Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.

OBJECTIVES: The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. RESULTS: At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. CONCLUSIONS: We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.

Fetal brain imaging provides valuable information in cCMV infected infants.

BACKGROUND: Congenital CMV infection (cCMV) is the most common congenital infection with 10-15% of cases developing symptomatic disease. Early antiviral treatment is of essence when symptomatic disease is suspected. Recently, the use of neonatal imaging has been implicated as a prognostic tool for long term sequalae among asymptomatic newborns at high risk. Even though neonatal MRI is commonly used in neonatal symptomatic cCMV disease, it is less often used in asymptomatic newborns, mainly due to cost, access and difficulty to perform. We have therefore developed an interest in assessing the use of fetal imaging as an alternative. Our primary aim was to compare the fetal and neonatal MRIs in a small cohort 10 asymptomatic neonates with congenital CMV infection. METHODS: We performed a single-center retrospective cohort study (case-series) on a convenience sample of children born from January 2014 to March 2021 with confirmed congenital CMV infection who had undergone both fetal and neonatal MRIs. We created a checklist of relevant cerebral abnormalities and asked 4 blinded radiologists to assess the MRIs (2 for each, namely fetal and neonatal) and then compared the findings between the fetal and neonatal imaging as well as the concordance in reporting of abnormalities within each category. FINDINGS: Overall concordance between prenatal and postnatal scans was high (70%). When comparing the two blinded reports for each MRI, we found high levels of concordance: 90% concordance for fetal MRIs and 100% for neonatal MRIs. The most common abnormalities identified in both fetal and neonatal scans were "abnormal white matter hyperintensity" and "subependymal cysts." INTERPRETATION: Even though this is a small descriptive study, it indicates that fetal MRI could potentially provide us with similar information as neonatal imaging. This study could form the basis for subsequent larger future studies.

The effects of biologic agents on cardiovascular risk factors and atherosclerosis in rheumatoid arthritis patients: a prospective observational study.

We aimed to evaluate the impact of biologic treatment on subclinical atherosclerosis and risk factors for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Forty-nine biologic naïve RA patients, treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), who were eligible for treatment with a biologic agent, were included in the study. The serum levels of lipid parameters, as well as disease activity parameters were determined in RA patients before and after 3 and 6 months of therapy. Carotid artery intima-media thickness (cIMT) was measured before and after treatment. A comparison analysis of change of these parameters was also performed between anti-tumor necrosis factor (anti-TNF) and non-anti-TNF users. Furthermore, 31 non-smoking healthy volunteers, matched for age and gender, were used as a control group. At baseline, RA patients had a decrease in serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels compared with controls (209 ± 63 vs 233 ± 44 and 58 ± 15 vs 61 ± 14, p < 0.004), while cIMT was higher versus controls [0.9 (0.8-1) vs 0.6 (0.5-0.7), p < 0.001]. TC, HDL-C and apolipoprotein A1 levels were significantly increased 3 months after treatment (209 ± 63, 58 ± 15, 162 ± 32, vs 227 ± 45, 60 ± 15, 169 ± 29, respectively, p < 0.03) and this observation remained stable at a 6-month follow-up. After 6 months, there was also a statistically significant decrease in the cIMT [0.9 (0.8-1) vs 0.7 (0.6-0.8), p < 0.001]. Anti-TNF and non-anti-TNF users had comparable changes in cardiovascular risk parameters. The atherogenic lipid profile and subclinical atherosclerosis are features of RA, which appeared improved after biologic therapy initiation.

A rare case of a neonate with agenesis of the corpus callosum and severe laryngomalacia.

BACKGROUND: Agenesis of the corpus callosum (ACC) is a rare congenital anomaly often associated with other congenital anomalies, syndromic, chromosomal, or genetic disorders. ACC may be detected antenatally. The postnatal diagnosis usually arises following neuroimaging evaluation for neurodevelopmental disorders during the first years of life. CASE DESCRIPTION: We report a case of a neonate with complete ACC, presenting with serious feeding-swallowing difficulties and respiratory symptoms. Coexisting severe laryngomalacia was diagnosed. ACC was detected on routine cranial ultrasound. Molecular karyotype revealed pericentric inversion of chromosome 9, inv(9)(p23q22.3), and whole exome sequencing was negative. CONCLUSION: The reported case presented unusual clinical manifestations. Laryngomalacia is an extremely rare associated anomaly in infants with ACC, with only a few cases reported in the literature. Moreover, to our knowledge, this is the first reported case of ACC and laryngomalacia associated with the polymorphism inv(9)(p23q22.3). HIPPOKRATIA 2022, 26 (3):118-120.

