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Silvia Solari

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Many authors have reported their results of mitral valve (MV) repair1,2 in acute and healed endocarditis. However, the results published from different authors highlight the fact that the reparability rate for this indication remains low. Over the last 3 decades our group has adopted an early and repair-oriented approach to the infective endocarditis with the objective to improve the repair rate and the long-term results.‬ ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬ In this paper we describe our institutional experience on mitral valve repair for infective endocarditis.‬‬‬‬‬‬‬‬‬ Data for this paper were extracted from our institutional database on heart valve disease. From 1991 to 2015, 160 consecutive patients in our institution underwent MV surgery for active IE on native MV. The median follow-up was 122 months. This study was approved by the institutional ethics review board, and written informed consent was waived for this study given its retrospective design. Hospital mortality was 11.6 % (n = 18). Early MV reoperation before hospital discharge was required in 5 (3.1%) patients. At 5, 10 and 15 years, overall survival in the MVr for endocarditis in group was 79 ± 4%, 65 ± 5%, 57 ± 6%, respectively. Freedom from reoperation at 5, 10 and 15 years was 95 ± 2%, 88 ± 4% and 81 ± 6%, respectively. Mitral infective endocarditis is an insidious pathology and his surgical approach can be challenging. An early and repair-oriented surgical approach can allow to improve reparability rates with good long-term durability and a low recurrence rate of endocarditis.

Vijay Kumar

and 1 more

Purpose: Early fitting of cochlear implant (CI) enables longer access of the critical period for language stimulation. In CI research, language assessment interval duration (LAID) which is a time gap between two language assessment phases, has been widely documented from the age of 2 months to 5 years and beyond. Thus, the objective of this review was to explore the potential role of the LAID in development of overall language outcomes. Method: A total of 1577 research articles were selected based on the age of implantation (AOI) below 24 months, at least two sessions of speech therapy per week, and occurrence of at least two formal language assessments. Twenty-one articles, consisting of 635 children with CI, were shortlisted for this review. Based on the LAID, the selected articles were classified into three categories based on AOI: <6 months, between 6-24 months and >24 months. Result: Children with LAID of <6 months performed better in language development in comparison of the other two categories. The shorter LAID of six months enables real-time, periodic feedback to the language stimulating program which can fasten the growth of speech and language. Conclusion: Based on the specific clinical protocol, participant’s availability, cost, and insurance cover the LAID is inconsistently practiced. Thus, the need of the development of a precise clinical protocol on the LAID is warranted. A shorter duration of the LAID of six months can optimize language outcomes in the children with early implantation, leading to enhancement of the CI effectiveness.
Fig1

Aditya Dey

and 2 more

We have performed a study on two cubic structured halide perovskites, CsMgX3 (X = Cl, Br) using ab-initio simulations in the outline of density functional theory. In this context, we extensively explored their structural, electronic, thermoelectric and optical properties. The cubic phases of these compounds were optimized and were found to be stable and energetically feasible. Their band structures implied that they are indirect wide gap semiconductors with band gaps of 6.35 and 4.26 eV for CsMgCl3 and CsMgBr3 respectively. Further, their thermoelectric properties comprised of high Seebeck coefficient and electrical conductivities with p-type as the majority charge carriers. Also their high figure of merit (ZT) of values 0.69 and 0.75 at room temperature, showed their efficient thermoelectric response along with the potential to be used for power generation and energy conversion applications. The wide band gaps and their optical behavior consisting of zero absorption, electron energy loss and negligible reflectance in visible region signified a important possibility to use these compounds as hole transport materials (HTM) in the solar cells, which can augment the efficiency of solar cell to a huge level. Moreover, the other calculated optical properties showed contrasting behavior in varying ranges of the electromagnetic spectrum. Thus, we speculate that the studied halide perovskites can emerge as very useful materials for thermoelectric energy conversion and solar cell applications.

Stefan Reichert

and 6 more

Background: Periodontitis is a risk factor for atherosclerosis and coronary heart disease (CHD). This research evaluated the relationship between periodontal conditions and postoperative outcome in patients undergoing coronary artery bypass grafting (CABG). Methods: 101 patients with CHD (age 69 years, 88.1 % males) and the necessity of a CABG surgery were included. Periodontal diagnosis was made according to the current classification of periodontal diseases (2018) and the guidelines of the “Centers for Disease Control and Prevention” (2007). Additionally, periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) were determined. Survival analyses were carried out after a one-year follow-up period with Kaplan-Meier survival plots and Logrank test. Hazard ratios (HRs) were determined using Cox regression. Results: 14 patients (13.9 %) suffered from a new cardiovascular event (11 x angina pectoris, 2 x cardiac decompensation, 1 x cardiac death). Patients with an event reported significantly more often tooth loss probably caused by periodontitis among 1st degree relatives, (HR = 2.2, 95 % CI 1.1-4.4, p = 0.006). No other periodontological parameter was significantly associated with the outcome. Internal risk factors were a history of peripheral arterial disease (HR = 3.7, 95 % CI 1.-11.4, p = 0.013), history of myocardial infarction (HR = 4.0, 95 % CI 1.4-11.5, p = 0.006) and borderline significant previous atrial fibrillation (HR = 2.9, 95 % CI 0.9-9.4, p = 0.056). Conclusion: Putative familial aggregation of periodontitis but not severity of the disease was associated with new adverse events after CABG surgery.
Figure 1

