Background:
Since the late ‘90s, infliximab (Remicade
®
) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, ...infliximab biosimilars, including Remsima
®
were introduced in clinical practice.
Aim:
To investigate the interchangeability of Remicade
®
(originator infliximab) and its biosimilar Remsima
®
in patients with rare immune-mediated inflammatory diseases (IMIDs).
Methods:
This two-phased prospective open label observational study was designed to monitor the transition from Remicade
®
to Remsima
®
in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation.
Results:
Forty eight patients treated with Remicade
®
were switched to Remsima
®
in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (
n
= 17), Behçet's disease (
n
= 12), non-infectious uveitis (
n
= 11), and other diagnoses (
n
= 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (
n
= 7) or adverse events (
n
= 5) within 2 years; 10 of these patients discontinued Remsima
®
treatment, one withdrew from the study and one received additional corticosteroid therapy.
Conclusions:
We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade
®
to Remsima
®
. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade
®
to Remsima
®
. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.
The importance of CD11b/CD18 expression in neutrophil effector functions is well known. Beyond KINDLIN3 and TALIN1, which are involved in the induction of the high-affinity binding CD11b/CD18 ...conformation, the signaling pathways that orchestrate this response remain incompletely understood.
We performed an unbiased screening method for protein selection by biotin identification (BioID) and investigated the KINDLIN3 interactome. We used liquid chromatography with tandem mass spectrometry as a powerful analytical tool. Generation of NB4 CD18, KINDLIN3, or SKAP2 knockout neutrophils was achieved using CRISPR-Cas9 technology, and the cells were examined for their effector function using flow cytometry, live cell imaging, microscopy, adhesion, or antibody-dependent cellular cytotoxicity (ADCC).
Among the 325 proteins significantly enriched, we identified Src kinase-associated phosphoprotein 2 (SKAP2), a protein involved in actin polymerization and integrin-mediated outside-in signaling. CD18 immunoprecipitation in primary or NB4 neutrophils demonstrated the presence of SKAP2 in the CD11b/CD18 complex at a steady state. Under this condition, adhesion to plastic, ICAM-1, or fibronectin was observed in the absence of SKAP2, which could be abrogated by blocking the actin rearrangements with latrunculin B. Upon stimulation of NB4 SKAP2-deficient neutrophils, adhesion to fibronectin was enhanced whereas CD18 clustering was strongly reduced. This response corresponded with significantly impaired CD11b/CD18-dependent NADPH oxidase activity, phagocytosis, and cytotoxicity against tumor cells.
Our results suggest that SKAP2 has a dual role. It may restrict CD11b/CD18-mediated adhesion only under resting conditions, but its major contribution lies in the regulation of dynamic CD11b/CD18-mediated actin rearrangements and clustering as required for cellular effector functions of human neutrophils.
The phagocyte NAPDH-oxidase complex consists of several phagocyte oxidase (phox) proteins, generating reactive oxygen species (ROS) upon activation. ROS are involved in the defense against ...microorganisms and also in immune regulation. Defective ROS formation leads to chronic granulomatous disease (CGD) with increased incidence of autoimmunity and disturbed resolution of inflammation. Because regulatory T cells (Tregs) suppress autoimmune T-cell responses and are crucial in down-regulating immune responses, we hypothesized that ROS deficiency may lead to decreased Treg induction. Previously, we showed that in p47 phox -mutated mice, reconstitution of macrophages (Mph) with ROS-producing capacity was sufficient to protect the mice from arthritis. Now, we present evidence that Mph-derived ROS induce Tregs. In vitro, we showed that Mph ROS-dependently induce Treg, using an NADPH-oxidase inhibitor. This finding was confirmed genetically: rat or human CGD Mph with mutated p47 phox or gp91 phox displayed hampered Treg induction and T-cell suppression. However, basal Treg numbers in these subjects were comparable to those in controls, indicating a role for ROS in induction of peripheral Tregs. Induction of allogeneic delayed-type hypersensitivity with p47 phox -mutated Mph confirmed the importance of Mph-derived ROS in Treg induction in vivo. We conclude that NAPDH oxidase activity in Mph is important for the induction of Tregs to regulate T cell-mediated inflammation.
