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- Gutierrez-Suarez, R., et al.
(författare)
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Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study
- 2007
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Ingår i: Rheumatology (Oxford). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 46:2, s. 314-320
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare health-related quality of life (HRQL) and to identify clinical determinants for poor HRQL of patients with juvenile idiopathic arthritis (JIA) coming from three geographic areas.METHODS: The HRQL was assessed through the Child Health Questionnaire (CHQ). A total of 30 countries were included grouped in three geographic areas: 16 countries in Western Europe; 10 in Eastern Europe; and four in Latin America. Potential determinants of poor HRQL included demographic data, physician's and parent's global assessments, measures of joint inflammation, disability as measured by Childhood Health Assessment Questionnaire (CHAQ) and erythrocyte sedimentation rate. Poor HRQL was defined as a CHQ physical summary score (PhS) or psychosocial summary score (PsS) <2 S.D. from that of healthy children.RESULTS: A total of 3167 patients with JIA, younger than 18 yrs, were included in this study. The most affected health concepts (<2 S.D. from healthy children) that differentiate the three geographic areas include physical functioning, bodily pain/discomfort, global health, general health perception, change in health with respect to the previous year, self-esteem and family cohesion. Determinants for poor HRQL were similar across geographic areas with physical well-being mostly affected by the level of disability while the psychosocial well-being by the intensity of pain.CONCLUSION: We found that patients with JIA have a significant impairment of their HRQL compared with healthy peers, particularly in the physical domain. Disability and pain are the most important determinants of physical and psychosocial well-being irrespective of the geographic area of origin.
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- Serwas, NK, et al.
(författare)
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Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3106-
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Tidskriftsartikel (refereegranskat)abstract
- Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11+CTLA-4+ vesicles in DEF6-mutated cells. One of the patients has been treated with CTLA-4-Ig and achieved sustained remission. Collectively, we uncover DEF6 as player in immune homeostasis ensuring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target for autoimmune and/or cancer therapy.
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- Illini, Oliver, et al.
(författare)
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Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN) : a retrospective analysis of patients treated through an access program
- 2021
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Ingår i: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY. - : Sage Publications. - 1758-8340 .- 1758-8359. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naive, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade > 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.
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