Who acquires infection from whom? A sensitivity analysis of transmission dynamics during the early phase of the COVID-19 pandemic in Belgium.

Age-related heterogeneity in a host population, whether due to how individuals mix and contact each other, the nature of host-pathogen interactions defining epidemiological parameters, or demographics, is crucial in studying infectious disease dynamics. Compartmental models represent a popular approach to address the problem, dividing the population of interest into a discrete and finite number of states depending on, for example, individuals' age and stage of infection. We study the corresponding linearised system whose operator, in the context of a discrete-time model, equates to a square matrix known as the next generation matrix. Performing formal perturbation analysis of the entries of the aforementioned matrix, we derive indices to quantify the age-specific variation of its dominant eigenvalue (i.e., the reproduction number) and explore the relevant epidemiological information we can derive from the eigenstructure of the matrix. The resulting method enables the assessment of the impact of age-related population heterogeneity on virus transmission. In particular, starting from an age-structured SEIR model, we demonstrate the use of this approach for COVID-19 dynamics in Belgium. We analyse the early stages of the SARS-CoV-2 spread, with particular attention to the pre-pandemic framework and the lockdown lifting phase initiated as of May 2020. Our results, influenced by our assumption on age-specific susceptibility and infectiousness, support the hypothesis that transmission was only influenced to a small extent by children in the age group [0,18) and adults over 60 years of age during the early phases of the pandemic and up to the end of July 2020.

Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads.

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.

Electrocardiographic Patterns in Patients with Neurally Mediated Syncope.

The baseline electrocardiogram (ECG) is less informative in neurally mediated syncope (NMS) than in arrhythmic syncope. However, some of the ECG patterns present in NMS can have diagnostic and prognostic value in such patients. Electrocardiographic documentation of a syncopal spell and thus identification of the ECG changes can be performed during tilt table test (TTT) or during prolonged ECG monitoring. This work reviews the specific ECG patterns in NMS, which are primarily related to the cardioinhibitory reflex. In addition, there are other ECG findings present in patients with NMS that are being analyzed, such as increased heart rate variability as well as specific QRS voltage patterns. In addition to the diagnostic and prognostic value, these ECG patterns in NMS may help improving the selection of patients for pacemaker implant.

Isolated very low QRS voltage predicts response to tilt-table testing in patients with neurally mediated syncope.

BACKGROUND: A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12-lead electrocardiogram (ECG). HYPOTHESIS: The aim of this study was to assess the importance of QRS voltage in predicting response to tilt-table testing (TTT) in patients with suspected NMS. METHODS: We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT-). The QRS voltage was measured in mV on 12-lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined. RESULTS: Very low voltage (QRSmin  ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT- group (74 vs 22%, respectively; P  < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT- group. QRSmin predicted a positive tilt-table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end-diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT- patients with a sensitivity of 78% and specificity of 68%. CONCLUSION: Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS.

Different synovial vasculogenic profiles of primary, rapidly destructive and osteonecrosis-induced hip osteoarthritis. An immunohistochemistry study.

PURPOSE: To present a hypothesis regarding the pathways of angiogenesis in primary versus secondary hip osteoarthritis (OA). METHODS: In synovial tissue samples provided by 57 consecutive patients who underwent hip arthroplasty, immunohistochemical examinations were performed using the following angiogenesis-related antibodies: VEGF-A, COX-2, maspin and the endothelial cells markers CD31 and CD105. The cases were divided into three categories: classic primary hip OA (group A; n = 16), rapidly destructive hip OA (group B; n = 24) and hip OA secondary to avascular osteonecrosis of the femoral head (group C; n = 17). The endothelial area (EA) was digitally quantified for both CD31 and CD105. RESULTS: The large mature vessels with CD105-positive activated endothelium predominated in group C, which also showed the highest CD105 median EA value (7.31 ± 4.01, compared to 4.76 ± 3.73 for group A and 6.69 ± 3.53 for group B). In groups A and B, synovial cell hyperplasia and the predominance of small immature vessels were characteristic. CD105, VEGF-A and COX-2 were focally seen in the synovial membrane, without maspin positivity. CONCLUSIONS: The severity of hip OA can be related to angiogenesis pathways that are not maspin-mediated. In primary hip OA, angiogenesis may be induced by a combined mechanism: hypoxia-related VEGF-dependent vasculogenesis and endothelial differentiation of the activated pluripotent cells, which are released from the hyperplastic synovial cells layer. An endothelial mesenchymal transition is assumed to be involved in the fibrotic process.

