Association between nutritional status and subjective health status in chronically ill children attending special schools

Purpose

In hospitalized children with a chronic disease, malnutrition was associated with a lower subjective health status. In outpatient children with a chronic disease attending special schools, this association has never been studied. The aim of this study was to assess the association between nutritional status and subjective health status in chronically ill children attending special schools.

Methods

Overall, 642 children, median age 9.8 years (IQR 7.7–11.5), 60 % male, 72 % Caucasian, were included in this prospective study in nine special schools for chronically ill children in the Netherlands. Overall malnutrition was assessed as: acute malnutrition (<?2 SDS for weight for height (WFH)) and chronic malnutrition (<?2 SDS for height for age). The malnutrition risk was assessed with the nutritional risk-screening tool STRONG_kids. Subjective health status was assessed with EQ-5D.

Results

Overall, 16 % of the children had overall malnutrition: 3 % acute and 13 % chronic malnutrition. Nurses reported ‘some/severe problems’ on the health status dimensions mobility (15 %), self-care (17 %), usual activities (19 %), pain/discomfort (22 %), and anxiety/depression (22 %) in chronically ill children. Their mean visual analogue scale score (VAS) was 73.0 (SD 11.1). Malnutrition, medication usage, and younger age explained 38 % of the variance of the VAS score.

Conclusions

The presence of overall malnutrition in chronically ill children attending special schools was associated with lower subjective health status, especially in younger children and in those with chronic medication usage. Therefore, it is important to develop and use profile-screening tools to identify these children.

     

Effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk

Premature infants are the main recipients of pasteurised donor human milk (PDHM), when their mothers are unable to provide their own. In this study, we evaluated the effect of pasteurisation on the concentrations of vitamin D compounds in donor breastmilk. Milk samples were obtained pre- and post-Holder pasteurisation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse the samples for vitamins D₂ and D₃ (D₂ and D₃) and 25-hydroxyvitamins D₂ and D₃ (25(OH)D₂ and 25(OH)D₃). The significance of differences in vitamin D concentrations between the two groups of milk samples was assessed using the Wilcoxon matched-pairs signed rank test, in which p?p?2, D₃, 25(OH)D₂ and 25(OH)D₃. The losses ranged from 10% to 20% following pasteurisation.     

Unrelated Future Costs and Unrelated Future Benefits: Reflections on NICE Guide to the Methods of Technology Appraisal

In this editorial, we consider the vexing issue of ‘unrelated future costs’ (for example, the costs of caring for people with dementia or kidney failure after preventing their deaths from a heart attack). The National Institute of Health and Care Excellence (NICE) guidance is not to take such costs into account in technology appraisals. However, standard appraisal practice involves modelling the benefits of those unrelated technologies. We argue that there is a sound principled reason for including both the costs and benefits of unrelated care. Changing this practice would have material consequences for decisions about reimbursing particular technologies, and we urge future research to understand this better. Copyright © 2016 John Wiley & Sons, Ltd.     

Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors

Microtubules are linear polymers of alpha- and beta-tubulin heterodimers and are the major constituents of mitotic spindles, which are essential for the separation of chromosomes during mitosis. Here we describe a synthetic compound, 2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene (T138067), which covalently and selectively modifies the beta1, beta2, and beta4 isotypes of beta-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to T138067 become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Subsequently, these cells undergo apoptosis. Furthermore, T138067 exhibits cytotoxicity against tumor cell lines that exhibit substantial resistance to vinblastine, paclitaxel, doxorubicin, and actinomycin D. T138067 is also equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. These observations suggest that T138067 may be clinically useful for the treatment of multidrug-resistant tumors.     

