Search

Zusammenfassung Hintergrund Regelmäßige Bewegung und spezifisches Training sind wichtige Bausteine in der Therapie rheumatischer Erkrankungen, weil ein gesundheitlicher Nutzen für die Patient*innen nachgewiesen ist. Basierend auf den internationalen Empfehlungen der WHO für Gesunde, geben die „2018 EULAR Empfehlungen zu körperlicher Aktivität von Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen“ erstmals evidenzbasierte Empfehlungen zu Gestaltung, Durchführung und Implementierung von Bewegungsübungen bei diesen Patient*innen. Ziel Übersetzung ins Deutsche und sprachliche Validierung in Deutschland, Österreich und der Schweiz. Methoden Eine professionelle Übersetzung der EULAR Bewegungsempfehlungen ins Deutsche wurde durch deutschsprachige Experten*innen aus allen 3 Ländern überarbeitet. Die Validierung erfolgte in einem Feldtest mit Rheumatolog*innen, Ergo- und Physiotherapeut*innen, Pflegefachpersonen und medizinischen Fachangestellten aus der Rheumatologie. In den 3 Ländern wurden jeweils 8 strukturierte Interviews zu Verständlichkeit, Wortwahl, Vollständigkeit und Umsetzbarkeit durchgeführt. Die Experten*innen diskutierten die Änderungsvorschläge, bis jeweils ein Konsens erreicht wurde. Zuletzt gaben sie den Grad ihrer Zustimmung zu der finalen Übersetzungsversion an. Ergebnisse Die professionelle Übersetzung wurde substanziell überarbeitet. Aufgrund der Ergebnisse der Feldtests wurden verschiedene Änderungen einzelner Worte sowie Umformulierungen zur besseren Verständlichkeit vorgenommen. Der Grad der Zustimmung lag mit durchschnittlichen Bewertungen zwischen 10 (SD 0,0) und 8,9 (SD 1,5) insgesamt sehr hoch. Diskussion Die vorliegende sprachlich validierte deutschsprachige Version der 2018 EULAR Bewegungsempfehlungen kann und soll dazu beitragen, Fachpersonal darin zu unterstützen, körperliche Aktivität bei Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen zu fördern.

ObjectiveEpionics SPINE (ES), a novel device that measures spinal movements using electronic sensors including range of motion (RoM) and speed (range of kinematics [RoK]), has already been validated in patients with mechanical back pain and healthy individuals. This study aimed to evaluate ES for quantification of spinal mobility in patients with axial spondyloarthritis (axSpA).MethodsA total of 153 individuals, 39 female and 114 male, were examined including 134 patients with axSpA, of whom 40 had nonradiographic (nr)-axSpA, 94 had radiographic (r)-axSpA; 19 were healthy controls (HCs). The results were compared using mean ES scores and modeling was performed using multivariable logistic regression models resulting in good validity and high discriminative power.ResultsES measurements showed meaningful differences between patients with axSpA and HCs (all P < 0.001), as well as between r- and nr-axSpA (P < 0.01). In patients with axSpA, a negative correlation between ES and Bath Ankylosing Spondylitis Metrology Index values was found: –0.76 ≤ r ≤ –0.52 (P < 0.05). Bath Ankylosing Spondylitis Functional Index scores showed a similar trend (r > –0.39). Patients with r-axSpA had a more limited and slower spinal mobility than those with nr-axSpA. Other patient-reported outcomes almost did not correlate.ConclusionThis study shows that the ES is an objective performance measure and a valid tool to assess spinal mobility in axSpA, also based on the Outcomes Measures in Rheumatology (OMERACT) criteria. RoK and RoM scores provide additional information on physical function of patients with axSpA.

\(\bf Hintergrund\) Patienten mit entzündlich rheumatischen Erkrankungen haben aufgrund ihrer Autoimmunerkrankung, aber auch bedingt durch die immunsuppressive Medikation ein erhöhtes Infektrisiko. Obwohl Impfungen in der Primärprophylaxe von Infektionen bekanntermaßen effektiv sind, ist die Impfrate in Deutschland generell zu niedrig. Wegen des zuletzt zunehmenden, teils epidemieartigen Auftretens von Masern ist die Lebendimpfung gegen Masern in Deutschland seit Kurzem gesetzlich vorgeschrieben. \(\bf Fragestellung\) Wie viele Patienten mit entzündlich rheumatischen Erkrankungen sind aktuell ausreichend gegen Masern geschützt? \(\bf Methode\) Patienten mit entzündlich rheumatischen Erkrankungen des Rheumazentrums Ruhrgebiet wurden zwischen Dezember 2017 und Oktober 2018 prospektiv und konsekutiv eingeschlossen. Dabei wurden Daten zu Erkrankung und Therapie auf Ebene von Substanzklassen sowie die Impf- und Infektanamnese erhoben. Alle Angaben zu Impfungen wurden im Impfpass kontrolliert. Antikörpertiter gegen Masern wurden mit ELISA bestimmt. Als Schwellenwert für einen ausreichenden Schutz gegen Masern wurden 150 mIU/ml festgelegt. \(\bf Ergebnis\) Von 975 Patienten konnten 540 (55,4 %) einen Impfausweis vorlegen. Bei 201 Patienten mit Ausweis (37,2 %) lagen dokumentierte Impfungen seit Geburt vor. Insgesamt hatten 45 von 267 nach 1970 geborene Patienten (16,9 %) einen suffizienten Impfschutz gegen Masern. Die anamnestischen Angaben zu einer Masernerkrankung in der Kindheit differenzierten nicht zwischen Patienten mit und ohne protektiven Masern-IgG-Antikörpern. Protektive Masern-IgG-Antikörper wurden bei 901 Patienten von 928 Patienten mit Messung der Masern-IgG-Antikörperspiegel (97,1 %) nachgewiesen. Die unterschiedlichen Wirkprinzipien der aktuellen immunsuppressiven Therapie hatten darauf keinen Einfluss. \(\bf Diskussion\) Diese Daten zeigen, dass mindestens 2,9 % der Patienten keinen ausreichenden Schutz gegen Masern haben. Interessanterweise hatte die Mehrheit der nach 1970 geborenen Patienten protektive Antikörper trotz fehlenden Impfschutzes gegen Masern. Die Anstrengungen sowohl im primär- als auch im fachärztlichen Bereich sollten dringend verstärkt werden, um eine adäquate Infektionsprophylaxe bei besonders gefährdeten Patienten gewährleisten zu können. \(\bf Background\) Patients with inflammatory rheumatic diseases have an increased risk of infections due to the autoimmune disease but also due to the immunosuppressive medication. Although vaccinations are known to be effective in the primary prophylaxis of infections, the vaccination rate in Germany is generally too low. Due to the recently increasing, sometimes epidemic-like occurrence of measles, the administration of live vaccine against measles has recently become required by law. \(\bf Objective\) How many patients with inflammatory rheumatic diseases are currently sufficiently protected against measles? \(\bf Method\) Between December 2017 and October 2018 patients with inflammatory rheumatic diseases at the Ruhrgebiet Rheumatism Center were prospectively and consecutively included. Data on the disease and treatment at the level of substance classes, patient history of vaccination and infections were collated. All information on vaccinations were controlled in the vaccination certificate. Antibodies against measles were determined using ELISA. The threshold for sufficient protection against measles was set at 150 mIU/ml. \(\bf Results\) Out of 975 patients 540 (55.4%) could present a vaccination certificate. In 201 patients with a certificate (37.2%) vaccination had been documented since birth. Overall, 45 out of 267 patients born after 1970 (16.9%) had sufficient protection against measles. The patient history of measles in childhood showed no differences between patients with and without protective measles IgG antibodies. Protective measles IgG antibodies were detected in 901 out of 928 patients with measurement of the measles IgG antibody level (97.1%). The different principles of action of the current immunosuppressive treatments had no influence on this. \(\bf Conclusion\) These data show that at least 2.9% of the patients did not have sufficient protection against measles. Interestingly, the majority of patients born after 1970 had protective antibodies despite the lack of vaccination against measles. The efforts in primary and also in the specialist medical care should be urgently strengthened in order to be able to guarantee an adequate infection prophylaxis in particularly endangered patients.

Multimodal rheumatologic complex treatment (MRCT) is based on an acute inpatient treatment concept for patients with clinically relevant functional impairments and exacerbation of pain, which are caused by rheumatic and musculoskeletal diseases. Patients with axial spondylarthritis (axSpA) including ankylosing spondylarthritis (AS) often suffer from such health problems. Regular movement exercises and physical therapy measures are an important pillar of treatment management. The ASAS Health Index (ASAS-HI) can be used to document the global functional ability and health of axSpA patients. The selectivity of the ASAS HI for nonpharmacological treatment changes has so far not yet been proven.Evaluation of the MRCT and ASAS HI for nonpharmacological treatment measures of patients with axSpA carried out in the Ruhr Area Rheumatism Center. The primary endpoint was an improvement of the ASDAS≥ 1.1. It was assumed that 25% of the patients would achieve this threshold.Consecutively included patients with active axSpA and relevant functional impairments received inpatient treatment for 14 days during MRCT. On days 1 (V1) and 14 (V2) all patients completed questionnaires on pain (NRS), disease activity (BASDAI, ASDAS) and function (BASFI, ASAS HI). The clinical examination was carried out using BASMI and measurement of C‑reactive protein (CRP) at both times.The 66 prospectively included patients had an average age of 47.2 years (SD 14.2 years), a duration of symptoms of ca. 20 years, 65.3% were male, 75% were positive for HLA B27 and CRP was elevated in 41.3%. The disease activity at V1 was elevated: BASDAI 5.6 (1.8), ASDAS 3.1 (0.9), whereas functional ability and mobility were reduced: BASFI 3.5 (1.8), BASMI 5.6 (2.1), ASAS-HI 8.4 (3.4). During the course the global patient verdict improved (NRS 0-10) from 6.9 (1.7) at V1 to 4.8 (1.8) at V2 and the pain from 6.9 (1.9) to 4.7 (2.0) (all p 0.001). The disease activity also decreased at V2: BASDAI 4.1 (1.9), ASDAS 2.4 (1.0), function and mobility were also improved: BASFI 4.3 (2.4), BASMI 2.7 (1.6), ASAS HI 6.5 (3.8) (all p 0.001).In this study the effectiveness of a 2‑week MRCT according to OPS 8-983.1 with respect to important patient-centered outcomes (PCO) could be proven and the results of previous studies could be confirmed. In this context ASAS-HI was also sensitive to change.HINTERGRUND: Die multimodale rheumatologische Komplexbehandlung (MRKB) beruht auf einem akutstationären Versorgungskonzept zur Behandlung von Patienten mit klinisch relevanten Funktionseinschränkungen und Schmerzexazerbationen, die durch rheumatische und muskuloskeletale Erkrankungen bedingt sind. Patienten mit axialer Spondyloarthritis (axSpA) einschließlich der ankylosierenden Spondylitis (AS) leiden häufig unter solchen Gesundheitsproblemen. Regelmäßige Bewegungsübungen und physikalische Therapiemaßnahmen sind ein wichtiger Pfeiler im Behandlungsmanagement. Mit dem ASAS Health Index (ASAS HI) können die globale Funktionsfähigkeit und Gesundheit von axSpA-Patienten erfasst werden. Die Trennschärfe des ASAS HI für nichtpharmakologische Therapieänderungen ist bisher noch nicht nachgewiesen worden.Evaluation der im Rheumazentrum Ruhrgebiet durchgeführten MRKB und des ASAS HI für nichtpharmakologische Therapiemaßnahmen bei Patienten mit axSpA. Als primärer Endpunkt wurde eine Verbesserung des ASDAS ≥ 1,1 festgelegt. Hierbei wurde angenommen, dass 25 % der Patienten diesen Schwellenwert erreichen.Konsekutiv eingeschlossene Patienten mit aktiver axSpA und relevanten Funktionseinschränkungen wurden im Rahmen einer MRKB 14 Tage stationär behandelt. Alle Patienten beantworteten am ersten (V1) und am 14. Tag (V2) des Aufenthalts Fragebögen zu Schmerzen (NRS), Krankheitsaktivität (BASDAI, ASDAS) und Funktion (BASFI, ASAS HI). Die klinische Untersuchung erfolgte mittels BASMI und eine Messung des C‑reaktiven Proteins (CRP) zu beiden Zeitpunkten.Die prospektiv eingeschlossenen 66 Patienten hatten ein mittleres Alter von 47,2 Jahren (SD 14,2), eine Symptomdauer von ca. 20 Jahren, 65,3 % waren Männer und 75 % HLA B27+, das CRP war bei 41,3 % erhöht. Die Krankheitsaktivität zu V1 war erhöht: BASDAI 5,6 (1,8), ASDAS 3,1 (0,9), während Funktionsfähigkeit und Mobilität vermindert waren: BASFI 3,5 (1,8), BASMI 5,6 (2,1), ASAS HI 8,4 (3,4). Im Verlauf verbesserte sich das globale Patientenurteil (NRS 0–10) von 6,9 (1,7) zu V1 auf 4,8 (1,8) zu V2 und der Schmerz von 6,9 (1,9) auf 4,7 (2,0) (alle p 0,001). Auch die Krankheitsaktivität nahm zu V2 ab: BASDAI 4,1 (1,9), ASDAS 2,4 (1,0), Funktion und Mobilität waren auch verbessert: BASFI 4,3 (2,4), BASMI 2,7 (1,6), ASAS HI 6,5 (3,8) (alle p 0,001).In dieser Studie konnte die Wirksamkeit einer 2‑wöchigen MRKB gemäß OPS 8–983,1 hinsichtlich wichtiger patientenzentrierter Outcomes (PRO) nachgewiesen und frühere Studienergebnisse konnten bestätigt werden. In diesem Rahmen war auch der ASAS-HI veränderungssensitiv.

A significant deceleration effect on a stored coasting ion beam by a continuous-wave laser light was observed in the Schottky-noise spectrum during the laser experiments with lithium-like oxygen ion beams stored at a relativistic energy of 275.7 MeV/u at the heavy-ion storage ring CSRe in Lanzhou, China. The observed deceleration range of the laser (Δp/p≈5.7×10−6) is much broader than the expected capture range (Δp/p≈3.6×10−8), as calculated from the natural linewidth of the O5+ ion’s electronic transition (2S1/2 −2 P1/2). In order to explain this huge deviation, a phase space tracking code has been developed to investigate the interaction between the stored coasting ion beam and the laser light. Simulations reveal that the deceleration range of the typically narrow CW laser force is highly enlarged by taking into account the transverse betatron oscillation of the ions with larger emittance and the angular misalignment of the laser light direction. The experimental observation is well described by the systematic simulations. The present work is crucial for forthcoming laser cooling and precision laser spectroscopy experiments and simulations on heavy highly charged ions at the CSRe and the future facility HIAF.

This review article presents the innovations in the update of the S3 guidelines on axial spondylarthritis. The total of eight new recommendations address the areas of the consideration of differential diagnoses, coordination of comorbidity management, including a vaccination strategy, treatment targets, safety of nonsteroidal anti-inflammatory drugs (NSAID), treatment response to biological disease-modifying antirheumatic drugs (bDMARD) and discontinuation strategies when remission has been achieved. In this article the authors deal particularly with the areas of early diagnosis and referral as well as exercise therapy and drug treatment.Die vorliegende Übersicht stellt die Neuerungen des Updates der S3-Leitlinie zur axialen Spondyloarthritis vor. Die insgesamt 8 neuen Empfehlungen adressieren die Bereiche der Beachtung von Differenzialdiagnosen, Koordination des Komorbiditätenmanagements einschließlich einer Impfstrategie, Therapieziele, der NSAR(nichtsteroidale Antirheumatika)-Sicherheit, Therapieansprechen von b(„biological“)DMARD („disease-modifying antirheumatic drugs“) und Absetzstrategien bei Erreichen einer Remission. Die Autoren gehen in dem Beitrag insbesondere auf die Bereiche Frühdiagnose und Überweisung sowie Bewegungstherapie und medikamentöse Therapie ein.

In this case series we present three patients with autoimmune dermatomyositis or polymyositis with rapid-progressive interstitial pulmonary involvement. Despite intensive escalation of the immunosuppressive therapy the patients developed acute respiratory distress syndrome with lethal outcome only a few months after diagnosis. All three patients had increased myositis-specific or myositis-associated antibodies - two patients were detected with anti-melanoma differentiation-associated gene (MDA5) antibodies and the third patient with anti-Ku antibodies. Dermatomyositis and polymyositis are rare autoimmune diseases with variable clinical manifestations and several different antibody constellations. In particular the presence of anti-MDA5 antibodies is associated with progressive pulmonary involvement, complicated progression and poor prognosis.

In Deutschland sind seit vielen Jahren Biosimilars zugelassen, seit wenigen Jahren auch in der Rheumatologie. Zwar haben die Biosimilars, die wie die Referenzbiologika biotechnologisch hergestellten Produkte sind, inzwischen in einigen Regionen schon erheblich Marktanteile erreicht, es gibt aber bei Patienten und Arzten immer noch viele Zweifler, die einen Qualitatsverlust befurchten – auch, wenn es dafur keinen Anhalt gibt. Ein Teil dieses Problems ist durch den Nocebo-Effekt zu erklaren, der aber auch daruber hinaus eine erhebliche medizinische Bedeutung hat. Dieser Effekt wird in diesem Artikel beschrieben und erlautert. Psychosoziale und kontextbezogene Faktoren wie die Beziehung zwischen Patient und Arzt, fruhere Behandlungserfahrungen und Behandlungserwartungen konnen die Wirksamkeit einer therapeutischen Intervention entweder verbessern oder beeintrachtigen. Diese Phanomene werden ublicherweise als Placebo- und Nocebo-Effekte bezeichnet. Da Placebo- und Nocebo-Effekte die Symptomentwicklung, die Haufigkeit unerwunschter Ereignisse und die Wirksamkeit der Behandlung beeinflussen konnen, ist es entscheidend, diese Effekte zu kennen und Strategien zur Pravention zu entwickeln, um die Behandlungsergebnisse zu optimieren. Wahrend experimentelle Studien in den letzten Jahren wesentliche Fortschritte bei der Aufklarung der psychosozialen und neurobiologischen Mechanismen von Placebo-Effekten erzielt haben, sind die detaillierten Mechanismen von Nocebo-Effekten noch weitgehend unerforscht. Ein besseres Verstandnis dieser Mechanismen verspricht die Entwicklung benutzerfreundlicher Strategien fur die klinische Versorgung zur Verbesserung der Behandlungsergebnisse und der Patientenzufriedenheit.

ZusammenfassungDie standardisierte Erfassung der klinischen Manifestation und Patienten-berichteter Endpunkte (heute international gebräuchlich Outcomes) von Patienten mit axialer Spondyloarthritis (axSpA) ist notwendig, um die Erkrankung hinsichtlich Ausmaß und Aktivität der Erkrankung so objektiv wie möglich abbilden zu können und damit die Grundlage für klinische Entscheidungen zu schaffen. Die standardisierte Erfassung bezieht sich auf Domänen wie Krankheitsaktivität, Lebensqualität, Funktions- und Erwerbsfähigkeit, aber auch auf einzelne Aspekte wie Schmerzen, Arthritis und Enthesitis. Sowohl die Domänen als auch die Einzelaspekte werden überwiegend als direkt vom Patienten berichtete Endpunkte mittels eines Selbstauskunftsbogens erhoben (patient reported outcomes (PRO)). Ausnahme bildet die Erfassung der entzündlichen Beteiligung von Gelenken und Sehnenansätzen und die körperliche Untersuchung der Wirbelsäulenmobilität. In interventionellen Studien werden Status- oder Response-Kriterien eingesetzt, um die Veränderung, oft ausgedrückt als20 oder 40%ige Verbesserung, quantitativ erfassen zu können. Die Instrumente sind in den 90er Jahren in Bath und in den letzten 20 Jahren von ASAS (Assessments in Axial Spondlyoarthritis International Society) entwickelt worden.

ZusammenfassungDie Bildgebung hat in der Diagnostik der axialen Spondyloarthritis, neben Anamnese, Klinik und der Bestimmung von HLA B27, einen zentralen Stellenwert, zum einen in der täglichen klinischen Praxis zur Diagnosefindung und zum anderen in der klinischen Forschung. Patienten mit axialer Spondyloarthritis leiden unter tiefsitzenden entzündlichen Rückenschmerzen sowie einer morgendlich betonten Steifigkeit des Achsenskelettes. Die zugrunde liegenden z. T. pathognomonischen bildgebenden Befunde sind osteoresorptive und osteoproliferative Veränderungen der Sakroiliakalgelenke und der Wirbelsäule. Initial sind entzündliche Veränderungen, hinweisend auf eine Sakroiliitis oder Spondylitis, die hauptsächlichen Manifestationen im Achsenskelett, gefolgt von strukturellen Läsionen, die zu Knochenneubildungen bis hin zur vollständigen Ankylose, wie sie bei fortgeschrittenen Erkrankungen zu beobachten sind, führen können. Die Darstellung von aktiven und chronischen Veränderungen sowie ihre richtige Interpretation ist die Herausforderung an die bildgebenden Verfahren sowie an die Befunder. Derzeit kann in der klinischen Routine nur die MRT, durch gleichzeitige Darstellung von aktiven und strukturellen Läsionen und ihrer anatomischen Lage, sowohl Entzündungen als auch Knochenumbauten erfassen. Da Knochenmarködeme in der MRT der Sakroiliakalgelenke auch bei Gesunden oder Sportlern auftreten können, sollten sie im Kontext mit gleichzeitig bestehenden strukturellen Schäden sowie zusammen mit den klinischen Symptomen und der Anamnese interpretiert werden. Obwohl die klassische Röntgenaufnahme des Beckens noch der aktuelle Standard der Bildgebung zur Diagnostik der axSpA ist und ein fester Bestandteil der New York Kriterien, ist ein kritisches Auseinandersetzen mit dem konventionellen Röntgen aufgrund eingeschränkter Sensitivität und Interreaderrealibilität sowie der bestehenden Strahlenbelastung durchaus gerechtfertigt. Die CT ist, v. a. zur detaillierten Darstellung struktureller Läsionen, weiterhin eher Gegenstand der klinischen Forschung. Wenn die apparative Möglichkeit besteht, sollte die MRT die bevorzugte bildgebende Methode zur Diagnostik der axSpA sein, um die Diagnose frühzeitig zu stellen. Die kontextbezogene Interpretation der bildgebenden Verfahren sowie die enge Zusammenarbeit zwischen Radiologen und Rheumatologen ist von größter Bedeutung.

Die axiale Spondyloarthritis (axSpA) ist eine chronisch entzundliche Erkrankung der Wirbelsaule, die langfristig mit einem Verlust korperlicher Funktionen, der Beweglichkeit und der aufrechten Haltung einhergehen kann. Bisher gangige Methoden zur Messung der Beweglichkeit basieren zum einen auf subjektiver Patientenwahrnehmung, wobei verschiedene Funktionen durch standardisierte Fragebogen (BASFI) semiquantitativ erfasst werden, und zum anderen werden im Rahmen einer korperlichen Untersuchung verschiedene Bewegungsbereiche v. a. des Achsenskeletts vermessen (BASMI). Vor Kurzem kam der erste Test hinzu, mit dem die Durchfuhrung und Geschwindigkeit bestimmter Aufgaben erfasst werden kann (ASPI). Da diese Tests nur begrenzt verlasslich und reproduzierbar sind, ware ein objektiverer Test wunschenswert. In der hier berichteten Studie wurde die Mobilitat der Wirbelsaule (WS) von Patienten mit axSpA mit dem Epionics SPINE-Gerat (ES) quantitativ untersucht und anhand der OMERACT(outcome measures in rheumatology)-Kriterien evaluiert. Das Gerat misst verschiedene Bewegungsmuster der Wirbelsaule anhand elektronischer Sensoren automatisiert, das schliest die Geschwindigkeit der Bewegungsdurchfuhrung ein. Als Kontrollen dienten Patienten mit Ruckenschmerzen anderer Genese und Menschen ohne Ruckenschmerzen. Die mit ES erhobenen Messungen unterschieden sich zwischen den Gruppen und korrelierten mit den BASMI-Werten (r =0,53–0,82, alle p =

Das Rheumazentrum Ruhrgebiet ist die groste deutsche Rheumaspezialklinik, die seit vielen Jahren alle Voraussetzungen fur die vom Verband der rheumatologischen Akutkliniken (VRA) geforderte Strukturqualitat erfullt und – auch wegen der regelmasigen Teilnahme am Benchmarkingprojekt KOBRA – regelmasig das VRA-Gutesiegel erhalt. Im Rheumazentrum Ruhrgebiet wurden im Jahr 2018 mehr als 7500 Patienten stationar versorgt, und im Rahmen der Versorgung uber § 116b (zukunftig ASV [ambulante spezialfacharztliche Versorgung]) gab es nahezu 25.000 ambulante Patientenkontakte. Daruber hinaus wurde vor 5 Jahren ein Fruhsichtungsprogramm (Triage) etabliert, um Patienten mit muskuloskeletalen Beschwerden und potenziell entzundlich rheumatischer Grundlage im Sinne einer Fruhdiagnose und -therapie gemas dem Treat-to-target-Konzept innerhalb von weniger als 4 Wochen (zunachst) ambulant hinsichtlich der erforderlichen Dringlichkeit sichten zu konnen, um sie anschliesend einer fundierten Diagnosesicherung zuzufuhren. Diese Frist konnte in den letzten beiden Jahren 2017 und 2018 in mehr als 90 % der Falle realisiert werden. Im Rahmen der stationaren Versorgung wurden in den letzten Jahren etwa ein Drittel der Patienten im Rahmen einer rheumatologischen Komplextherapie und ca. 10 % mit einer Schmerzkomplextherapie behandelt, etwa 3 % werden mit einer geriatrischen Komplextherapie versorgt, und ca. 65 % waren Kurzlieger (

Zusammenfassung Anamnese Eine 68-jährige Patientin wurde mit seit 6 Monaten bestehender Verschlechterung des Allgemeinzustandes, Rückenschmerzen, 20 kg Gewichtsverlust sowie akuten Paresen der Hände aufgenommen. Untersuchungen und Diagnose Es zeigten sich beidseitige Paresen der Hand- und Fingermuskulatur mit Nachweis entsprechender motorischer Defizite im EMG. Die MRT zeigte eine intraspinale Raumforderung mit Myelonkompression in HWS und BWS. Das Biopsat einer Hemilaminektomie bei HWK 7 zeigte IgG4-positive Plasmazellen, und eine IgG4-assoziierte Erkrankung (IgG4-RD) mit spinalem Pseudotumor wurde diagnostiziert. Therapie und Verlauf Nach Einleitung einer Therapie mit hochdosierten Glukokortikoiden (GC) und einer Cyclophosphamidpulstherapie verbesserte sich der Allgemeinzustand und die motorischen Defizite der Patientin erheblich. Folgerung Das ZNS ist eine seltene Manifestation der IgG4-RD. Typischerweise entsteht dabei eine verdrängend wachsende Raumforderung, die in der MRT oder im PET-CT gut dargestellt werden kann und die klinisch meist mit Schmerzen und neurologischen Defiziten imponiert und eine charakteristische Histologie zeigen kann. Initial hochdosierte GC und eine darüber hinausgehende immunsuppressive Therapie führen in der Regel zu gutem klinischen Erfolg.

Physical activity and exercise are beneficial for people with rheumatic diseases; however, recommendations for the management of rheumatoid arthritis (RA), spondyloarthritis (SpA) and hip- and knee osteoarthritis (HOA/KOA) are usually unspecific with respect to mode and dose of exercise. This is why the 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis were formulated. The recommendations consist of 4 overarching principles and 10 recommendations. These were also published as a lay version in the English language.Translation of the lay version into German and its linguistic validation in Austria, Germany and Switzerland.A professional translation was reviewed by the authors, including people with, RA, SpA, HOA/KOA from the three German-speaking countries, which provided a prefinal lay version. Subsequently, eight interviews with people with RA, SpA, HOA/KOA were conducted in each country to evaluate understandability, wording, completeness and feasibility of the prefinal lay version. Finally, the authors, i.e. those with RA, SpA, and osteoarthritis, anonymously rated their agreement to the final lay version on a 0-10 scale.The professional translation was substantially revised by the authors and based on the interviews. Formulations were adapted to increase readability and understandability and specify statements. Comments that would have changed content or structure were not considered. Average agreement with the particular recommendations was between 10 (SD 0) and 7.6 (SD 1.67).For people with RA/SpA/HOA/KOA the EULAR physical activity recommendations should be available in their mother language. The final German lay version is valid and accepted across all three German-speaking countries. Thus, the physical activity recommendations can be provided to people with rheumatic diseases in an understandable and feasible way.HINTERGRUND: Körperliche Aktivität und spezifisches Training haben großen gesundheitlichen Nutzen. Empfehlungen zum Management von rheumatoider Arthritis (RA), Spondyloarthritis (SpA) sowie Hüft- und Kniegelenkarthose (HKA) sind bisher in Bezug auf Art und Dosierung aber unspezifisch. Darum wurden die 2018 EULAR Empfehlungen zu körperlicher Aktivität für Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen formuliert. Sie bestehen aus 4 übergeordneten Prinzipien und 10 Empfehlungen. Die EULAR Bewegungsempfehlungen wurden auch als laienverständliche Version in englischer Sprache publiziert. ZIEL: Übersetzung der laienverständlichen Version ins Deutsche und sprachliche Validierung in Deutschland, Österreich und der Schweiz.Eine professionelle Übersetzung ins Deutsche wurde von den Autor*innen einschließlich Personen mit RA, SpA und HKA zu einer präfinalen Version bearbeitet. Anschließend wurden in den 3 Ländern je 8 Interviews mit Personen mit RA, SpA und HKA durchgeführt, um die Verständlichkeit, Wortwahl, Vollständigkeit und Umsetzbarkeit zu prüfen. Die Patientenvertreter*innen der Autor*innengruppe bewerteten anonym ihre Zustimmung zur finalen Version auf einer Skala von 0 bis 10.Die professionelle Übersetzung wurde von den Autor*innen und auf Grundlage der Interviews substanziell überarbeitet. Dabei wurden Formulierungen angepasst, um Lesbarkeit und Verständlichkeit zu verbessern und Aussagen zu präzisieren. Inhalt und Struktur des Originaltextes wurden dabei nicht verändert. Die Zustimmung zu den einzelnen Empfehlungen lag zwischen 10 (SD 0) und 7,6 (SD 1,67).Für Menschen mit RA/SpA/HKA sollten die EULAR Bewegungsempfehlungen in deren Muttersprache vorliegen. Die laienverständliche deutsche Version ist valide und wurde in allen 3 Ländern gut akzeptiert. Damit können die EULAR Bewegungsempfehlungen verständlich und praktikabel vermittelt werden.

ObjectiveTo evaluate the prevalence of infections, prevalence of hospitalisation due to infections, the vaccination status and perceived screening of infections prior to the start of biologic disease modifying antirheumatic drugs (bDMARDs) of a patient cohort with chronic inflammatory rheumatic diseases (CIRD).MethodsConsecutive CIRD patients reporting to our specialised centre were prospectively included (n=975) in this cross-sectional study. Data on comorbidities including infections, treatment, vaccination status, screening for latent tuberculosis infection (LTBI) and hepatitis B (HepB) were collected. Antibodies against measles and HepB were measured by ELISA. The vaccination status was assessed by a predefined vaccination score (0–26) categorising patients into four immunisation states: low (0–6), moderate (7–13), good (14–20), high (21–26).ResultsAll patients on bDMARDs (n=499) were screened for LTBI, and 469 for HepB (94%). All LTBI patients (n=16) received isoniazid (3.2%) and 16 chronic HepB patients received lamivudine (3.4%). Protective measles specific IgG-antibodies were found in 901 patients (92.4%). Although 629 patients were educated about vaccination strategies (64.5%), only 540 showed a vaccination card (55.4%). Only 49% of patients had undergone pneumococcal vaccination and less than 30% were protected against HepB and influenza, while 7.6% have not protective antibody titres against measles. No patient met the German national vaccination recommendations requiring a complete documentation of vaccines. The mean vaccination score was 13.3±4.2 with 5.7% of patients having a low, 43.9% a moderate, 47.0% a good and 3.3% a high score.ConclusionsThe majority of CIRD patients are n0t sufficiently vaccinated against pneumococci, HepB, influenza and measles. Although CIRD patients and general practitioners regularly receive professional information about the need of vaccination, vaccination rates were low to moderate. Interdisciplinary quality projects should be planned to change that inacceptable result.

