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The effect of density-driven flow on the transport of solutes with high concentration...
Guangqiu Jin
Yongfei Hao

Guangqiu Jin

and 6 more

May 18, 2020
In this study, both laboratory experiments and numerical simulations were conducted to investigate the effect of density-driven flow on the transport of high-concentration pollutants in the hyporheic zone. The results show that the density gradient can change the flow of pore water and the strong density-driven flow can lead to an unstable flow, which increases the effect of preferential flow and thus causes the appearance of solute fingers in the hyporheic zone. Notably, these solute fingers become more obvious with the increase of depth. The appearance of solute fingers depends on the relative strength of the pumping exchange and density gradient, which are represented by the dimensionless number M* and N* respectively. Finger flows appear near the interface when M* is less than 0.5 N*. This study may contribute to better understanding the transport and destination of solutes and thus may provide some insights into the assessment on pollution incidents.
Prognostic value of CD4+T cell in patients with severe COVID-19
xuesong wen
Lei Gao

xuesong wen

and 10 more

May 18, 2020
Prognostic value of CD4+T cell in patients with severe COVID-19
Asthma and the COVID-19 pandemic: literature review
Mário Morais-Almeida
Helena Pite

Mário Morais-Almeida

and 4 more

May 18, 2020
Even though respiratory viruses are one of the most common triggers for asthma exacerbations, not all of these viruses affect patients equally. There is no strong evidence supporting that patients with asthma have a higher risk of becoming seriously ill from coronavirus disease 2019 (COVID-19), although recent reports from the United States of America and the United Kingdom suggest that asthma is much more common in children and adults with mild to severe COVID-19 than it was previously reported in Asia and in Europe. As in previous severe acute respiratory syndrome (SARS) outbreaks, patients with asthma, especially children, appear to be less susceptible to the coronavirus with a low rate of asthma exacerbations. Different expression of viral receptors and T2 inflammation can be responsible for different outcomes. Future studies focused on asthma and on other allergic disorders are needed to provide greater understanding of the impact of underlying asthma and allergic inflammation on COVID-19 susceptibility and disease severity. But, for the moment, it’s crucial that asthmatic patients maintain their controller medication, from inhaled corticosteroids to biologics, without self-making any dose adjustments or stopping medication. New data are emerging daily, rapidly updating our understanding of this novel coronavirus.
Hemophagocytic lymphohistiocytosis associated with HBV-HCV coinfection in adult: case...
BENDARI MOUNIA
nouama bouanani

mounia bendari

and 6 more

May 18, 2020
Hemophagocytic syndrome have experienced a very significant revival in recent years, we report a rare case of secondary HLH to Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection. In addition to the treatment for hepatitis the patient underwent therapy for HLH, with this treatment we obtained complete remission.
Prominent Hemophagocytosis in Cerebrospinal Fluid in A Patient With Bacterial Meningi...
Alauldeen Alqasim
Rajeev Kariyattil

Alauldeen Alqasim

and 1 more

May 18, 2020
A 39 year old patient was presented with bacterial meningitis after having endoscopic surgery for removal of a benign pituitary tumor. Cerebrospinal cytology showed a marked hemophagocytic activity.
Role of serum albumin and proteinuria in patients with SARS-CoV-2 pneumonia
Cinzia Bassoli
Letizia Oreni

Cinzia Bassoli

and 10 more

May 18, 2020
BACKGROUND Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with clinical outcome still need to be clarified. METHODS We retrospectively evaluated in patients with COVID-19 hospitalized at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. RESULTS Serum albumin levels < 30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (p<0.0001) and death (p=0.003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r = -0.487 and r = -0.479, respectively; p< 0.0001). Finally, a positive correlation was found between albumin levels and eGFR (r= 0.137; p=0.049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin > 30 g/L (81% and 67%, respectively; p=0.09). CONCLUSION In patients with COVID-19 hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.
GLOBAL IMPLEMENTATION OF THE WORLD HEALTH ORGANIZATION’S INTERNATIONAL CLASSIFICATION...
LUCIANA TANNO
Robert Chalmers

LUCIANA TANNO

and 25 more

May 18, 2020
The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019 and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the sub-sections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.
Medical algorithm: Treatment of Atopic Dermatitis in Early Childhood (part II)
Sherief Janmohamed
Johannes Ring

Sherief Janmohamed

and 3 more

May 18, 2020
Medical algorithm: Treatment of Atopic Dermatitis in Early Childhood (part II)Sherief R. Janmohamed MD PhD1, Johannes Ring MD2, Lawrence F. Eichenfield MD3, Jan Gutermuth MD11Department of Dermatology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090 Jette, Brussels, Belgium2Department of Dermatology and Allergology Biederstein, Technical University Munich, München, Germany3Departments of Dermatology and Pediatrics, University of California, San Diego School of Medicine and Rady Children’s Hospital, San Diego CA, USA
Prevalence and incidence of nasal polyposis at a Health Area of Madrid, Spain
Laura Ortega-Martin
Diana Betancor

Laura Ortega-Martin

and 6 more

May 18, 2020
A document by Laura Ortega-Martin. Click on the document to view its contents.
Characteristics and roles of SARS-CoV-2 specific antibodies in patients with differen...
Zhifeng Huang
Hao Chen

Zhifeng Huang

and 8 more

May 18, 2020
Abstract: Background: The diagnosis of COVID-19 relies mainly on viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis. SARS-CoV-2-specific antibody detection is convenient, safe, and highly sensitive. IgM and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA, and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. Methods: COVID-19 patients, divided into a severe & critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA, and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results, and other data were recorded for all patients. Results: Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are better for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe & critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Conclusions: Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.
An Exploration of the Enablers and Barriers to the Implementation of the Scottish Str...
Iona Lancaster
Linda Martindale

Iona Lancaster

and 1 more

May 18, 2020
Rationale, aims and objectives The Scottish Stroke Care Bundle (SSCB) aims to significantly improve patient outcomes and the consistency with which stroke patients are managed. The identification of key enablers and barriers to implementation will allow a future focus on the development of appropriate interventions to promote reliability of implementation. The aim of this study was to explore and describe the reasons why doctors and nurses in one Health Board area in Scotland feel that the SSCB is not being applied in a consistent and reliable way. The research objective was ‘to explore and describe the factors associated with compliance and non-compliance with the Scottish stroke care bundle’. Method A qualitative approach was used to understand the perspectives of medical and nursing staff involved in implementing the SSCB. Eight semi-structured interviews were undertaken across two sites. Cane et al’s Theoretical Domains Framework (TDF) guided data collection and analysis providing context-based explanations as to why reliable implementation of the SSCB is not being achieved.1 Results Three significant factors were identified that significantly influence the likelihood of patients receiving the SSCB: knowledge; resources; and organisational culture. The interrelationships between these factors revealed key enablers and barriers to the consistent application of the SSCB in this Health Board area. Conclusions Many of the findings are commonly identified as being crucial to the implementation of care bundles and potentially have national implications for SSCB implementation. Multifaceted quality improvement interventions, based on these findings, would improve the consistency of SSCB implementation in this Health Board area.
Remdesivir---Overview of the most debatable Antiviral of Recent Times
DWAIPAYAN SARATHI CHAKRABORTY
SHOUVIK CHOUDHURY

DWAIPAYAN SARATHI CHAKRABORTY

and 2 more

May 18, 2020
Viral infections constitute the biggest pandemic threat in the modern era due to lack of novel ‘broad-spectrum’ antiviral agents. Remdesivir is newer antiviral drug acts as RNA-dependent RNA polymerase (RdRp) inhibitor, targeting the viral genome replication process. Therapeutic efficacy was first demonstrated by suppressing viral replication in Ebola infected infected rhesus monkeys. Then further studies show its efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV). It is available for parenteral application with reasonable safety and tolerability profile. Recently the drug has received emergency use authorization from USFDA for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease due to lack of other approved treatment options. Multiple clinical trials are going on in many countries to evaluate its efficacy, safety and tolerability. Results are awaited in most cases and if the drug becomes a success it will be capable of meeting the demand generated by both the current pandemic and future outbreak.
Insights into the Mechanisms of action of Chloroquine and Hydroxychloroquine and its...
monalisa sahu
Arvind Kumar

