Modeling and Simulation of VEGF Receptors Recruitment in Angiogenesis

Angiogenesis, the process of new blood vessel formation from preexisting ones, plays a pivotal role in tumor growth. Vascular endothelial growth factor receptor-2 (VEGFR2) is the main proangiogenic tyrosine kinase receptor expressed by endothelial cells (ECs). VEGFR2 binds different ligands triggering vascular permeability and growth. VEGFR2-ligands accumulate in the extracellular matrix (ECM) and induce the polarization of ECs as well as the relocation of VEGFR2 in the basal cell membrane in contact with ECM. We propose here a multiphysical model to describe the dynamic of VEGFR2 on the plasma membrane. The governing equations for the relocation of VEGFR2 on the membrane stem from a rigorous thermodynamic setting, whereby strong simplifying assumptions are here taken and discussed. The multiphysics model is validated against experimental investigations

Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): Distinct from Kawasaki disease or part of the same spectrum?

One of the most challenging and intriguing phenomena observed during the COVID-19 pandemic has been the multisystem inflammatory syndrome in children (MIS-C). Patients with this condition present with some clinical features similar to those of Kawasaki disease (KD) and display signs and symptoms that are uncommon or rarely occur in this disorder, such as gastrointestinal complaints and myocarditis, often leading to myocardial failure and shock. In addition, patients\u2019 age is older than that of children with classic KD. Management is based on administering intravenous immunoglobulin, glucocorticoids, and anakinra in the most severe instances. It is still debated whether MIS-C and KD are different illnesses or represent a disease continuum

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

2.4 Magnetic resonance imaging, ultrasonography and conventional radiography in the assessment of bone erosions in juvenile idiopathic arthritis

OBJECTIVE: To compare magnetic resonance imaging (MRI), conventional radiography, and ultrasonography in identifying bone erosions in patients with juvenile idiopathic arthritis (JIA), and to determine the validity and reliability of an MRI scale in detecting and grading joint damage. METHODS: In 26 JIA patients, the clinically more affected wrist was studied with MRI, radiography, and ultrasonography, coupled with standard clinical assessment and biochemical analysis. MR images were assessed independently by 2 readers according to an apposite devised scoring system. RESULTS: Of 26 patients, 25 (96.1%) had 1 or more erosions as detected by MRI, whereas conventional radiography and ultrasonography revealed erosions in 13 (50%) of 26 and 12 (50%) of 24 patients, respectively. The ability of MRI to detect erosive changes was significantly higher with respect to conventional radiography (P = 0.002 with Bonferroni correction [P(B)]) and ultrasonography (P(B) = 0.0002) in the group of patients with <3 years' disease duration. Ultrasonography and conventional radiography were of equivalent value for the detection of destructive changes. Wrist MRI score correlated highly with radiographic erosion score (r(s) = 0.82) and with wrist limited range of motion score (r(s) = 0.69). The interreader intraclass correlation coefficient (ICC) for MRI score was excellent (0.97); intrareader ICCs were good for both investigators (0.97 and 0.79). CONCLUSION: MRI seems to be a powerful tool to detect early structural damage in JIA. The proposed MRI scale for bone erosions appears promising in terms of reliability and construct validity. The pathophysiologic meaning and the prognostic value of bone erosions revealed only by MRI remain to be established in longitudinal studies

Using HAQ-DI to estimate HUI-3 and EQ-5D utility values for patients with rheumatoid arthritis in Spain

AbstractBackground/ObjectiveUtility values are not usually assessed in clinical trials and do not allow cost-utility analysis to be performed with the data collected. The aim of this study was to derive relation functions so that Health Assessment Questionnaire – Disability Index (HAQ-DI) scores could be used to estimate Health Utilities Index - 3 (HUI-3) and EQ-5D utility values for patients with rheumatoid arthritis (RA).MethodsAn observational, cross-sectional, naturalistic, multicentre study was conducted. A total of 244 patients aged 18 years or older, with RA according to American College of Rheumatology diagnostic criteria, were recruited. Sociodemographic and clinical variables were recorded and patients completed three generic HRQoL questionnaires: the HAQ-DI, the HUI-3, and the EQ-5D. Two linear regression models were used to predict HUI-3 and EQ-5D utility values as functions of HAQ-DI scores, age, and gender.ResultsPatient mean age was 57.8 years old (standard deviation [SD], 13.3 years); 75.8% of the patients were women and 95.9% were white. Mean disease duration was 10.8 years (SD, 9 years). Patient distribution according to HAQ-DI severity was as follows: HAQ-DI < 0.5, 29%; 0.5 ≤ HAQ-DI < 1.1, 28%; 1.1 ≤ HAQ-DI < 1.6, 16%,1.6 ≤ HAQ-DI < 2.1, 15%; and HAQ-DI ≥ 2.1, 12%. HAQ-DI and EQ-5D mean scores were 1.02 (SD, 0.78) and 63.1 (SD, 20.3), respectively. Mean utility values for HUI-3 and time trade-off (TTO) were 0.75 (SD, 0.21) and 0.65 (SD, 0.3), respectively. The equations converting HAQ-DI scores to utilities were HUI-3 = 0.9527 – (0.2018 × HAQ-DI) +ε (R2=0.56), and TTO = 0.9567 – (0.309 × HAQ-DI) + ε (R2=0.54). Error distribution was non-normal. Age and gender were found to have no bearing on the utility functions.ConclusionsHAQ-DI scores can be used to estimate HUI-3 and EQ-5D utility values for patients with RA in data obtained from studies where utility values have not been collected