Precise replacement of diseased or dysfunctional organs is the goal of regenerative medicine and has appeared to be a distant goal for a long time. In the field of hematopoietic stem cell transplantation, this goal is now becoming tangible as gene-editing technologies and novel conditioning agents are entering the clinical arena. Targeted immunologic depletion of hematopoietic stem cells (HSCs), which are at the very root of the hematopoietic system, will enable more selective and potentially more effective hematopoietic stem cell transplantation in patients with hematological diseases. In contrast to current conditioning regimes based on ionizing radiation and chemotherapy, immunologic conditioning will spare mature hematopoietic cells and cause substantially less inflammation and unspecific collateral damage to other organs. Biological agents that target the stem cell antigen CD117 are the frontrunners for this purpose and have exhibited preclinical activity in depletion of healthy HSCs. The value of anti-CD117 antibodies as conditioning agents is currently being evaluated in early clinical trials. Whereas mild, antibody-based immunologic conditioning concepts might be appropriate for benign hematological disorders in which incomplete replacement of diseased cells is sufficient, higher efficacy will be required for treatment and elimination of hematologic stem cell malignancies such as acute myeloid leukemia and myelodysplastic syndrome. Antibody–drug conjugates, bispecific T-cell engaging and activating antibodies (TEAs), or chimeric antigen receptor (CAR) T cells might offer increased efficacy compared with naked antibodies and yet higher tolerability and safety compared with current genotoxic conditioning approaches. Here, we summarize the current state regarding immunologic conditioning concepts for the treatment of HSC disorders and outline potential future developments. © 2021 ISEH – Society for Hematology and Stem Cells, Experimental Hematology, 95

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch), Hintergrund: Körperliche Aktivität und spezifisches Training haben großen gesundheitlichen Nutzen. Empfehlungen zum Management von rheumatoider Arthritis (RA), Spondyloarthritis (SpA) sowie Hüft- und Kniegelenkarthose (HKA) sind bisher in Bezug auf Art und Dosierung aber unspezifisch. Darum wurden die 2018 EULAR Empfehlungen zu körperlicher Aktivität für Menschen mit entzündlich-rheumatischen und degenerativen Erkrankungen formuliert. Sie bestehen aus 4 übergeordneten Prinzipien und 10 Empfehlungen. Die EULAR Bewegungsempfehlungen wurden auch als laienverständliche Version in englischer Sprache publiziert. Ziel: Übersetzung der laienverständlichen Version ins Deutsche und sprachliche Validierung in Deutschland, Österreich und der Schweiz. Methoden: Eine professionelle Übersetzung ins Deutsche wurde von den Autor*innen einschließlich Personen mit RA, SpA und HKA zu einer präfinalen Version bearbeitet. Anschließend wurden in den 3 Ländern je 8 Interviews mit Personen mit RA, SpA und HKA durchgeführt, um die Verständlichkeit, Wortwahl, Vollständigkeit und Umsetzbarkeit zu prüfen. Die Patientenvertreter*innen der Autor*innengruppe bewerteten anonym ihre Zustimmung zur finalen Version auf einer Skala von 0 bis 10. Ergebnisse: Die professionelle Übersetzung wurde von den Autor*innen und auf Grundlage der Interviews substanziell überarbeitet. Dabei wurden Formulierungen angepasst, um Lesbarkeit und Verständlichkeit zu verbessern und Aussagen zu präzisieren. Inhalt und Struktur des Originaltextes wurden dabei nicht verändert. Die Zustimmung zu den einzelnen Empfehlungen lag zwischen 10 (SD 0) und 7,6 (SD 1,67). Diskussion: Für Menschen mit RA/SpA/HKA sollten die EULAR Bewegungsempfehlungen in deren Muttersprache vorliegen. Die laienverständliche deutsche Version ist valide und wurde in allen 3 Ländern gut akzeptiert. Damit können die EULAR Bewegungsempfehlungen verständlich und praktikabel vermittelt werden. Background: Physical activity and exercise are beneficial for people with rheumatic diseases; however, recommendations for the management of rheumatoid arthritis (RA), spondyloarthritis (SpA) and hip- and knee osteoarthritis (HOA/KOA) are usually unspecific with respect to mode and dose of exercise. This is why the 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis were formulated. The recommendations consist of 4 overarching principles and 10 recommendations. These were also published as a lay version in the English language. Aim: Translation of the lay version into German and its linguistic validation in Austria, Germany and Switzerland. Methods: A professional translation was reviewed by the authors, including people with, RA, SpA, HOA/KOA from the three German-speaking countries, which provided a prefinal lay version. Subsequently, eight interviews with people with RA, SpA, HOA/KOA were conducted in each country to evaluate understandability, wording, completeness and feasibility of the prefinal lay version. Finally, the authors, i.e. those with RA, SpA, and osteoarthritis, anonymously rated their agreement to the final lay version on a 0–10 scale. Results: The professional translation was substantially revised by the authors and based on the interviews. Formulations were adapted to increase readability and understandability and specify statements. Comments that would have changed content or structure were not considered. Average agreement with the particular recommendations was between 10 (SD 0) and 7.6 (SD 1.67). Discussion: For people with RA/SpA/HOA/KOA the EULAR physical activity recommendations should be available in their mother language. The final German lay version is valid and accepted across all three German-speaking countries. Thus, the physical activity recommendations can be provided to people with rheumatic diseases in an understandable and feasible way

The [Formula: see text] and [Formula: see text] transitions in Li-like carbon ions stored and cooled at a velocity of [Formula: see text] in the experimental storage ring (ESR) at the GSI Helmholtz Centre in Darmstadt have been investigated in a laser spectroscopy experiment. Resonance wavelengths were obtained using a new continuous-wave UV laser system and a novel extreme UV (XUV) detection system to detect forward emitted fluorescence photons. The results obtained for the two transitions are compared to existing experimental and theoretical data. A discrepancy found in an earlier laser spectroscopy measurement at the ESR with results from plasma spectroscopy and interferometry has been resolved and agreement between experiment and theory is confirmed.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) is considered a metabolic condition, characterized by new bone formation affecting mainly at entheseal sites. Enthesitis and enthesopathies occur not only in the axial skeleton but also at some peripheral sites, and they resemble to some extent the enthesitis that is a cardinal feature in spondyloarthritis (SpA), which is an inflammatory disease. We review the possible non-metabolic mechanism such as inflammation that may also be involved at some stage and help promote new bone formation in DISH. We discuss supporting pathogenic mechanisms for a local inflammation at sites typically affected by this disease, and that is also supported by imaging studies that report some similarities between DISH and SpA. Local inflammation, either primary or secondary to metabolic derangements, may contribute to new bone formation in DISH. This new hypothesis is expected to stimulate further research in both the metabolic and inflammatory pathways in order to better understand the mechanisms that lead to new bone formation. This may lead to development of measures that will help in earlier detection and effective management before damage occurs.

Acute myeloid leukemia (AML) initiating and sustaining cells maintain high cell-surface similarity with their cells-of-origin, i.e., hematopoietic stem and progenitor cells (HSPCs), and identification of truly distinguishing leukemia-private antigens has remained elusive to date. To nonetheless utilize surface antigen-directed immunotherapy in AML, we here propose targeting both, healthy and malignant human HSPC, by chimeric antigen receptor (CAR) T-cells with specificity against CD117, the cognate receptor for stem cell factor. This approach should spare most mature hematopoietic cells and would require CAR T termination followed by subsequent transplantation of healthy HSPCs to rescue hematopoiesis. We successfully generated anti-CD117 CAR T-cells from healthy donors and AML patients. Anti-CD117 CAR T-cells efficiently targeted healthy and leukemic CD117-positive cells in vitro. In mice xenografted with healthy human hematopoiesis, they eliminated CD117-expressing, but not CD117-negative human cells. Importantly, in mice xenografted with primary human CD117-positive AML, they eradicated disease in a therapeutic setting. Administration of ATG in combination with rituximab, which binds to the co-expressed CAR T-cell transduction/selection marker RQR8, led to CAR T-cell depletion. Thus, we here provide the first proof of concept for the generation and preclinical efficacy of CAR T-cells directed against CD117-expressing human hematopoietic cells. ISSN:1476-5551 ISSN:0887-6924

Einleitung: Antinukleäre Antikörper (ANA) sind häufig bei Patienten mit Kollagenosen nachweisbar, können aber auch in der Normalbevölkerung vorkommen, daher kommt es bei ANA positiven (ANA+) Patienten mit muskuloskelettalen oder anderen Symptomen gehäuft zu differenzialdiagnostischen[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

We read with interest the publication on COVID-19 outcomes related to hospitalisation of people with chronic inflammatory rheumatic diseases (CIRD) by Gianfrancesco et al .1 In our centre, we have taken a different approach by contacting 1495 patients with CIRD by telephone to ask for COVID-19 tests and symptoms. A total of 917 patients who agreed to participate (61%) was interviewed between 15 April and 15 June 2020: about 60% women, mean age 54, mean disease duration 12 years. Most had spondyloarthritis (SpA) including psoriatic arthritis (51%), 41% rheumatoid arthritis (RA) and 7% connective tissue diseases (CTD), mainly lupus. In RA, rheumatoid factor was found in 88%, anti-citrullinated protein antibodies (ACPA) in 77% and human leukocyte antigen (HLA) B27 in 73% of patients with axSpA, while 92% with CTD had antinuclear antibodies. Less than half of patients were vaccinated against pneumococci (43%) and influenca (47%). The German government started a national shutdown on 22 March 2020. To give some guidance to rheumatologists, the German Society of Rheumatology (DGRh) released recommendations on 29 April 2020.2 Our survey started about 2 weeks earlier. The care of our patients with CIRD is largely based on the ‘treat to …

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a "simple" OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.

The most prevalent health concerns in patients with axial spondyloarthritis (axSpA) include spinal stiffness, spinal pain, mobility limitations, fatigue, and disturbed sleep. Many patients experience impairments related to extraspinal disease, extra-articular disease, or drug side effects. To capture overall life impact, self-reported measurement instruments assessing health-related quality of life (HRQoL) have been developed. This article summarizes the literature on relevant concepts and frameworks when measuring overall health or HRQoL, available measures assessing this outcome in axSpA, the hierarchical relations between overall health/ HRQoL and specific axSpA impairments, and the role of context when interpreting interventions for overall health or HRQoL outcomes.