Childhood anxiety is a problem not only because of its negative consequences on the well-being of children but also because of its adverse effects on society and its role in mental disorders later in ...life. Adequate prevention might be the key in tackling this problem. The effectiveness of Coping Cat, as an indicated CBT-based prevention program in Dutch primary school children, was assessed by means of a randomized controlled trial. In total, 141 children aged 7–13 with elevated levels of anxiety and their mothers were included and randomly assigned to an intervention group and a waiting list control group. After screening, all participants completed baseline, post-intervention, and 3-month follow-up assessments. The results showed that Coping Cat, as an indicated prevention program, reduces children’s self-reported anxiety symptoms, with Cohen’s effect size
d
of 0.66 at the 3-month follow-up. A moderating effect was found for baseline anxiety level; specifically, children with high levels of baseline anxiety who received the Coping Cat program had lower anxiety levels at follow-up compared to children with high levels of anxiety in the control condition. No moderating effects of gender or age were found. An unexpected decline in anxiety levels from screening to pre-assessment was found in both groups, and this decline was stronger in the experimental group. These promising results warrant the implementation of Coping Cat as an indicated prevention program.
The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies ...(DMTs) in relation to timing of vaccination and B-cell count.
OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70.
87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL).
Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.
Objective
Children with juvenile idiopathic arthritis (JIA) experience functional impairment due to joint manifestations of the disease. The aim of our present study was to assess health‐related ...quality of life (HRQOL) and its predictors in a group of children and adolescents with JIA.
Methods
The study sample includes all JIA patients (ages 6–18 years) who consulted a pediatric rheumatologist in Amsterdam, The Netherlands, between February 2009 and March 2010. HRQOL was measured using the Paediatric Quality of Life Inventory 4.0 (ages 6–18 years). Functional ability was measured using the Childhood Health Assessment Questionnaire, and medical and sociodemographic parameters were assessed. The study sample was compared to a Dutch youth norm population including children with other chronic health conditions. The proportion of children with JIA with an impaired HRQOL (<1 SD) was evaluated and multivariate regression analyses were performed to predict HRQOL outcome.
Results
Of the eligible patients, 64.1% (n = 152) participated. Both children (ages 6–12 years) and adolescents (ages 13–18 years) with JIA reported a significantly lower HRQOL in almost all domains compared to either healthy controls or children with other chronic health conditions. Approximately half of the children with JIA showed an impaired HRQOL. The main predictors of HRQOL were functional ability, pain, subjective burden of medication use, and school absence.
Conclusion
The HRQOL is severely affected in children and adolescents with JIA. These findings underline the necessity to systematically monitor HRQOL in daily clinical practice.
Acquired cardiovascular diseases, such as coronary artery disease (CAD) and cerebrovascular accident (CVA) or transient ischemic attack (TIA), were reported main determinants of mortality in elderly ...patients with mainly anatomically classified simple congenital heart disease (CHD) (1,2). Out of 794 adult TOF patients within 6 participating centers in the prospective Dutch nationwide CONCOR (Congenital Corvitia) registry, a total of 167 patients >50 years of age were included (55% men, 40% previous shunt, 32% >18 years...
This study investigated secondary traumatic stress (STS) and secondary posttraumatic growth (SPG) in a sample of Dutch police family liaison officers (N = 224). Our study had two aims: (a) to ...identify potential risk and protective factors for STS and (b) to investigate the association between STS and SPG. None of the risk (caseload and a personal trauma history) and protective factors (age, work experience, and support by supervisors and coworkers) identified in previous research correlated with STS. However, a small positive association was found between STS and SPG. In the discussion section we warn against the use of interventions that aim to prevent STS until more is known about risk and protective factors for STS and provide directions for future research.
Novel advances in cardiac rehabilitation Vromen, T.; Brouwers, R. W. M.; Jorstad, H. T. ...
Netherlands heart journal,
10/2021, Letnik:
29, Številka:
10
Journal Article
Odprti dostop
Cardiac rehabilitation (CR) has evolved as an important part of the treatment of patients with cardiovascular disease. However, to date, its full potential is fairly underutilised. This review ...discusses new developments in CR aimed at improving participation rates and long-term effectiveness in the general cardiac population. It consecutively highlights new or challenging target groups, new delivery modes and new care pathways for CR programmes. These new or challenging target groups include patients with atrial fibrillation, obesity and cardiovascular disease, chronic coronary syndromes, (advanced) chronic heart failure with or without intracardiac devices, women and frail elderly patients. Also, the current evidence regarding cardiac telerehabilitation and loyalty programmes is discussed as new delivery modes for CR. Finally, this paper discusses novel care pathways with the integration of CR in residual risk management and transmural care pathways. These new developments can help to make optimal use of the benefits of CR. Therefore we should seize the opportunities to reshape current CR programmes, broaden their applicability and incorporate them into or combine them with other cardiovascular care programmes/pathways.
This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment.This ...cross-sectional observational study compared 28 perinatally HIV-infected children (8-18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance.HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = -0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found.CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.
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