The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The ...aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria.
A retrospective-prospective longitudinal cohort analysis.
Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3-22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients' records and re-evaluated if tissue samples were available (n = 32).
Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At follow-up, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110).
Long-term endocrine and metabolic complications are very frequent in childhood- and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.
Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral ...nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health “Burlo Garofolo” of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field.
Purpose
The objectives of this study were (1) to develop a population pharmacokinetic model of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukaemia (ALL) and malignant ...lymphoma (ML) in order to investigate the influence of common polymorphisms in
SLC19A1
,
MTHFR
and
ABCB1
on plasma levels of MTX and (2) to estimate MTX exposure in individual patients to study the association of genetic variability in the folate metabolic pathway with MTX toxicity.
Methods
The study population comprised 64 children with ALL/ML (age 1.6–16.8 years) who had received a total of 252 MTX courses (2–4 per patient). Common putative functional polymorphisms in the
SLC19A1
,
MTHFR
,
MS
,
MTRR
,
TS
and
ABCB1
genes were analysed by PCR-based genotyping. Nonlinear mixed effects modelling was used for the pharmacokinetic analysis.
Results
The population typical value of clearance was 7.43 L/h (inter-individual variability 43.9%), central compartment volume was 16.7 L (46.6%), peripheral compartment volume was 2.6 L (63.3%) and distribution clearance was 0.0952 L/h (66.6%). MTX clearance decreased to 73.8% in patients with the
MTHFR
677TT genotype. Patients homozygous for the variant
MTHFR
1298A > C odds ratio (OR) 0.14, 95% confidence interval (CI) 0.037–0.54 and
SLC19A1
80A > G (OR 0.15, 95% CI 0.039-0.60) were at decreased risk for leucopenia. The
TS
2R > 3R polymorphism was associated with a lower incidence of thrombocytopenia (OR 0.15, 95% CI 0.039–0.61) and mucositis (OR 0.016, 95% CI 0.0012-0.20). In contrast, the
MTHFR
677TT polymorphism was associated with an increased incidence of mucositis (OR 23, 95% CI 2.1-240).
Conclusions
A population pharmacokinetic model developed in this study implies only a limited influence of genetic factors on the systemic disposition of MTX. Clearance is moderately reduced in patients with the
MTHFR
677TT genotype. Genetic polymorphisms in the folate metabolic pathway and
SLC19A1
were associated with HD-MTX toxicity.
The high serum concentrations of TNF-α characterize acute graft-versus-host disease (aGVHD), for which infliximab treatment may be beneficial. In 28 pediatric patients, four doses of 10 mg/kg ...infliximab every seven days were administered after steroid failure (Standard Group, n = 14) or as a first-line therapy (Early Group, n = 14). Population pharmacokinetic analyses and evaluation of serum cytokines were performed. After two months of treatment, complete response in gastrointestinal and liver aGVHD was achieved in 43% and 100% of patients in the Standard and Early groups, respectively. During follow-up, four patients in the Standard Group (but none in the Early Group) experienced an aGVHD recurrence. Viral infections occurred more frequently in the Standard Group after the fifth dose. Infliximab clearance did not differ between groups or according to treatment outcome for each organ involved in aGVHD, whereas serum levels of cytokines significantly differed. Therefore, present findings show that use of first-line, TDM-driven infliximab to treat aGVHD in children may result in better clinical outcomes and tolerability, with a different pattern of cytokines generated according to the moment of beginning of treatment.
Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment ...sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient's quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor's molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.
Light transmission aggregometry with lumiaggregometry are methods commonly recommended as a first-line test in platelet dysfunction diagnostic work-up. They are poorly standardized and usually ...performed in specialized laboratories. For proper interpretation, each laboratory should establish its own diagnostic approach in order to recognize abnormal aggregation patterns. The aim of this study was to measure plasma lumiaggregometry with basic agonists to establish the analyzer-reagent reference intervals (RI) for adults and to test the method response to aspirin.
The Chrono-Log Model 700 lumiaggregometer using Chrono-Par and Chrono-lume reagents (Chrono-Log Corp., Havertown, PA, USA) was used to measure the maximal aggregation and adenosine triphosphate release using adenosine diphosphate (2 μmol/L), collagen (2 μg/mL), arachidonic acid (1 μmol/L), epinephrine (5.5 μmol/L) and ristocetin (1.25 mg/mL), and thrombin (1 U/mL). The effect of aspirin on platelet aggregation and granule release was inspected.
