Autoinflammatory diseases in childhood,part 1: monogenic syndromes

Autoinflammatory diseases constitute a family of disorders defined by aberrant stimulation of inflammatory pathways without involving antigen-directed autoimmunity. They may be divided into monogenic and polygenic types. Monogenic autoinflammatory syndromes are those with identified genetic mutations, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency or hyperimmunoglobulin D syndrome, cryopyrin-associated periodic fever syndromes (CAPS), pyogenic arthritis pyoderma gangrenosum and acne (PAPA) syndrome, interleukin-10 and interleukin-10 receptor deficiencies, adenosine deaminase 2 deficiency and pediatric sarcoidosis. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory disorders are defined by repeating episodes or persistent fever, rash, serositis, lymphadenopathy, arthritis and increased acute phase reactants, and thus may mimic infections clinically. Most monogenic autoinflammatory syndromes present in childhood. However, because of their infrequency, diverse and nonspecific presentation, and the relatively new genetic recognition, diagnosis is usually delayed. In this article, which is Part 1 of a two-part series, the authors update monogenic autoinflammatory diseases in children with special emphasis on imaging features that may help establish the correct diagnosis.

     

In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm² images and 12 diffusion‐sensitized images at b = 500 s/mm²). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.     

Endovascular treatment versus intravenous thrombolysis alone in isolated M2 occlusion: a meta-analysis

Neurological Sciences - Optimal reperfusion strategies for M2 occlusion are still uncertain, with previous studies questioning benefit of mechanical thrombectomy (MT) over intravenous thrombolysis...     

Ceftriaxone‐associated biliary pseudolithiasis in children: do we know enough?

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone‐associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:’ceftriaxone’, ‘cholelithiasis’, ‘biliary sludge’ ‘gallstones’ ‘neonates’ ‘children’ ‘clinical aspects’ ‘management’. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone‐associated biliary pseudolithiasis is dose‐dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone‐associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow‐up may be necessary. A personalized assessment of factors predisposing to ceftriaxone‐associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs.     

Enhanced antibacterial nanocomposite mats by coaxial electrospinning of polycaprolactone fibers loaded with Zn-based nanoparticles

ZnO and Zn acetate nanoparticles were embedded in polycaprolactone coaxial-fibers and uniaxial-fibers matrices to develop potential antibacterial nanocomposite wound dressings (mats). Morphology, composition, wettability, crystallinity and fiber structure of mats were characterized. Antibacterial properties of mats were tested against E. coli and S. aureus by turbidity and MTT assays. The effect of UVA illumination (prior to bacteria inoculation) on mats’ antibacterial activity was also studied. Results showed that a coaxial-fibers design maintained nanoparticles distributed in the outer-shell of fibers and, in general, enhanced the antibacterial effect of the mats, in comparison to conventional uniaxial-fibers mats. Results indicated that mats simultaneously inhibited planktonic and biofilm bacterial growth by, probably, two main antibacterial mechanisms; 1) release of Zn²⁺ ions (mainly from Zn acetate nanoparticles) and 2) photocatalytic oxidative processes exerted by ZnO nanoparticles. Antibacterial properties of mats were significantly improved by coaxial-fibers design and exposure to UVA-light prior to bacteria inoculation.     

Effect of enamel matrix proteins on the treatment of intrabony defects: a split-mouth randomized controlled trial study

The objective of this split-mouth, double-blind, randomized controlled trial was to compare the clinical effect of treatment of 2- or 3-wall intrabony defects with open flap debridement (OFD) combined or not with enamel matrix proteins (EMP). Thirteen volunteers were selected with one pair of or more intrabony defects and probing pocket depth (PPD) > or = 5 mm. All individuals received instructions regarding oral hygiene and were submitted to scaling and root planing. Each participant received the two treatment modalities: test sites were treated with OFD and EMP, and control sites received only OFD. After 6 months, a significant reduction was observed in PPD for the EMP group (from 6.42 +/- 1.08 mm to 2.67 +/- 1.15 mm) and for the OFD group (from 6.08 +/- 1.00 mm to 2.00 +/- 0.95 mm) (p < 0.0001), but with no significant difference between groups (p = 0.13). A significant gain in relative attachment level (RAL) was observed in both groups (EMP: from 13.42 +/- 1.88 mm to 10.75 +/- 2.26 mm, p < 0.001; OFD: from 12.42 +/- 1.98 mm to 10.58 +/- 2.23 mm, p = 0.013), but with no significant difference between groups (p = 0.85). Gingival recession (GR) was higher in the EMP group (from 1.08 +/- 1.50 mm to 2.33 +/- 1.43 mm; p = 0.0009) than in the OFD group (from 0.66 +/- 1.15 mm to 1.16 +/- 1.33 mm; p = 0.16), but this difference was not significant (p = 0.06). In conclusion, the results showed that OFD combined with EMP was not able to improve treatment of intrabony defects compared to OFD alone.     

Effects of crude venom, tityustoxin and toxin Ts-gamma from Tityus serrulatus scorpion on secretion and structure of the rat submandibular gland

Changes in the rat submandibular glands after intravenous injections of Tityus serrulatus scorpion venom, tityustoxin or toxin Ts-gamma were studied histologically and morphometrically. The acini and the granular convoluted tubules presented the most prominent changes. The following variables were measured: (a) relative volume occupied by the glandular structures; (b) diameter of the granular convoluted tubules and thickness of their epithelium; (c) diameter of the acini. The cytoplasm of the acinar cells was extensively occupied by large confluent vacuoles and had a reduced number of secretory granules after intravenous injections of venom or toxins. The morphological changes caused by toxin Ts-gamma were greater than those evoked by tityustoxin or crude venom injections. In spite of the changes in acinar cells, acinar diameter showed no significant alterations after venom or toxin injections. Reduction of diameter and depletion of the cytoplasmic secretory granules were observed in the granular convoluted tubules 2 h after intravenous injections of crude venom, or after 1 h with tityustoxin or toxin Ts-gamma. The intravenous injection of crude venom did not induce any visible change in the granular convoluted tubules after 1 h. These structural changes could explain the concomitant intense sialagogue effect elicited by crude venom, tityustoxin and toxin Ts-gamma. The sialagogue effect induced by toxin Ts-gamma was larger than those induced by crude venom or tityustoXin.     

Trigeminal neuralgia: evaluation of percutaneous neurodestructive procedures

The treatment of trigeminal neuralgia (TN), which is resistant to medical therapy, has benefited from many surgical techniques. It is not possible, in light of the present level of knowledge, to establish exactly which method is the most suitable. It does, however, seem significant that certain side effects appear, in varying percentages, in all kinds of operations. In 13 years, 2,094 patients suffering from TN have been treated by the authors with percutaneous Gasserian neurolysis, 128 patients with radiofrequency trigeminal neurolysis, and 1,966 with selective ethanolic trigeminal neurolysis (SETN). Our experience treating TN with controlled increments of ethanol by means of a needle introduced through the oval foramen in the Gasserian ganglion is related here. The tip of the needle is accurately placed among the roots desired under fluoroscopic control. The clinical effects on the conscious patient of a prognostic block with local anesthetics are evaluated before producing the neurolysis. Follow-up has been long enough to show that SETN is a highly selective procedure, which shouldn't be underrated in the centers that use it routinely.