Is Low-Grade Intraventricular Hemorrhage in Very Preterm Infants an Innocent Condition? Structural and Functional Evaluation of the Brain Reveals Regional Neurodevelopmental Abnormalities.

BACKGROUND AND PURPOSE: There is increasing evidence of abnormal neurodevelopmental outcomes in very preterm infants with low-grade intraventricular hemorrhage grades I and II. Our purpose was to evaluate the effects of low-grade intraventricular hemorrhage on gray and white matter integrity. MATERIALS AND METHODS: MR imaging at around term-equivalent age was performed in 16 very preterm infants (mean gestational age, 28.8 ± 5.3 weeks) with mild intraventricular hemorrhage on brain sonography and 13 control subjects (mean gestational age, 29.6 ± 4.1 weeks) without intraventricular hemorrhage. Structural and functional evaluation of the cortex was performed using regional measurements of surface area, thickness and volume, and resting-state fMRI, respectively, and of WM microstructural integrity, applying Tract-Based Spatial Statistics to diffusion tensor imaging data. RESULTS: Compared with the control infants, the infants with low-grade intraventricular hemorrhage had decreases in the following: 1) GM surface area in Brodmann areas 19 left and 9 and 45 right, and GM volume in Brodmann areas 9 and 10 right; 2) fractional anisotropy bilaterally in major WM tracts; and 3) brain activity in the left lower lateral and in the right higher medial somatosensory cortex. CONCLUSIONS: Very premature infants with low-grade intraventricular hemorrhage at around term-equivalent age may present with regional abnormalities, appearing on imaging studies as cortical underdevelopment, functional impairment, and microstructural immaturity of major WM tracts.

Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI.

BACKGROUND: Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL). OBJECTIVE: Evaluate changes in the volume of 116 GM areas in preterm children with dPVL. METHODS AND MATERIALS: Eleven preterm children with dPVL, gestational age 32.8 ± 2.6 weeks, examined at corrected age 22.0 ± 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation. RESULTS: Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume (P < 0.05). WM/CSF ratios also differed (P < 0.05). CONCLUSIONS: Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory.

Age-related grey matter changes in preterm infants: an MRI study.

Grey matter (GM) maturation has not been previously studied in healthy preterm children. The purpose of this study was to evaluate the age dependency of GM development in 116 GM areas in preterm subjects. Sixty one preterm infants (corrected age: 13.7+/-9.92 months, gestational age: 33.4+/-1.9 weeks) with normal structural appearance on MRI were included in the study. Using a T1-weighted high resolution 3D spoiled gradient echo sequence, volumes of 116 GM areas were calculated after their segmentation using the Voxel Based Morphometry Toolboxes and the Individual Brain Atlas Statistical Parametric Mapping (IBASPM) software packages. Non linear regression analysis assessed age dependency of volume data for every GM area using the monoexponential function y=A-Bexp(-x/C). All supratentorial GM areas followed the monoexponential function model reasonably well. Cerebellar structures had a poor goodness of fit. Volume increase of the individual GM areas followed an inferior to superior and a posterior to anterior pattern. The putamen, thalamus, and caudate nucleus reached 99% of the final volume earlier than most cortical GM areas. The visual cortex and the postcentral and precentral cortices matured earlier than the parietal, frontal and temporal cortices. The fronto-occipital asymmetry or torque seen in adults was observed in the preterm infants; the left occipital areas reached maturation earlier than the right, while the right prefrontal and frontal areas matured earlier than the left. To conclude, GM development progresses in a region-specific manner coinciding with functional, phylogenetical and regional white matter (WM) maturation.

The height of the pituitary in preterm infants during the first 2 years of life: an MRI study.

Pituitary secretory activity is different in premature and full-term infants. The height of the pituitary is a marker of its secretory activity. Our purpose was to use MRI to measure height of the pituitary of premature infants and to compare it with full-term controls. The height was measured on a midline sagittal T1-weighted image in 86 premature infants (gestational age 26-36.9 weeks, mean 32.3+/-2.85 weeks, corrected age 0.33-2 years, mean 0.76+/-0.42 years) and in 70 age- and sex-matched full-term controls. The children were was divided into four age groups: A: > or =0.5 years; B: 0.51-1.0 year; C: 1.01-1.5 years; and D: 1.51-2.00 years. The gland was significantly (P<0.01) higher in the preterm infants than in the controls (3.88+/-0.61 vs 3.31+/-0.64 mm). In the preterm group no significant difference was found between children small or appropriate for gestational age or between those with and without periventricular leukomalacia. Pituitary height by age group was: A: 3.71+/-0.57, B: 3.81+/-0.56, C: 4.09+/-0.68; and D:4.45+/-0.57 mm; statistically significant (P<0.01) differences were found between groups A and D and B and D. The pituitary is thus higher in premature than in full-term controls and shows a trend to increase after the first year of corrected-age life.

MRI measurements of the pons and cerebellum in children born preterm; associations with the severity of periventricular leukomalacia and perinatal risk factors.

Our purpose was to measure the size of the pons and cerebellum in preterm babies with periventricular leukomalacia (PVL), and to study their relationship with the severity of PVL and with perinatal risk factors. We examined 33 premature children, mean gestational age 31 weeks, range 26-36 weeks with PVL on MRI, and 27 full-term controls. On MRI at 0.4-5.5 years (mean 1.4 years) we measured the area of the corpus callosum and vermis, the anteroposterior diameter of the pons and the volume of the cerebellum. The area of the corpus callosum was used as a marker of white matter loss and PVL severity. All regional brain measurements except that of the vermis were significantly lower in patients than controls: corpus callosum (mm(2)): 239.6+/-92.5 vs 434.8+/-126.8, P <0.01; pons (mm): 14.8+/-3.0 vs 17.9+/-1.4, P <0.01]; cerebellum (cm(3)): 68.2+/-31.6 vs 100.6+/-28.3, P <0.01; vermis (mm(2)): 808.1+/-292.2 vs 942.2+/-246.2, NS. Significant reduction in the area of the vermis: 411.3+/-203.3 vs 935+/-252.6 mm(2); cerebellar volume: 16.3+/-12.5 vs 96.6+/-20.2 mm(3); and the diameter of the pons: 10.1+/-2.2 vs 17.5+/-1.3 mm ( P<0.01) were observed in seven children with gestational age < or =28 weeks, severe hypotension and large patent ductus arteriosus (PDA). There was a significant correlation between the duration of mechanical ventilation and the size of the vermis, pons and cerebellum (R=-0.65, -0.57 and -0.73, respectively, P <0.01).

Distensibility and pulse wave velocity of the thoracic aorta in patients with juvenile idiopathic arthritis: an MRI study.

OBJECTIVE: An increased incidence of cardiovascular disease has been found in rheumatic disorders. Changes in the variables of aortic elasticity in patients with juvenile idiopathic arthritis (JIA) were evaluated and their relationship to inflammation, anti-rheumatic drugs and traditional cardiovascular risk factors were investigated in this study. METHODS: Phase contrast MR was performed in 31 patients with JIA and 28 age and sex matched controls to evaluate the aortic distensibility and pulse wave velocity (PWV). Disease activity variables, plasma lipid profile, homocysteine, thyroid hormones, glucose and insulin were assessed in the patients. RESULTS: Eighteen patients had oligoarticular, 6 polyarticular and 7 systemic disease. Distensibility was lower (mean: 10.25; SD: 4.18) and PWV was higher (mean: 3.68; SD: 1.59) in the patients compared to the controls (mean: 13.4; SD: 4.99), (mean: 1.38; SD: 0.54) respectively (p < 0.01). A positive correlation between PWV and age was observed in the patients (rs = 0.47, p < 0.01) and controls (rs = 0.72, p < 0.01), and a negative correlation between distensibility and age in the patients (rs = -0.59, p < 0.01) and controls (rs = -0.63, p < 0.01). No statistically significant correlations were found between distensibility and PWV and metabolic and disease activity parameters. When distensibility and PWV were adjusted for age no significant differences were found between the three subtypes of JIA. CONCLUSION: JIA is associated with increased aortic stiffness that might suggest subclinical atherosclerosis. Early detection and follow-up by non-invasive methods may be useful in the prevention of future cardiovascular disease.