Malnutrition is associated with worse health-related quality of life in children with cancer

Purpose:\ud Malnutrition in childhood cancer patients has been associated with lower health-related quality of life (HRQOL). However, this association has never actually been tested. Therefore, we aimed to determine the association between nutritional status and HRQOL in children with cancer.\ud \ud Methods:\ud In 104 children, aged 2–18 years and diagnosed with hematological, solid, or brain malignancies, nutritional status and HRQOL were assessed at diagnosis and at 3, 6, and 12 months using the child- and parent-report versions of the PedsQL 4.0 Generic scale and the PedsQL 3.0 Cancer Module. Scores on both scales range from 0 to 100.\ud \ud Results:\ud Undernourished children (body mass index (BMI) or fat-free mass < −2 standard deviation score (SDS)) reported significantly lower PedsQL scores compared with well-nourished children on the domains physical functioning (−13.3), social functioning (−7.0), cancer summary scale (−5.9), and nausea (−14.7). Overnourished children (BMI or fat mass >2 SDS) reported lower scores on emotional (−8.0) and cognitive functioning (−9.2) and on the cancer summary scale (−6.6), whereas parent-report scores were lower on social functioning (−7.5). Weight loss (>0.5 SDS) was associated with lower scores on physical functioning (−13.9 child-report and −10.7 parent-report), emotional (−7.4) and social functioning (−6.0) (child-report), pain (−11.6), and nausea (−7.8) (parent-report). Parents reported worse social functioning and more pain in children with weight gain (>0.5 SDS) compared with children with stable weight status.\ud \ud Conclusions:\ud Undernutrition and weight loss were associated with worse physical and social functioning, whereas overnutrition and weight gain affected the emotional and social domains of HRQL. Interventions that improve nutritional status may contribute to enhanced health outcomes in children with cancer

Body composition of patients with neuroblastoma using computed tomography

Background Computed tomography (CT) is often used to investigate muscle and fat mass in adult patients with cancer. However, this method has rarely been used in the pediatric cancer population. The present retrospective study aimed to investigate changes in body composition using CT during treatment in children with neuroblastoma. Procedure CT images of 29 patients with high-risk neuroblastoma were retrospectively analyzed at diagnosis and longitudinally during treatment. The cross-sectional area of skeletal muscle, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) and skeletal muscle density at the level of the third lumbar vertebra were examined. To correct for height, cross-sectional areas were divided by height in meters squared. A linear mixed model was estimated to investigate changes in body composition over time. Results A small increase in skeletal muscle (p = .029), skeletal muscle density (p = .002), and IMAT (p < .001) was found. Furthermore, a rapid increase in VAT (p < .001) and SAT (p = .001) was seen early during treatment with the highest volumes after six cycles of chemotherapy. Conclusions CT scans obtained during standard care provide insight into the direction and timing of changes in skeletal muscle and different types of adipose tissue in childhood cancer patients. Future research is needed regarding the consequences of the rapid increase of VAT and SAT early during treatment.Development and application of statistical models for medical scientific researc

Prophylactic treatment with vitamins C and B2 for methotrexate-induced gastrointestinal mucositis

Mucositis is a common side-effect of chemotherapy treatment, inducing alterations in the composition of the gut microbiota. Redox active compounds, such as vitamins B2 and C, have been shown to reduce inflammation and enhance the growth of anaerobic bacteria in the gut. We therefore aimed to (1) validate the ability of these compounds to promote bacterial cell growth in vitro, and (2) determine their prophylactic efficacy in a rat model of methotrexate (MTX)-induced mucositis. Bacterial growth curves were performed to assess the growth kinetics of bacteria exposed to Vitamins C and B2 (0.5 mM). Male wistar rats (150–200 g) received vitamins B2 (12 mg/day) and C (50 mg/day) via daily oral gavage (from day −1 to day 10). MTX (45 mg/Kg) was administrated via I.V. injection (N = 4–8/group) on day 0. Body weight, water/food consumption and diarrhea were assessed daily. Blood and faecal samples were collected longitudinally to assess citrulline levels (mucositis biomarker) and gut microbiota composition. Vitamins C/B2 enhanced the in vitro growth of anaerobic bacteria Blautia coccoides and Roseburia intestinalis. Contrarily to vitamin B2, in vivo administration of Vitamin C significantly attenuated clinical symptoms of mucositis. Despite their influence on the composition of the gut microbiota, both vitamins did not modulate the course of MTX-induced mucositis, as accessed by plasma citrulline. Vitamins B2 and C enhanced anaerobic bacterial growth in vitro, however their ability to mitigate MTX-induced mucositis was limited.Ana Rita da Silva Ferreira, Hannah R. Wardill, Rick Havinga, Wim J. E. Tissing and Hermie J. M. Harmse

