| 1. |
- Karlsson, Sofia, et al.
(författare)
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The facial nerve palsy and cortisone evaluation (FACE) study in children : protocol for a randomized, placebo-controlled, multicenter trial, in a Borrelia burgdorferi endemic area.
- 2021
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Ingår i: BMC Pediatrics. - : BioMed Central (BMC). - 1471-2431. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults.METHOD: This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1-17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy.DISCUSSION: This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas.TRIAL REGISTRATION: The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017-004187-35) and published at ClinicalTrials.gov ( NCT03781700 , initial release 12/14/2018).
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| 2. |
- Laestadius, Åsa, et al.
(författare)
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Altered proportions of circulating CXCR5+helper T cells do not dampen influenza vaccine responses in children with rheumatic disease
- 2019
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 37:28, s. 3685-3693
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Tidskriftsartikel (refereegranskat)abstract
- Biological therapy options for the treatment of rheumatic disease target molecules that can affect the cross-talk between innate and adaptive immune responses upon vaccination. Influenza vaccination in children with rheumatic disease has been recommended, but there are only sparse data on the quality of vaccine responses from pediatric patients treated with biological therapy. We conducted an influenza vaccine study over 3 consecutive seasons where the antibody response to TIV was evaluated in children with PRD (n = 78), including both non-treated (n = 17) and treated (with methotrexate, TNF-inhibitors with or without methotrexate, or IL-inhibitors, n = 61) children as well as healthy age-matched controls (n = 24). Peripheral B cells, T and NK cell populations, as well as CXCR5+ (follicular) helper T cells (T-FH) and chemokines involved in antibody responses were assessed prior to immunization in the same cohort. Data on disease duration, therapy and data on previous influenza vaccinations were retrieved. The proportion of circulating T-FH cells were significantly lower in non-treated children with PRD compared to treated patients and healthy controls. The significantly lower proportion of T-FH cells was mirrored by a marked significant increase in CXCL13 serum level, the ligand for CXCR5, with higher levels in non-treated children with PRD compared to treated patients and healthy controls. However, the proportion of T-FH cells or CXCL13 level at the time of vaccination was not a predictor of the antibody response to TIV in this cohort of children. Children with PRD had an overall similar response to TIV as healthy children. Although not significant, children treated with TNF-inhibitors differed as a few children remained seronegative towards H3N2- and influenza B viruses after immunization. Our data show that children with PRD respond to TIV as healthy children. Furthermore, plasma CXCL13 levels did not correlate to the proportion of T-FH cells in blood prior to immunisation, or to antibody responses following immunization.
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| 3. |
- Laestadius, Åsa
(författare)
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Cellular mechanisms of interaction between uropathogenic Escherichia coli and renal epithelial cells
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections will often, particularly in children, lead to renal scar formation or hypoplastic small kidneys post-infectiously. The most common causative agent is uropathogenic Escherichia coli (E. coli). The severity of the renal injury is considered to be determined by the host immunological response and the bacterial virulence factors. Here, we have examined cellular mechanisms by which the host cells respond to E. coli exposure. We found a novel role for the E. coli exotoxin, a-hemolysin (Hly) as an inducer of a low frequency intracellular calcium (Ca2+i) oscillation that acts as a second messenger to induce release of proinflammatory cytokines in rat proximal tubule (RPT) cells. The Ca2+i oscillation exhibited a constant periodicity of 12 minutes and was generated by a combination of calcium influx through voltage-dependent calcium channels and the release from Ca2+i stores through IP3 receptor activation. We show indicating evidence that Hly can act through a cell- membrane receptor. We also found that Hly exerts a dual function on RPT cells. At high concentrations Hly induces sustained elevation of Ca2+i leading to cell lysis whereas at low concentrations it induces Ca2+i oscillations that may serve as a host-cell defense response. Infant rat renal tissue seems to have a fully developed innate immune defense to bacterial toxins. Cytokine release, LPS signaling pathway through Toll-like receptor-4 and Hly induced Ca2+i oscillations responded similarly in infant and adult renal cells. We could show that E. coli pyelonephritis in the infant rat kidney caused a decrease in cell proliferation and increased apoptosis in the renal cortex distant from the site of infection. The higher vulnerability in infants to post-pyelonephritogenic renal growth retardation is likely due to intrarenal cellular effects in the growing kidney, maybe due to bacterial secreted factors. In conclusion, we show a novel, dual role for the E. coli exotoxin, Hly as a virulence factor in childhood pyelonephritis. The higher susceptibility to pyelonephritis in infants is not likely due to an immature innate response to bacterial toxins but rather to anatomical and epithelial cell immaturity that permits bacteria and toxins to accumulate in the renal tissue. Our results shed a new light on the role of pore-forming toxin in disease. Increased knowledge in this field may have therapeutic implications.
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