Congenital Aortic Stenosis in Adults: Update on clinical outcome, diagnostic methods and pregnancy

Background and aim of the study: The pulmonary autograft has been recommended as the valve of choice for aortic valve replacement (AVR) in young women contemplating pregnancy. However, current information on maternal and perinatal outcome of pregnancy in women with pulmonary autograft valve replacement is limited. Methods: Using a nationwide Dutch registry (CONCOR) and a local Belgian tertiary care centre database, 17 women (age range: 18-45 years) with pulmonary autograft valve replacement were enrolled into the study. Twelve pregnancies were observed among five different women, including one miscarriage and one elective abortion. Results: Clinically significant (non-)cardiac complications were documented in two of 10 completed pregnancies. Complications included: (I) placental abruption necessitating Cesarean delivery at 29 weeks’ gestation, further complicated by postpartum hemorrhage; and (II) preterm premature rupture of the membranes resulting in premature delivery at 29 weeks’ gestation with postpartum demise of the immature born child. Two women reported primary female infertility, but both became pregnant after hormonal substitution therapy. Four women reported irregularities of their natural menstrual cycle (menorrhagia, dysmenorrhea, polymenorrhea, oligomenorrhea, or amenorrhea). Conclusions: Successful pregnancy in women with pulmonary autograft valve replacement is possible, although serious and clinically significant events occurred during gestation. Infertility and menstrual cycle disorders appear to be more prevalent

Pathophysiological Mechanisms of Premature Ventricular Complexes

Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia. Despite the high prevalence, the cause of PVCs remains elusive in most patients. A better understanding of the underlying pathophysiological mechanism may help to steer future research. This review aims to provide an overview of the potential pathophysiological mechanisms of PVCs and their differentiation

Enhancing Production of Recombinant Proteins from Mammalian Cells

The bio-manufacturing of recombinant proteins from mammalian cell cultures requires robust processes that can maximize protein yield while ensuring the efficacy of these proteins as human therapeutics. Recognizing that the challenge of improving protein yield and quality can be met through various approaches, this paper presents three strategies currently being developed in our group. A method for rapidly selecting subpopulations of cells with high production characteristics is proposed. This method combines the efficiency of green fluorescent protein/fluorescence-activated cell sorting (GFP/FACS)–based screening with homologous recombination to generate and select high-producing subclones. Next, the development of chemically defined, protein-free media for enhancing monoclonal antibody production is described. Analysis of culture media effects on the genome-wide transcriptional program of the cell is presented as a means to optimize the culture media and identify potential targets for genetic manipulation. Finally, we propose a method for increasing the extent of intracellular sialylation by improving the transport of CMP-sialic acid into the trans-Golgi. This is hypothesized to increase the sialic acid availability, and may enhance the degree of sialylation in the glycoprotein product.Singapore-MIT Alliance (SMA

EXECUTIVE SUMMARY OF ARTS IN EDUCATION RESEARCH PROJECT

Since 1999, the South Carolina Arts Commission, the South Carolina Department of Education, and later the Arts in Basic Curriculum Project (ABC) have co-sponsored the Arts Education Research Project to track the progress and effects of arts education reform efforts in various ABC schools across the state. This report addresses the specific purposes of the Arts Education Research Project which were to (a) document the arts instruction in place prior to reform implementation, (b) determine the effects of increased, modified, or integrated arts instruction, and (c) identify potential influences that promote, inhibit, or sustain changes in schools that implemented arts reform

Engineering Mammalian Cells for Improved Recombinant Protein Production

The production of recombinant glycoproteins from mammalian cell cultures requires robust processes that can achieve high protein yield while ensuring the efficacy of these proteins as human therapeutics. We describe two approaches currently being developed in our group to genetically engineer cell lines with desirable characteristics for recombinant protein production. To enhance the degree of sialylation in the glycoprotein product, we propose to increase intracellular sialic acid availability by overexpressing the CMP-sialic acid transporters. We are also interested in engineering mammalian cells that can proliferate at reduced cultivation temperatures. Low temperature cultivation of mammalian cells has been shown to enhance glycoprotein production but reduces cell growth. It is hypothesized that a mutant cell line that can proliferate at low temperatures may be coupled with low temperature cultivation to improve recombinant protein production.Singapore-MIT Alliance (SMA