A Locus Linked to p16 Modifies Melanoma Risk in Dutch Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome Families

The CDKN2A gene that encodes the cell cycle inhibitor p16 shows mutations in many but not all 9p21-linked melanoma families. Most Dutch melanoma families segregate for a unique founder mutation (p16-Leiden), encoding a truncated nonfunctional p16 protein. The highly variable risk for p16-Leiden carriers to develop melanoma suggests a role for other genetic and/or environmental factors. We hypothesized that a 9p21 gene other than CDKN2A may be relevant in the remaining 9p21-linked melanoma families without p16 mutations but may also act as a risk modifier in p16-Leiden carriers. Haplotype analysis for 9p21 was performed using microsatellite markers in six p16-Leiden families originating from a founder population. p16-Leiden carriers in two families shared an unexpectedly large founder haplotype ( approximately 20-cM) around CDKN2A, mostly in proximal direction. Melanoma-positive p16-Leiden carriers from these families showed this extensive proximal haplotype compared with melanoma-negative p16-Leiden carriers from the same families. Additional p16-Leiden families less heavily affected with melanoma showed shorter haplotypes sharing, excluding the region proximally of CDKN2A. The presence of a gene involved in melanoma susceptibility proximal of CDKN2A is corroborated by somatic deletions of 9p in tumors, which frequently do not include CDKN2A but a more proximal chromosomal area instead. Our results provide a candidate region for further gene mapping in p16-negative 9p21-linked melanoma families and guide the search for risk modifiers in melanoma development.     

Macrophage heterogeneity in atherosclerosis: A matter of context

During atherogenesis, plaque macrophages take up and process deposited lipids, trigger inflammation, and form necrotic cores. The traditional inflammatory/anti-inflammatory paradigm has proven insufficient in explaining their complex disease-driving mechanisms. Instead, we now appreciate that macrophages exhibit remarkable heterogeneity and functional specialization in various pathological contexts, including atherosclerosis. Technical advances for studying individual cells, especially single-cell RNA sequencing, indeed allowed to identify novel macrophage subsets in both murine and human atherosclerosis, highlighting the existence of diverse macrophage activation states throughout pathogenesis. In addition, recent studies highlighted the role of the local microenvironment in shaping the macrophages’ phenotype and function. However, this remains largely undescribed in the context of atherosclerosis. In this review we explore the origins of macrophages and their functional specialization, shedding light on the diverse sources of macrophage accumulation in the atherosclerotic plaque. Next, we discuss the phenotypic diversity observed in both murine and human atherosclerosis, elucidating their distinct functions and spatial distribution within plaques. Finally, we highlight the importance of the local microenvironment in both phenotypic and functional specialization of macrophages in atherosclerosis and elaborate on the need for spatial multiomics approaches to provide a better understanding of the different macrophage subsets’ roles in the pathogenesis of atherosclerosis.     

2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde

According to the updated International Myeloma Working Group criteria, smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by an M-component >3 g/dL, bone marrow plasma cell infiltration >10% and <60%, and absence of any myeloma-defining event. Active multiple myeloma is preceded by SMM, with a median time to progression of approximately 5 years. Cases of SMM range from the extremes of “monoclonal gammopathy of undetermined significance-like”, in which patients never progress during their lifetimes, to “early multiple myeloma”, in which transformation into symptomatic disease, based on genomic evolution, may be rapid and devastating. Such a “split personality” makes the prognosis and management of individual patients challenging, particularly with regard to the identification and possible early treatment of high-risk SMM. Outside of clinical trials, the conventional approach to SMM generally remains close observation until progression to active multiple myeloma. However, two prospective, randomized trials have recently demonstrated a significant clinical benefit in terms of time to progression, and of overall survival in one of the two studies, for some patients with higher-risk SMM treated with lenalidomide ± dexamethasone, raising the question of whether such an approach should be considered a new standard of care. In this paper, experts from the European Myeloma Network describe current biological and clinical knowledge on SMM, focusing on novel insights into its molecular pathogenesis, new prognostic scoring systems proposed to identify SMM patients at higher risk of early transformation, and updated results of completed or ongoing clinical trials. Finally, some practical recommendations for the real-life management of these patients, based on Delphi consensus methodology, are provided.