BackgroundCalcium pyrophosphate dihydrate crystal deposition disease (CPPD, chondrocalcinosis) is known to affect fibrocartilaginous tissue in the large and smaller peripheral joints. The affection of similar structures in the axial skeleton is unclear.ObjectivesTo assess the frequency and severity of structural changes in the lower spine in patients with established CPPD in comparison to degenerative disc disease (DDD).MethodsIn a retrospective study, patients with CPPD or DDD as a main diagnosis with available spinal conventional radiographs (CR) performed during 2014 – 2020 were included. Definite other inflammatory conditions affecting the spine were excluded. The CR segments T7/8-L5/S1 were evaluated for the occurrence of disc calcification, intradiscal vacuum phenomenon, disc height (normal, narrowing, complete loss), endplate erosion, osteophytes and spondylolisthesis. When lumbar spine MRIs of the same time point were available, discovertebral units were evaluated for the occurrence of vacuum phenomena, endplate erosion, Modic changes and disc dehydration (Pfirrmann). Follow up CR were assessed if available. All available images were evaluated by 2 independent readers and discrepancies were solved by consensus.ResultsCR of 140 patients (1.171 discovertebral units) with CPPD and 99 DDD (803 discovertebral units) were evaluated (mean age 74.4±9.9 and 71±6.2, 20% vs. 20.2% males, respectively). MRIs of the spine were available from 48 CPPD and 44 DDD patients. Vacuum phenomena, disc calcification, osteophytes and erosion were significantly more frequently seen in patients with CPPD compared to DDD (Table 1) with no differences between the thoracic and the lumbar spine. Follow-up CR were available for 29 patients with CPPD and 46 DDD. Both groups presented statistically significant progression of endplate erosions and osteophytes (p 0.001 - 0.02 for both groups). Notably, even though CR follow-up times in the CPPD group were, compared to DDD (median (IQR) 1.9 (2.4) vs 3.0 (3.1) years, p=0.033, respectively), shorter, radiographic progression was noted more frequently in CPPD vs. DDD for erosive changes (6.8% vs. 0.6%, p=0.018) and disc calcification (5.8% vs. 0.6%, p=0.007), respectively. When comparing MRIs, a higher number of discovertebral units was affected by vacuum phenomena (34 vs 13, p=0.04) and endplate erosions (L4/5 (45.5% vs 24.4%, p=0.04), L5/S1(40.4% vs 19.5%, p=0.03) in patients with CPPD vs. DDD, respectively.Table 1.Frequency of affected discovertebral units on conventional radiographsCPPDDDDpVacuum phenomenon156 (13.3%)44 (5.5%)Disc calcification193 (16.5%)42 (5.2%)Endplate erosion159 (13.6%)26 (3.2%)Osteophytes861 (73.5%)480 (59.8%)Spondylolisthesis126 (10.8%)69 (8.6%)0.264CPPD: calcium pyrophosphate dihydrate crystal deposition disease DDD: degenerative disc diseaseConclusionPatients with chondrocalcinosis showed more severe and progressive degenerative findings in the lower spine as assessed by both, CR and MRI, even more in comparison to established DDD. This data shows that disease manifestations of CPPD in the axial skeleton are clinically relevant.Disclosure of InterestsNone declared

BackgroundThe main goal of treatment for patients (pts) with rheumatoid arthritis (RA) is remission to preserve physical function and prevent radiographic damage. However, less than 50% of pts with early RA have achieved remission in clinical studies and inception cohorts 1. Little is known about the course of disease and the clinical patterns when remission is tried to be achieved in pts with RA.ObjectivesTo identify subgroups with distinct trajectories of DAS28-CRP in pts with RA.MethodsLongitudinal data from adult RA pts presenting to a tertiary centre were used. Socio-demographic data, disease characteristics and standard assessments including established outcome parameters for disease activity (DAS28-CRP) and physical function (FFbH) were retrospectively analysed. Group-based trajectory modelling (GBTM) was used to identify homogeneous classes of DAS28-CRP trajectories, where the number of classes was selected using Nagin’s Bayesian information criterion (BIC). Differences between the identified classes and clinical variables were studied.ResultsData of 134 pts with 849 DAS28-CRP values were analysed. Retrospective chart data were available for a follow-up of 33.7 (SD 18.0) months. One third of pts already had erosions and severe limitations in physical functioning. About half of the pts were on bDMARDS and Table 1.Patients demographics and disease characteristics at baseline in trajectory groupsClass 1(N=10)Class 2(N=36)Class 3(N=56)Class 4(N=23)Class 5(N=9)Age, years65.8 (12.7)60.6 (10.6)56.7 (16.0)50.5 (15.4)56.8 (12.0)Gender, female80.0% (N=8)77.8% (N=28)82.1% (N=46)52.2% (N=12)66.7% (N=6)Education level university0.0% (N=0)11.1% (N=4)16.1% (N=9)21.7% (N=5)0.0% (N=0)Employment10.0% (N=1)33.3% (N=12)53.6% (N=30)69.6% (N=16)33.3% (N=3)Body mass index30.6 (5.4)27.8 (4.3)27.1 (4.7)25.2 (4.2)29.0 (6.4)Symptom duration, years12.8 (7.3)10.4 (8.3)9.5 (9.6)6.7 (3.6)12.4 (13.2)Anti-CCP49.2 (63.9)101.3 (89.7)98.6 (95.6)94.9 (78.2)114.5 (84.6)CRP1.0 (1.1)0.7 (0.9)0.4 (0.4)0.4 (0.5)1.2 (1.1)Erosions20.0% (N=2)36.1% (N=13)28.6% (N=14)45.5% (N=10)44.4% (N=4)At least one Comorbidity100.0% (N=10)94.4% (N=34)78.6% (N=44)65.2% (N=15)88.9% (N=8)Charlson Comorbidity Index (0-29)1.1 (1.4)1.1 (1.3)0.6 (0.9)0.4 (0.7)1.2 (1.3)No. of patients on steroids0.0% (N=0)0.0% (N=0)2.9% (N=1)15.4% (N=2)0.0% (N=0)No. of patients on bDMARD77.8% (N=7)45.8% (N=11)41.2% (N=14)30.8% (N=4)71.4% (N=5)No. of patients on tsDMARD0.0% (N=0)0.0% (N=0)5.9% (N=2)7.7% (N=1)0.0% (N=0)Pain (NRS 0-10)6.1 (1.8)5.8 (1.8)4.2 (2.0)2.3 (2.6)4.2 (2.0)Patient Global (NRS 0-10)5.8 (2.8)5.3 (1.7)3.7 (2.1)2.8 (3.0)6.3 (2.2)DAS28-CRP5.3 (1.2)3.9 (0.7)2.5 (0.7)2.1 (1.0)4.6 (0.9)FFbH38.5 (29.0)48.8 (21.8)74.2 (18.9)90.4 (8.8)61.1 (19.4)RAID (0-10)6.5 (2.0)5.3 (2.1)3.8 (1.9)1.8 (1.8)4.6 (1.8)Figure 1.Longitudinal DAS-28-CRP in trajectory groupsConclusionUsing GBTM five distinct trajectories in pts with RA were identified. Only a small proportion of pts showed a reduction in disease activity over time, whereas the largest proportion of pts showed rather constant high or constant low disease activity. The cohort size may have impacted the modelling and further analyses in larger cohorts are needed. Importantly, even though well established in our hospital it is unclear how consequent the T2T strategy was followed and which intervention was successful to reach remission. The impact of pts global assessment on DAS28 values also needs further study.References[1]Nikiphorou Rheumatol 2020Disclosure of InterestsNone declared

INTRODUCTION: Hematopoietic stem and progenitor cells (HSPCs) support life-long hematopoiesis. A single HSPC can also be at the origin of hematological malignancies, such as Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). Allogeneic HSCT with the intent to eliminate recipient AML or MDS and at the same time replace recipient HSPC with donor-HSPC and immune cells is a life-saving therapeutic option for many patients. However, chemotherapy (and sometimes in addition gamma-irradiation based conditioning regiments) prior to HSCT are associated with substantial toxicity. Thus, due to benefit-outweighing treatment-related toxicity and mortality, frail, multi-morbid and elderly patients are usually excluded from potentially curative allo-HSCT approaches. For these reasons, more selective preconditioning strategies, leading to residual AML/MDS elimination and creating "space" for incoming HSPCs, are required. Selective targeting of CD117 with monoclonal antibodies has been proposed as a strategy to remove endogenous HSPCs, enabling an effective but mild preconditioning. However, specific conditioning of AML and MDS patients, prior to HSCT, might require a more potent effector cell type. We hypothesized that a CD117 and CD3 binding, T cell engaging and activating antibody construct (CD117xCD3 TEA) with a short half-life might be an ideal means to selectively eliminate CD117-expressing healthy HSPCs and residual CD117-expressing AML or MDS cells prior to allo-HSCT. METHODS: We cloned and expressed CD117xCD3 TEA in tandem scFv format and produced it by transient gene expression in Chinese hamster ovary cells (CHO-S). The fusion proteins were purified to homogeneity by protein A affinity chromatography. We derived target cell lines with varying surface levels of CD117 (high, medium and low) from CD117 negative parental cell lines HL-60 and MOLM-14 (Myburgh et al., Leukemia, 2020). To assess T cell mediated killing of target cells, we mixed them with human T cells (purified and enriched after negative selection) at varying Effector-to-Target (E:T) cell ratios and added CD117xCD3 TEA at different concentrations. The mixture was incubated and specific killing was quantified via flow cytometry at different time-points. RESULTS: In order to characterize the biocidal properties of CD117xCD3 TEA, we performed in vitro killing experiments against cell lines, HSCPs from healthy donors and blast cells from AML patients. A dose-dependent in vitro killing of the cell lines was observed in the presence of various concentrations of CD117xCD3 TEA and of human T cells at an E:T cell ratio of 10:1 after 24h. The HL60 CD117 high cell line was efficiently lysed (~90%) at 100 ng/ml of CD117xCD3 TEA, corresponding to ~1.8 nM. In similar experiments with different E:T cell ratios, we observed that both HL60 CD117 high and CD117 medium cells could be quantitatively killed at E:T ratios as low as 1:1, while the killing of CD117 low cells required a higher density of T cells. The biocidal effect on non-transduced HL60 cells was negligibly low, confirming the requirement of a simultaneous engagement of CD117 and CD3 for specific killing. We repeated the same experiment with an engineered MOLM14 cell line, which also expressed CD117 at comparable high levels, incubating the target cell line with human T cells at an E:T of 1:1 for 24, 48 or 72, 120 or 192 hours. Complete killing of the target cell line was achieved at 120 and 192 hours and after supplemental addition of T cells and CD117xCD3 TEA at 72 hours (see example figure). Experiments with primary cells (HSPCs from healthy donors or blast cells from AML patients) at an E:T of 1:1 confirmed specific killing of target cells in an antigen-density- and concentration-dependent manner after 48h. CONCLUSIONS: We have generated a novel bispecific antibody, which binds to human CD117 (expressed on HSCPs and AML/MDS blast cells) and to CD3 (expressed on T cells), which we term CD117xCD3 TEA. The antibody induces selective T cell-mediated killing of cell lines with different surface levels of CD117, as well as of healthy HSPCs and primary human AML cells. Thus, the newly generated CD117xCD3 TEA might be developed clinically in order to erradicate residual AML/MDS and at the same time serve as a milder preconditioning approach prior to allo-HSCT in frail AML/MDS patients. Figure 1 Figure 1. Disclosures Kiefer: ETH Zurich: Current Employment, Patents & Royalties: CD117xCD3 TEA. Myburgh: University of Zurich: Patents & Royalties: CD117xCD3 TEA. Guggisberg: F. Hoffmann-La Roche AG: Current Employment. Abdelmotaleb: F. Hoffmann-La Roche AG: Current Employment. Mock: Philogen S.p.A.: Current Employment. Neri: Philogen S.p.A.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Multiple patents on vascular targeting; ETH Zurich: Patents & Royalties: CD117xCD3 TEA. Manz: University of Zurich: Patents & Royalties: CD117xCD3 TEA; CDR-Life Inc: Consultancy, Current holder of stock options in a privately-held company.

Designed armadillo repeat proteins (dArmRP) are α-helical solenoid repeat proteins with an extended peptide binding groove that were engineered to develop a generic modular technology for peptide recognition. In this context, the term "peptide" not only denotes a short unstructured chain of amino acids, but also an unstructured region of a protein, as they occur in termini, loops, or linkers between folded domains. Here we report two crystal structures of dArmRPs, in complex with peptides fused either to the N-terminus of Green Fluorescent Protein or to the C-terminus of a phage lambda protein D. These structures demonstrate that dArmRPs bind unfolded peptides in the intended conformation also when they constitute unstructured parts of folded proteins, which greatly expands possible applications of the dArmRP technology. Nonetheless, the structures do not fully reflect the binding behavior in solution, that is, some binding sites remain unoccupied in the crystal and even unexpected peptide residues appear to be bound. We show how these differences can be explained by restrictions of the crystal lattice or the composition of the crystallization solution. This illustrates that crystal structures have to be interpreted with caution when protein-peptide interactions are characterized, and should always be correlated with measurements in solution.

Connective tissue diseases (CTD) are autoimmune diseases highly associated with the presence of antinuclear antibodies (ANA). Since ANA and musculoskeletal symptoms are not uncommon in the general population, differential diagnostic challenges frequently occur for the treating physician. Dense fine speckled antibodies (DFS70) were recently discovered but their presence appeared to be rare in CTD.In this cross-sectional study a total of 270 patients treated in the Rheumatism Center of the Ruhr Area (Rheumazentrum Ruhrgebiet) were preferentially included, when they were ANA+ (≥1:80). Other autoantibodies and DFS70 antibodies were also investigated. The diagnosis of CTD was confirmed by rheumatologists. The sensitivity, specificity and the positive predictive value of DFS70 antibodies were differentially evaluated for various ANA titers.In 91 (33.7%) of the ANA+ patients (33.7%) the diagnosis of CTD was confirmed and in 84 (92.3%) the ANA titer was ≥1:160. The DFS70 antibodies were detected in 17 out of 130 ANA+ patients without CTD (13.1%) versus 2 ANA+ patients (2.2%) with CTD (p = 0.027). None of the patients with ANA 1:80 had DFS70 antibodies. The specificity of DFS70 antibodies to detect the absence of CTD was 97.6%, the sensitivity was 13.1% and the positive predictive value was 89.5%. There was almost no effect of the strength of the different ANA titers.It was found that DFS70 antibodies are rarely present in ANA+ patients with CTD but the diagnosis of CTD cannot be reliably ruled out solely by the presence of DFS70 antibodies; however, the high specificity of DFS70 antibodies can be of clinical importance in unclear situations and in cases of anxious patients.HINTERGRUND: Antinukleäre Antikörper (ANA) sind häufig bei Kollagenosen, können aber auch in der Normalbevölkerung vorkommen, daher kommt es bei ANA+-Patienten mit muskuloskeletalen Symptomen gehäuft zu differenzialdiagnostischen Problemen. Die relativ neuen Anti-dense fine speckled-Antikörper (DFS70-AK) werden bei Kollagenosen möglicherweise nur selten nachgewiesen.In diese Querschnittstudie wurden insgesamt 270 Patienten, die im Rheumazentrum Ruhrgebiet behandelt wurden, bevorzugt eingeschlossen, wenn sie ANA+ (≥1:80) waren. Andere Autoantikörper und DFS70-AK wurden ebenfalls untersucht. Die Diagnose einer Kollagenose wurde fachärztlich gestellt. Sensitivität, Spezifität und der positive prädiktive Wert der DFS70-AK wurden für verschiedene ANA-Titer differenziert ermittelt.Eine Kollagenose wurde bei 91 ANA+-Patienten diagnostiziert (33,7 %), wobei bei 84 ein Titer ≥1:160 vorlag (92,3 %). DFS70-AK wurden bei 17 von 130 ANA+-Patienten ohne Kollagenose (13,1 %) vs. 2 ANA+-Patienten mit Kollagenose (2,2 %) nachgewiesen (p = 0,027). Kein Patient mit ANA 1:80 hatte DFS70-AK. Im Hinblick auf das Nicht-Vorhandensein einer Kollagenose zeigten die DFS70-AK 97,6 % Spezifität, 13,1 % Sensitivität und einen positiven prädiktiven Wert von 89,5 %, die Höhe des ANA-Titers hatte hierauf keinen Einfluss.DFS70-AK kommen bei ANA+-Patienten mit Kollagenose nur selten vor, eine solche ist jedoch durch das Vorhandensein von DFS70-AK auch nicht ganz sicher auszuschließen. Die hohe Spezifität der DFS70-AK kann aber z. B. in unklaren Situationen und bei ängstlichen Patienten durchaus von klinischer Bedeutung sein.

Biosimilars have been approved for use in Germany for many years and in the meantime also in rheumatology but only a few years ago. Biosimilars, which are biotechnologically manufactured products the same as reference biologicals, have actually now achieved a substantial proportion of the market in some regions but there are still doubters among patients and physicians who fear a loss of quality even if there is no evidence for this. A part of this problem can be explained by the nocebo effect but which furthermore also has a substantial medical importance. This effect is described and explained in this article. Psychosocial and context-related factors, such as the relationship between patient and physician, previous experience with treatment and treatment expectations can either improve or impair the efficacy of treatment interventions. These phenomena are commonly known as placebo and nocebo effects. As placebo and nocebo effects can influence the development of symptoms, the frequency of undesired events and the efficacy of treatment, it is decisive to know these effects and to develop strategies for prevention in order to optimize the treatment results. Although in recent years experimental studies have achieved substantial progress in the clarification of the psychosocial and neurobiological mechanisms of placebo effects, detailed mechanisms of nocebo effects are still widely unexplored. An improved understanding of these mechanisms promises the development of user-friendly strategies for the clinical care to improve treatment results and patient satisfaction.

Axial spondylarthritis (axSpA) is a chronic inflammatory disease of the spine that can be associated with loss of physical function, mobility and upright postural impairment. Established tools for the assessment of function that are largely based on subjective perception are semiquantitatively recorded by standardized questionnaires (Bath ankylosing spondylitis functional index, BASFI), while measurement of spinal mobility of patients with axSpA is based on physical examination of various movement regions particularly the axial skeleton (Bath ankylosing spondylitis metrology index, BASMI). Recently, a performance test has been added to assess the range of motion and speed of certain tasks (AS performance-based improved test, ASPI); however, since these tests have limited reliability and reproducibility, more objective tests would be desirable. In this study the spinal mobility of patients with axSpA was quantified using the Epionics SPINE device (ES) and data were evaluated using the outcome measures in rheumatology (OMERACT) criteria. The ES automatically measures various patterns of spinal movements using electronic sensors, which also assess the range and speed of carrying out movements. Patients with back pain from other causes and persons without back pain served as controls. The measurement results obtained with ES differed between the groups and correlated with BASMI values (r = 0.53-0.82, all p = 0.03). Patients with radiographically detectable axSpA had more limited and slower mobility than those with non-radiographically detectable axSpA. Overall, the results presented here suggest that ES measurements represent a valid and objective measurement procedure of spinal mobility for axSpA patients.Die axiale Spondyloarthritis (axSpA) ist eine chronisch entzündliche Erkrankung der Wirbelsäule, die langfristig mit einem Verlust körperlicher Funktionen, der Beweglichkeit und der aufrechten Haltung einhergehen kann. Bisher gängige Methoden zur Messung der Beweglichkeit basieren zum einen auf subjektiver Patientenwahrnehmung, wobei verschiedene Funktionen durch standardisierte Fragebögen (BASFI) semiquantitativ erfasst werden, und zum anderen werden im Rahmen einer körperlichen Untersuchung verschiedene Bewegungsbereiche v. a. des Achsenskeletts vermessen (BASMI). Vor Kurzem kam der erste Test hinzu, mit dem die Durchführung und Geschwindigkeit bestimmter Aufgaben erfasst werden kann (ASPI). Da diese Tests nur begrenzt verlässlich und reproduzierbar sind, wäre ein objektiverer Test wünschenswert. In der hier berichteten Studie wurde die Mobilität der Wirbelsäule (WS) von Patienten mit axSpA mit dem Epionics SPINE-Gerät (ES) quantitativ untersucht und anhand der OMERACT(outcome measures in rheumatology)-Kriterien evaluiert. Das Gerät misst verschiedene Bewegungsmuster der Wirbelsäule anhand elektronischer Sensoren automatisiert, das schließt die Geschwindigkeit der Bewegungsdurchführung ein. Als Kontrollen dienten Patienten mit Rückenschmerzen anderer Genese und Menschen ohne Rückenschmerzen. Die mit ES erhobenen Messungen unterschieden sich zwischen den Gruppen und korrelierten mit den BASMI-Werten (r =0,53–0,82, alle p = 0,03). Röntgenologische axSpA-Patienten hatten zudem eine eingeschränktere und langsamere Beweglichkeit als die mit nr-axSpA. Insgesamt sprechen die Ergebnisse dieser Arbeit dafür, dass Messungen mit dem ES ein valides und objektives Messverfahren der Wirbelsäulenbeweglichkeit für axSpA-Patienten darstellen.

The Ruhrgebiet Rheumatism Center, which is highly specialized for rheumatic diseases, is the largest of its kind in Germany. For many years it has fulfilled all the requirements for structural quality required by the Association of Rheumatological Acute Clinics (VRA) including regular participation in the KOBRA benchmarking project. Therefore, the center regularly receives the VRA seal for quality of care. In 2018 more than 7500 patients were treated as inpatients. Within the framework of care according to §116b (ASV since May 2019) there were nearly 25,000 outpatient patient contacts. Furthermore, an early screening program (triage) was established 5 years ago in order to be able to identify patients with musculoskeletal complaints on a potentially inflammatory rheumatic basis. This functions in the sense of an early diagnosis and treatment in accordance with the treat-to-target concept within less than 4 weeks (initially) on an outpatient basis with respect to the required urgency, in order to subsequently provide sound diagnostic support. In the last 2 years 2017 and 2018, this deadline was met in more than 90% of cases. Within the scope of inpatient care approximately one third of patients were treated in recent years with a defined rheumatological complex therapy and 10% with pain complex therapy. Approximately 3% were treated with geriatric complex therapy and 65% were short-stay patients (4 days), i.e. patients who received the necessary diagnostics and treatment on an inpatient basis at short notice. The overall structure of the rheumatism center, the cooperation with rheumatologists in private practice, many cooperation partners, referring physicians and patients represents a model for rheumatological care in large conurbations. The care of large numbers of patients also enables the further training of many assistants and this is essential for the future of good rheumatological medicine.

Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional assays and time-resolved antibody repertoire sequencing. We establish that antibody responses initially converge in both infection types on a functional and repertoire level, but diverge later during chronic infection, showing increased clonal diversity, the appearance of mouse-specific persistent clones, and distinct phylogenetic signatures. Chronic infection is characterized by a longer-lasting germinal center reaction and a continuous differentiation of plasma cells, resulting in the emergence of higher-affinity plasma cells exhibiting increased antibody secretion rates. Taken together, our findings reveal the emergence of a personalized antibody response in chronic infection and support the concept that maintaining B cell diversity throughout chronic LCMV infection correlates with the development of infection-resolving antibodies., Cell Reports, 30 (4), ISSN:2666-3864, ISSN:2211-1247

Background:Functioning of patients (pts.) with axial spondyloarthritis (axSpA) is influenced by a variety of factors. In contrast to clinical factors, the influence of contextual factors on functioning has not been well studied. According to the According to the International Classification of Functioning, Disability and Health (ICF), functioning is a complex interaction between health status and contextual factors such as social support, relationships and attitudes.Objectives:The aim of this study is to understand limitations in participation and to investigate barriers and facilitators of contextual factors in pts. with axSpA.Methods:Consecutive axSpA pts. underwent a standardized assessment with collection of patient and disease characteristics, patient-reported outcomes (ASDAS, BASFI, BASMI, PHQ-9, ICF Measure of Participation and ACTivities questionnaire (IMPACT-S (0-100%)), ASAS Health Index (ASAS HI and environment factor item set (EFIS) (1). The EFIS contains 9 dichotomous questions addressing ICF categories of products and technologies (e1), support and relationship (e3), attitudes (e4) and health services (e5). Validated cut-offs of ASAS HI were used to categorize global functioning.Results:A total of 200 axSpA pts. were included: 69% males, 44.3±12.5 years, symptom duration 17.9±12.6 years, ASDAS 2.5±1.1, BASFI 4.0±2.7, BASMI 3.5±1.8, ASAS HI 7.0±4.1. Pts. reported limitations in the IMPACT-S activity and participation domain (82.3% (15.2) and 83.5% (16.8), respectively. The majority of pts. reported as barrier that treatment of axSpA requires time (e4, 58.5%). A minority of pts. but quite a few reported as barrier the need for support by family members (e3, 43.5%), the need to modify home and work environment (e1, 39.5%) and that they cannot rely on family members for help (e3, 22%). Some pts. (< 20%) reported that they have problems to be understood by health care professionals when experiencing a flare (e5, 18.5%), that pts. at home are not adequately taken care of (e4, 18.5%), disliking friends’ behavior toward them (e4, 13.5%), and that friends are too demanding (e4, 13%). The majority of pts. (e4, 75.9%) identified attitudes of friends as the only and major facilitator. All pts. reporting at least one barrier had significantly worse global functioning (ASAS HI, IMPACT-S), and depression (PHQ-9) compared to patients who reported no barriers in the respective ICF categories (p< 0.01). Similarly, pts. with poor functioning are more likely to report barriers in contextual factors compared to pts. with good functioning (Table 1). Pts. having to ask for more support from their families expressed the feeling that they cannot rely on that.Conclusion:Barriers more than facilitators of contextual factors are present in pts. with axSpA. This study shows that barriers in contextual factors are more common in pts. with impairments in self-reported and performed functioning as in those without impairments. This underlines the importance of contextual factors in the management of axSpA pts.References:[1]Kiltz et al. Ann Rheum Dis 2013;72(s3):572Table 1.Presence of contextual factors, stratified for global functioning categoriesICF categoryEFIS ItemGlobal Functioning (ASAS HI 0-17)Good ≤ 5(n= 69)Moderate (n= 106Poor ≥ 12(n= 25)e3EFIS 1: As a result of my rheumatic disease, the children take more responsibility for household tasks.11 (15.9)55 (51.9)21 (84)e3EFIS 2: I don’t like the way my friends acts around me.0 (0)15 (14,2)12 (48,0)e3EFIS 3: I can’t count on my relatives to help me with my problems11 (15,9)24 (22,6)9 (36)e1EFIS 4: I modify my home and work environments.16 (23,2)47 (44,3)9 (36)e5EFIS 5: I have difficulties getting worsening of my disease acknowledged by a health care professional3 (4,3)21 (19,8)16 (64)e5EFIS 6: Treatment of my rheumatic disease is taking up time22 (31,9)73 (68,9)22 (88)e4,EFIS 7: My friends expect too much of1 (1,4)18 (17,0)7 (28)e4EFIS 8: No one pays much attention to me at home10 (14,5)20 (18,9)7 (28)e4EFIS 9: My friends understand me56 (17,4)83 (78,3)12 (48)values given as number (%)Disclosure of Interests:None declared.

Background:The best treatment options of patients with chronic inflammatory rheumatic diseases (CIRD) in the pandemic have not been completely clear, especially in the beginning of the lockdown. Whether and to which degree pandemic-related therapy changes have occurred, has not been studied in detail.Objectives:To study the behaviour of patients with CIRD initially facing the COVID 19 pandemic related to their disease status and medication.Methods:Patients with CIRD were contacted by telephone to assess their health status and ask for changes in medication. Standardized assessment tools were used to assess disease activity, depression and anxiety. High disease activity was assumed if RADAI-5 ≥ 3.2 and BASDAI ≥ 4. Anxiety (HADS-A) and depression (HADS-D) of patients were assessed using HADS. A score < 8 was taken as indication of no major problem in this regard.Results:A total of 886 patients was interviewed between April 15 and June 15 of 2020. Here we report on 550 patients with complete information on standard assessments (62%). About 60% were female, mean age 54.4±13.7, mean disease duration 12.2±10.5 years. Most had spondyloarthritis (SpA, n=287) including axial SpA (axSpA, n=172) and psoriatic arthritis (PsA, n=116), in total 52.2%, while 40.2% had rheumatoid arthritis (RA, n=221), and 7.6% connective tissue diseases (CTD, n=42). Most RA patients were on methotrexate (48.8%), while 43.8% took glucocorticoids. In addition, 61.0% of patients were on bDMARDs, mostly on TNF inhibitors (59.6%). More SpA than RA patients were on bDMARDs: 71.0% vs 49.7% respectively. A recent change in medication was reported by 182 patients (33.1%): 89 with RA (40.2%), 88 with SpA (30.6%) and 5 with CTD (11.9%). Half of those who changed (n=92; 50.5%) admitted that the change was mainly made due to fear of the pandemic (16.7% of all patients). Altogether, significantly more patients changed bDMARDs (68.5%) than csDMARDs (57.3%). The data of patients who changed vs patients who didn’t change is shown in the Table 1, including subgroup analyses. The median HADS scores were < 8.Table 1.RA and SpA patients who changed and who did not change their medicationGroup (N) / ReasonNActive disease (%)HADS-D≥ 8 (%)HADS-A≥ 8 (%)bDMARD therapy (%)Rheumatoid arthritis221134 (60.6)76 (35.0) [4]94 (43.3) [4]110 (50.9) [5]Spondyloarthritis287130 (45.4)83 (29.5) [6]109 (38.8) [6]204 (72.6) [6] Pa (RA vs SpA)0.2280.354Patients did not change their medication Rheumatoid arthritis (%)132 (59.7)84 (63.6)46 (35.9) [4]58 (45.3) [4]62 (48.4) [4] Spondyloarthritis (%)199 (69.3)88 (44.2)58 (30.1) [6]69 (35.8) [6]137 (71.0) [6] P (RA vs SpA)0.0310.3580.101Patients changed their medication Rheumatoid arthritis89 (40.3)50 (56.2)30 (33.7)36 (40.4)48 (54.5) [1] P (vs no change)0.3310.8460.5670.457 Reason[9] Pandemic41 (51.3)15 (36.6)11 (26.8)14 (34.1)24 (60.0) [1] Inactive disease23 (28.8)12 (52.2)6 (26.1)10 (43.5)12 (52.2) Active disease b16 (20.0)14 (87.5)6 (37.5)7 (43.8)7 (43.8) P (reasons)0.0030.6870.6870.526 Spondyloarthritis88 (30.7)42 (47.7)25 (28.4)40 (45.5)67 (76.1) P (vs no change)0.6730.8890.1570.451 Reason[6] Pandemic50 (61.0)22 (44.0)13 (26.0)22 (44.0)42 (84.0) Inactive disease15 (18.3) 7 (46.7)4 (26.7)7 (46.7)10 (66.7) Active disease b17 (20.7)11 (64.7)6 (35.3)6 (35.3)11 (64.7) P (reasons)0.3310.7560.7740.156 P (RA vs SpA)0.0310.2940.9500.6030.004Data are presented as numbers (percentage proportions; across rows except for column N) or medians (interquartile ranges). Missing values are in square brackets.a P values calculated using χ2 test or Mann-Whitney rank sum test.b Self-reported claim of disease activity.Conclusion:Two thirds of patients did not change medication but one third changed. A relatively high number of patients did so due to fear of the pandemic, mostly those on biologics. There were no major differences between RA and SpA. Anxiety and depression do not seem to play an important role for the decision to change medication (Table 1 below).Disclosure of Interests:None declared

Background:Assessment and monitoring of disease activity and functioning is of major importance for the course of axial spondyloarthritis (axSpA). This is equally important for patient monitoring in daily routine as also for tight control strategies. Even though there is evidence that a closer monitoring of patients is better than routine care, more intensive treatment schedules are often not realized in daily practice for several reasons including shortage of time and personal resources. Using application software devices (apps) in clinical routine for the recording of disease-specific patient reported outcomes (PRO) may facilitate monitoring and improve clinical decision processes but there is a lack of data on the use of apps.Objectives:To investigate the use of such App technology in respect to usability, feasibility and equivalence of data in daily care of patients with axSpA. In more detail, it will be first determined how many patients are capable and ready to use the technology in a routine setting. Furthermore, the usage and behavior of patients using the app will be studied, the usability of the app and the equivalence of the collected parameters as well as the adherence to the documentation of disease activity over time.Methods:Patients diagnosed with axSpA were consecutively included in this ongoing monocentric prospective cohort study. In addition to patient and disease characteristics, information on previous experience with digital health apps was collected. Patients were asked to submit BASDAI and BASFI scores regularly every 2 weeks. The free to use AxSpA Live App is available for Android and iOS as a Class I certified medical device.Results:Out of 103 axSpA patients asked, 69 patients with axSpA (mean age 41.5 ± 11.3, 58% male, 76.8% use of bDMARDs, BASDAI 4.3 ± 2.0, BASFI 3.8 ± 2.5) out of 103 patients (67%) agreed to use participate, while 5 did not have a smartphone, 1 was unable to download the app for technical reasons, 28 reported other personal reasons). Of the 69, 62 patients (89.9%) reported using electronic media frequently and had used digital health apps (mean apps used 1.0 ± 1.3) in everyday life before. There were no systematic differences between pain levels documented on paper or by app at baseline (ICC 0.9 (95%CI 0.82 – 0.93). Out of 55 patients who completed week 2, only 33 patients (60%) used the App regularly to transmit their BASDAI/BASFI responses within the first two weeks (60%). Patients who started a new drug treatment because of high disease activity, reported BASDAI values more often than patients without a treatment change within a follow-up period of 5.5± 2.4 weeks (Table).Conclusion:The majority of patients with axSpA were able to use the AxSpA Live App. Most patients report scores regularly. The current disease activity seems to influence the adherence to reporting.Patients without change in their medication (n=53)Patients with change in their medication (n=16)Age, years42.0 (11.9)39.8 (9.3)Sex, male (%)62.343.8BASDAI, baseline4.1 (2.1)4.9 (1.7)BASFI, baseline3.8 (2.6)3.8 (2.3)Time of follow-up, in weeks5.4 (2.4)5.6 (2.5)Number of transmitted BASDAI values at week 222 (41%)11 (69%)Median number of transmitted BASDAI values during follow up1.0(3.6)1.5 (1.4)This work was supported by an unrestricted Grant by Novartis Pharma GmbH, GermanyAcknowledgments:n/aDisclosure of Interests:Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Robin Kempin: None declared, Anna Schlegel: None declared, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Styliani Tsiami: None declared, Bjoern Buehring Grant/research support from: GE/Lunar, Kinemed, Consultant of: Gilead, Abbvie, Lilly, GE/Lunar, Janssen, Amgen, Speakers bureau: UCB, David Kiefer Grant/research support from: Novartis, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma

Background:Current demographic data predict that the number of older adults with rheumatic diseases will considerably increase in the coming years. Geriatric patients differ from younger adults in many ways including their clinical presentation, co-morbidities and response to medication. The management of such patients is often challenging due to the presence of multi-morbidity, polypharmacy and geriatric syndromes (i.e. conditions in which symptoms result from impairments in multiple systems rather than a discrete disease). To systematically assess geriatric patients, specific tools have been developed; however, they are not routinely utilized by rheumatologists. Using these tools could improve patient management and satisfaction in rheumatologic care.Objectives:To examine the prevalence of 17 common geriatric health problems using validated geriatric assessment tools in older patients with rheumatic and musculoskeletal diseases.Methods:Adults 65 years and older who presented to a tertiary rheumatologic hospital were included after informed consent. All patients recruited were assessed using theMAngableGeriatrICAssessment (MAGIC) which addresses 14 common geriatric health problems. In addition, polypharmacy (≥ 5 medication), muscle function using the Short Physical Performance Battery and frailty applying the Fried definition were assessed. Disability was quantified with the “Funktionsfragebogen Hannover” (FFbH), a validated tool for patients with rheumatologic diseases that can be easily converted to Health Assessment Questionnaire (HAQ) scores. Primary outcome was the frequency of the selected 17 geriatric health problems; the correlation of the total number of problems with HAQ scores was a secondary outcome.Results:Of the 300 individuals included 67% were female with a mean age of 73±6.6 years; 85% (> 50% with rheumatoid arthritis) had a rheumatologic diagnosis. The remaining participants had either a chronic pain syndrome or degenerative joint/spine disease. On average participants had 7 out of 17 assessed geriatric problems. Females had more such problems than males (8 vs. 6, p2= 0.44, pConclusion:A systematic geriatric assessment can be successfully used to discover and quantify geriatric health problems in older patients with rheumatic and musculoskeletal diseases. These problems appear to be very common and importantly, patients with more problems had poorer functional status. Frailty, depression, incomplete vaccination status, cognitive impairment or polypharmacy are all known to negatively impact patient care. Recognizing and addressing geriatric problems has the potential to lead to health care improvements including adherence and medication side effects and might increase patient satisfaction and functional status independent of disease activity.References:[1]Buehring, B. and S. Barczi, Assessing the Aging Patient, in Spine Surgery in an Aging Population, N. Brooks and A. Strayer, Editors. 2019, Thieme: New York. p. 208.[2]Cleutjens F, Boonen A, van Onna MGB. Geriatric syndromes in patients with rheumatoid arthritis: a literature overview. Clin Exp Rheumatol 2019;37(3):496-501Geriatric Problem% presentProblems with Daily Activities67Problems with Vision28Problems with Hearing38Problems with Falls11Problems with Urinary Incontinence38Problems with Depression57Lack of Social Support10Incomplete Vaccinations53Problems with Cognition31Problems with Chronic Pain90Problems with Dizziness44Problems with Mobility41Problems with Unintentional Weight Loss30Inappropriate Medications present17Polypharmacy present81Frailty present46Short Physical Performance Battery low57Acknowledgments:NoneDisclosure of Interests:Anna Berrisch: None declared, Ioana Andreica: None declared, Styliani Tsiami: None declared, David Kiefer Grant/research support from: Novartis, Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Bjoern Buehring Grant/research support from: GE/Lunar, Kinemed, Consultant of: Gilead, Abbvie, Lilly, GE/Lunar, Janssen, Amgen, Speakers bureau: UCB

Induction hardening is a widely used surface treatment technique that has extensively been investigated. In contrast, induction tempering with short heating times ≤ 1 s has not been investigated thoroughly, nor by experiment neither by simulations. Also, the influence of rapid tempering on the residual stresses after induction surface hardening has only been investigated superficially. Induction quench and temper experiments were performed, both with heating times ≤ 1 s. A significant change of the residual stress state was observed, leading to a shift from compressive to tensile residual stresses in the surface layer. A multiphysical FE-model for the whole quench-and-temper process has been developed and validated. A good agreement with the experiments for the relevant mechanical properties hardness and residual stress could be achieved. The recently reported transformation induced plasticity during tempering has been found to play a key role in the development of residual stresses during tempering. The simulations further indicate that conventional heat treatment leads to more favorable residual stress states after tempering to a prescribed surface hardness. By accounting for tempering processes during austenitization, the hardening simulation could be generalized to different initial states and allows for the prediction of hardness minima in the transition zone.

IgG therapeutics directed against solid tumor antigens can be effective in preventing disseminated cancer spread in mouse models, but are typically ineffective in eradicating established solid tumor masses. Here, we have studied the anti-tumor activity of the recombinant murine IgG2a antibody TA99, directed against a melanoma antigen. As previously reported, IgG2a(TA99) was extremely efficacious in preventing the growth of B16 lung metastases. However, the same antibody only mediated a minimal tumor growth retardation, when used to treat established neoplastic masses. The therapeutic activity of IgG2a(TA99) could be substantially enhanced by co-administration with an antibody-cytokine fusion (TA99-mTNF), consisting of the TA99 antibody in scFv format fused to murine TNF. This fusion protein efficiently killed endothelial cells in vitro, while displaying only minimal activity against B16 melanoma cells. In vivo, TA99-mTNF boosted the influx of NK cells into B16 melanoma lesions. Therapy studies with two different administration schedules revealed that the combination of TA99-mTNF and IgG2a(TA99) was superior to the individual products used as single agents. The combination treatment converted most of the tumor mass into a necrotic lesion, but a vital tumor rim eventually regrew. The treatment modality described in this article may be applicable for the treatment of melanoma patients, given the specificity of the gp75 antigen and its conservation across species. Addition of a third combination partner may be required, in order to eradicate the last tumor cells, which survive treatment.

Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction. R11.1.6 directly blocks interaction with Raf and reduces signaling through the Raf/MEK/ERK pathway. Our results support greater consideration of the state of switch I and provide a novel tool to study Ras biology. Most importantly, this work makes an unprecedented contribution to Ras research in inhibitor development strategy by revealing details of a targetable binding surface. Unlike the polar interfaces found for Ras/effector interactions, the K-Ras/R11.1.6 complex reveals an extensive hydrophobic interface that can serve as a template to advance the development of high affinity, non-covalent inhibitors of K-Ras oncogenic mutants., Scientific Reports, 7, ISSN:2045-2322

Quantifying protein location and concentration is critical for understanding function in situ. Scaffold conjugated to environment-sensitive fluorophore (SuCESsFul) biosensors, in which a reporting fluorophore is conjugated to a binding scaffold, can, in principle, detect analytes of interest with high temporal and spatial resolution. However, their adoption has been limited due to the extensive empirical screening required for their development. We sought to establish design principles for this class of biosensor by characterizing over 400 biosensors based on various protein analytes, binding proteins, and fluorophores. We found that the brightest readouts are attained when a specific binding pocket for the fluorophore is present on the analyte. Also, interaction of the fluorophore with the binding protein it is conjugated to can raise background fluorescence, considerably limiting sensor dynamic range. Exploiting these two concepts, we designed biosensors that attain a 100-fold increase in fluorescence upon binding to analyte, an order of magnitude improvement over the previously best-reported SuCESsFul biosensor. These design principles should facilitate the development of improved SuCESsFul biosensors. Keywords: solvatochromism; Sso7d scaffold; sensors; protein engineering; directed evolution, National Science Foundation (U.S.) (Grant MCB-115803), National Institutes of Health (U.S.) (Grant U54CA112967), National Cancer Institute (U.S.) (Grant U54CA112967), National Institutes of Health (U.S.) (Grant R01 EB 010246)

The Sso7d protein from the hyperthermophilic archaeon Sulfolobus solfataricus is an attractive binding scaffold because of its small size (7 kDa), high thermal stability (Tm of 98 °C), and absence of cysteines and glycosylation sites. However, as a DNA-binding protein, Sso7d is highly positively charged, introducing a strong specificity constraint for binding epitopes and leading to nonspecific interaction with mammalian cell membranes. In the present study, we report charge-neutralized variants of Sso7d that maintain high thermal stability. Yeast-displayed libraries that were based on this reduced charge Sso7d (rcSso7d) scaffold yielded binders with low nanomolar affinities against mouse serum albumin and several epitopes on human epidermal growth factor receptor. Importantly, starting from a charge-neutralized scaffold facilitated evolutionary adaptation of binders to differentially charged epitopes on mouse serum albumin and human epidermal growth factor receptor, respectively. Interestingly, the distribution of amino acids in the small and rigid binding surface of enriched rcSso7d-based binders is very different from that generally found in more flexible antibody complementarity-determining region loops but resembles the composition of antibody-binding energetic hot spots. Particularly striking was a strong enrichment of the aromatic residues Trp, Tyr, and Phe in rcSso7d-based binders. This suggests that the rigidity and small size of this scaffold determines the unusual amino acid composition of its binding sites, mimicking the energetic core of antibody paratopes. Despite the high frequency of aromatic residues, these rcSso7d-based binders are highly expressed, thermostable, and monomeric, suggesting that the hyperstability of the starting scaffold and the rigidness of the binding surface confer a high tolerance to mutation.