Jianda Li

and 6 more

Dablu Gupta

and 7 more

Trauma is a major cause of morbidity and mortality throughout the world. Alarmingly the mortality rate, owing to multiple causes with or without sepsis, is now reported to cross the value of 50%. The preliminary study was conducted in humans to investigate the 1) safety of estrogen therapy following trauma hemorrhage 2) Does estrogen reduced the inflammatory storms caused due to trauma 3) Does estrogen affects the survival of THS patients and prevent the advancement of sepsis-associated problems. 40, THS patients and 20 healthy controls were recruited. THS patients were divided into experimental groups and placebo controls based on the estrogen administration in the ED. Serum level of cytokines and immune cells were measured at different time points on days 0, 3, 7, and 14 in both groups of THS patients. Patients receiving intravenous estrogen beside standard of care as per ATLS guidelines did not develop any major or minor adverse events and showed favorable clinical outcomes during their course of stay in the ED and ICU. The levels of T regulatory cells, monocytes, and systemic cytokines were significantly reduced in THS patients who received estrogen. Again, THS patients who received estrogen recovered early, do not have side effects and showed a balanced inflammatory response. In conclusion, this preliminary study showed that intravenous estrogen therapy is safe and overcame the problem of inflammatory insults caused due to trauma hemorrhagic shock. It may protect from sepsis-associated complications among THS patients.

Suvitesh Luthra

and 5 more

Introduction - The impact of manufacturer labelled prosthesis size and predicted effective orifice area (EOA) on long term survival after aortic valve replacement is not clear although indexed effective orifice area (iEOA) has been associated with worse survival. Methods - Data was retrospectively collected from Jan 2000 – Dec 2019 for prosthesis type, model and size for isolated aortic valve replacements. Stratified survival was compared between groups and subgroups for labelled valve size, EOA and predicted PPM. Results – Total of 3444 patients were included. Moderate and severe PPM was 15.6% and 1.6% respectively. Cumulative life time hazard was worse for biological valves (mortality: biological 77.7% vs mechanical 64.8%, p=0.001). Mean survival was 132.7 months for biological versus 191.3 months for mechanical valves (p=0.001). Moderate prosthetic AS (EOA = 1-1.5 cm2) was12.1% and severe prosthetic AS (EOA≤1 cm2) was 0.8% respectively. Worse survival in the presence of moderate-severe prosthetic AS was seen in biological valves (115.2 months versus 133.7 months, p=0.001 for EOA≤1.5cm2 and >1.5cm2 respectively). There was a statistically significant correlation between survival and iEOA (Spearman’s rho=0.084, p=0.001, BCa bootstrap 95% CI;0.050, 0.120). Moderate to severe PPM (iEOA≤0.85cm2/m2) was a predictor of worse long term survival (HR 3.56; 95% CI: 1.37 - 9.25; p=0.009). Conclusion - Predicted prosthetic moderate to severe AS and moderate to severe PPM adversely affect long term survival. Smaller valves are associated with reduced survival in all groups.
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Inmaculada Doña

and 8 more

Background: Although ibuprofen and other arylpropionic acid derivatives (APs) are among the non-steroidal anti-inflammatory drugs (NSAIDs) most consumed worldwide at all age ranges, little is known about hypersensitivity to this group of drugs. Our aim was to characterise in detail patients reporting hypersensitivity reactions induced by APs. Methods: We prospectively evaluated patients with symptoms suggestive of hypersensitivity to APs and analysed their clinical characteristics, the reported reactions, and the diagnosis approach. Results: A total of 662 patients confirmed as hypersensitive to APs were included: 489 as cross-reactive (CR) hypersensitivity type (73.86%) and 173 as selective responders (26.13%) (SR). The percentage of subjects reporting reactions induced by ibuprofen and dexketoprofen was higher in CRs (p=0.005 and p=0.01, respectively), whereas reactions induced by naproxen and ketoprofen were more frequent in SRs (p=0.0002 and p=0.00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria combined or not with angioedema in both NIUA and SNIUAA. NPT-LASA was positive in 156 cases (77.14% of NERD and 68.18% of blended) and DPT to ASA was needed in 246 (50.3%) CR patients. In 28 SR cases (25 SNIUAA and 3 SNIDR), DPT with the culprit AP was required. Conclusions: Skin is the most common organ involved in hypersensitivity to APs, in both CR and SR, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are needed to clarify the underlying mechanism in DHR induced by APs.

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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.
To the Editor, For the EU funded project PERMEABLE (PERsonalized MEdicine Approach for Asthma and Allergy Biologicals SeLEction), which addresses the availability of and access to advanced therapy of asthma in children across Europe, we performed a survey including 37 major pediatric asthma and allergy centers between September 2019 and July 2020. In total, the centers contributing to the survey treated approximately 1.000 young patients with severe asthma in 25 major European countries and Turkey with biologicals. In the light of the Corona Pandemic, we extended our survey asking the responsible clinicians if they experienced a SARS-CoV-2 infection in any of the children they are caring for. The questions pertaining to Corona infections were asked between March and July 2020.Given the prevalence of SARS-CoV-2 infections in the general population and in children, one would expect that at least 1% of the patients would be affected (1). In fact, none of the centers was aware of any symptomatic COVID-19 case in their patient populations or any positive SARS-CoV-2 tests.This leads to the conclusion, that either SARS-CoV-2 infections have a mild or even asymptomatic course also in children with severe asthma or that children with severe asthma (and their parents) were extremely successful in avoiding SARS-CoV-2 infections. Thus, we investigated by structured interview, how centers in those 26 countries had instructed their patients to avoid COVID-19. Interestingly, only 4 European countries (UK, Ireland, Portugal and Malta) had a strict, so called shielding policy in place which followed a principle of maximal segregation of severe asthmatics from the rest of the population: not leaving the house at all, not attending school even when they reopened, wearing face masks also at home, and social distancing even with family members. All other countries followed the principle of continuing or even enforcing asthma treatment in patients and advising to follow the same Corona rules as the general population.Both strategies led to the same result: An absence of COVID-19 cases in children with severe asthma. We conclude from this observation, that shielding is not necessary in children with severe asthma as they and their families are perfectly able to avoid Corona infections. The harm done to children by enforcing seclusion, separation and stigmatization needs to be acknowledged. Deprivation of school, social contact and friends weights heavy on children and the absence of any COVID-19 cases in major European centers for severe asthma in children does not justify a policy of compulsory shielding of children with severe asthma, neither in the first nor in any further Corona wave.Michael Kabesch, M.D.University Children’s Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.Member of the Research and Development Campus Regensburg (WECARE) at the Hospital St. Hedwig of the Order of St. John, Regensburg, Germany.ReferencesStringhini S, Wisniak A, Piumatti G, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study [published online ahead of print, 2020 Jun 11]. Lancet . 2020;S0140-6736(20)31304-0.

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 uropedia.com.tr, 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.

Colin Garroway

and 1 more

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.