monalisa sahu

and 5 more

May 18, 2020
The global outbreak of Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2/2019-nCoV) has put forth a serious threat to the international public health and has ruined the global economy. Till date, no drugs have been approved for Coronavirus Disease-2019 (COVID-19), although use of some drugs in trial phase has been attempted. The drugs being used for management of COVID-19 disease include chloroquine (CQ), hydroxychloroquine (HCQ), and remdesivir. In this article, we have aimed to review existing literature and mechanism by which CQ and HCQ have an effect on COVID-19, most importantly by interfering with autophagy, lysosomal activity, receptor binding and membrane fusion. We have systematically searched the PubMed database upto April, 2020 and analysed all the articles published on CQ, HCQ and COVID-19. The available data provides insights into the immunomodulatory potency of HCQ, along with the molecular mechanism of action of the drug on the SARS-CoV-2.
Long-term Outcome of Ventricular Tachycardia Ablation in Patients who did not Undergo...
Takeshi Kitamura
Seiji Fukamizu

Takeshi Kitamura

and 7 more

May 18, 2020
Background: Ventricular arrhythmia inducibility is one of the ideal endpoints of ventricular tachycardia(VT) ablation. However, it may be challenging to implement programmed electrical stimulation (PES) at the end of the procedure under several circumstances. The long-term outcome of patients who did not undergo PES after VT ablation remains largely unknown. Purpose: To investigate the details and long-term outcome of VT ablation in patients who did not undergo PES at the end of the ablation procedure. Methods: Among 184 VT ablation procedures in patients with structural heart disease who underwent VT ablation using an irrigated catheter, we enrolled those who did not undergo PES after VT ablation. VT ablation strategy involved targeting induced VT plus pacemap-guided substrate ablation if inducible. If VT was not inducible, substrate-based ablation was performed. The primary endpoint was VT recurrence. Results: In 58 procedures, post-ablation VT inducibility was not assessed. The causes were non-inducibility of sustained VT before ablation(27/58, 46.6%), long procedure time(27.6%, mean 392 min), complications(10.3%), intolerant hemodynamic state(10.3%), and inaccessible or unsafe target(6.9%). With regard to the primary endpoint, 23 recurrences(39.7%) were observed during a mean follow-up period of 2.5 years. Patients with non-inducibility before ablation showed less VT recurrences(4/27, 14.8%) during follow-up than patients with other causes of untested PES after ablation(19/31, 61.2%)(Log-rank<0.001). Conclusions: VT recurrence was not observed in approximately 60% of the patients who did not undergo PES at the end of the ablation procedure. PES after VT ablation may be not needed among patients with pre-ablation non-inducibility.
The association of new-onset atrial fibrillation and risk of cancer: A systematic rev...
Mengxia Zhang
Linling Li

Mengxia Zhang

and 9 more

May 18, 2020
Background There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size. Methods Electronic databases, such as PubMed and EMBASE, were searched for published relevant studies on NOAF patients diagnosed with cancer after and during follow-ups, including reported records of baseline information and the statistical result of morbidity. Two investigators independently reviewed the articles and extracted the data using uniform standards and definitions. The meta-analysis was conducted using the Cochrane Program Review Manager. Results This meta-analysis consisted of five cohort studies and one case-control study, which comprised of 533,514 participants. The pooled relative risk (RR) for incident cancer was 1.24 (95% CI: 1.10-1.39, P=0.0003). The temporal trends analysis demonstrated that an increased risk of cancer was observed during the initial 90 days (RR: 3.44, 95% CI: 2.29-5.57, P<0.00001), but not after that. Lung cancer (RR: 1.51, 95% CI: 1.47-1.55, P<0.00001) was associated with NOAF, but not colorectal cancer and breast cancer. Conclusion This meta-analysis provides evidence that NOAF is associated with increased risk of cancer. The risk of incident cancer particularly increases within 90 days after NOAF diagnosis, but not after that.
Refractory Ventricular Tachycardia in a Patient with a Left Ventricular Assist Device...
Tomoya Sato
Rui Kamada

Tomoya Sato

and 9 more

May 18, 2020
Neuraxial modulation therapies, such as stellate ganglion block, thoracic epidural anesthesia, and cardiac sympathetic denervation, are effective for ventricular arrhythmias. However, these treatments are invasive and can increase the risk of bleeding and infection. In this case report, stellate ganglion phototherapy (SGP) was safely and effectively performed for refractory ventricular tachycardia in patients with a history of cardiac resynchronization therapy-defibrillator (CRT-D) and left ventricular assist device (LVAD) implantation for dilated cardiomyopathy. SGP might have the potential to treat refractory ventricular arrhythmias and can be useful because of its safety and simplicity.
Are all Non-sustained Ventricular Tachycardia the Same in Hypertrophic Cardiomyopathy...
Khaled Sabeh
Marwan Refaat

