| 1. |
- Jackmann, Natalja, 1968-, et al.
(författare)
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Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
- 2024
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Ingår i: JBMR Plus. - : Oxford University Press. - 2473-4039. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease.This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2–17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen.Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes −45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure.In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
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| 2. |
- Rodriguez-Wallberg, Kenny A., et al.
(författare)
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ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden : a phase III randomised double-blinded placebo-controlled study
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.Methods and analysis A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.Ethics and dissemination This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.Study registration The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.Trial registration number NCT05328258; EudraCT number:2020-004780-71.
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| 3. |
- Hassan, Jasmin, et al.
(författare)
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Reference standards for follicular density in ovarian cortex from birth to sexual maturity
- 2023
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Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:4
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Tidskriftsartikel (refereegranskat)abstract
- Research question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean +/- SD 11 +/- 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.Results: No difference was observed between Z-scores in samples from untreated patients (0.3 +/- 3.5, n = 30) and patients treated with (0.5 +/- 2.9, n = 48) and without (0.1 +/- 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 +/- 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 +/- 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 +/- 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 +/- 4.2 versus 10.7 +/- 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009).Conclusion: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
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| 4. |
- Jackmann, Natalja, et al.
(författare)
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Prevalence of and factors influencing vitamin D deficiency in paediatric patients diagnosed with cancer at northern latitudes
- 2021
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 110:7, s. 2252-2258
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the prevalence of vitamin D deficiency among children with non-haematological malignancies and to explore possible causes of low vitamin D levels among these patients. Methods We performed a cross-sectional study of 458 children diagnosed with solid tumours, brain tumours, non-Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25-hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25-hydroxyvitamin D level below 50 nmol/L. Results The prevalence rate of vitamin D deficiency among children with non-haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25-hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25-hydroxyvitamin D and parathyroid hormone. Conclusion Vitamin D deficiency is common among children diagnosed with cancer, particularly among school-aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients.
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| 5. |
- Jackmann, Natalja, et al.
(författare)
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The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases
- 2022
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 198:6, s. 1023-1031
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Tidskriftsartikel (refereegranskat)abstract
- The human cathelicidin hCAP-18 (pro-LL-37) is the pro-protein of the antimicrobial peptide LL-37. hCAP-18 can be produced by many different cell types; bone marrow neutrophil precursors are the main source of hCAP-18 in the circulation. Neutrophil count is used as a marker for myelopoiesis but does not always reflect neutrophil production in the bone marrow, and thus additional markers are needed. In this study, we established the reference interval of serum hCAP-18 level in healthy children and compared serum hCAP-18 levels between different diagnostic groups of children with haemato-oncological diseases, at diagnosis. We found that children with diseases that impair myelopoiesis, such as acute leukaemia, aplastic anaemia, or myelodysplastic syndrome, presented with low hCAP-18 levels, whereas patients with non-haematological malignancies displayed serum hCAP-18 levels in the same range as healthy children. Children with chronic myeloid leukaemia presented with high circulating levels of hCAP-18, probably reflecting the high number of all differentiation stages of myeloid cells. We suggest that analysis of serum hCAP-18 provides additional information regarding myelopoiesis in children with haemato-oncological diseases, which may have future implications in assessment of myelopoiesis in clinical management.
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| 6. |
- Jackmann, Natalja, 1968-
(författare)
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Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden.In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis. Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children.Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels.The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment.
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| 7. |
- Jackmann, Natalja, 1968-, et al.
(författare)
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Vitamin D status in children with leukemia, its predictors, and association with outcome
- 2020
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 67:4, s. e28163-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. PROCEDURE: We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. RESULTS: The 25-hydroxyvitamin D level was deficient (< 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (> 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. CONCLUSION: It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.
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| 8. |
- Kristiansen, Ingela, et al.
