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  • 1
    In: European Journal of Haematology, Wiley, Vol. 110, No. 6 ( 2023-06), p. 762-771
    Abstract: Although neutropenic fever is frequently observed during chemotherapy, only a minor proportion is caused by blood stream infections (BSI). This study investigated measurements of neutrophil chemotaxis as risk markers for BSI in children with acute lymphoblastic leukemia (ALL). Methods The chemokines CXCL1 and CXCL8 were measured weekly in 106 children with ALL during induction treatment. Information regarding BSI episodes was collected from the patients' medical records. Results During induction treatment, 102 (96%) patients developed profound neutropenia and 27 (25%) were diagnosed with BSI, debuting on median day 12 (range: 4–29). Patients developing BSI had increased levels of CXCL1 on days 8 and 15 as well as increased CXCL8 on days 8, 15, 22, and 29 compared to patients without BSI (all p   〈  0.05). Patients with BSI  〈  day 12 exhibited increased CXCL1 and CXCL8 levels as early as day 8 (81  vs. 4 pg/mL, p  = 0.031 and 35 vs. 10 pg/mL, p   〈  0.0001, respectively), while CXCL1 and CXCL8 were increased on day 15 (215 vs. 57 pg/mL, p  = 0.022 and 68 vs. 17 pg/mL, p  = 0.0002) and after (all p   〈  0.01) in patients with BSI ≥ day 12. Conclusion The markers of neutrophil chemotaxis, CXCL1, and CXCL8 may help to identify patients at increased risk of BSI during chemotherapy‐induced neutropenia.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2027114-1
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  • 2
    In: Pediatric Blood & Cancer, Wiley, Vol. 65, No. 3 ( 2018-03)
    Abstract: The congenital dyserythropoietic anemias (CDAs) are a group of rare inherited blood disorders characterized by ineffective erythropoiesis as the principal cause of anemia. We present a child with CDA 1b—the rarest and least well‐described type—due to a mutation in the C15orf41 gene. The patient presented with severe in utero and neonatal manifestations, typical peripheral limb anomalies as well as rarely reported cardiac manifestations, visual impairment, short stature, and hip dysplasia. Anemia was complicated by iron overload and pronounced extra medullary erythropoiesis leading to skull deformities. The patient responded to treatment with pegylated interferon alfa‐2a.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2130978-4
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  • 3
    In: Pediatric Blood & Cancer, Wiley, Vol. 70, No. 2 ( 2023-02)
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2130978-4
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  • 4
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-3-23)
    Abstract: Introduction: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a frequent, severe and dose-limiting side effect. Few treatments have proven effective for CIGT. CIGT is characterized by activation of the nuclear factor kappa B pathway which, leads to upregulation of proinflammatory cytokines. The innate immune protein peptidoglycan recognition peptide 2 (PGLYRP2) binds to and hydrolyzes microbial peptidoglycan. Expression of PGLYRP2 is upregulated in the intestine of chemotherapy-treated piglets. In this experimental study, we investigated the role of Pglyrp2 in the development and severity of murine CIGT. Methods: Pglyrp2 wildtype and Pglyrp2 knockout mice received intraperitoneal injections of chemotherapy (Doxorubicin 20 mg/kg) to induce CIGT. Weight was monitored daily, and animals were euthanized after 2 or 7 days. Expression of proinflammatory cytokines in the jejunum was measured by quantitative real-time polymerase-chain reaction and enzyme-linked immunosorbent assay. Villus height, crypt depth, and histologic inflammation were evaluated on haematoxylin and eosin stained tissue specimens. Results: Chemotherapeutic treatment induced weight loss ( p & lt; 0.05), shortening of the small intestine ( p & lt; 0.05), elongation of villus height ( p & lt; 0.05), increased crypt depth ( p & lt; 0.05), and led to elevated mRNA levels of II1β ( p & lt; 0.05), II6 ( p & lt; 0.05), and Tnf ( p & lt; 0.001) at day 2. Protein levels of IL1β, IL6, and TNFα did not change after exposure to chemotherapy. Doxorubicin treated wildtype mice had a more pronounced weight loss compared to knockout mice from day 3 to day 7 (D3-D6: p & lt; 0.05 and D7: p & lt; 0.01). No other phenotypic differences were detected. Conclusion: Pglyrp2 aggravates chemotherapy-induced weight loss but does not induce a specific pattern of inflammation and morphological changes in the small intestine.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-12-15)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-15)
    Abstract: A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[ 18 F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[ 18 F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin. Methods In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[ 18 F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[ 18 F]FDG corrected for body weight (SUV BW ). Results Abdominal SUV BW was significantly increased on day 1 (p & lt; 0.0001), day 3 (p & lt; 0.0001), and day 6 (p & lt; 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUV BW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p & lt; 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p & lt; 0.05), and jejunal levels of tumour necrosis factor and interleukin-1β were significantly increased on day 3 (p & lt; 0.05). Discussion Together, these findings indicate that sequential 2-[ 18 F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 6
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 11 ( 2023-4-26)
