Make new friends, but keep the old: Methotrexate treatment in psoriasis patients

Psoriasis is a chronic and inflammatory skin disease, with a current prevalence of 1.92% - 3.46% (Western Europe). There are different treatment options for psoriasis: topical therapy, phototherapy, systemic treatment with pills and biological treatment with subcutaneous injections.The aim of this thesis was to study the systemic treatment option methotrexate in psoriasis vulgaris and other dermatological diseases. Due to the low treatment costs of methotrexate, this drug has the ability to keep dermatological healthcare affordable and accessible. Methotrexate was investigated by summarizing the evidence for the off-label use of methotrexate and the dosing of this drug used in psoriasis patients. In this thesis, we also tried to reach international consensus on the dosing regimen of methotrexate, and we investigated the long-term effects of the combination of methotrexate with adalimumab (adalimumab is a better affordable biological since biosimilars are available). In the last part, shared decision making for the systemic treatment decisions in psoriasis was studied

Make new friends, but keep the old: Methotrexate treatment in psoriasis patients

Psoriasis is a chronic and inflammatory skin disease, with a current prevalence of 1.92% - 3.46% (Western Europe). There are different treatment options for psoriasis: topical therapy, phototherapy, systemic treatment with pills and biological treatment with subcutaneous injections.The aim of this thesis was to study the systemic treatment option methotrexate in psoriasis vulgaris and other dermatological diseases. Due to the low treatment costs of methotrexate, this drug has the ability to keep dermatological healthcare affordable and accessible. Methotrexate was investigated by summarizing the evidence for the off-label use of methotrexate and the dosing of this drug used in psoriasis patients. In this thesis, we also tried to reach international consensus on the dosing regimen of methotrexate, and we investigated the long-term effects of the combination of methotrexate with adalimumab (adalimumab is a better affordable biological since biosimilars are available). In the last part, shared decision making for the systemic treatment decisions in psoriasis was studied

Abnormal actomyosin assembly in proliferating and differentiating myoblasts upon expression of a cytosolic DMPK isoform

Contains fulltext : 97603.pdf (publisher's version ) (Closed access)DMPK, the product of the mutated gene in myotonic dystrophy type 1, belongs to the subfamily of Rho-associated serine-threonine protein kinases, whose members play a role in actin-based cell morphodynamics. Not much is known about the physiological role of differentially localized individual DMPK splice isoforms. We report here that prominent stellar-shaped stress fibers are formed during early and late steps of differentiation in DMPK-deficient myoblast-myotubes upon complementation with the short cytosolic DMPK E isoform. Expression of DMPK E led to an increased phosphorylation status of MLC2. We found no such effects with vectors that encode a mutant DMPK E which was rendered enzymatically inactive or any of the long C-terminally anchored DMPK isoforms. Presence of stellar structures appears associated with changes in cell shape and motility and a delay in myogenesis. Our data strongly suggest that cytosolic DMPK participates in remodeling of the actomyosin cytoskeleton in developing skeletal muscle cells. This article is part of a Special Issue entitled: 11th European Symposium on Calcium

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger