Ultraschall und Arthritis

Zusammenfassung: Die Arthrosonographie ist ein etabliertes und validiertes diagnostisches Verfahren in der Rheumatologie. Durch ihren hohen Weichteilkontrast ist die Sonographie in der Lage, Weichteilveränderungen wie z.B. Synovialisveränderungen zu detektieren. Knorpel- oder Knochenveränderungen im Rahmen einer rheumatoiden Arthritis (RA), einer Spondyloarthritis oder einer Kristallarthritis können teilweise nur sonographisch oder in vielen Fällen zu einem früheren Zeitpunkt als mit der konventionellen Bildgebung erfasst werden. Die Aktivität entzündlicher Veränderungen kann mit Hilfe der Doppler- und Power-Dopplersonographie gut dargestellt werden. In der Früharthritisdiagnostik gewinnt die Sonographie zunehmend an Bedeutung, insbesondere bei undifferenzierter Arthritis und bei unauffälligem Röntgenbefund. Neben der Diagnostik der Früharthritis und dem Therapiemonitoring einer RA erlaubt die Sonographie die Darstellung pathognomonischer Veränderungen bei seronegativen Spondyloarthritiden und Kristallablagerungserkrankungen wie Gicht, Chondrokalzinose und Apatitose. Sonographiegesteuerte diagnostische und therapeutische Interventionen zeichnen sich durch eine extrem hohe Treffsicherheit und Verbesserung der klinischen Wirksamkeit verglichen mit ungesteuerten Verfahren aus. Zusammenfassend nimmt die Sonographie zunehmend einen zentralen Stellenwert ein in der Abklärung und Behandlungssteuerung bei entzündlichen Gelenkerkrankunge

Webbasiertes Lernen in der Sonographie des Bewegungsapparates

Zusammenfassung: Die Ausbildung in der Sonographie des Bewegungsapparates erfolgt durch das Besuchen von Kursen, durch praktisches Üben und durch Selbststudium. In den letzten Jahren wurde webbasiertes Lernen auch in der Sonographie untersucht. Die vorliegende Arbeit setzte sich zum Ziel, Normalbefunde und pathologische Befunde nach den Richtlinien international anerkannter Fachgesellschaften in einem webbasierten Tool zu erfassen. In einer Zeitspanne von 3Jahren wurden im Rahmen einer prospektiven Arbeit Normalbefunde und häufige pathologische Befunde des Bewegungsapparates dokumentiert und katalogisiert. 1240 Aufnahmen, aus 1057 Ultraschallbildern und 183 Videos bestehend, wurden erfasst. Insgesamt waren 14,4% Normalbefunde und 85,6% der Bilder oder Videos pathologische Befunde. 61% der Aufnahmen betrafen die obere Extremität, 39% die untere Extremität und andere Gelenke. Die hauptsächlich dokumentierten Pathologien beschreiben eine Arthritis (33,3%), gefolgt von mechanischen oder entzündlichen Pathologien der Sehnen (19,6%). Mit 20% ist die rheumatoide Arthritis die Krankheit, die am meisten vertreten ist. Weitere häufig vorkommende Krankheiten sind die Kalziumpyrophosphatarthropathie (CPPD) mit 8,2%, die Gicht mit 7,1% und die Arthrose mit 6,9%. Zudem werden ultraschallgesteuerte Infiltrationen dargestellt. Die Aufnahmen wurden beschriftet und in ein einfach zu bedienendes webbasiertes Lernwerkzeug zusammengefass

Silver Linings: Design Strategies and Projects for Packages Born in Times of Crisis and Analyzed with a Systemic Approach

La emergencia de salud Covid-19 ha cambiado nuestros hábitos y comportamientos de compras, hábitos alimentarios y también la relación con los embalajes. Para muchos modelos de negocios la pandemia representa un punto de inflexión; para otros, la crisis ha sido la prueba de vulnerabilidades ocultas y de una potencial insuficiencia para el mundo contemporáneo. Sin embargo, el sector del embalaje no se ha detenido. Fue necesario organizar, coordinar y planificar nuevos métodos de distribución, y al mismo tiempo se abrió a nuevas oportunidades para la innovación. La industria del embalaje ha demostrado una actitud proactiva y resolutiva, y ha podido lidiar inconscientemente con problemas que van más allá del Diseño de un contenedor. El análisis de las estrategias y prácticas adoptadas por el sector del embalaje en la gestión de emergencias nos ha permitido definir el marco de investigación. Esta contribución investiga los cambios no sólo a nivel económico, sino también a nivel cognitivo-conductual y ambiental, hacia el cual el Diseño está llamado a actuar con responsabilidad cada vez mayor. Un Diseño que necesariamente debe cambiar la visión de lineal a sistémica, a partir de la formación.The Covid-19 health emergency has changed buying habits and behaviour, eating habits, as well as the relationship with packaging. For many business models, the pandemic represents a turning point; for others, the crisis, reveals hidden vulnerabilities and a potential inadequacy for the contemporary world. However, the packaging sector has not stopped. It had to organize, coordinate, find new ways of distribution, and at the same time, it opened to new opportunities in terms of innovation. The packaging industry has shown a proactive and resolute attitude, and unconsciously has been able to deal with problems that go beyond the Design of a container. The analysis of strategies and practices adopted by the packaging sector in managing the emergency allowed us to define the research framework. This contribution investigates the changes not only at an economic level but also at a cognitive-behavioural and environmental level, towards which Design is called to act with increasing responsibility. A Design that will necessarily have to shift the vision from linear to systemic, starting from education

Scalable process for high-yield production of PfCyRPA using insect cells for inclusion in a Malaria virosome-based vaccine candidate

Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) has been identified as a promising blood-stage candidate antigen to include in a broadly cross-reactive malaria vaccine. In the last couple of decades, substantial effort has been committed to the development of scalable cost-effective, robust, and high-yield PfCyRPA production processes. Despite insect cells being a suitable expression system due to their track record for protein production (including vaccine antigens), these are yet to be explored to produce this antigen. In this study, different insect cell lines, culture conditions (baculovirus infection strategy, supplementation schemes, culture temperature modulation), and purification strategies (affinity tags) were explored aiming to develop a scalable, high-yield, and high-quality PfCyRPA for inclusion in a virosome-based malaria vaccine candidate. Supplements with antioxidants improved PfCyRPA volumetric titers by 50% when added at the time of infection. In addition, from three different affinity tags (6x-His, 4x-His, and C-tag) evaluated, the 4x-His affinity tag was the one leading to the highest PfCyRPA purification recovery yields (61%) and production yield (26 mg/L vs. 21 mg/L and 13 mg/L for 6x-His and C-tag, respectively). Noteworthy, PfCyRPA expressed using High Five cells did not show differences in protein quality or stability when compared to its human HEK293 cell counterpart. When formulated in a lipid-based virosome nanoparticle, immunized rabbits developed functional anti-PfCyRPA antibodies that impeded the multiplication of P. falciparum in vitro. This work demonstrates the potential of using IC-BEVS as a qualified platform to produce functional recombinant PfCyRPA protein with the added benefit of being a non-human expression system with short bioprocessing times and high expression levels

Scalable Process for High-Yield Production of PfCyRPA Using Insect Cells for Inclusion in a Malaria Virosome-Based Vaccine Candidate.

Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) has been identified as a promising blood-stage candidate antigen to include in a broadly cross-reactive malaria vaccine. In the last couple of decades, substantial effort has been committed to the development of scalable cost-effective, robust, and high-yield PfCyRPA production processes. Despite insect cells being a suitable expression system due to their track record for protein production (including vaccine antigens), these are yet to be explored to produce this antigen. In this study, different insect cell lines, culture conditions (baculovirus infection strategy, supplementation schemes, culture temperature modulation), and purification strategies (affinity tags) were explored aiming to develop a scalable, high-yield, and high-quality PfCyRPA for inclusion in a virosome-based malaria vaccine candidate. Supplements with antioxidants improved PfCyRPA volumetric titers by 50% when added at the time of infection. In addition, from three different affinity tags (6x-His, 4x-His, and C-tag) evaluated, the 4x-His affinity tag was the one leading to the highest PfCyRPA purification recovery yields (61%) and production yield (26 mg/L vs. 21 mg/L and 13 mg/L for 6x-His and C-tag, respectively). Noteworthy, PfCyRPA expressed using High Five cells did not show differences in protein quality or stability when compared to its human HEK293 cell counterpart. When formulated in a lipid-based virosome nanoparticle, immunized rabbits developed functional anti-PfCyRPA antibodies that impeded the multiplication of P. falciparum in vitro. This work demonstrates the potential of using IC-BEVS as a qualified platform to produce functional recombinant PfCyRPA protein with the added benefit of being a non-human expression system with short bioprocessing times and high expression levels

Impact of obesity on the response to tumor necrosis factor inhibitors in axial spondyloarthritis.

Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA. Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months). Patients were categorized according to BMI: normal (BMI 18.5 to <25), overweight (BMI 25-30), and obese (BMI >30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued the TNFi were considered nonresponders. We controlled for age, sex, HLA-B27, axSpA type, BASDAI, BASMI, elevated C-reactive protein (CRP), current smoking, enthesitis, physical exercise, and co-medication with disease-modifying antirheumatic drugs, as well as with nonsteroidal anti-inflammatory drugs in multiple adjusted logistic regression analyses. A total of 624 axSpA patients starting a first TNFi were considered in the current study (332 patients of normal weight, 204 patients with overweight, and 88 obese patients). Obese individuals were older, had higher BASDAI levels, and had a more important impairment of physical function in comparison to patients of normal weight, while ASDAS and CRP levels were comparable between the three BMI groups. An ASAS40 response was reached by 44%, 34%, and 29% of patients of normal weight, overweight, and obesity, respectively (overall p = 0.02). Significantly lower odds ratios (ORs) for achieving ASAS40 response were found in adjusted analyses in obese patients versus patients with normal BMI (OR 0.27, 95% confidence interval (CI) 0.09-0.70). The respective adjusted ASAS40 OR in overweight versus normal weight patients was 0.62 (95% CI 0.24-1.14). Comparable results were found for the other outcomes assessed. Obesity is associated with significantly lower response rates to TNFi in patients with axSpA

EULAR Points to Consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs)

OBJECTIVES: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel. CONCLUSION: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs

Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

BACKGROUND\ud \ud This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.\ud \ud METHODS\ud \ud The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.\ud \ud RESULTS\ud \ud No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).\ud \ud CONCLUSION\ud \ud These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT00513669

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity