Establishment of ionic channels and signalling cascades in the embryonic stem cell-derived primitive endoderm and cardiovascular system

The first organ system to be established in early embryogenesis is the cardiovascular system which develops upon interaction with hypoblastic cells of the primitive endoderm. Here we focus on recent work on embryoid bodies derived from pluripotent embryonic stem (ES) cells. Ca(2+) oscillations and Ca(2+) signalling pathways during the differentiation of primitive endodermal cell layers are reported. Furthermore, the development-dependent expression of ion channels and the buildup of signalling cascades involved in the modulation of voltage-dependent L-type Ca(2+) channels during early cardiomyogenesis and the formation of functional vascular structures in the process of vasculogenesis and angiogenesis are reviewed. We also report on the use of green fluorescent protein reporter gene expression under the control of cardiac-specific promoters, e.g. the human cardiac alpha-actin promoter, which enables the identification and in vivo characterization of cardiomyocytes at very early stages of cardiomyogenesis.     

Localisation of myocardial ischaemia from the magnetocardiogram using current density reconstruction method: computer simulation study

A computer simulation study is performed to investigate the method of current density reconstruction to localise myocardial ischaemia. A computer model of the entire human heart is used to simulate the excitation and repolarisation process in eight topographically different cases of myocardial ischaemia. The associated magnetocardiogram is calculated at 37 positions of the KRENIKON^* biomagnetic measurement equipment. The method of current density reconstruction is applied at the S-point (the last discemible deviation from the ST-segment at the end of the QRS-complex) of the MCG to find characteristics of the myocardial ischaemia simulated by the model. The results show that it is possible to determine the location of the ischaemia. The current density distribution may be interpreted physiologically in terms of the so-called ‘injury current’. This indicates that magnetocardiography might be a suitable method for noninvasive ischaemia diagnosis, and further investigations of the current density reconstruction method for the injury current should be performed on patients with ischaemic heart disease.     

Cardiac myxomas

Cardiac myxoma is the most common primary tumor of the heart. Between 1970 and 1998, 33 myxomas from patients operated at the Cardiosurgical Department were submitted for pathological examination. A review of age, sex and clinical symptoms of the patients as well as of gross and histological features of the tumors is presented. Immunohistochemical examination was performed on 10 selected myxomas-reactivity to vimentin, desmin, S-100 protein, cytokeratin and FVIIIR-Ag. The necessity of histological examination of the embolectomy material is stressed.     

Mathematical analysis of arterial enhancement and optimization of bolus geometry for CT angiography using the discrete fourier transform.

PURPOSE: The goal of this work was to develop a clinically applicable mathematical algorithm to analyze and optimize individual arterial enhancement in CT angiography (CTA). METHOD: Assuming a time-invariant linear system, the discrete Fourier transform was used to calculate the transfer function of the system ("patient function") from the arterial time-attenuation response to a test bolus. The patient function was subsequently used to predict aortic enhancement in five select patients and to calculate optimized biphasic injection protocols in two of these patients undergoing CTA of the abdominal aorta. RESULTS: Arterial time-attenuation curves were accurately predicted in all patients. Optimized biphasic contrast agent injection protocols resulted in uniform aortic enhancement at the predefined level over the entire scanning period in both subjects despite markedly different contrast agent volumes and injection rates used. CONCLUSION: Fourier analysis of the time-attenuation response to a test bolus is a simple and feasible approach to optimize arterial enhancement in CTA.     

Axillary-coronary artery bypass reconstruction as an alternative in coronary artery reoperations

BACKGROUND AND AIMS: The increasing incidence of reoperations in coronary surgery associated with higher perioperative risks is a challenge for refinement of the surgical methods. The aim of the work is to prove the feasibility and satisfactory intermediate results of minimally invasive axillary-coronary artery bypass reconstruction in redo coronary surgery in case the left internal mammary artery had already been harvested. MATERIAL AND METHODS: Three patients (six months, two and six years after primary coronary artery bypass grafting) admitted for redo coronary surgery because of a recurrence of angina and proven malfunction of the left internal mammary artery-left anterior descending coronary artery anastomosis. An axillary-coronary venous graft was performed via left anterior small thoracotomy (LAST) on a beating heart in all three cases. RESULTS: Excellent patency of the graft was noted on control angiography within 9 days after the procedure together with good clinical improvement in midterm follow-up. CONCLUSION: Minimally invasive axillary-coronary artery bypass via LAST access in redo coronary surgery is a good alternative in cases where the left internal mammary artery cannot be used.     

Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes

The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects.Subject terms: Disease genetics, Genetic counselling, Biological sciences     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.     

Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters

BackgroundCardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes.HypothesisWe therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19.MethodsWe included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis.ResultsOut of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor.ConclusionRisk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.     

A polymorphism of the interleukin-1 beta gene is associated with sperm pathology in humans

In a prospective case-control study of 127 normozoospermic and 435 non-normozoospermic Caucasian men, the genotype frequencies of a polymorphism of the interleukin-1 beta gene (IL-1beta Taq C-->T) were statistically significantly different between groups (homozygous wild-type C/C [57%], heterozygous C/T [42%], and homozygous mutant T/T [1%] vs. C/C [57%], C/T [36%], T/T [7%] for normozoospermic and non-normozoospermic men, respectively; odds ratio, 4.8; 95% confidence interval, 1.13 to 20.28). This association was restricted to men with the oligoasthenoteratozoospermia (OAT) syndrome. We conclude that the investigated polymorphism is associated with sperm pathology in Caucasians.