Impact of parental body mass index at diagnosis on obesity in survivors of pediatric craniopharyngioma

Objective It is well known that both genetic background and lifestyle influence the development of ‘general’ obesity. However, the role of parental body mass index (BMI) on the development of obesity in long-term survivors of childhood-onset craniopharyngioma (CP) is not well understood. This study analyzed the correlation of patients’ BMI at diagnosis and last visit and parental BMI at CP diagnosis and further explored potential risk factors for obesity in CP patients. Design This is a registry-based retrospective cohort study. Methods In total,291 CP patients and their parents recruited in the German KRANIOPHARYNGEOM studies were included. Correlations between patient’s BMI SDS at CP diagnosis and last visit and parental BMI at CP diagnosis were analyzed. The associations between hypothalamic damage, maternal/paternal BMI and CP patients’ obesity at last visit were analyzed by multivariable logistic regression. Results At follow-up, 52% of CP patients developed obesity (BMI > 3SDS). Patient’s BMI SDS at last visit was moderately correlated with BMI-SDS at CP diagnosis (r = 0.48, 95% CI: 0.38–0.58, P < 0.001), and also with maternal BMI at diagnosis (r = 0.28, 95% CI: 0.17–0.38, P < 0.001) and paternal BMI at diagnosis (r = 0.3, 95% CI: 0.19–0.41, P < 0.001). However, the contributing role of parental BMI to the pathogenesis of obesity was small compared to the impact of hypothalamic damage. Conclusion We conclude that besides hypothalamic damage, parental disposition for obesity is associated with the development of obesity in patients after CP. Our results indicate that also the family situation could have an influence on the development of obesity after CP and might be a therapeutic target. Significance statement Survivors of childhood-onset craniopharyngioma are at risk of developing morbid obesity. So far, patients with posterior hypothalamic involvement and lesion were identified as a high risk group. With this study, the influence of parental body mass index on the risk of obesity was investigated. Patient’s body-mass-index at last visit was correlated with maternal and paternal body mass index at diagnosis. With increasing maternal or paternal body mass index, the likelihood of obesity in individuals with CP increased. Nevertheless, the parents’ weight had only a small effect on the development of patients’ obesity compared to hypothalamic damage

Perinatally diagnosed congenital craniopharyngiomas in the Kraniopharyngeom trials

Background Craniopharyngiomas (CPs) are rare embryonic tumors. Clinical presentation and outcome of patients perinatally diagnosed with congenital CP (cCP) are not clear and refer mainly to a few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP. Study design Three hundred and sixty-one patients diagnosed with adamantinomatous CP were recruited 2007–2022 in KRANIOPHARYNGEOM 2007/Registry 2019 and prospectively observed. In two cases, cCP was diagnosed prenatally and in one case on the second day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, and therapeutic interventions and outcome in these three cases of cCP were analyzed. Results All patients survived. One patient developed psychomotor retardation and a mild hemiparesis. Prenatal routine ultrasound examination led to the diagnosis of cCP. Tumor resection was performed during the early postnatal period (range: 11–51 days of age). Functional capacity, measured by Fertigkeitenskala-Münster-Heidelberg (FMH) was reduced in three and behavioral parameters, measured by the Strength and Difficulties Questionnaire (SDQ) were abnormal in two cases. Conclusion cCP is a rare diagnosis with a prevalence of 0.83% in our study group. Compared to cases reported in the literature, the presented cases were treated immediately and had a better prognosis. Based on improvements of diagnostic and therapeutic techniques, prenatal diagnosis of cCP should lead to transfer prior to delivery of cCP patients to a specialized center for delivery and postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure the improved prognosis of these patients. Significance statement We previously reported that lower event-free survival rates after craniopharyngioma are associated with younger age at diagnosis. Perinatally diagnosed congenital craniopharyngiomas are very rare. This article presents three unique cases with congenital craniopharyngioma, comparing their diagnostics, therapy, and development. All three cases had surgery during the early postnatal period with sparing of the posterior hypothalamus. In each case, endocrinopathy was present at follow-up. Low functional capacity was reported in all cases and an abnormal total difficulties score in two cases. Compared to the literature, the presented cases had better prognosis in morbidity and mortality. This report and the review of the literature confirm the importance of a multidisciplinary approach in the diagnostic and treatment of the very rare condition of congenital craniopharyngioma

Outcome after proton beam therapy versus photon-based radiation therapy in childhood-onset craniopharyngioma patients — results of KRANIOPHARYNGEOM 2007

Background: Proton beam therapy (PBT) is being increas16ingly used to treat residual craniopharyngioma (CP) after hypothalamus-sparing surgery. Compared to photon-based radiation therapy (XRT) with PBT, less irradiation in the penumbra reduces the scattered dose to critical organs neighboring but outside the area of treatment, minimizing the risk of sequelae. Patients and methods: Between 2007 and 2019, 99 of 290 (34%) childhood-onset CP patients recruited in KRANIOPHARYNGEOM 2007 received external radiation therapy (RT) (65% PBT, 35% XRT). Outcome was analyzed in terms of survival, endocrinological and anthropometric parameters (BMI and height SDS), quality of life (QoL using PEDQOL), and functional capacity (FMH) with special regard to irradiation technique. Results: PBT became predominant (used in 43% and 72% of all irradiated patients registered within the first and second halves of the recruitment period, between 2008 and 2013 and 2013 and 2018, respectively). Five-year event-free survival rates after PBT or XRT were comparable (92% ± 4% vs. 91% ± 4%, p = 0.42) and higher than for the whole cohort since diagnosis, including non-RT patients (37% ± 4%). Radiation doses to the hypothalamus and pituitary did not differ between PBT and XRT. Endocrine deficits due to disturbances of the hypothalamic-pituitary axis (HPA) were already common before irradiation. During the first 5 years after CP diagnosis/RT, no differences between PBT, XRT, and non-RT CP patients concerning functional capacity and anthropometric parameters have been obtained. Only for the PEDQOL domain “physical function”, parental-assessed QoL was lower 12 months after PBT versus XRT or non-RT patients. Conclusion: QoL, functional capacity, degree of obesity, and endocrinopathy varied over time from diagnosis, but by 5 years, there was no significant difference between PBT and XRT upfront or delayed, nor was there any compromise in historic survival rates, which remained high >90%. RT of any type is extremely effective at stabilizing disease after hypothalamic-sparing surgery. The purported specific benefits of PBT-reducing sequelae are not proven in this study where the organ of critical interest is itself diseased, increasing an urgent need to better address and treat the tumor-induced endocrine harm from diagnosis in dedicated pituitary services. Other hypothesized benefits of PBT versus XRT on vascular events and secondary cancers await longer comparison. Clinical trial registration number: https://clinicaltrials.gov/study/, identifier NCT01272622

Diagnostic criteria for the hypothalamic syndrome in childhood

OBJECTIVE: Hypothalamic syndrome (HS) in childhood is a rare condition. Its epidemiology is not well known because incidence and prevalence are related to very rare underlying diseases. In addition, different criteria for the syndrome are used across studies. Recognizing the HS may be difficult, due to its rareness and variety of symptoms. Having diagnostic criteria for signs and symptoms of hypothalamic dysfunction may aid in early recognition and diagnosis, in the reporting and understanding of its etiology, in predicting its course and its management. We aimed to define diagnostic criteria for hypothalamic dysfunction and a score for the presence of HS in childhood. METHODS: Diagnostic criteria for hypothalamic dysfunction were developed and subdivided into hyperphagia, hypophagia, body mass index, behavioral problems, sleep disorders, temperature regulation disorders, pituitary dysfunction, radiological hypothalamic assessment, and presence/suspicion of a hypothalamic genetic syndrome. Subsequently, the scoring system was tested in a retrospective cohort of 120 patients at risk for hypothalamic dysfunction. RESULTS: A score for presence of HS was developed. Using this new hypothalamic score, in total 52.5% were scored as having HS. Of these patients, 76.7% were diagnosed with pituitary dysfunction, 32.5% with hyperphagia, 40% with sleep disorders, and 14.2% with temperature dysregulation. For several criteria, clinical data was missing in more than 50% of cases. CONCLUSIONS: The here proposed diagnostic criteria for hypothalamic dysfunction and score for presence of HS may be used for care purposes and to aid in early recognition. Also it will be useful for research or registration purposes