Quantitative analysis of polarity in 3D reveals local cell coordination in the embryonic mouse heart.

Anisotropies that underlie organ morphogenesis have been quantified in 2D, taking advantage of a reference axis. However, morphogenesis is a 3D process and it remains a challenge to analyze cell polarities in 3D. Here, we have designed a novel procedure that integrates multidisciplinary tools, including image segmentation, statistical analyses, axial clustering and correlation analysis. The result is a sensitive and unbiased assessment of the significant alignment of cell orientations in 3D, compared with a random axial distribution. Taking the mouse heart as a model, we validate the procedure at the fetal stage, when cardiomyocytes are known to be aligned. At the embryonic stage, our study reveals that ventricular cells are already coordinated locally. The centrosome-nucleus axes and the cell division axes are biased in a plane parallel to the outer surface of the heart, with a minor transmural component. We show further alignment of these axes locally in the plane of the heart surface. Our method is generally applicable to other sets of vectors or axes in 3D tissues to map the regions where they show significant alignment.

Icy: an open bioimage informatics platform for extended reproducible research.

Current research in biology uses evermore complex computational and imaging tools. Here we describe Icy, a collaborative bioimage informatics platform that combines a community website for contributing and sharing tools and material, and software with a high-end visual programming framework for seamless development of sophisticated imaging workflows. Icy extends the reproducible research principles, by encouraging and facilitating the reusability, modularity, standardization and management of algorithms and protocols. Icy is free, open-source and available at http://icy.bioimageanalysis.org/.

Extracting 3D cell parameters from dense tissue environments: application to the development of the mouse heart.

MOTIVATION: In developmental biology, quantitative tools to extract features from fluorescence microscopy images are becoming essential to characterize organ morphogenesis at the cellular level. However, automated image analysis in this context is a challenging task, owing to perturbations induced by the acquisition process, especially in organisms where the tissue is dense and opaque. RESULTS: We propose an automated framework for the segmentation of 3D microscopy images of highly cluttered environments such as developing tissues. The approach is based on a partial differential equation framework that jointly takes advantage of the nuclear and cellular membrane information to enable accurate extraction of nuclei and cells in dense tissues. This framework has been used to study the developing mouse heart, allowing the extraction of quantitative information such as the cell cycle duration; the method also provides qualitative information on cell division and cell polarity through the creation of 3D orientation maps that provide novel insight into tissue organization during organogenesis.

Frenemies within: An Endocarditis Case in Behçet's Disease.

A 57-year female patient diagnosed with Behçet's disease, on azathioprine, was noticed to have at a routine examination antinuclear and antiphospholipid antibodies. An overlapping lupus-like syndrome was diagnosed; hydroxychloroquine and aspirin were added. Three years later, the patient presented with dyspnea and sweating, with no fever. A cardiac bruit was noted; a giant vegetation was detected by echocardiography. Laboratory revealed severe thrombocytopenia, antiphospholipid antibodies and low complement. Blood cultures were positive for Abiotrophia defectiva serology and also revealed a chronic Coxiella burnetii infection. Antibiotic therapy, low-dose anticoagulation and control of the underlying disease mildly improved the platelet count, which fully recovered only after cardiac valve replacement. However, the Behçet's disease, initially quiescent, flared after the therapy of infections. We discuss potential links between Behçet's disease and the occurrence of antinuclear and antiphospholipid antibodies and Coxiella endocarditis in this setting. We also highlight the differences between the endocarditis in Behçet's disease, antiphospholipid syndrome, Coxiella burnetii and Abiotrophia defectiva infection, respectively. Intracellular infections may modify the presentation of autoimmune diseases. Confounding clinical features of Coxiella persistent infection and non-bacterial thrombotic endocarditis in Behçet's disease warrant further insight.

