Activated CD90/Thy-1 fibroblasts co-express the Δ133p53ß isoform and are associated with highly inflamed rheumatoid arthritis.

BACKGROUND: The p53 isoform Δ133p53ß is known to be associated with cancers driven by inflammation. Many of the features associated with the development of inflammation in rheumatoid arthritis (RA) parallel those evident in cancer progression. However, the role of this isoform in RA has not yet been explored. The aim of this study was to determine whether Δ133p53ß is driving aggressive disease in RA. METHODS: Using RA patient synovia, we carried out RT-qPCR and RNAScope-ISH to determine both protein and mRNA levels of Δ133p53 and p53. We also used IHC to determine the location and type of cells with elevated levels of Δ133p53ß. Plasma cytokines were also measured using a BioPlex cytokine panel and data analysed by the Milliplex Analyst software. RESULTS: Elevated levels of pro-inflammatory plasma cytokines were associated with synovia from RA patients displaying extensive tissue inflammation, increased immune cell infiltration and the highest levels of Δ133TP53 and TP53ß mRNA. Located in perivascular regions of synovial sub-lining and surrounding ectopic lymphoid structures (ELS) were a subset of cells with high levels of CD90, a marker of 'activated fibroblasts' together with elevated levels of Δ133p53ß. CONCLUSIONS: Induction of Δ133p53ß in CD90+ synovial fibroblasts leads to an increase in cytokine and chemokine expression and the recruitment of proinflammatory cells into the synovial joint, creating a persistently inflamed environment. Our results show that dysregulated expression of Δ133p53ß could represent one of the early triggers in the immunopathogenesis of RA and actively perpetuates chronic synovial inflammation. Therefore, Δ133p53ß could be used as a biomarker to identify RA patients more likely to develop aggressive disease who might benefit from targeted therapy to cytokines such as IL-6.

Case report: tuberous sclerosis and persistent hyperplastic primary vitreous.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV) in a patient with tuberous sclerosis (TS) has been described in one previous case report in 1999. Otherwise, there is no literature around this potential association. We describe a case of an infant with TS and PHPV. CASE PRESENTATION: An 11-month old male was under investigation for leukocoria, microphthalmia and suspected PHPV after being seen in ophthalmology clinic. He presented to hospital with seizures and was diagnosed with TS on imaging. Imaging also showed the known microphthalmia and a mass associated with the lens. Subsequent paediatric ophthalmology review and examination under anaesthesia confirmed microphthalmia, PHPV and a retrolental mass which was thought to represent total retinal detachment or a retinal hamartoma within a retinal detachment. CONCLUSIONS: This is the second case report of PHPV in a patient with TS. The previous case report postulated that the atypical location of the retinal hamartoma was secondary to the abnormal globe development in PHPV.

Abusive head trauma in children: radiographs of the skull do not provide additional information in the diagnosis of skull fracture when multiplanar computed tomography with three-dimensional reconstructions is available.

BACKGROUND: Some data suggest that CT is more accurate than skull radiographs in diagnosing skull fractures in abusive head trauma. OBJECTIVES: We investigated whether multiplanar CT with three-dimensional (3-D) reconstructions alone is non-inferior to combination CT/skull radiography for the diagnosis of skull fracture in suspected physical abuse. MATERIALS AND METHODS: We identified children who had skull radiographs and concurrent multiplanar CT with 3-D reconstructions obtained during suspected physical abuse imaging between 2010 and 2019, and a fracture diagnosis in the formal report. We included all fracture cases and an equal number of randomly selected non-fracture controls in an anonymised dataset. This dataset was independently reviewed for skull fracture by two paediatric radiologists and one less-experienced trainee using either radiography alone, CT alone or CT/skull radiography. The primary outcome was discordance in diagnosis of skull fracture between CT alone and CT/skull radiography, with a result > 0.03 deemed to indicate inferiority of CT alone. The Fleiss kappa was used to assess interobserver agreement. RESULTS: We included 106 children, 53 with and 53 without skull fracture. A single case was discordant between CT alone and CT/skull radiography, resulting in discordance of 0.009, consistent with non-inferiority of CT alone. The sensitivity and specificity of CT alone and CT/skull radiography were 98% and 96-98%, respectively, whereas radiography alone was more inaccurate (81% sensitivity and 96% specificity). Interobserver agreement for all modalities was very high (kappa 0.86-0.95). CONCLUSION: Multiplanar CT with 3-D reconstructions alone is not inferior (and clinically equivalent) to CT/skull radiography for diagnosing skull fracture in suspected physical abuse imaging and was as accurate when reported by a less-experienced trainee. This suggests that skull radiography can be removed from suspected physical abuse imaging guidelines.

Closure of the anterior and posterior fontanelle in the New Zealand population: A computed tomography study.

AIM: Significant ethnic variation has been demonstrated in the closure of the anterior fontanelle (AF); however, to date, this has not been investigated in the Maori/Pasifika population. METHODS: The computed tomography scans of 163 individuals (116 Maori/Pasifika and 47 New Zealand (NZ) European) aged between birth and 4 years were retrospectively analysed to investigate the surface area (SA) and time of closure of the anterior and posterior fontanelles in New Zealand. RESULTS: The Maori/Pasifika group showed clinical AF closure (SA < 114 mm2 ) rates of 25% at 4-6 months, increasing to 47% at 10-12 months and 80% at 13-18 months. The posterior fontanelle was clinically unfused in 17% of the Maori/Pasifika group aged <1 month and in 7% of the 1-3-month-old group. No cases of posterior fontanelle non-fusion were identified in the NZ European population. CONCLUSION: This study establishes normal values for AF size and closure frequency for the first time in the paediatric Maori/Pasifika population.