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Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR 5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.

Antimalariamittel (AM) haben eine grose Bedeutung in der Therapie rheumatischer Erkrankungen. Es werden aktualisierte evidenzbasierte Empfehlungen zum Sicherheitsmanagement der rheumatologischen Therapie mit AM aufgezeigt. Durch eine systematische Literaturrecherche in den Datenbanken Medline (PubMed) und Cochrane wurden 1160 Arbeiten zur Sicherheit der Therapie mit AM in der Rheumatologie identifiziert. Erganzend wurde eine Handsuche durchgefuhrt. Es wurden 67 von den Autoren als besonders relevant eingeschatzte Publikationen genauer analysiert. Diese dienen als Grundlage fur konsensbasierte Empfehlungen. Eine Therapie mit AM in der Rheumatologie sollte mit Hydroxychloroquin (HCQ) erfolgen und die Dosis von 5 mg/kg Korpergewicht/Tag nicht uberschreiten. In den ersten 6 Monaten der Therapie mit AM ist eine augenarztliche Basisuntersuchung empfohlen. Vorbestehende Makulopathie, Niereninsuffizienz (GFR [glomerulare Filtrationsrate] 5 mg/kg HCQ oder Therapie mit Chloroquin (CQ) gehen mit einem erhohten Risiko fur eine AM-induzierte Retinopathie einher. Diese Patienten sollten daher von Beginn an jahrlich augenarztliche Kontrollen erhalten, wahrend dies bei Patienten ohne Risikofaktoren erst ab 5 Jahren Einnahmedauer empfohlen wird. Die ophthalmologische Untersuchung sollte mindestens je eine geeignete subjektive und objektive Methode nutzen, in der Regel sind dies das automatisierte Gesichtsfeld (aGF) und die optische Koharenztomographie (OCT). Anzeichen einer moglichen AM-Retinopathie sind im aGF eine parafoveale Empfindlichkeitsabnahme und im OCT eine umschriebene Verdunnung der Photorezeptorschicht parafoveal und/oder fokale Unterbrechungen der Ausensegmentstrukturlinie. Die Bestimmung der Kreatinkinase (CK) und Laktatdehydrogenase (LDH) im Blut ist als Screeninguntersuchung auf eine evtl. Myopathie oder Kardiomyopathie geeignet und sollte ca. 3-monatlich erfolgen. Der Einsatz von kardialen Biomarkern im Serum wie „brain natriuretic peptide“ (BNP) oder Troponin, EKG (Elektrokardiogramm) oder kardiale Bildgebung sollte je nach Situation erwogen werden. Die Einnahme von HCQ ist in Schwangerschaft und Stillzeit nach gegenwartigem Wissen sicher und bei Patientinnen mit systemischem Lupus erythematodes protektiv fur Mutter und Kind. Die aktualisierten Empfehlungen der Therapie mit AM in der Rheumatologie beinhalten v. a. strengere Dosisvorgaben, eine Risikostratifizierung im Monitoring sowie definierte augenarztliche Untersuchungsmethoden zur Erkennung einer evtl. Retinopathie.

Hintergrund: Die proliferative Vitreoretinopathie (PVR) bleibt eine ungelöste Herausforderung in der klinischen Versorgung der Netzhautablösung und kann zu häufigen Folgeoperationen und zu eingeschränkten Visusergebnissen führen. Das Ziel dieser Studie war es, die zellulären[zum vollständigen Text gelangen Sie über die oben angegebene URL], 33. Jahrestagung der Retinologischen Gesellschaft

Hintergrund: Die proliferative diabetische Retinopathie (PDR) geht mit der Ausbildung von retinalen Neovaskularisationen einher, die zu einer traktiven Netzhautablösung und zur Glaskörperblutung führen können. In dieser Studie wurde zum ersten Mal das Transkriptom von diabetischen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 33. Jahrestagung der Retinologischen Gesellschaft

Einleitung: Antimalariamittel (AM) spielen eine wichtige Rolle in der Behandlung des SLE und weiterer rheumatologischer Erkrankungen. Ziel dieser Arbeit war es, die Grundlage für aktualisierte Empfehlungen zum Sicherheitsmanagement der rheumatologischen Therapie mit AM zu erarbeiten. Methoden:[zum vollständigen Text gelangen Sie über die oben angegebene URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

British journal of ophthalmology : BJO 100(3), 405-410 (2016). doi:10.1136/bjophthalmol-2015-306732, Published by BMJ Publ. Group, London

Hintergrund: Mit Hilfe der SD-OCT kann der Abstand zwischen einer epiretinalen Membran und neurosensorischer Netzhaut bestimmt werden. Das GapMap-Modul des Cirrus 5000 OCT (Zeiss) erlaubt es, das räumliche Verhältnis dieser für die Entfernung epiretinaler Membranen wichtigen Schichten[zum vollständigen Text gelangen Sie über die oben angegebene URL], 29. Jahrestagung der Retinologischen Gesellschaft