Correlation between Volumes Determined by Echocardiography and Cardiac MRI in Controls and Atrial Fibrillation Patients.

AIMS: We aimed to compare cardiac volumes measured with echocardiography (echo) and cardiac magnetic resonance imaging (MRI) in a mixed cohort of healthy controls (controls) and patients with atrial fibrillation (AF). MATERIALS AND METHODS: In total, 123 subjects were included in our study; 99 full datasets were analyzed. All the participants underwent clinical evaluation, EKG, echo, and cardiac MRI acquisition. Participants with full clinical data were grouped into 63 AF patients and 36 controls for calculation of left atrial volume (LA Vol) and 51 AF patients and 30 controls for calculation of left ventricular end-diastolic volume (LV EDV), end-systolic volume (ESV), and LV ejection fraction (LV EF). RESULTS: No significant differences in LA Vol were observed (p > 0.05) when measured by either echo or MRI. However, echo provided significantly lower values for left ventricular volume (p < 0.0001). The echo LA Vol of all the subjects correlated well with that measured by MRI (Spearmen correlation coefficient r = 0.83, p < 0.0001). When comparing the two methods, significant positive correlations of EDV (all subjects: r = 0.55; Controls: r = 0.71; and AF patients: r = 0.51) and ESV (all subjects: r = 0.62; Controls: r = 0.47; and AF patients: r = 0.66) were found, with a negative bias for values determined using echo. For a subgroup of participants with ventricular volumes smaller than 49.50 mL, this bias was missing, thus in this case echocardiography could be used as an alternative for MRI. CONCLUSION: Good correlation and reduced bias were observed for LA Vol and EF determined by echo as compared to cardiac MRI in a mixed cohort of patients with AF and healthy volunteers. For the determination of volume values below 49.50 mL, an excellent correlation was observed between values obtained using echo and MRI, with comparatively reduced bias for the volumes determined by echo. Therefore, in certain cases, echocardiography could be used as a less expensive, less time-consuming, and contraindication free alternative to MRI for cardiac volume determination.

Integrating Electrocardiography and Vectorcardiography in the Differential Diagnosis of Wide Complex Tachycardia in a Patient with Left Ventricular Noncompaction: A Case Report and Brief Literature Review.

A 69-year-old woman with a history of hypertension and obesity, hospitalized with atypical chest pain, was diagnosed with left ventricular noncompaction. In-hospital monitoring of the cardiac rhythm revealed multiple episodes of atrial tachycardia and one episode of wide complex tachycardia (WCT) with left bundle branch block-like morphology and a right superior QRS axis. The electrocardiographic criteria were suggestive of a supraventricular origin of the WCT. Given the importance of reaching the correct diagnosis when dealing with a WCT, we tried to further define the pattern of ventricular activation using vectorcardiography (VCG). We analyzed the QRS loops during WCT in comparison to a sinus beat, a narrow complex tachycardia beat, and a premature ventricular contraction. The fast initial activation seen in the efferent limb of the QRS loop during the WCT was thought to be reflective of the fast initial activation via the conduction system seen in SVT with aberrancy, which was our final diagnosis for the WCT episode. This case illustrates a novel use of vectorcardiography as an additional diagnostic tool in the differential diagnosis of WCT.

Usefulness of the Electrocardiogram in a Patient Presenting with Right-Sided Pneumothorax and Presyncope.

We present the case of a 71-year-old man with history of smoking, pulmonary emphysema, hypertension, multivessel coronary artery disease and prior coronary artery bypass graft surgery who presented with spontaneous right-sided pneumothorax associated with phasic changes of the QRS amplitude on the electrocardiogram. While several case reports have described QRS amplitude changes associated with left-sided pneumothorax, reports of phasic ECG changes in right-sided pneumothorax are exceedingly rare. Such changes, when present in a patient with sudden onset chest pain and dyspnea, should prompt a diagnostic workup for possible pneumothorax.

Isolated very low QRS voltage in the frontal leads predicts recurrence of neurally mediated syncope.

BACKGROUND: The study was prompted by our observation that some patients with neurally mediated syncope (NMS) have an isolated QRS complex, of very low voltage (≤0.3 mV cutoff), in 1 of the frontal leads on the 12-lead electrocardiogram. OBJECTIVE: To prospectively evaluate whether the presence of isolated very low voltage (VLV) predicts recurrence of NMS. METHODS: We included 205 patients (aged 50 ± 17 years) with a median of 3 syncopal episodes. Tilt testing was performed in all patients and was positive in 87 (42%). The patients were followed for a median of 14 months. RESULTS: VLV in frontal leads was present in 92 patients (45%). During the follow-up period 60 patients experienced recurrence of syncope. The actuarial total syncope recurrence rate at 1 year was 32% (95% confidence interval [CI 23%-44%) in patients with isolated VLV in frontal plane leads, and 14% (95% CI 8%-24%) in patients without VLV (log-rank test P < .0001). The significant relationship between the presence of isolated VLV in the frontal leads and syncope recurrence was retained in Cox multivariate analysis that included the history of presyncope and syncope as well as the left ventricular end-diastolic diameter. The presence of isolated VLV in frontal leads was associated with a 3-fold increase of the risk of recurrent syncope. CONCLUSIONS: Isolated very low QRS voltage in the frontal leads predicts recurrence of NMS independent of clinical factors that predict recurrence of syncope in such patients. This phenomenon may help generate new diagnostic tools and insights into the pathogenesis of NMS.

Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth.

Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus. The nuclear translocation of Amotl1 is accompanied by Yap1 to promote cardiomyocyte proliferation. We, therefore, identify Amotl1, which is not present in flies, as a mammalian intermediate for non-canonical Hippo signalling, downstream of Fat4. This work uncovers a mechanism for the restriction of heart growth at birth, a process which impedes the regenerative potential of the mammalian heart.

Anomalies of the inferior vena cava in patients with deep venous thrombosis. Pictorial essay.

The incidence of agenesis of inferior vena cava in the general population was estimated at 0.6 - 0.8%. In patients with deep vein thrombosis the frequency of agenesis was estimated between 5 and 6.7% in young people. In this pictorial essay, we present the ultrasound findings obtained in 8 patients with high deep venous thrombosis and inferior vena cava anomaly (absence of a segment), compared with images obtained by angio-computed tomography or magnetic resonance imaging. At the end we discuss the place of abdominal ultrasound in the evaluation of these patients.

Ultrasound features of lacrimal gland in Sjogren's syndrome: case report.

A case is presented of bilateral lacrimal gland hypertrophy with secondary glaucoma due to the increased episcleralvenous pressure. Diagnostic work-up included clinical methods associated with ultrasound (A- and B-scan, Doppler ultrasound) and magnetic resonance imaging techniques. Clinical data revealed proptosis, episcleral congestion, and elevated intraocular pressure. Abnormal Schirmer's test and xerophthalmia were also present. Ultrasound examination identified enlarged masses of a cystic structure in lacrimal fossae bilaterally, superotemporally to the globe, more pronounced on the left side. Doppler ultrasound revealed vascularization and magnetic resonance imaging completed the findings offered by ultrasound methods. Based on the clinical aspect and the possible visual impairment due to secondary glaucoma, the mass lesion on the left side was removed by neurosurgical approach. Histopathology confirmed destruction of the lacrimal gland and immunohistochemistry indicated Sjogren's syndrome lesions. Sonography is able to provide noninvasively much of the information needed by the clinician. The A-scan and B-scan ultrasound techniques and color Doppler allow tracking and discrimination of orbital diseases, such as lacrimal gland lesions. Associated with clinical features, these methods provide the basis of correct diagnosis and appropriate therapy for lacrimal gland pathology.