Alessandro Perri

and 2 more

Image1

Enrico Heffler

and 16 more

To the Editor Since the end of February 2020 Italy, first non- Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200,000 confirmed Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected subjects and resulted in more than 34000 deaths (data updated to June 19th, 20201).Patients with asthma are potentially more severely affected by by SARS-CoV-2 infection 2 and it is well established that respiratory viral infections are associated with severe adverse outcomes in patients with asthma, including increased risk of asthma exacerbation episodes 3. Nonetheless, according to the epidemiological studies published so far, chronic pulmonary diseases are not amongst the most common clinical conditions in COVID-19 patients4About 5-10% of entire asthma population, are severe asthmatics5 and one would expect increased vulnerability to SARS-CoV-2 infection, but no data is so fare available ti confirm this hypothesis.We investigated the incidence of COVID-19, describing its clinical course, in the population of the Severe Asthma Network in Italy (SANI), one of the largest registry for severe asthma worldwide6, and in an additional Center (Azienda Ospedaliero Univeristaria di Ferrara, Ferrara, Italy). All centers, have been contacted and inquired to report confirmed (i.e. patients with positive test result for the virus SARS-CoV-2 from analysis of nasopharyngeal or oropharyngeal swab specimens) or highly suspect cases of COVID-19 (i.e. patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical data of the entire cohort of severe asthmatics enrolled in the study and all reported cases of confirmed or suspect cases of COVID-19, have been obtained from the registry platform and collected from the additional Center. Additional data about COVID-19 symptoms, treatment and clinical course have been collected for all cases reported.Ethical issues and statistical analysis are reported in the online supplementary material.Twenty-six (1.73%) out of 1504 severe asthmatics had confirmed (11 out of 26) or highly suspect COVID-19 (15 out 26); eighteen (69.2%) were females and mean age was 56.2 ± 10 years. The geographical distribution of COVID-19 cases is presented in Figure 1.Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms.The most frequent COVID-19 symptoms reported were fever (100% of patients), malaise (84.6%), cough (80.8%), dyspnea (80.8%), headache (42.3%) and loss of smell (42.3%). Four patients (15.3%) have been hospitalized, one of which in intensive care unit; among hospitalized patients, two (7.7%) died for COVID-19 interstitial pneumonia. No deaths have been reported among the non-hospitalized patients.Severe asthmatics affected by COVID-19, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) compared to non-infected severe asthma patients (15.4% vs 3.8%, p=0.002; odds ratio: 4.7). No difference was found in other comorbidities (including rhinitis, chronic rhinosinusitis with or without nasal polyps, bronchiectasis, obesity, gastroesophageal reflux, arterial hypertension, cardiovascular diseases).Twenty-one patients with COVID-19 were on biological treatments: 15 (71%) were on anti-IL-5 or anti-IL5R agents (Mepolizumab n= 13; Benralizumab n=2 - counting for the 2.9% of all severe asthmatics treated with anti-IL5 in our study population) and 6 (29%) were on anti IgE (Omalizumab - 1.3% of all severe asthmatics treated with omalizumab in our study population).Table I summarizes demographic and clinical characteristics of the 26 COVID-19 patients.In conclusion, in our large cohort of severe asthmatics, COVID-19 was infrequent, not supporting the concept of asthma as a particularly susceptible condition to SARS-COV2 infection 2. This is in line with the first published large epidemiological data on COVID-19 patients, in which asthma is under-reported as comorbidity4. The COVID-19 related mortality rate in our cohort of patients was 7.7%, lower than the COVID-19 mortality rate in the general population (14.5% in Italy 1). These findings suggest that severe asthmatics are not at high risk of the SARS-CoV-2 infection and of severe forms of COVID-19. There are potentially different reasons for this. Self-containment is the first, because of the awareness of virus infections acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing, lockdown and hygiene rules of prevention, and being more careful in regularly taking asthma medications.Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. Respiratory allergies and controlled allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression 7, the cellular receptor for SARS-CoV-2. Interestingly, ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) (another protein mediating SARS-CoV-2 cell entry) have been found highly expressed in asthmatics with concomitant NIDDM8, the only comorbidity that was more frequent reported in our COVID-19 severe asthmatics.The third possible explanation refers to the possibility that inhaled corticosteroids (ICS) might prevent or mitigate the development of Coronaviruses infections. By definition, patients with severe asthma are treated with high doses of ICS 5 and this may have had a protective effect for SARS-CoV-2 infection.Noteworthy, among the patients of our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologics was higher (71%) compared to the number of patients treated with anti-IgE (29%). Although the number of cases is too small to draw any conclusion, it is tempting to speculate that different biological treatments can have specific and different impact on antiviral immune response. In addition we may speculate of the consequence of blood eosinophils reduction: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide and it has been suggested as a risk factor for more severe COVID-19 9.In conclusion, in our large cohort of severe asthmatics only a small minority experienced symptoms consistent with COVID-19, and these patients had peculiar clinical features including high prevalence of NIDDM as comorbidity. Further real-life registry-based studies are needed to confirm our findings and to extend the evidence that severe asthmatics are at low risk of developing COVID-19.
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.
Image1

Enrico Heffler

and 16 more

BACKGROUND: COronaVIrus Disease 19 (COVID-19) pandemic is affecting almost the entire world since February 2020. Patients with chronic pulmonary diseases, such as asthma and chronic obstructive lung disease potentially and theoretically may be more vulnerable and therefore seriously ill if infected by SARS-CoV-2; however, according to the first epidemiological studies published so far, chronic pulmonary diseases are under-reported. No data is available, so far, about the incidence of COVID-19 in severe asthmatics and about which are the COVID-19 outcomes in this subgroup of patients. METHODS:: In this study, we investigated the incidence of COVID-19 cases in a large population of severe asthmatics in Italy, describing their clinical characteristics and clinical course of COVID-19 disease. RESULTS: Twenty-six (1.73%) out of 1504 severe asthmatics were identified as confirmed or highly suspect with COVID-19. Nine (34.6%) of infected patients experienced worsening of asthma during the COVID-19 symptomatic period. Severe asthmatics affected by COVID-19, compared to those who did not contracted the infection, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) (15.4% vs 3.8%, p=0.002); among COVID-19 patients the proportion of those treated anti-IL5 biologic agents was higher (71%) compared to the number of patients treated with anti-IgE (29%). CONCLUSIONS: In our large cohort of severe asthmatics, the incidence of COVID-19 was particularly low, with higher prevalence of NIDDM as comorbidity, suggesting that NIDDM might be a risk factor for COVID-19 in severe asthmatics.

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