Introduction: The CRUK SMP2 programme was set-up to evaluate\ud the feasibility of performing large scale molecular analysis within the\ud NHS on the (often small) diagnostic biopsies obtained in NSCLC. The\ud results are used to allocate patients to an appropriate molecular therapy\ud within the “umbrella” MATRIX trial. Newcastle opened SMP2 on\ud 01/10/2014. Here we report our first year’s experience.\ud Methods: NSCLC patients with PS 0–2 were consented onto the CRUK\ud SMP2. Matched residual diagnostic tissue and blood were sent to All\ud Wales Genetics Laboratory, Cardiff. Samples with >70ng DNA were\ud assessed for 28 oncogenes using Next Genuine Sequencing on the Illumina\ud SMP2 panel.\ud Results: 116 patients were consented from 6/10/14–1/10/15 referred\ud from 12 oncologists. The data on patient/sample flow is shown in Fig\ud 1. Median survival was 161 days from consent. The 1st sample was\ud sent to Cardiff on 28/1/15 as the Illumina panel was undergoing fi-\ud nal validation. 50 samples have been sent; 11 had insufficient DNA;\ud these samples had lower cell number (but with no impact of necrosis/tumour\ud proportion); The most commonly altered gene was K-Ras\ud (13 of 22 adenocarcinomas). Only 2 patients with results from >25\ud of the 28 genes had no tier 1 or 2 ie potentially treatable molecular\ud abnormalities. The median time from consent to result was 109 days\ud (range 45–250) with delays occurring throughout the pathway.\ud Conclusion: Patients and oncologists are keen to be involved in\ud molecular profiling; but patients need to be consented early to allow\ud results to guide therapy. Prioritisation of samples is key. Not all\ud samples are suitable for analysis due to small cell number or low tumour\ud proportion. Molecular analysis may require extra resource in\ud pathology, if it is to become standard of care. The first 4 patients to\ud start treatment on MATRIX were enrolled from 27/8/15 in Newcastle.\ud Disclosure: All authors have declared no conflicts of interest.

Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent inflammatory stimuli, pathways previously linked to oncogene-initiated carcinogenesis instruct a long-lived granuloma-resident macrophage differentiation program that regulates granulomatous tissue remodeling. © 2016 Elsevier Inc.

OA gold Purpose : To evaluate whether a mycophenolate sodium-based treatment regimen is able to reduce the probability of a relapse compared to corticosteroid therapy alone in patients with non-infectious intermediate uveitis. Methods : Investigator-initiated, phase 3 open, prospective, controlled, randomized national multicenter trial (protocol MYCUV-IIT02). To be eligible, patients had to suffer from a documented at least 6 months history of unilateral or bilateral intermediate uveitis, either idiopathic or due to non-infectious systemic disease, that was active at study entry. All patients received initial treatment with oral prednisolone 1 mg/kg, followed by a slow tapering over 3 months. For maintenance therapy, subjects were randomized in a 1:1 ratio to either mycophenolic sodium 1440 mg/day (Myfortic®, Novartis Pharma) plus prednisolone 5 mg/day (treatment arm) or prednisolone 5mg/day alone (control arm). Maximum treatment duration was 15 months. The primary endpoint was defined as the time from study entry to the first relapse defined as a deterioration of best corrected visual acuity ≥ 3 lines and/or an at least 2-step increase of vitreous haze and/or an at least 2-step increase of anterior chamber cells and/or a new onset or worsening of preexisting cystoid macular edema, proven by optical coherence tomography, and/or a new onset or worsening of retinal vasculitis, proven by fluorescein angiography. Results : Fourty-four subjects at 8 sites were included. Of these, 41 patients (16 males, 25 females; median age 41.5 years, 18.6 – 82.7 years) were eligible for further analysis. Twenty-two patients (53.7 %) were randomized to treatment arm, 19 patients (46.3%) to control arm. In a first analysis using the Kaplan-Meier method, the proportion of relapse-free patients was estimated as 58.2 % in the treatment arm and 26.3 % in the control arm at 9 months after study entry, and as 52.9 % in the treatment arm and 19.7 % in the control arm at 15 months after study entry. The difference between treatment arm and control arm regarding relapse-free survival was statistically significant (log-rank test p = 0.011). Conclusions : During an observation period of 15 months, a combination of mycophenolate sodium plus low-dose corticosteroids resulted in a significant reduction of relapse rate compared to treatment with low-dose corticosteroids alone in patients with non-infectious intermediate uveitis.