Khaled Sabeh

and 1 more

May 18, 2020
Are all Non-sustained Ventricular Tachycardia the Same in Hypertrophic Cardiomyopathy Risk Stratification for Sudden Cardiac Death?Mohamad Khaled Sabeh MD1, Marwan M. Refaat MD21Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts - USA2Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center Beirut, LebanonRunning Title: NSVT in HCM SCD Risk StratificationWords (excluding references): 664Disclosures: NoneFunding: NoneKeywords: Hypertrophic Cardiomyopathy, Non-sustained Ventricular Tachycardia, Cardiac Arrhythmias, Cardiovascular DiseasesCorrespondence:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonFax: +961-1-370814Clinic: +961-1-350000/+961-1-374374 Extension 5800Office: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: mr48@aub.edu.lbCardiomyopathies with reduced systolic function predispose to sudden cardiac death (SCD) and many studies helped in decreasing that risk by Implantable Cardioverter Defibrillator (ICD) implantation and pharmacologic management (1-4). Many types of cardiomyopathies with preserved systolic function, including hypertrophic cardiomyopathy (HCM), can predispose to malignant ventricular arrhythmias and SCD. HCM is the most common inherited cardiac disease that affects 1 in 200 live births (5,6). SCD remains one of the main causes of death in HCM and the SCD rate peaks in early adulthood (7-14). Data from ICDs suggest that SCD in HCM is most commonly caused by ventricular fibrillation (VF) (15). One major clinical challenge is identifying patients at risk for SCD. Multiple studies showed that non-sustained ventricular tachycardia (NSVT) is a risk actor for SCD (16,17). However the strength of the data was variable across these studies due to difference in populations and the low sensitivity of Holter ECG. Moreover, other studies looked at the rate and duration of the ventricular arrhythmias and their relationship to SCD in HCM (17-19) yet the effect of the morphology of NSVT on SCD has not been well investigated.In this single center study Adduci et al . explore the prognostic impact of different NSVT morphologies in a cohort of 109 consecutive HCM patients. The study included patients who had an ICD implanted in the authors’ institution from January 2001 to December 2018. The ICDs were mostly implanted for primary prevention in HCM patient with 1) one or more risk factor including maximal LV thickness ≥30 mm, family history of SD in at least 1 first-degree relative <50 years of age, non-sustained ventricular tachycardia (NSVT), recent (≤ 6 months) unexplained syncope, 2) hypotensive blood pressure during exercise with at least one additional major risk factor for SD 3) end-stage HCM regardless of other established risk markers of SCD. Devices were interrogated on evaluation every 3 to 6 months and the data was assessed for appropriate or inappropriate ICD therapies. Two independent electrophysiologists analyzed the ICD near field and far field EGMs from the ventricular tachycardia runs. They classified the VTs as either monomorphic (MMVT) or polymorphic (PMVT).During a mean follow up of 71+/- 48 months, 377 NSVT episodes of NSVT were retrieved from ICD memory in 46 patients; of these episodes, 7(2%) were polymorphic and 370 (98%) were monomorphic (MM). The mean HR of The MM NSVT had an average HR of 171+/- 32 BPM and lasted for 17 +/- 12 beats while the PMVT were faster at 241BPM +/- and longer at 28+/- 16 beats. The appropriate intervention rate was 5.1% per year and interestingly NSVT did not predict the occurrence of ICD therapy. However patients with polymorphic NSVT had a statistically higher risk for ICD intervention as compared to monomorphic NSVT. Further analysis noted a trend for increased risk of ICD therapy with patients with >1 NSVT morphology. Moreover 75% of the treated VTs had been previously observed as NSVT.Risk stratification is very important in this young patient population; decreasing the risk threshold for ICD implants leads to missed arrhythmias and bad outcomes while increasing it increases the risk for complications from unnecessarily implanted devices. There are several types of ICDs: Transvenous ICD, Subcutaneous ICD and Extravascular ICD. The results of this study suggest that the risk of SCD in patients with PMVT and/or NSVT with multiple morphologies is different from that of patients with a MMVT, and that the presence of short MMVT doe not predict the future ICD therapies. As such, one may consider a conservative approach in low-risk patients with short bursts of slow MM NSVT, and a more aggressive approach in patients with frequent, rapid rate burst of PMVT. Although this study suggests that different NSVT morphologies affect the prognosis in HCM patients, the low number of events lacked the statistical power to redefine ICD candidacy. Larger multicenter studies are needed to confirm these findings and to help delineate the “at risk patients” who would truly benefit from ICDs.
A Cardiac Sodium Channel Mutation Associated with Epinephrine-Induced Marked QT-Prolo...
Mohamad El Moheb
Marwan Refaat

