Preclinical validation of the advection diffusion flow estimation method using computational patient specific coronary tree phantoms.

Coronary computed tomography angiography (CCTA) does not allow the quantification of reduced blood flow due to coronary artery disease (CAD). In response, numerical methods based on the CCTA image have been developed to compute coronary blood flow and assess the impact of disease. However to compute blood flow in the coronary arteries, numerical methods require specification of boundary conditions that are difficult to estimate accurately in a patient-specific manner. We describe herein a new noninvasive flow estimation method, called Advection Diffusion Flow Estimation (ADFE), to compute coronary artery flow from CCTA to use as boundary conditions for numerical models of coronary blood flow. ADFE uses image contrast variation along the tree-like structure to estimate flow in each vessel. For validating this method we used patient specific software phantoms on which the transport of contrast was simulated. This controlled validation setting enables a direct comparison between estimated flow and actual flow and a detailed investigation of factors affecting accuracy. A total of 10 CCTA image data sets were processed to extract all necessary information for simulating contrast transport. A spectral element method solver was used for computing the ground truth simulations with high accuracy. On this data set, the ADFE method showed a high correlation coefficient of 0.998 between estimated flow and the ground truth flow together with an average relative error of only 1 % . Comparing the ADFE method with the best method currently available (TAFE) for image-based blood flow estimation, which showed a correlation coefficient of 0.752 and average error of 20 % , it can be concluded that the ADFE method has the potential to significantly improve the quantification of coronary artery blood flow derived from contrast gradients in CCTA images.

Fish Allergy: Fishing for Novel Diagnostic and Therapeutic Options.

Fish allergy is one of the most common food allergies. The currently recommended treatment commonly consists of avoiding all fish species. Recent literature suggests that these recommendations are overprotective for the majority of fish-allergic patients. This review summarizes recent findings and provides practical information regarding management of fish allergy in the individual patient. After precise history taking supported by additional specific IgE measurements and/or skin prick tests, fish-allergic patients can generally be categorized into the following clinical clusters: (A) poly-sensitized patients reacting to all fish species due to their sensitization to the panallergen ß-parvalbumin, (B) mono-sensitized patients with selective reactions to individual fish species only, and (C) oligo-sensitized patients reacting to several specific fish. A number of allergens including parvalbumin, enolase, and aldolase can be involved. Depending on the specific cluster the patient belongs to, oral food challenges for one or more fish species can be performed with the aim to provide safe alternatives for consumption. This way, several alternative fish species can be identified for mono- and oligo-sensitized patients that can safely be consumed. Notably, even poly-sensitized patients generally tolerate fish species low in ß-parvalbumin such as tuna and mackerel, particularly when processed. Taken together, allergological evaluation of patients with a documented fish allergy should be strongly considered, as it will allow the majority of patients to safely reintroduce one or more fish species.

Increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies.

PURPOSE: Gastrointestinal disease occurs frequently in antibody deficiencies. This study aims to explore the relation between gastrointestinal infections and mucosal homeostasis in patients with antibody deficiencies. METHODS: We performed an observational study including 54 pediatric antibody deficient patients (48 % CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores and stool samples were collected prospectively. Stool samples were evaluated for bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results were compared between patients and controls. RESULTS: 24 % of antibody deficient patients versus 9 % of healthy controls tested positive for gastrointestinal viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus positive patients compared to virus negative patients (p = 0.002). However, in controls, fecal calprotectin levels were similar between virus positive and virus negative controls. Moreover, gastrointestinal virus positive patients had low serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus negative patient group (p = 0.04). The virus positive patient group also displayed significantly lower secretory IgA levels in stool (median 13 ug/ml) than patients without gastrointestinal viruses detected or healthy controls (median 155 ug/ml) (p = 0.046). CONCLUSION: We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy.

Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a common primary immune deficiency, caused by undefined defects in lymphocyte function, and is treated routinely by immunoglobulin substitution. CVID complications include airway disease (AD) and interstitial lung disease (ILD). It was not known if AD and ILD in CVID have a common immunological aetiology and should be considered separate features of the same disease, or as distinct syndromes that require specialized monitoring and treatment. We used high-resolution computed tomography (CT) to diagnose AD or ILD in paediatric CVID patients. Spirometry and body plethysmography did not differentiate between ILD and AD. Patients with AD (n = 11, 20%) developed more pneumonias while children with ILD (n = 8, 15%) showed immune dysregulation characterized by autoimmune complications, more severe memory B cell reduction and expansion of non-naive cytotoxic T cells. In conclusion, ILD and AD in CVID have dissimilar clinical and immunological characteristics, suggesting distinct aetiology requiring tailored monitoring and treatment of these patient subgroups.

High-resolution computed tomography and pulmonary function in children with common variable immunodeficiency.

High-resolution computed tomography (HRCT) may be useful to monitor lung disease in children with common variable immunodeficiency disorder (CVID). We evaluated interobserver agreement and correlation with pulmonary function tests (PFTs) for automated quantification and visual scoring of air trapping and airway wall thickening on HRCT in paediatric CVID patients. In a cohort of 51 children with CVID, HRCT was analysed visually and automated for presence of air trapping and airway wall thickening. PFTs were expressed as % predicted. Disease duration, physician-diagnosed pneumonias and antibiotic prophylaxis were recorded. Interobserver agreement for automated airway wall thickening was good with an intra-class correlation coefficient of 0.88, compared with 0.51 for visual scoring. Presence of air trapping on HRCT correlated significantly with PFTs and disease duration, but was not associated with previous pneumonias. Airway wall thickening did not correlate significantly with PFTs or disease duration and was not associated with previous pneumonias or prophylactic antibiotic use. In children with CVID disorders, HRCT air trapping measurements are significantly correlated with PFTs and disease duration. Quantitative air trapping is a feasible and promising technique for small airway disease quantification that may be applied to monitor (silent) disease progression in CVID.

A model for arterial adaptation combining microstructural collagen remodeling and 3D tissue growth.

Long-term adaptation of soft tissues is realized through growth and remodeling (G&R). Mathematical models are powerful tools in testing hypotheses on G&R and supporting the design and interpretation of experiments. Most theoretical G&R studies concentrate on description of either growth or remodeling. Our model combines concepts of remodeling of collagen recruitment stretch and orientation suggested by other authors with a novel model of general 3D growth. We translate a growth-induced volume change into a change in shape due to the interaction of the growing tissue with its environment. Our G&R model is implemented in a finite element package in 3D, but applied to two rotationally symmetric cases, i.e., the adaptation towards the homeostatic state of the human aorta and the development of a fusiform aneurysm. Starting from a guessed non-homeostatic state, the model is able to reproduce a homeostatic state of an artery with realistic parameters. We investigate the sensitivity of this state to settings of initial parameters. In addition, we simulate G&R of a fusiform aneurysm, initiated by a localized degradation of the matrix of the healthy artery. The aneurysm stabilizes in size soon after the degradation stops.

A note on the reduced creep function corresponding to the quasi-linear visco-elastic model proposed by Fung.

For description of the visco-elastic behavior of soft biological tissues, Fung proposed a visco-elastic model formulated in terms of a relaxation function and corresponding relaxation spectrum. For the corresponding creep function, Fung proposed an expression which needs correction to obtain a consistent formulation. This creep function and the corresponding creep spectrum are derived in this note.