Publications by authors named "G Petur Nielsen"

794 Publications

High TIL, HLA, and Immune Checkpoint Expression in Conventional High-Grade and Dedifferentiated Chondrosarcoma and Poor Clinical Course of the Disease.

Front Oncol 2021 12;11:598001. Epub 2021 Apr 12.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Purpose: The aim of this study was to characterize chondrosarcoma tumor infiltration by immune cells and the expression of immunologically relevant molecules. This information may contribute to our understanding of the role of immunological events in the pathogenesis of chondrosarcoma and to the rational design of immunotherapeutic strategies.

Patients And Methods: A tissue microarray (TMA) containing 52 conventional and 24 dedifferentiated chondrosarcoma specimens was analyzed by immunohistochemical staining for the expression of parameters associated with tumor antigen-specific immune responses, namely, CD4 and CD8 tumor infiltrating lymphocytes (TILs) and the expression of HLA class I heavy chain, beta-2 microglobulin (β2m), HLA class II and immune checkpoint molecules, B7-H3 and PD-1/PD-L1. The results were correlated with histopathological characteristics and the clinical course of the disease.

Results: CD8 TILs were present in 21% of the conventional and 90% of the dedifferentiated chondrosarcoma tumors tested. B7-H3 was expressed in 69% of the conventional and 96% of the dedifferentiated chondrosarcoma tumors tested. PD-1 and PD-L1 were expressed 53% and 33% respectively of the dedifferentiated tumors tested. PD-L1 expression was associated with shorter time to metastasis.

Conclusion: The tumor infiltration by lymphocytes suggests that chondrosarcoma is immunogenic. Defects in HLA class I antigen and expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 suggest that tumor cells utilize escape mechanisms to avoid immune recognition and destruction. This data implies that chondrosarcoma will benefit from strategies that enhance the immunogenicity of tumor antigens and/or counteract the escape mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.598001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071983PMC
April 2021

Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma.

Oncologist 2021 Apr 27. Epub 2021 Apr 27.

Foundation Medicine, Inc., Cambridge, Massachusetts, USA.

Background: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking.

Methods: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes.

Results: Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen-activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance.

Conclusion: A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors.

Implications For Practice: This study presents comprehensive genomic profiling results on 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs). MAPK pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCSs. In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytosis. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/onco.13801DOI Listing
April 2021

Six Weeks of Basketball Combined With Mathematics in Physical Education Classes Can Improve Children's Motivation for Mathematics.

Front Psychol 2021 26;12:636578. Epub 2021 Mar 26.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

This study investigated whether 6 weeks of basketball combined with mathematics once a week in physical education lessons could improve children's motivation for mathematics. Seven hundred fifty-seven children (mean age = 10.4 years, age range: 7-12 years) were randomly selected to have either basketball combined with mathematics once a week (BM) or to have basketball sessions without mathematics (CON). Children in BM and CON motivation for classroom-based mathematics were measured using the Academic Self-Regulation Questionnaire (SRQ-A) before (T0) and after the intervention (T1). Among the BM, levels of intrinsic motivation, feelings of competence, and autonomy were measured using the Post-Experimental Intrinsic Motivation Inventory (IMI) questionnaire acutely after a basketball session combined with mathematics and immediately after a session of classroom-based mathematics. BM had significantly higher acute levels of perceived autonomy (+14.24%, < 0.0001), competencies (+6.33%, < 0.0001), and intrinsic motivation (+16.09%, < 0.0001) during basketball sessions combined with mathematics compared to when having classroom-based mathematics. A significant decrease in the mean for intrinsic motivation was observed from T0 to T1 for CON (-9.38%, < 0.001), but not for BM (-0.39%, = 0.98). BM had a more positive development in intrinsic motivation compared to CON from T0 to T1 ( = 0.006), meaning that BM had a positive influence on children's intrinsic motivation for classroom-based mathematics. This study indicates that basketball combined with mathematics is an intrinsically motivating way to practice mathematics, which also has a positive influence on children's general intrinsic motivation for mathematics in the classroom.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.636578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034423PMC
March 2021

Does rocking motion calm delirious patients in ICU? A multicentre randomised clinical trial protocol (RockingICU).

Acta Anaesthesiol Scand 2021 Mar 18. Epub 2021 Mar 18.

Department of Intensive Care, Rigshospitalet University Hospital, Copenhagen, Denmark.

Background: Rocking chair therapy has been explored in patients with dementia to promote the feeling of relaxation, but not in Intensive Care Unit (ICU) patients with delirium.

Aim: The aim is to investigate the effect of a chair with or without rocking motion on the duration of delirium and intensity of agitation in critically ill patients admitted to the ICU.

Design: This is an investigator-initiated pragmatic, multicentre, parallel-grouped, centrally randomised, stratified, data analyst-blinded trial.

Method: We will include patients for 1:1 web-based randomisation, stratified by site in patients 18 y or older with a positive delirium score identified by a validated tool. We will exclude patients mainly due to mobilisation restrictions, body weight exceeding 130 kg, inability to provide consent, and presence of multiresistant bacteria or viral droplet infections. The intervention group will receive a minimum of 20 min of rocking therapy daily. The control group will be transferred to the same type of chair but without rocking therapy daily. A power calculation with a risk reduction of 20%, a power of 80% with an alpha cut-off on 5% and further 20% inclusion gives 76 patients in intervention and control group reaching a total of n = 152 inclusion in the trial.

Conclusion: The RockingICU trial will provide important new knowledge and raise research questions regarding nonpharmacological interventions to alleviate delirium in ICU patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aas.13821DOI Listing
March 2021

Decade of progress in motor functional neurological disorder: continuing the momentum.

J Neurol Neurosurg Psychiatry 2021 Mar 15. Epub 2021 Mar 15.

Psychiatry and Neurology, Rhode Island Hospital, Providence, Rhode Island, USA

Functional neurological disorder (FND) is a prevalent, disabling and costly condition at the neurology-psychiatry intersection. After being marginalised in the late 20th century, there has been renewed interest in this field. In this article, we review advances that have occurred over the past decade (2011-2020) across diagnosis, mechanisms, aetiologies, treatments and stigma in patients with motor FND (mFND, that is, functional movement disorder and functional limb weakness). In each content area, we also discuss the implications of recent advances and suggest future directions that will help continue the momentum of the past decade. In diagnosis, a major advance has been the emphasis on rule-in physical signs that are specific for hyperkinetic and hypokinetic functional motor symptoms. Mechanistically, greater importance has been given to determining 'how' functional neurological symptoms develop, highlighting roles for misdirected attention, expectation and self-agency, as well as abnormal influences of emotion/threat processing brain areas on motor control circuits. Aetiologically, while roles for adverse life experiences remain of interest in mFND, there is recognition of other aetiologic contributors, and efforts are needed to investigate links between aetiological factors and mechanisms. This decade has seen the first randomised controlled trials for physiotherapy, multidisciplinary rehabilitation and psychotherapy performed in the field, with consensus recommendations for physiotherapy, occupational therapy and outcome measures also published. Across patients, clinicians, healthcare systems and society, stigma remains a major concern. While challenges persist, a patient-centred integrated clinical neuroscience approach is primed to carry forward the momentum of the past decade into the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2020-323953DOI Listing
March 2021