Schlosspark-Klinik

Abstract Background/Aims The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European Alliance of Associations for Rheumatology (EULAR) developed recommendation sets for psoriatic arthritis (PsA) treatment based on current evidence. All biologic disease-modifying anti-rheumatic drugs (bDMARDs) are equally recommended for peripheral arthritis. Different treatments exist for relevant skin and axial involvement. Interleukin 17 (IL-17) inhibitors (i) and IL-12/23i are recommended over tumour necrosis factor inhibitors (TNFi) for PsA with significant skin involvement. IL-12/23i are not recommended with axial manifestations. PRO-SPIRIT is the first large sample prospective multi-national observational PsA study. The objective of this study was to report the real-world treatment patterns reflecting PsA recommendations using results from the PRO-SPIRIT study. Methods PRO-SPIRIT enrolled adults with PsA from 2019 to 2022 who initiated or switched to approved biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD). Treatment groups included TNFi, IL-17Ai, IL-12/23i, IL-23i, Janus kinase (JAKi), and phosphodiesterase-4 (PDE4i). Mode of action (MoA) was at the discretion of the treating physician. Patient demographic, disease activity, treatment characteristics, and clinical and patient-reported outcomes were collected at baseline (BL). Descriptive results are presented. Missing BL values were imputed. Results Analysis includes 1,192 patients with PsA treated by different MoA. Patients with arthritis (defined by swollen joint count (SJC) and tender joint count (TJC) ≥5) were equally distributed across treatment classes except for a lower percentage in PDE4i. Patients receiving IL-17Ai commonly presented with joint, skin, and nail involvement. Patients with higher skin (body surface area (BSA) ≥3%) and nail involvement were more commonly treated by IL-17Ai and IL-23i, less so with JAKi. Patients receiving JAKi presented with more joint and axial, and less skin involvement. After IL-23i, PDE4i had the second highest proportion of patients with nail involvement. PDE4i patients were low and reported less active domain affectation in general. Line of therapy results showed more patients treated with IL-12/23i, JAKi, and IL-17Ai after prior b/tsDMARDs treatment. Conclusion In general, patients had polyarticular disease at BL. Pts with skin and nail involvement were more commonly treated with IL-17Ai and IL-23i over TNFi and JAKi. Patients with axial manifestations were more commonly treated with IL-17Ai and JAKi over IL-12/23i and IL-23i. Findings add to the evidence on real-world PsA treatment patterns and recommendations sets for guiding individualised PsA treatment. Disclosure W. Tillett: Honoraria; AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. M. Nisar: Honoraria; AbbVie, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly and Company, Merck Sharp and Dohme, Novartis, Pfizer, Roche, and UCB Pharma. V. Chandran: Grants/research support; AbbVie, and is a consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma. K. Ng: Shareholder/stock ownership; Employee and shareholder of Eli Lilly and Company. M. Ngantcha: Shareholder/stock ownership; Employee and shareholder of Eli Lilly and Company. C. Laedermann: Shareholder/stock ownership; Employee and shareholder of Eli Lilly and Company. S. Moyano: Shareholder/stock ownership; Employee and shareholder of Eli Lilly and Company. R. Alten: Grants/research support; AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Novartis, Pfizer, and UCB Pharma. L. Kristensen: Consultancies; AbbVie, Amgen, Biogen, Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Biogen, Eli Lilly and Company, Gilead Sciences, Janssen, Novartis, Pfizer, and UCB Pharma.

ObjectivesDARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.MethodsEligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.Results739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient’s decision or ‘sponsor request’). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.ConclusionFilgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

Alterations in the structure and composition of Bruch’s membrane (BrM) and loss of retinal pigment epithelial (RPE) cells are associated with various ocular diseases, notably age-related macular degeneration (AMD) as well as several inherited retinal diseases (IRDs). We explored the influence of stiffness as a major BrM characteristic on the RPE transcriptome and morphology. ARPE-19 cells were plated on soft (E=30kPa\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$E={30}\\,\\hbox {kPa}$$\\end{document}) or stiff (E=80kPa\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$E={80}\\,\\hbox {kPa}$$\\end{document}) polyacrylamide gels (PA gels) or standard tissue culture plastic (TCP). Next-generation sequencing (NGS) data on differentially expressed small RNAs (sRNAs) and messenger RNAs (mRNAs) were validated by qPCR, immunofluorescence or western blotting. The microRNA (miRNA) fraction of sRNAs grew with substrate stiffness and distinct miRNAs such as miR-204 or miR-222 were differentially expressed. mRNA targets of differentially expressed miRNAs were stably expressed, suggesting a homeostatic effect of miRNAs. mRNA transcription patterns were substrate stiffness-dependent, including components of Wnt/beta-catenin signaling, Microphthalmia-Associated Transcription Factor (MITF) and Dicer. These findings highlight the relevance of mechanical properties of the extracellular matrix (ECM) in cell culture experiments, especially those focusing on ECM-related diseases, such as AMD.

Ich berichte über eine 48-jährige Patientin ohne wesentliche psychische oder somatische Vorerkrankungen, die vor ca. 6 Jahren erstmals plötzliche Hautrötungen bemerkte, später Ameisenlaufen im Bereich der Hautregionen der Hände, Finger und Fußsohlen ([ Abb. 1 ]). Die damalige neurologische Abklärung ergab unauffällige Befunde der Nervenleitgeschwindigkeiten sowie der sensibel evozierten Potenziale. Monate später kam es zu Muskelschmerzen sowie Tachykardien in Verbindung mit Luftnot. Eine ausführliche kardiologische Abklärung – u. a. EKG, Koronarangiografie, Kernspintomografie – ergab ebenfalls unauffällige Befunde. Auch mehrere orthopädische Untersuchungen ergaben keinen Hinweis für eine organische Genese der muskulären Beschwerden. Zuletzt traten gastroenterologische Symptome auf, die u. a. dazu führten, dass eine Defäkation nur im Intervall möglich war, sodass dies einen Zeitrahmen von mindestens 20–30 Minuten benötigte. 3 Jahre nach den ersten Symptomen befand sich die Patientin in einer psychosomatischen Rehabilitationsklinik, und es wurde ausgegangen von psychischen Erkrankungen in Form von dissoziativen Sensibilitäts- und Empfindungsstörungen, sonstigen somatoformen Störungen etc.

IntroductionThe role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis.MethodsWe conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated.ResultsNone of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059).ConclusionsRadiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.

BGPN-Mitglied Mazda Adli beschäftigt sich als Psychiater und Forscher schwerpunktmäßig mit der psychischen Gesundheit in der Stadt. Er ist Chefarzt der Fliedner Klinik Berlin. Wir trafen ihn zum Interview.

Abstract Introduction: The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant, yet its preoperative prognostic value for postoperative complications and CD relapse remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence after ileocecal resection (ICR) using magnetic resonance imaging (MRI). Primary endpoint of the study was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. Methods: We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. From this cohort, 223 patients with available high-quality preoperative MRI scans were included in the study. We recorded patient demographics, postoperative outcomes, and rates of CD recurrence at the anastomosis. To assess adipose tissue distribution, we measured the total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using an established image-analysis method on MRI cross-sectional images. Additionally, we calculated ratios of the aforementioned values. Results: None of the radiological variables showed an association with anastomotic leakage (TFA p=0.932, VFA p=0.982, SFA p=0.951, SFA/TFA p=0.422, VFA/TFA p=0.422), postoperative complications’ rate or CD recurrence (TFA p=0.264, VFA p=0.916, SFA p=0.103, SFA/TFA p=0.059, VFA/TFA p=0.059). Conclusions: None of the radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Measurement of visceral fat may be a good parameter to evaluate the severity of CD activity but is rather unspecific considering the prediction of possible postoperative complications and CD relapse.