lesions between CBA and RFCA with non-CF sensing catheters11. It is notable that whilst the lesion width in their previous study was also significantly greater in the CBA group than the RFCA group, the mean number of gaps in the RFCA group was higher. This suggests that the modern technique of delivering LSI-guided contiguous RFCA lesions has resulted in a material improvement in PVI durability, something that is borne out in clinical studies too3.Some limitations of the work should be mentioned. Patients were not randomised to RFCA or CBA; rather, patients undergoing CBA were pre-selected with those with left common PV or large PVs excluded. The ablation technique used for CBA was unusual in that the use of RFCA was allowed if PVI could not be achieved after a single 3-minute freeze. This low bar for defining CBA failure led to as many as 3 patients out of 25 being excluded from the study. Many readers will feel that the mean procedural times of 129 minutes and fluoroscopy times of 39 minutes for CBA are much longer than what is the norm today. They may also find the RF powers used in this study unusual; only 30W was used on the anterior wall, and 20-25W on the posterior wall, which was reduced even further if esophageal temperature rise was observed. The field is moving towards using higher power short duration (HPSD) RF applications, and as HPSD lesions have been shown to be wider12, it is possible that the gaps on the posterior wall identified in this study may not have been present had HPSD applications been used. Finally, the definition of visual gap on MRI used in this study, a non-LGE site larger than 4 mm, almost certainly overestimated the number of true gaps. For instance, the authors observed at least one visual gap in each of the 16 segments around the PVs in more than 10% CB patients; this is at odds with data obtained with ultrahigh density mapping9, and also with the good clinical outcomes reported here. Future research should look at correlating these MRI-visualised gaps with actual gaps seen on repeat electrophysiological study, so that the clinical significance of these can be better defined.What can we take away from this study? Firstly, the use of MRI to assess post-ablation scar is now a reality in many labs, allowing assessment of PVI durability to help decide whether or not to offer a repeat procedure to a patient with AF recurrence. Secondly, the evolution of the RFCA technique to include target lesion indices and inter-lesion distance has made RFCA at least as effective as CBA in achieving durable PVI. Finally, this is an area ripe for further research, and we look forward to similarly valuable contributions from Kurose and colleagues in the future.
Figure 1

Chan Sol Park

and 7 more

Background and Purpose: After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Experimental Approach: Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. Key Results: GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Conclusions and Implications: Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.

Jorge Casanova

and 4 more

ABSTRACT Background: COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11st, 2020. Responses to this crisis integrated resource allocation for the increased amount of infected patients, while maintaining an adequate response to other severe and life-threatening diseases. Though cardiothoracic patients are at high risk for Covid-19 severe illness, postponing surgeries would translate in increased mortality and morbidity. We reviewed our practice during the initial time of pandemic, with emphasis on safety protocols. Methods: From March 11st to May 15th 2020, 148 patients underwent surgery at the Department of Cardiothoracic Surgery of CHUSJ. The clinical characteristics of the patients were retrospectively registered, along with novel containment and infection prevention measures targeting the new Corona Virus. Results: The majority of adult cardiac patients were operated on an urgent basis. Hospital mortality was 1.9% (n = 2 patients). Most of adult thoracic patients were admitted from home, with a diagnosis of neoplasic disease in 60% patients. Hospital mortality was 3.3% (1). Fifteen children underwent cardiothoracic surgery. There was no mortality. The infection prevention procedures applied, totally excluded the transmission of Covid-19 in the Department. Conclusion: While guaranteeing a prompt response to emergent, urgent and high priority cases, novel safety measures in individual protection, patients circuits and pre-operative diagnose of symptomatic and asymptomatic infection were adopted. The surgical results corroborate that it was safe to undergo cardiothoracic surgery during the initial time of Covid-19 pandemic. The new policies will be maintained while the virus stays in the community.
Letter to the editorTry as we might to make the manuscript selection process as objective as possible, the crapshoot element is unquestionable. Prospective papers are being submitted more frequently than ever, which has broadened the number of reviewers. Medical students and senior faculty alike are being tasked with assessing manuscripts. Different levels of experience, knowledge and variable personal research interests introduce undeniable biases in how papers are ultimately critiqued. We’ve become keenly aware of the importance of evaluating research techniques and the studies themselves for risks of biases; PRISMA, MINORS, MOOSE and ROBINS tools lead a growing list of objective protocols and assessments.1,2,3,4 Have we ever thought of addressing potential biases in how we actually select articles for publication?Obviously, this would be no simple task, but that shouldn’t be a deterrent to making improvements in the process where possible; personal connections come to mind in this regard. Generally speaking, very little is being done to prevent reviewers from being aware of who the authors are and where they’re coming from. Additionally, many submission platforms allow for the selection of preferred reviewers as well as the ability to decline undesired reviewers. While these tendencies are understandable for multiple reasons, their potential to introduce personal biases is noteworthy. For the sake of argument, let’s assign a very simple “risk of personal bias reduction score” for a journal’s manuscript submission platform: One point is given for a) maintaining author confidentiality, b) maintaining institution/location confidentiality and c) avoiding the option to select or decline particular reviewers. As such, the scores range from 0 to 3, with 3 being the most favorable.So how are we doing? Table 1 shows a list of the top 20 otolaryngology journals to date as determined by the h -index, an increasingly popular measure of journal quality based on the number of publication citations.5 Ten of the 19 eligible journals did not take any measures to reduce the potential for personal biases, thus scoring 0. Eight journals earned one point for avoiding the opportunity to select or decline reviewers. Of note, several journals cite this feature as a means of reducing bias; encouraging the submitting author to target “unbiased” reviewers. The value of this is debatable as this feature can easily be used paradoxically. Lastly, one journal scored two points for blinding the reviewers to both the author names and locations.It may seem trivial at first glance, as we’ve grown so accustomed to these aspects of the submission process, but it really isn’t. The notion that editors reviewing manuscripts are immune to biases from prior personal connections and experiences would be extremely shortsighted. Do we really think a given reviewer can assess a submission from a beloved former trainee in a reliably unbiased fashion? How about a manuscript from an institution with which there was a falling out of some kind? These themes are getting increasingly acknowledged in academic publishing, with growing numbers of journals implementing safeguarding measures. At most, there appears to be a nascent interest in addressing these topics within otolaryngology field. With rejection rates at all-time highs, it behooves us to reflect upon what can be done to ensure that the best manuscript wins: Who the authors are, who they know, and where they’re from shouldn’t be significant factors. As it stands currently, our submission platforms leave open avenues for personal connections to have a considerable influence. Reforming these potential biases, or at the very least acknowledging them, is in order.

Wenhui Zhao

and 6 more

Drought has become one of the major constraints on agricultural development, particularly in areas lacking water. Studying the effects of different water stresses on photosynthesis, growth, yield, water use efficiency (WUE) and water productivity (IWP) of winter wheat will provide scientific irrigation strategies for developing water-saving agriculture. According to the water field capacity, four different water stress levels were set, i.e., 30–40% of water field capacity (severe stress), 40–50% (moderate stress), 50–60% (mild stress) and 60–80% (well-watered), through an automatic irrigation system by controlling the irrigation amount. The results showed that the diurnal and seasonal changes in photosynthetic parameters such as net photosynthetic rate (Pn), intercellular carbon concentration (Ci), stomatal conductance (Gs), and transpiration (E) significantly decreased under moderate and severe stress. The Pn of mild stress only slightly decreased compared to that of well-watered and was even higher after May 16th. As a result, the dry biomass and 1000-grain weight under mild stress increased 2.07% and 1.95% compared with well-watered. Under all water stresses, the heights and straw weights of the winter wheat significantly decreased. It was also found that mild water stress increased the WUE and IWP, which further resulted in the negligible decrease of the fresh weight of the aboveground biomass, dry biomass weight, spike weight, grain weight. Conversely, WUE and IWP significantly decreased under moderate and severe stress, which can affect the growth of winter wheat. So the fresh weight of the aboveground biomass, dry biomass weight, spike weight, grain weight also significantly decreased under moderate and severe stress. Thus, mild stress results in the optimal use of water resources without a significant reduction in yield in the North China Plain. Therefore, mild stress can be considered as a suitable environment for winter wheat growth in arid areas.
Figure 1 (2)

Aviram Hochstadt

and 13 more

Background: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of longitudinal diastolic strain time (Dst) with the routine echocardiography diastolic parameters and to estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. Methods: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy were included. Echocardiography, including Global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity were determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. =diastolic time (ms) measured. Results: Among 69 patients, 67 (97.1%) were females with a mean age 52±13years. Diastolic strain timeDst measurement was significantly associated with the standard routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3 . Both in a univariate and a multivariate analyses the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (p<0.04). Conclusions: Among breast cancer patients, Dst time showed high correlation to standard the routine diastolic echocardiography parameters. Relative reductionChange in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Sergey Moiseev

and 10 more

Objectives. We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Methods. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. Results. The median concentrations of MAC, C5a, C3a, and factor B were higher in active AAV patients (p<0.001). Achievement of remission was associated with reductions in C3a (p=0.005), C5a (p=0.035), and factor B levels (p=0.045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered in the meta-analysis. Plasma MAC, C5a, and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Conclusion. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Amer Harky

and 3 more

Dear Editor,We read with interest the published article by Ikeda et al. [1], they performed thoracic endovascular aortic repair (TEVAR) in a patient with Marfan syndrome (MFS) for acute complicated type B aortic dissection (TBAD) during COVID-19 pandemic.The evidence around TEVAR for MFS is scarce and open repair remains the gold treatment[2]. During the COVID-19 pandemic, many patients are either being denied treatment or given inferior options on the basis of age, comorbidities and risk of COVID pneumonia; however, the guidelines for aortic intervention in the United Kingdom have remained largely unchanged from pre-COVID-19 era [3]. Our questions to the authors relate to whether their solution was an unnecessary compromise. There is no clear indication defined in their case as a cold leg doesn’t necessary means an ischaemic limb. The TEVAR procedure performed aiming to minimise hospital stay, yet this approach may have put the patient at higher risk of developing paraplegia and visceral organ malperfusion, while compromising her long-term care.There is need to clarify if she had risk factors that prone her to a higher risk acquiring severe COVID-19 which necessitated deviating from the traditional open surgery recommended for MFS patients with TBAD [2]. The authors did not report on renal function, evidence of bowel malperfusion or whether there was resistant hypertension that needed immediate intervention. If the need to expediate intervention was the fear of limb ischaemia, is it conceivable a femoro-femoral bypass could have saved the limb and definitive open surgery on her aorta could have been performed at a later stage, especially since she was haemodynamically stable.Moreover, as Marfan-diseased aortas are prone to further dilatation, we believe their justification for opting for endovascular repair should also have been more balanced, exploring the know high rate of long-term TEVAR-associated complications in MFS patients including endoleaks, retrograde dissection, stent-graft-induced new entry tears, surgical conversions and reintervention. There is also need for imaging follow-up to assess the success of TEVAR and early detection of aforementioned complications.

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