(författare)
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Cognitive, language, and school performance in children and young adults treated for low-grade astrocytoma in the posterior fossa in childhood
- 2022
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Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long-term outcome is sparse.AimThe aim of this study was to investigate whether children treated for pilocytic astrocytoma in the posterior fossa had late complications affecting cognition, language and learning.MethodsThis descriptive single-centre study includes eight children and 12 adults treated as children for pilocytic astrocytoma in the posterior fossa, with a mean follow-up time of 12.4 (range 5–19) years. Well-established tests of intelligence, executive, language and academic function were used.ResultsIntelligence tests showed average results compared with norms. Five patients scored <−1 SD (70–84) and 3 low average (85–92) on full scale IQ. The patients scored average on subtests regarding executive function, except for significantly lower results in inhibition/switching (p = .004). In Rey complex figure test half of the patients scored below −1 SD. Language tests were normal except for significantly lower results in naming ability (p = .049) and in inference (p = .046).In academic tests, results were average, except for significantly lower results in reading speed (p = .024). Patients with learning difficulties performed worse in the tests.ConclusionsThe patients' functional outcome was favourable but, a not-negligible part of the patients displayed neurocognitive difficulties as revealed by extensive neuro-cognitive and academic testing. Thus, it is important to identify those in need of more thorough cognitive and pedagogic follow-up programmes, including school interventions.
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| 9. |
- Kristiansen, Ingela, 1961-
(författare)
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Medical, cognitive and motor outcome after treatment of pilocytic astrocytoma in the posterior fossa in childhood
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Pilocytic astrocytoma is the most common brain tumour in childhood. The aim of the studies was to investigate late medical, cognitive and motor complications in patients treated in childhood for pilocytic astrocytoma in the posterior fossa. Methods: We present a retrospective study including 193 children treated for CNS tumours 1995-2006 and, from the same cohort, 3 descriptive studies including 20 patients (out of 27 eligible patients) treated for pilocytic astrocytoma in the posterior fossa 1995-2011. The patients participated in an interview, a neurological investigation, screening tools for psychiatric symptoms, health-related quality of life (HRQoL), and tests of cognitive, language, academic and motor functions. Results: Ten patients reported problems with motor skills, mainly from the upper limbs, and 8 reported learning difficulties. None had low results in screening for psychiatric symptoms or HRQoL. Intelligence tests showed average results, but 5 scored <-1 SD (70-84) and 3 low average (85-92) on full scale IQ. Patients scored average compared with norms in tests of executive function, except for significantly lower results in inhibition/switching (p= 0.004). In language and academic tests patients scored significantly lower results in naming ability (p=0.049), inference (p=0.046) and reading speed (p=0.024). Results in tests of motor function were normal, but in the Bruininks-Oseretsky Test of Motor Proficiency, patients had significantly lower results in manual dexterity (p=0.008). In the Mini-Balance Evaluation Systems Test, patients had significantly lower results compared with matched controls (p=0.036). Patients who reported learning difficulties had worse results in the performed tests. Conclusions: Although long-term functional outcome for patients treated for pilocytic astrocytoma was generally favourable, 40% of the patients display cognitive, learning and motor difficulties. Therefore, it is imperative to identify those in need of more thorough cognitive and motor follow-up programmes, including pedagogic interventions in school and training of motor functions.
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| 10. |
- Kristiansen, Ingela, et al.
(författare)
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Motor performance after treatment of pilocytic astrocytoma in the posterior fossa in childhood
- 2022
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Ingår i: Cancer Reports. - : Wiley-Blackwell Publishing Inc.. - 2573-8348. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long-term outcome is sparse. Aims: The aim was to investigate if patients treated for pilocytic astrocytoma in the posterior fossa had motor complications, including balance, motor and process skills. Methods and results: This descriptive single-centre study includes eight children and 12 adults, treated for pilocytic astrocytoma as children. Motor performance was investigated with Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and dynamic balance with the mini-balance evaluation systems test. Physiological cost index, six-minute walk test, hand grip strength and assessment of motor and process skills were also evaluated. Ten patients reported motor difficulties, mainly from the upper limbs. The motor performance test showed results within normal limits except for manual dexterity, which was significantly below mean (p = .008). In the dynamic balance test patients had significantly lower results compared with controls (p = .036). Physiological cost index, six-minute walk tests and hand grip strength showed results within normal limits. In the Assessment of Motor and Process Skills, patients over 16 years had significantly lower results compared with test norms for motor activities of daily living (ADL) and 30% of all patients scored below the cut-off level for difficulties with motor skills. Conclusions: Motor performance for patients treated for pilocytic astrocytoma in the posterior fossa in childhood is satisfactory but some patients display difficulties with balance, manual dexterity and ADL motor skills. Thus, it is important to identify those in need of motor follow-up and training.
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