Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.     

Feasibility and usability of measuring receipt of sealants in 2 states

BackgroundThe authors examined the reliability and validity of the Dental Quality Alliance childhood sealant measure under actual use conditions in Texas and Florida. The 2 states provide care for almost 20% of children in Medicaid nationally.MethodsThe authors used dental claims data to examine the reliability of the caries risk assessment component of the measure. They examined validity using a 3-year look-back period to identify children who were inaccurately included in the measure denominator as sealant eligible when they were not owing to already sealed, missing, or restored teeth.ResultsThe children identified at elevated risk varied between the states, with 85% at elevated risk in Texas and 39% in Florida in 2017. Different methods can be used to calculate risk, raising questions about reliability. In Texas, 31% of children included in the denominator were not eligible to receive sealants owing to already sealed, missing, or restored teeth. The magnitude of the underestimation increased with age, so by the time children were 9 years old, 40% were not measure eligible yet included in the denominator. Similar results were observed for Florida.ConclusionsThe authors propose eliminating the caries risk assessment requirement and incorporating a 3-year look-back period to identify already sealed, missing, or restored molars.Practical ImplicationsThe reliability and validity of the sealant measure needs to be enhanced. Measure misspecification in which children are not correctly identified as needing sealants can contribute to inaccurate development of quality improvement goals, performance improvement projects, or pay-for-quality programs.     

Renal parenchymal thickness in children with solitary functioning kidney

Background

Reduced renal parenchymal thickness (PT) is a parameter used by clinicians to assess the degree of hydronephrosis. In patients with a congenital hydronephrotic solitary functioning kidney (SFK), PT is difficult to determine as there is no comparison with the contralateral kidney. The aim of this study was to obtain ultrasound measurements of PT in children with normal SFK and to compare these data with PT measurements in children with two functioning kidneys.

Methods

This was a prospective multicenter study carried out between 2006 and 2011 in which 236 children aged 11 days to 18.96 years with healthy SFK were examined. The SFK etiologies were unilateral renal agenesis or a nonfunctioning contralateral kidney, mostly due to multicystic dysplasia. In addition to determining other parameters, we measured PT in the middle third of the kidney by ultrasound. Correlations between PT and age, height and weight were assessed.

Results

Correlation analysis showed a positive correlation with renal PT for all parameters. The correlation coefficients for age, height and weight were 0.863, 0.873 and 0.874, respectively. In most age categories, the renal parenchyma was significantly thicker in the SFK than in two functioning kidneys.

Conclusions

Based on our results, we suggest that PT in the SFK is correlated with height, weight and age of the patient. Consequently, measurements of PT may be used for monitoring the development of the healthy SFK and may contribute to a more accurate assessment of the severity of SFK anomalies.     

Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

The aim of our study was to evaluate the significance of IL-28B single-nucleotide polymorphism and hepatic expression of IFI27, SOCS3 and miR-122 in order to predict early virological response (EVR) in patients infected with HCV genotype 1 or 4. The study group consisted of 65 patients: 46 with HCV mono- and 19 with HIV/HCV co-infection. Analyses of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood and expression of SOCS3, IFI27 and miR-122 in liver biopsy samples obtained before PegIFN and ribavirin treatment were performed by the RT-PCR method. EVR was defined as a >2log decline in HCV viremia at week 12. EVR was associated with a lower expression of IFI27 and a more frequent presence of the IL28BCC genotype. IFI27 expression was lower in patients with the CC genotype, irrespective of EVR. In multivariate logistic regression, only IL28B CC genotype and age above 40 years influenced EVR (OR =5.09 and 0.29 respectively). In contrast to IFI27, expression of miR-122 and SOCS3 in patients with different IL28B genotypes was not statistically significantly different. A correlation between miR-122 and SOCS3 was found (Rho =0.495094 p< 0.0001). Analysis of IFI27, SOCS3 and miR-122 hepatic expression does not provide substantial benefits for the prognosis of EVR. The only independent prognostic factors for EVR are age and IL28B genotype. The prognostic significance of IFI27 expression for EVR is dependent on the genetic polymorphism of IL28B.     

Ocena zależności między stosowaniem inhibitorów pompy protonowej a występowaniem uczulenia na wybrane alergeny pokarmowe

Proton pump inhibitors are considered to be highly selective and effective drugs, which have few side effects. They are used in both adults and children (including infants) as well as in pregnant women. By increasing the gastric fluid pH, they impair the activation process and reduce the secretion of pepsin, secretin and pancreatic proteases, thereby impairing protein degradation. The remaining peptides are immunoreactive and lead to the development of an allergic response, while the increased permeability of the gastrointestinal tract mucosa may also induce sensitization. Observational studies conducted in patients with gastroenterological disorders, children with allergy diseases and experimental studies in animals have demonstrated that the use of anti-ulcer drugs favours sensitization to selected food allergens.     

Patterns of change in cortical morphometry following traumatic brain injury in adults

Progressive cortical volumetric loss following moderate–severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage post‐injury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time‐points spanning 5 months to 7 years post‐injury, and 18 controls at 2 time‐points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions. No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi‐directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci. These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.     

Viscoelastic Polyurethane Foams with Reduced Flammability and Cytotoxicity

Consistent and proper use of respiratory protective devices (RPD) is one of the essential actions that can be taken to reduce the risk of exposure to airborne hazards, i.e., biological and nonbiological aerosols, vapours, and gases. Proper fit of the facepiece and comfort properties of RPDs play a crucial role in effective protection and acceptance of RPDs by workers. The objective of the present paper was to develop viscoelastic polyurethane foams for use in RPD seals characterised by proper elasticity, allowing for the enhancement of the device fit to the face and the capability of removing moisture from the skin in order to improve the comfort of RPD use. Moreover, it was pivotal to ensure the non-flammability of the foams, as well as a simultaneous reduction in their cytotoxicity. The obtained foams were characterised using scanning electron microscopy, infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. Measurements also involved gel fraction, apparent density, compression set, rebound resilience, wettability, flammability, and cytotoxicity. The results are discussed in the context of the impact of modifications to the foam formulation (i.e., flame-retardant type and content) on the desired foam properties. The test results set directions for future works aimed to develop viscoelastic polyurethane foams that could be applied in the design of respiratory protective devices.     

Reductive Modification of Carbon Nitride Structure by Metals—The Influence on Structure and Photocatalytic Hydrogen Evolution

Pt, Ru, and Ir were introduced onto the surface of graphitic carbon nitride (g-C₃N₄) using the wet impregnation method. A reduction of these photocatalysts with hydrogen causes several changes, such as a significant increase in the specific surface area, a C/N atomic ratio, a number of defects in the crystalline structure of g-C₃N₄, and the contribution of nitrogen bound to the amino and imino groups. According to the X-ray photoelectron spectroscopy results, a transition layer is formed at the g-C₃N₄/metal nanoparticle interphase, which contains metal at a positive degree of oxidation bonded to nitrogen. These structural changes significantly enhanced the photocatalytic activity in the production of hydrogen through the water-splitting reaction. The activity of the platinum photocatalyst was 24 times greater than that of pristine g-C₃N₄. Moreover, the enhanced activity was attributed to significantly better separation of photogenerated electron–hole pairs on metal nanoparticles and structural distortions of g-C₃N₄.     

Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age‐matched controls: Role of cytomegalovirus

Many treatment complications that occur late in childhood cancer survivors resemble age‐related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late‐differentiated memory CD57⁺CD28^? T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age‐matched controls. We found that markers of systemic inflammation—IL‐6 and human C‐reactive protein and immune activation—CD38 and HLA‐DR on T cells, soluble CD (sCD)163 from monocytes and macrophages—were increased in survivors compared to controls. T‐cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL‐6, human C‐reactive protein, sCD163, and CD57⁺CD28^? memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age‐related comorbidities in this group.