Mohamad El Moheb

and 1 more

May 18, 2020
A Cardiac Sodium Channel Mutation Associated with Epinephrine-Induced Marked QT-ProlongationMohamad N. El Moheb MD1, Marwan M. Refaat MD21Division of Trauma Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts - USA2Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center Beirut, LebanonRunning Title: SCN5A mutation associated with epinephrine-induced LQTSWords (excluding references): 746Disclosures: NoneFunding: NoneKeywords: Long QT Syndrome, Genetics, Variants, Cardiac Arrhythmias, Cardiovascular DiseasesCorrespondence:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonFax: +961-1-370814Clinic: +961-1-350000/+961-1-374374 Extension 5800Office: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: mr48@aub.edu.lbThe hereditary long QT syndrome (LQTS) is an important cause of polymorphous ventricular tachycardia (torsades de pointes) and sudden cardiac death in otherwise young and healthy individuals. Clinically, this condition is caused by delayed ventricular repolarization and manifests as an abnormally prolonged QT interval on the electrocardiogram (ECG). The most common subtypes of LQTS are LQT1, LQT2, and LQT3 (1-10). The life-threatening arrhythmias occur most frequently during exercise in LQT1, upon auditory stimulation or emotional stress in LQT2, and at rest or during sleep in LQT3 (11). Patients with LQT1 have a mutation in the KCNQ1 gene which codes for the subunit of the slow outward potassium current channel (IKs) while patients with LQT3 have a mutation in the SCN5A gene, which codes for the cardiac voltage-dependent sodium channel (INa) (12). LQT1-affected individuals are more vulnerable to β-adrenergic modulation than LQT3-affected individuals. Exercise and epinephrine-infusion ECG tests are therefore useful in differentiating between the LQTS subtypes and optimizing therapeutic strategies in order to prevent sudden cardiac death. While beta-blockers have been established as the standard of care for the treatment of the LQT1 and LQT2 subtypes, their use in LQT3 remains controversial (13, 14). A new missense mutation has been recently identified in the SCN5A-encoding INA channels and was found to be associated with sinus node dysfunction and epinephrine-induced QT prolongation (1). This atypical phenotype of LQT3 has so far been observed in only one patient. Whether other mutations exist that can cause a similar manifestation has yet to determined.In the current issue of the Journal of Cardiovascular Electrophysiology, Nakajima et al. describe a family with LQT3 that exhibited epinephrine-induced marked QT prolongation. The SCN5A V1667I mutation was found to be responsible for this atypical phenotype which resulted in prolongation of the QT interval in the proband as well as in family members carrying the mutation. The SCN5A V1667I mutation is a gain of function mutation located in domain IV-segment 5 (DIV-S5) of the sodium channel encoding SCN5A gene. To elucidate the pathophysiology of the disease, the authors transfected a human kidney cell line (tsA-201) to induce expression of wild-type and mutated sodium channels and measured the membrane sodium currents (INA). They showed that SCN5A V1667I mutation was associated with larger INA peak density, depolarizing shift in steady-state inactivation (SSI) leading to increased window current, and accelerated recovery from depolarization. Additionally, an increased hump in the INA of V1667I mutant cells (V1667I-INA) was observed during a ramp pulse protocol consistent with increased window current. There was no difference in fast inactivation rate and steady-state activation between the V1667I-INA and wild-type INA(WT-INA). The authors further examined the effects of protein kinase A (PKA) activation on V1667I-INA to mimic the effect of epinephrine. PKA activation resulted in a less significant hyperpolarizing shift in SSI in V1667I-INA compared to WT-INA leading to increased window current. Additionally, V1667I mutation was found to be associated with accelerated recovery from depolarization, and increased hump during ramp pulse protocol in the setting of PKA activation. Chen et al. have also reported the case of an individual with a mutation in SCN5A who exhibited marked QT-prolongation after epinephrine infusion (1). However, contrary to the SCN5A V1667I mutation described by Nakajima et al, the SCN5A V2016M defect was a loss of function mutation causing a decrease in INA peak density. The clinical manifestations of the SCN5A mutations described by Chen et al. and Nakajima et al. are more comparable to individuals with the LQT1 subtype than those with the LQT3 subtype. Therefore, it should be considered whether certain patients with SCN5A would benefit from beta-blocker therapy.Overall, the authors should be commended on their efforts to describe for the first time a family with the SCN5A V1667I mutation and show that this mutation is associated with epinephrine-induced marked QT prolongation. The authors have also provided important insight into the electrophysiological properties of the mutant channels and the structure-function relationship of SCN5A. Further studies are needed to elucidate the precise molecular mechanisms of PKA activation on WT-INa and V1667I-INa. The results of this study have important clinical implications. The efficacy of beta-blockers for the treatment of LQTS has so far only been proven for the LQT1 and LQT2 subtypes, with conflicting results for the LQT3 subtype (13, 14). Given the marked QT prolongation in response to epinephrine infusion in carriers of the SCN5A V1667I mutation, certain LQT3 patients may benefit from beta-blocker therapy. Future studies should clarify whether beta-blockers are effective in these patients.
Impact of cascade reservoir on continuity of river water temperature: a temperature t...
You Xu
Zhengjian Yang