    Abstract: Overall survival after cancer is increasing for the majority of cancer types, but survivors can be burdened lifelong by treatment-related severe toxicities. Integration of long-term toxicities in treatment evaluation is not least important for children and young adults with cancers with high survival probability. We present modified consensus definitions of 21 previously published physician-defined Severe Toxicities (STs), each reflecting the most serious long-term treatment-related toxicities and representing an unacceptable price for cure. Applying the Severe Toxicity (ST) concept to real-world data required careful adjustments of the original consensus definitions, translating them into standardized endpoints for evaluating treatment-related outcomes to ensure that (1) the STs can be classified uniformly and prospectively across different cohorts, and (2) the ST definitions allow for valid statistical analyses. The current paper presents the resulting modified consensus definitions of the 21 STs proposed to be included in outcome reporting of cancer treatment.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711999-3
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  • 7
    Online Resource
    Online Resource
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 314, No. 2 ( 2018-02-01), p. G231-G246
    In: American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 314, No. 2 ( 2018-02-01), p. G231-G246
    Abstract: Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs, and several animal models of CIM have been developed, mainly in rodents and piglets, to help understand the progression of CIM and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g., GIT) insights, standardized, clinically relevant treatment regimens, and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM management and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients, which vary according to the antineoplastic drugs, dose, underlying (cancer) disease, and patient characteristics (e.g., age, genetics, and body constitution). Another factor that hinders the direct use of results from animals is inadequate collaboration between basic science and clinical science in relation to CIM. Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g., milk fractions, colostrum, and plant extracts), nutrients (e.g., polyunsaturated fatty acids, short-chain fatty acids, and glutamine), and growth factor peptides (e.g., transforming growth factor and glucagon-like peptide-2), as well as manipulations of the gut microbiota (e.g., prebiotics, probiotics, and antibiotics). Rodent CIM models allow well-controlled, in-depth studies of animals with or without tumors while pig models more easily make clinically relevant treatment regimens possible. In synergy, animal models of CIM provide the basic physiological understanding and the new ideas for treatment that are required to make competent decisions in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0193-1857 , 1522-1547
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477329-6
    SSG: 12
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  • 8
    In: Pediatric Blood & Cancer, Wiley, Vol. 64, No. 3 ( 2017-03)
    Abstract: Surfactant protein D (SP‐D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP‐D levels are associated with chemotherapy‐induced mucositis and infectious morbidity in children with acute lymphoblastic leukemia (ALL). Procedure In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP‐D, interleukin‐6 (IL‐6), C‐reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP‐D were compared with healthy controls. Results Baseline values of circulating SP‐D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P 〉 0.05). After initiation of chemotherapy, a significant reduction in SP‐D levels was observed at all time points: 704 ng/ml at day 8, 413 ng/ml at day 15, 395 ng/ml at day 22, and 520 ng/ml at day 29 (all, P 〈 0.05). No significant associations between SP‐D values, the occurrence of mucosal toxicity, or infectious morbidity were observed. However, loss of circulating SP‐D from days 8 to 15 was associated with more systemic inflammation, and lower SP‐D values at day 15 were associated with elevated intestinal mucositis scores ( P 〈 0.05). Conclusions The current study supports the hypothesis that the detrimental effect of chemotherapy on patients’ immune functions includes decreased circulating levels of innate mucosal molecules such as SP‐D, potentially aggravating mucosal and systemic inflammatory responses.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2130978-4
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  • 9
    In: Pediatric Blood & Cancer, Wiley, Vol. 68, No. 1 ( 2021-01)
    Abstract: Systemic infections are a major cause of morbidity in children with acute lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without bacteraemia during induction treatment. Procedure We prospectively included 61 children with ALL treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL‐2008 protocol. ANC and plasma C‐reactive protein (CRP) were measured on treatment days 1, 8, 15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia episodes during induction treatment were recorded retrospectively. Results Nineteen of sixty‐one (31%) patients experienced bacteraemia occurring on median day 13 (range 5‐20). Patients with bacteraemia during induction treatment had lower citrulline level on day 15 ( P   〈  .01) compared to patients without bacteraemia, indicating more severe enterocyte loss. Nevertheless, ANC was similar in the two patient groups on days 8 and 15. CRP was negatively correlated with same‐day citrulline ( P   〈  .03 for all) and ANC ( P   〈  .04 for all). Conclusions During chemotherapy‐induced neutropaenia, plasma citrulline may help identify patients at increased risk of bacteraemia.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2130978-4
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  • 10
    In: Child's Nervous System, Springer Science and Business Media LLC, Vol. 38, No. 8 ( 2022-08), p. 1479-1485
    Type of Medium: Online Resource
    ISSN: 0256-7040 , 1433-0350
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1463024-2
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