The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of disease modification. Today, the vast amount of patients suffering from serious, chronic joint diseases can only be offered treatments aimed at improving symptoms, such as pain and acute inflammation, and are not aimed at protecting the joint tissue. This huge, unmet medical need has been the driver behind the development of improved analytical techniques allowing better and more efficient clinical trial design, implementation and analysis. With this review, we aim to provide a brief and general overview of biochemical markers of joint tissue, with special focus on neoepitopes. Furthermore, we highlight recent studies applying biochemical markers in joint degenerative diseases. These disorders, including osteoarthritis, rheumatoid arthritis and spondyloarthropathies, are the most predominant disorders in Europe and the USA, and have enormous socioeconomical impact.

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR–Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients.

Background The MANKIN score is the most widely used histology evaluation on osteoarthritis (OA). It has been modified in number of studies by different research groups since it was first published 40 years ago. The MANKIN score investigate the degradation level of the articular cartilage by assessing four parameters including: cartilage structure, cellularity, proteoglycan depletion and tidemark integrity. However, it is well-established that the interaction between cartilage and subchondral bone, such as the new vessel invasion from subchondral bone into calcified cartilage and the accompanied nerve formation, play essential role in the onset and progression of OA. Objectives As to better assess the pathologic changes in joint during OA, we developed a new modified MANKIN scoring system with special attention to the subchondral bone. Methods Besides 4 categories of evaluation on cartilage, we also performed type X collagen immunohistochemical staining, tartrate-resistant acidic phosphatase (TRAP) staining, cartilage and subchondral bone thickness measurement, the number of vessels counting (CD34), Vascular Endothelial Growth Factor Receptor (VEGFR) immunostaining and nerve growth factor receptor (NGFR, P75staining) immunostaining in 2 areas (lateral femur condyle and lateral tibia plateau) of 11 OA patients undergoing knee replacement surgery at Frederikshavn hospital. Each new evaluation was analyzed the correlation with MANKIN score, of which with moderate correlation would be included into the new scoring table. Furthermore, statistical analysis was performed for inter-/intra- observers variability according to the criteria of new modified scoring system. Results After carful assessment of the different novel parameters, following were found to be associated with cartilage quality: 1) number of vessels (moderate correlation with MANKIN score, Spearman's r=0.6), 2) number of positive cells expressing NGFR (moderate correlation with MANKIN score, Spearman's r=0.4), and 3) the thickness of cartilage/subchondral bone (moderate correlation with MANKIN score, Spearman's r=0.7). A final scoring scheme was put together (table 1) and tested in 11 patients. The inter-observer variability among two observers for the new score system showed reliability (Person's r=0.80). Repeating scoring by one of two observers showed good reproducibility (Person's r=0.73). Conclusions The new scoring system was constructed with valuable information to indicate the changes in subchondral bone and the severity of OA, which might be used as a rapid and reliable histology evaluation on both human OA and experiment induced OA animal models. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4224