The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and ...neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.
Tp-e /QT ratio as an index of arrhythmogenesis Gupta, Prasad, MD; Patel, Chinmay, MD; Patel, Harsh, MBBS ...
Journal of electrocardiology,
11/2008, Letnik:
41, Številka:
6
Journal Article
Recenzirano
Abstract An increasing number of basic and clinical studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e ) may correspond to the transmural ...dispersion of repolarization and that amplification of the Tp-e interval is associated with malignant ventricular arrhythmias. In this review, we outline the utility of the Tp-e interval and the Tp-e /QT ratio as an electrocardiographic index of arrhythmogenesis for both congenital and acquired ion channel disease leading to ventricular arrhythmias. In healthy individuals, the Tp-e /QT ratio has a mean value of approximately 0.21 in the precordial leads and it remains relatively constant between the heart rates from 60 to 100 beats per minute. Interestingly, the Tp-e /QT ratio is significantly greater in the patients at risk for arrhythmic event such as those with long QT syndrome, Brugada syndrome, short QT syndrome, and also in patients with organic heart disease such as acute myocardial infarction. Functional reentry is the underlying mechanism for arrhythmogenesis associated with an increased Tp-e /QT ratio.
Motivation: Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has ...been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences. Results: Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text. Availability: Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/ Contact: artemis@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
Immunization is one of the greatest public health achievements of the 20
century. Vaccines have enabled the eradication of deadly diseases and decreased the morbidity and mortality associated with ...various infections. Most vaccines are safe to administer and cause only minor side effects. Although very rare, various glomerular diseases and acute kidney injury have been reported following immunization with certain vaccines including influenza, pneumococcal, and hepatitis B vaccines. This review summarizes these rare renal complications that have been published in the literature. Physicians and other health-care providers administrating vaccines should be aware of these very rare but possible renal side effects.
Dronedarone PATEL, Chinmay; YAN, Gan-Xin; KOWEY, Peter R
Circulation (New York, N.Y.),
08/2009, Letnik:
120, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during ...chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation.
Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using ...photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring.
We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (
=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%).
Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.
Summary Hypothyroidism is a common medical condition and is often easily managed with excellent outcomes, when treated adequately. Compliance with levothyroxine (LT4) therapy is often compromised ...because of the need for a daily and lasting schedule. Overt rhabdomyolysis due to under-treatment or non-compliance is a rare occurrence. We report a case of rhabdomyolysis leading to acute kidney injury (AKI) on chronic kidney disease (CKD) requiring hemodialysis (HD) in a 68-year-old Caucasian male due to non-compliance with levothyroxine (LT4) therapy. Our patient 'ran out of levothyroxine' for approximately 4 weeks and developed gradually progressive muscle pain. The diagnosis of severe AKI due to rhabdomyolysis was made based on oliguria, elevated creatinine kinase (CK), and renal failure. Resuming the home dose of LT4 failed to correct CK levels, and there was a progressive decline in renal function. Although increasing doses of LT4 and three cycles of HD improved CK levels, they remained above baseline at the time of discharge. The patient recovered gradually and required HD for 4 weeks. CK levels normalized at 6 weeks. Through this case report, we highlight that non-compliance with LT4 therapy can lead to life-threatening complications such as renal failure and hence the need to educate patients on the significance of compliance with LT4 therapy should be addressed. Learning points Non-compliance to levothyroxine therapy is common and can lead to serious complications, including rhabdomyolysis. Rhabdomyolysis is an uncommon presentation of hypothyroidism and severe rhabdomyolysis can result in renal failure requiring hemodialysis. Rhabdomyolysis associated with hypothyroidism can be further exacerbated by concomitant use of statins.
Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of ...arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype-phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS.
Echocardiography frequently serves as the first-line treatment of diagnostic imaging for several pathological entities in cardiology. Artificial intelligence (AI) has been growing substantially in ...information technology and various commercial industries. Machine learning (ML), a branch of AI, has been shown to expand the capabilities and potential of echocardiography. ML algorithms expand the field of echocardiography by automated assessment of the ejection fraction and left ventricular function, integrating novel approaches such as speckle tracking or tissue Doppler echocardiography or vector flow mapping, improved phenotyping, distinguishing between cardiac conditions, and incorporating information from mobile health and genomics. In this review article, we assess the impact of AI and ML in echocardiography.
Plain Language Summary
Echocardiography is the most common test in cardiovascular imaging and helps diagnose multiple different diseases. Machine learning, a branch of artificial intelligence (AI), will reduce the workload for medical professionals and help improve clinical workflows. It can rapidly calculate a lot of important cardiac parameters such as the ejection fraction or important metrics during different phases of the cardiac cycle. Machine learning algorithms can include new technology in echocardiography such as speckle tracking, tissue Doppler echocardiography, vector flow mapping, and other approaches in a user-friendly manner. Furthermore, it can help find new subtypes of existing diseases in cardiology. In this review article, we look at the current role of machine learning and AI in the field of echocardiography.
Abstract Objectives The purpose of this study was to examine the role of mexiletine, a late sodium current (INa-L ) blocker, in acute termination of torsades de pointes (TdP) refractory to ...conventional therapy in acquired long QT syndromes (LQTS). Background Long QT interval can predispose to TdP and is therefore associated with significant mortality. Currently, there is no available pharmacotherapy to target directly the ionic basis of most LQTS for the acute termination of TdP. Earlier evidence highlighted the role of INa-L in the pathophysiology of long QT and TdP, particularly in patients with congenital LQTS. Methods Twelve patients with TdP caused by acquired LQTS were treated with mexiletine after failure of conventional treatment including discontinuation of QT-prolonging drugs, intravenous administration of magnesium, and correction of serum electrolyte abnormalities. Results No recurrence of TdP occurred within 2 h after initiation of treatment with mexiletine in all 12 patients. Macro T-wave alternans accompanied by QT prolongation, an electrocardiographic precursor of TdP that was seen in 3 patients, was also abolished by mexiletine. Treatment with mexiletine shortened the QTc interval from 599 ± 27 ms to 514 ± 16 ms (p = 0.001). The interval from the peak to the end of the T-wave (Tp-e interval) decreased from 145 ± 18 ms to 106 ± 9 ms (p = 0.005). The Tp-e /QT ratio decreased from 0.27 ± 0.02 to 0.23 ± 0.018 (p = 0.01). Mexiletine had no significant effect on QRS complex duration. Conclusions INa-L blockade with mexiletine may be an effective treatment approach to terminate refractory TdP from several acquired causes of LQTS.
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