RIs derived from 40 healthy adults were calculated using the non-parametric approach. Wider intervals and low lower limits were determined for weak agonist as well as absence or impaired aggregation in up to one of 7 healthy controls. The response of platelets to aspirin shows response comparable to previously reported study.
Locally established RI in our study enable us to investigate platelet function in patients with a high probability of bleeding disorders. Values are agonist and equipment specific. The variability of the method can be reduced by considering standardized preanalytical and analytical variables. Pathological results must be interpreted in the context of other hemostasis test results and clinical findings.
Ultrasound (US) has been proven to be reliable in the assessment of early haemophilic arthropathy in the adult haemophilic population, however few studies so far focused on the reliability of US ...specifically in the paediatric haemophilic population. We were interested if the changing appearance of the growing bone hinders the ultrasonographic evaluation of the pathologic processes caused by haemophilic arthropathy. The aim of the study was to assess the reliability of US for evaluation of haemophilic arthropathy in children in comparison to magnetic resonance imaging (MRI).
The study included all children aged 6 years or more with severe haemophilia in the country (n = 10). We assessed their elbows, knees, and ankles bilaterally by US and compared the results to the MRI as the reference standard. Pearson correlation coefficient (r) was used to analyse correlation.
The correlation with MRI for the US for the total score was excellent for all joints (r = 0.849 for the elbows, r = 1 for knees, r = 0.842 for ankles). The correlation of scores for specific joint components showed fair, moderate, or excellent correlation for all joint components in all joints. The correlation was the lowest for the evaluation of cartilage and bone in the ankles (r = 0.546 and r = 0.478) and bone in the elbows (r = 0.499).
Our study proved that US using the HEAD-US method performed by paediatric radiologists is a reliable tool for detection and quantification of haemophilic arthropathy in children in comparison to MRI.
Information about the impact of hemophilia on daily living and information preferences for patients and their caregivers in Central Europe has been limited.
This cross-national survey was conducted ...between April 1 and October 15, 2020 and utilized a self-administered questionnaire to collect data (Typeform™) from people living with hemophilia in Bulgaria, Croatia, Czech Republic, Hungary, Slovakia and Slovenia. The questionnaire included 22 questions regarding difficulties in daily life and preferences for receiving hemophilia-related information. Respondents were stratified into two main groups, people with hemophilia (PwH) or their caregivers (CPwH). Results were analyzed using descriptive statistics.
Of the 364 respondents, 232 were PwH (63.7%) and 132 were CPwH (36.3%). In total, 70.3% of hemophilia patients/caregivers responded that they are kept sufficiently informed about life with hemophilia, with 68.0%, 59.1% and 56.3% of respondents obtaining information from their physicians, patient associations and via digital media (internet and social media), respectively. However, 97.8% of respondents expressed an interest in additional information, particularly new hemophilia treatment options (62.1%), which in contrast to other topics was indicated most frequently by both patients and caregivers in all six countries. Most frequent difficulties in everyday life with hemophilia were identified as mobility problems (41.8%), unexpected bleeding (38.5%), pain (35.4%), and uncertainty with what they can or cannot do (25.0%). During the 2020 COVID-19 pandemic, 52.5% of respondents reported that they did not experience any major change in daily living with hemophilia.
Based on our Central European survey, hemophilia mostly affects peoples' lives by causing mobility difficulties, unexpected bleeding, pain and uncertainty in daily activities. Although the majority of respondents reported being educated about hemophilia, most PwH and CPwH respondents sought additional information, highlighting the need for continuous personalized patient education to cope with present challenges.
The development of neutralizing antibodies is a rare complication of von Willebrand disease treatment. In major surgical procedures for severe forms of the disease, the recognition of ineffective ...therapy and alternative treatment protocols are lifesaving. We report the case of a 6-year-old girl with type 3 von Willebrand disease in whom inhibitors were sought due to ineffective haemostasis together with lower than expected von Willebrand factor (VWF) recoveries after a surgical procedure. Replacement therapy first with recombinant factor VIIa and then with high doses of recombinant factor VIII in continuous infusion successfully stopped the bleeding. A high level of anti-VWF antibodies was determined by the immunological method. A frameshift mutation associated with premature termination codon (c.2435delC, p.Pro812ArgfsTer31) was determined in our patient. Although the reports on association of this mutation with inhibitor risk are inconsistent, it represents an evidence-based diagnostic and management practice in recognition of high-risk VWF genotype.
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