Taste function in children: normative values and associated factors

Background Although less frequent than in adults, taste loss also occurs in childhood. "Taste Strips" are frequently used for diagnosing taste dysfunction; however, normative values are lacking for children. In this study, we will create normative values for the "Taste Strips" in children. Methods This cross-sectional study included 609 children aged 6-15 years. "Taste Strips" were used to determine sweet, sour, salty, and bitter taste scores by a non-forced procedure. The 10th percentile was used to distinguish normal taste function from a reduced sense of taste. Multivariable generalized linear models (GLM) were estimated to study the effect of age (group), sex, and 6-n-propylthiouracil (PROP) status on taste function. Results Taste function changed with age, allowing for a distinction of three age groups: (I) 6-7 years, (II) 8-9 years, and (III) 10-15 years. Normative values were created for the age groups and boys and girls separately. Additionally, GLM showed a significant effect of (1) age (group) on sweet, salty, bitter, and total taste scores; (2) sex on sweet, sour, and total taste scores; and (3) PROP status on total taste scores. Conclusions This study provided normative values for the "Taste Strips" in children, highlighting age- and sex-related differences. Impact Taste dysfunction can be harmful and impacts quality of life, a topic that became increasingly important since the COVID-19 pandemic. Although taste dysfunction is thought to be rare in childhood, the detrimental impact of such dysfunction might be large, as children's eating habits are strongly influenced by input from the chemical senses. Measuring taste function may elucidate the relationship between taste dysfunction and disease, fostering the development of more appropriate supportive strategies. However, adequate tools are lacking for children. Normative values of the "Taste Strips" are now available for children, which bolster the clinical utility of this test.Development and application of statistical models for medical scientific researc

Smell and taste function in childhood cancer patients: a feasibility study

Purpose Chemotherapy can affect smell and taste function. This has never been investigated in childhood cancer patients during chemotherapy. The objective of this study was to determine whether psychophysical smell and taste tests are suitable for children with cancer. Taste and smell function, fungiform papillae density, and eating behavior were measured before (T1) and after (T2) a cycle of chemotherapy and compared with healthy controls. Methods Thirty-one childhood cancer patients treated for a hematological, solid, or brain malignancy (median age 12 years, 16 girls), and 24 healthy controls (median age: 11 years, 10 girls) participated. Smell function was measured using Sniffin' Sticks, including a threshold, discrimination, and identification test. Taste Strips were used to determine recognition thresholds for sweet, sour, salty, and bitter taste. Papillae density was investigated by counting the fungiform papillae of the anterior tongue. Eating behavior was assessed using the Behavioral Pediatrics Feeding Assessment Scale (BPFAS). Results Smell and taste function could be investigated in more than 90% of the patients, while fungiform papillae density could be determined in 61% of the patients. A significant difference in smell threshold was found between patients and controls (p = 0.001), showing lower thresholds in patients. In patients, sweet taste (p < 0.001), bitter taste (p = 0.028), and total taste function (p = 0.004) were significantly different after a cycle of chemotherapy, with higher scores at T2. Conclusion The assessment of smell, taste, and fungiform papillae density is feasible in children with cancer. Results of the current study suggest that smell and taste sensitivity increased in children with cancer.Development and application of statistical models for medical scientific researc

Does chemotherapy-induced gastrointestinal mucositis affect the bioavailability and efficacy of anti-infective drugs?

Antimicrobial prophylaxis is increasingly being used in patients with hematological malignancies receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). However, few studies have focused on the potential impact of gastrointestinal mucositis (GI-M), a frequently observed side effect of chemotherapy in patients with cancer that affects the gastrointestinal microenvironment, on drug absorption. In this review, we discuss how chemotherapy leads to an overall loss of mucosal surface area and consequently to uncontrolled transport across the barrier. The barrier function is depending on intestinal luminal pH, intestinal motility, and diet. Another factor contributing to drug absorption is the gut microbiota, as it modulates the bioavailability of orally administrated drugs by altering the gastrointestinal properties. To better understand the complex interplay of factors in GI-M and drug absorption we suggest: (i) the longitudinal characterization of the impact of GI-M severity on drug exposure in patients, (ii) the development of tools to predict drug absorption, and (iii) strategies that allow the support of the gut microbiota. These studies will provide relevant data to better design strategies to reduce the severity and impact of GI-M in patients with cancer.Ana Rita da Silva Ferreira, Anne-Grete Märtson , Alyse de Boer, Hannah R. Wardill, Jan-Willem Alffenaar, Hermie J. M. Harmsen and Wim J. E. Tissin

Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

Background Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is essential for DNA methylation. We hypothesize that MTX inhibits DNA methylation, which results into adverse effects. We studied DNA methylation markers during high-dose methotrexate treatment in pediatric acute lymphoblastic leukemia (ALL) in relation to developing oral mucositis. Materials & methods S-Adenosyl-Methionine (SAM) and S-Adenosyl-Homocysteine (SAH) levels and LINE1 DNA methylation were measured prospectively before and after high-dose methotrexate (HD-MTX 4 x 5g/m2) therapy in 82 children with ALL. Methotrexate-induced oral mucositis was registered prospectively. Oral mucositis (grade 3 National Cancer Institute Criteria) was used as clinical endpoint. Results SAM levels decreased significantly during methotrexate therapy (-16.1 nmol/L (-144.0 – +46.0), p<0.001), while SAH levels and the SAM:SAH ratio did not change significantly. LINE1 DNA methylation (+1.4% (-1.1 –+6.5), p<0.001) increased during therapy. SAM and SAH levels were not correlated to LINE1 DNA methylation status. No association was found between DNA methylation markers and developing oral mucositis. Conclusions This was the first study that assessed DNA methylation in relation to MTX-induced oral mucositis in children with ALL. Although global methylation markers did change during methotrexate therapy, methylation status was not associated with developing oral mucositis

Acute activation of metabolic syndrome components in pediatric acute lymphoblastic leukemia patients treated with dexamethasone

Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3-16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment