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- Campbell, Kristin L, et al.
(författare)
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Exercise Recommendation for People With Bone Metastases : Expert Consensus for Health Care Providers and Exercise Professionals.
- 2022
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Ingår i: JCO oncology practice. - 2688-1535. ; 18:5, s. e697-e709
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion.METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement.RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential.CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.
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- Quist-Paulsen, P., et al.
(författare)
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T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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- Tulstrup, M., et al.
(författare)
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Effects of germ line DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:10, s. 1161-1168
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Tidskriftsartikel (refereegranskat)abstract
- Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 x 10(-8)) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 x 10(-9)) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
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| 6. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 7. |
- Henjum, K., et al.
(författare)
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CSF sTREM2 in deliriumrelation to Alzheimer's disease CSF biomarkers A42, t-tau and p-tau
- 2018
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDelirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer's disease.MethodsWe analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n=120), and some of the patients developed delirium (n=65). A medical delirium cohort (n=26) was also examined. ELISA was used to determine the level of sTREM2 in CSF.ResultsDelirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p=0.046, n=15, n=44), particularly among patients developing delirium after CSF sampling (p=0.02, n=7, n=44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (r(S)=0.39, p=0.002, n=60) and correlated well with the CSF Alzheimer's disease biomarkers, A42, and t-tau/p-tau (r(S)=0.40, p=0.002, r(S)=0.46, p<0.001/ r(S)=0.49, p<0.001, n=60). Among patients with dementia, the level of A38 and A40 also correlated positively with sTREM2 in CSF (A38(MSD)r(S)=0.44, p=0.001; A40(MSD)r(S)=0.48, p<0.001; A42(MSD)r(S)=0.43, p<0.001, n=60).ConclusionThe findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.
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| 8. |
- Toft, N, et al.
(författare)
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Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 32, s. 606-615
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Tidskriftsartikel (refereegranskat)abstract
- Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.Leukemia advance online publication, 22 September 2017; doi:10.1038/leu.2017.265.
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| 9. |
- Aamodt, A. H., et al.
(författare)
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Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
- 2021
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
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Tidskriftsartikel (refereegranskat)abstract
- Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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