You Xu

and 5 more

May 18, 2020
Water temperature is an important habitat factor in river ecosystems that exhibits the characteristics of continuous change. Dam construction disrupts the continuity of the water temperature and reset it, thus exerting range reduction and hysteresis effects on the characteristics of water temperature change. The effect of a dam on river continuity is directly related to the dam size. To explain this relationship, two rivers in China were selected: one river without reservoirs and one river with cascade reservoirs. Through the analysis of the longitudinal change of water temperature in free-flowing rivers, we found that water temperature changes continuously and uniformly in the longitudinal direction. Based on this, a temperature trend hypothesis in river was proposed, and the discontinuity of the water temperature in the reservoir section was evaluated. The result is as follows: (1) In mixed reservoirs, river water temperature remained as continuous as free-flowing rivers. However, the river water temperature had a large discontinuity in the stratified reservoir; (2) Water residence time was used as an indicator of the continuity of reservoir water temperature; (3) Selective withdrawal of stratified reservoirs in January could not remove the discontinuity caused by itself, but it worked in June.
Into the looking glass: Post-viral syndrome post COVID-19
Ray Perrin
Lisa Riste

Ray Perrin

and 4 more

May 18, 2020
We are writing to highlight the potential for a post-viral syndrome to manifest following COVID-19 infection as previously reported following Severe Acute Respiratory Syndrome (SARS) infection, also a coronavirus. After the acute SARS episode some patients, many of whom were healthcare workers went on to develop a Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) - like illness which nearly 20 months on prevented them returning to work. We propose that once an acute COVID-19 infection has been overcome, a subgroup of remitted patients are likely to experience long-term adverse effects resembling CFS/ME symptomatology such as persistent fatigue, diffuse myalgia, depressive symptoms, and non-restorative sleep. In a contracted future economy, managing likely Post COVID-19 syndrome cases, in addition to existing CFS/ME cases will put additional burden on our already hard pressed healthcare system. We suggest that priority is given to exploration of pragmatic relatively low cost techniques to treat post-viral fatigue, to alleviate symptoms and improve quality of life for those affected by the longer term sequelae of COVID-19.
A Comparison of Figure-of-8-Suture vs Manual Compression for Venous Access Closure af...
Mark Terence Mujer
Abdullah Al-abcha

Mark Terence Mujer

and 4 more

May 18, 2020
Background Manual compression (MC) is the current standard to achieve post-procedural hemostasis in patients who need venous vascular access closure after cardiovascular procedures. Figure-of-8 (F8) suture for venous access closure has been reported to be a safe and efficacious alternative to MC. Methods A systematic search was done using PubMed, Google Scholar, EMBASE, SCOPUS and ClinicalTrials.gov without language restriction up until April 15, 2020 for studies comparing F8 suture vs MC. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated using a random effects model. Results Time to achieve hemostasis was significantly reduced in the F8 arm [MD -21.04 mins (95% CI: -35.66 to -6.42; p=.005)]. Access site bleeding was significantly lower in the F8 group [RR 0.35 (95% CI: 0.18 to 0.66; p=0.001)] along with a lower incidence of hematoma formation [RR 0.42 (95% CI 0.26 to 0.67; p=0.0003)]. There was no significant difference in rates of fistula or pseudoaneurysm formation between the two groups. Overall access site complications were lower in the F8 arm [RR 0.38 (95% CI: 0.26 to 0.55; p<0.00001)] and the effect was more pronounced for sheaths ≥10 Fr [RR 0.33 (95% CI: 0.18 to 0.60; p=0.0003)]. There was lower post-procedural protamine use in the F8 group [RR 0.07 (95% CI:0.01 to 0.36; p=0.001)]. Conclusion For large-bore venous access closure, the F8 suture results in a shortened time to achieve hemostasis along with a lower overall risk of access site complications and post-procedural protamine use.
Non-vitamin K Oral Anticoagulants in Hypertrophic Cardiomyopathy Patients Undergoing...
Antonio Creta
Ross Hunter

Antonio Creta

and 14 more

May 18, 2020
Introduction: Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to a high thromboembolic risk. Evidence supporting use of non-vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in HCM patients undergoing catheter ablation of AF. Methods: Observational non-randomised study in 4 European Centres. We aimed to investigate the safety and efficacy of NOACs compared with vitamin-K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF. Results: One hundred thirty-seven HCM patients (mean age 55.0±13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7±1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure-related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA 0.6%; NOAC 0%; p=1.0) or minor bleeding (VKA 0.6%; NOAC 1.4%; p=0.54). There was a non-significant trend towards a lower incidence of major bleeding (VKA 6.8%; NOAC 1.4%; p=0.09). Conclusion: These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF.
Intertwin differences in umbilical artery PI supersede the TTTS Quintero classificati...
Jimmy Espinoza
Michael Belfort (FETAL MEDICINE ISSUE EDITOR)

Jimmy Espinoza

and 11 more

May 18, 2020
Objective: To evaluate the role of intertwin differences in umbilical artery (UA) pulsatility index (DUAPI) in predicting infant survival in twin-to-twin transfusion syndrome (TTTS) Design: Retrospective cohort study Setting: Baylor College of Medicine, Texas Children’s Hospital and University of Maryland School of Medicine Population: Women who underwent laser surgery due to TTTS between 2002 and 2018. Methods: Absolute DUAPI were calculated prior to laser surgery. ROC analysis was done to derive a DUAPI cutoff value of 0.4 for the prediction of double infant survival. Regression analyses were performed to evaluate the association of DUAPI <0.4 and infant survival in the whole cohort, in TTTS cases with Quintero stages I/II and in those with Quintero stage III/IV; adjustments for gestational age at delivery, Quintero stage, selective fetal growth restriction (sFGR) and other confounders were done. Main Outcome Measure: Double infant survival to 30 days of life Results: 349 TTTS cases were included. Double twin survival to 30 days was observed in 67% (234/349) of cases. Intertwin DUAPI <0.4 was associated with increased double twin survival in the whole cohort (aOR: 3.40; 95% CI: 2.02-5.70; p<0.001), in women with TTTS Quintero stage I or II (aOR: 3.05; 95% CI: 1.32-7.09; p=0.009) and in women with TTTS Quintero stage III or IV (aOR: 3.23; 95% CI: 1.52-8.85; p=0.002). Neither Quintero stage nor sFGR were associated with infant survival. Conclusions: Intertwin differences in UA pulsatility index supersede the Quintero classification in the prediction of double infant survival following laser surgery in TTTS cases.
Tailoring hydrogen sulfide as therapeutic target in multiple sclerosis? Upregulation...
Milica Lazarević
Giuseppe Battaglia

Milica Lazarević

and 9 more

May 18, 2020
The aim of the study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-beta expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, peripheral blood mononuclear cells obtained from MS patients had lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
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