Reducing radiation exposure in second-generation cryoballoon ablation without compromising clinical outcome

Purpose: Pulmonary vein isolation (PVI) using cryoballoon (CB) ablation is associated with an increased radiation exposure compared with radiofrequency ablation. Previous studies showed that radiation exposure in CB PVI can be reduced by optimizing the fluoroscopy protocol without comprising acute efficacy and safety. We evaluated the mid-term outcome of a modified fluoroscopy protocol in patients undergoing CB PVI. Methods: The study population comprised 90 consecutive patients who underwent second-generation CB-based PVI. The first 46 patients underwent CB PVI with conventional fl

Outcome of Insertable Cardiac Monitors in Symptomatic Patients with Brugada Syndrome at Low Risk of Sudden Cardiac Death

Introduction: There is limited data on the experience with insertable cardiac monitors (ICMs) in patients with Brugada syndrome. Objective: To evaluate the outcome of ICM in symptomatic patients with Brugada syndrome who are at suspected low risk of sudden cardiac death (SCD). Methods: We conducted a prospective single-center cohort study including all symptomatic patients with Brugada syndrome who received an ICM (Reveal LINQ) between July 2014 and October 2019. The main indication for monitoring was to exclude ventricular arrhythmias as the cause of symptoms and to establish a symptom-rhythm relationship. Results: A total of 20 patients (mean age, 39 ± 12 years; 55% male) received an ICM during the study period. Nine patients (45%) had a history of syncope (presumed nonarrhythmogenic), and 5 patients had a recent syncope (<6 months). During a median follow-up of 32 months (interquartile range, 11-36 months), 3 patients (15%) experienced an episode of nonsustained ventricular arrhythmia. No patient died suddenly or experienced a sustained ventricular arrhythmia, and no

Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis

Background: Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis. This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks, although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Platelet count, spleen length, and platelet count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices. Objectives: Primary objectives To determine the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis, irrespective of aetiology. We aimed to perform pair-wise comparisons between the three index tests, while considering predefined cut-off values. We investigated sources of heterogeneity. Search methods: The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science) (14 June 2016). We applied no language or document-type restrictions. Selection criteria: Studies evaluating the diagnostic accuracy of platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age with chronic liver disease or portal vein thrombosis, who did not have variceal bleeding. Data collection and analysis: Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. Main results: We included 71 studies, 67 of which enrolled only adults and four only children. All included studies were cross-sectional and were undertaken at a tertiary care centre. Eight studies reported study results in abstracts or letters. We considered all but one of the included studies to be at high risk of bias. We had major concerns about defining the cut-off value for the three index tests; most included studies derived the best cut-off values a posteriori, thus overestimating accuracy; 16 studies were designed to validate the 909 (n/mm3)/mm cut-off value for platelet count-to-spleen length ratio. Enrolment of participants was not consecutive in six studies and was unclear in 31 studies. Thirty-four studies assessed enrolment consecutively. Eleven studies excluded some included participants from the analyses, and in only one study, the time interval between index tests and the reference standard was longer than three months. Diagnosis of varices of any size. Platelet count showed sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000 to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources of heterogeneity, we found that of all predefined factors, only aetiology had a role: studies including participants with chronic hepatitis C reported different results when compared with studies including participants with mixed aetiologies (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from 110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and specificity of 0.84 (95% CI 0.75 0.91) in 17 studies, and 2637 participants had a cut-off value for platelet count-to-spleen length ratio of 909 (n/mm3)/mm. We found no effect of predefined sources of heterogeneity. An overall indirect comparison of the HSROCs of the three index tests showed that platelet count-to-spleen length ratio was the most accurate index test when compared with platelet count (P 909 (n/mm3)/mm, the presence of oesophageal varices of any size can be excluded and only 7% of adults with varices of any size would be missed, allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations. This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis. Future studies should assess the diagnostic accuracy of this test in specific subgroups of patients, as well as its ability to predict variceal bleeding. New non-invasive tests should be examined