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development:the Norwegian Mother and Child Cohort

Background Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design We studied 61,676 school-age children (born during 2002–2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233. © 2018 American Society for Nutrition. This work is written by (a) US Government employee(s) and is in the public domain in the US

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. RESULTS: Minimal significant beneficial exercise effects on self-reported CF (β=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, β=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=-0.14 [-0.25; -0.04]) or 24 weeks or longer (β=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (β=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (β=-0.19 [-0.31; -0.06]). No other significant moderators were identified. CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors

The use and applicability of Internet search queries for infectious disease surveillance in low- to middle-income countries

Uncontrolled outbreaks of emerging infectious diseases can pose threats to livelihoods and can undo years of progress made in developing regions, such as Sub-Saharan Africa. Therefore, the surveillance and early outbreak detection of infectious diseases, e.g., Dengue fever, is crucial. As a low-cost and timely source, Internet search queries data [e.g., Google Trends data (GTD)] are used and applied in epidemiological surveillance. This review aims to identify and evaluate relevant studies that used GTD in prediction models for epidemiological surveillance purposes regarding emerging infectious diseases. A comprehensive literature search in PubMed/MEDLINE was carried out, using relevant keywords identified from up-to-date literature and restricted to low- to middle-income countries. Eight studies were identified and included in the current review. Three focused on Dengue fever, three analyzed Zika virus infections, and two were about COVID-19. All studies investigated the correlation between GTD and the cases of the respective infectious disease; five studies used additional (time series) regression analyses to investigate the temporal relation. Overall, the reported positive correlations were high for Zika virus (0.75-0.99) or Dengue fever (0.87-0.94) with GTD, but not for COVID-19 (-0.81 to 0.003). Although the use of GTD appeared effective for infectious disease surveillance in low- to middle-income countries, further research is needed. The low costs and availability remain promising for future surveillance systems in low- to middle-income countries, but there is an urgent need for a standard methodological framework for the use and application of GTD

Fatigue in patients with hypothalamic syndrome – A cross-sectional analysis of the German childhood-onset craniopharyngioma cohort

Objective: Patients with suprasellar tumors are at risk for hypothalamic syndrome (HS), including fatigue and excessive daytime sleepiness. The aim of this cross-sectional study was to determine the severity of fatigue in patients with and without HS. Methods: Patients diagnosed with CP or pilocytic astrocytoma were recruited from the KRANIOPHARYNGEOM studies. Eligibility criteria were availability of one completed Multidimensional Fatigue Inventory-20 (MFI-20) questionnaire and complete medical records on criteria for HS. The associations between HS and levels of fatigue symptoms (MFI-20 sum score) were assessed. MFI-20 scores were compared to sex- and age-matched reference values from a German normative population. Results: Data on 41 patients, with a median age of 22 years, were available for analyses of which 25 (61 %) patients presented with HS. After adjustment for age and sex, patients with HS reported higher scores in the physical (β= 3.39 [95 %-CI:1.18–5.60]) and sum MFI-20 (β=11.42 [95 %-CI:2.06–20.79]) domain than patients without HS. Compared to reference values, all patients reported higher mean scores in each fatigue domain. Abnormal self-reported daytime sleepiness was reported in 6 of 25 (24 %) patients with HS. Regardless of the level of daytime sleepiness in patients with HS, the reported fatigue scores were high. Daytime sleepiness did not correlate with fatigue. Conclusions: Fatigue symptoms are present in patients with CP. However, patients with HS are more affected with physical and overall fatigue. It is crucial in clinical practice, to distinguish between daytime sleepiness and fatigue and to target patients with HS