There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA. A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers. During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage. This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.
The purpose of this prospective study was to assess the patient referrals to King Edward V111 hospital with respect to communication, quality of referral letters, transfer times, investigations, diagnostic accuracy, initial management, associated and missed injuries. 88 Patient referrals were assessed prospectively over 4 months by a single investigator utilizing a questionnaire. The average age was 41 years. Eighteen (20%) were compound fractures. The average transfer time of closed injuries was 10h08 and compound injuries 4h20. 20 Patients (23%) were not discussed prior to transfer and 1 (1%) patient did not present with a referral letter. Referring physician details were deficient in name 10 (11%), contact details 58 (66%) and designation 82 (93%). No receiving physician was listed in 23 (26%) referrals. Mechanism of injury was provided in 51 (58%) referrals, time of injury in 41 (47%), type of splinting in 53 (60%) and type of analgesia in 11 (12%) referrals. Referrals of compound fractures showed a description of wound care in 11 (61%) referrals, antibiotic therapy in 9 (50%) and tetanus prophylaxis in 3 (16%). 53 (60%) referrals presented without haematological investigations and 84 (95%) presented with radiological investigations of which 54 (64%) were inadequate. Splinting was satisfactory in 35 (40%) and analgesia was adequate in 9 (10%). Wound care was appropriate in only 5 (27%) and antibiotics were administered in 7 (39%) compound fractures. Diagnostic errors emerged in 14 (16%) of referrals with a missed injury rate of 10% (9 pts). 1 Patient required urgent intervention due to blunt abdominal trauma. Supervision, training and regular assessment of junior doctors is essential to improve the quality of patient care by the referring hospitals.
