Osteoarthritis (OA) is the most common degenerative joint disorder and genetic factors have been shown to have a significant role in its etiology. The first metatarsophalangeal joint (MTP I) is highly susceptible to development of OA due to repetitive mechanical stress during walking. We used whole exome sequencing to study genetic defect(s) predisposing to familial early-onset bilateral MTP I OA inherited in an autosomal dominant manner. A nonsynonymous single nucleotide variant rs41310883 (c.524C>T, p.Thr175Met) in TUFT1 gene was found to co-segregate perfectly with MTP I OA. The role of TUFT1 and the relevance of the identified variant in pathogenesis of MTP I OA were further assessed using functional in vitro analyses. The variant reduced TUFT1 mRNA and tuftelin protein expression in HEK293 cells. ATDC5 cells overexpressing wild type (wt) or mutant TUFT1 were cultured in calcifying conditions and chondrogenic differentiation was found to be inhibited in both cell populations, as indicated by decreased marker gene expression when compared with the empty vector control cells. Also, the formation of cartilage nodules was diminished in both TUFT1 overexpressing ATDC5 cell populations. At the end of the culturing period the calcium content of the extracellular matrix was significantly increased in cells overexpressing mutant TUFT1 compared to cells overexpressing wt TUFT1 and control cells, while the proteoglycan content was reduced. These data imply that overexpression of TUFT1 in ATDC5 inhibits chondrogenic differentiation, and the identified variant may contribute to the pathogenesis of OA by increasing calcification and reducing amount of proteoglycans in the articular cartilage extracellular matrix thus making cartilage susceptible for degeneration and osteophyte formation.

Height at the age of 31 was associated with incidence of early knee OA, diagnosed prior to age 46. However, the low incidence of hip OA made our results for hip OA inconclusive.

Background Invasive surgical procedures carry risk of harm to patients. In addition to avoidable harm, disparities between patient expectations and the outcome of a procedure may lead to patient injury claims. The follow-up of claims and compensation is an important entity for patient safety. The number of claims should be related to the surgical volume, so that a healthcare provider can benchmark with similar organizations and see if its trends are developing favourably or deteriorating. Our objective was to find out the claims and compensation rates due to surgery in an insurance-based system. Methods Data related to surgical claims and reference volume in the period 2011–2015 were collected from the claim register of the Finnish Patient Insurance Centre and benchmarking community register of Finnish operating departments. The data included age, gender, hospital, year of surgery, surgical code, and outcome of the claim. Results There were 8,901 claims related to the corresponding reference group of 1,470,435 surgical procedures. The claims rate was 0.61% and compensation rate was 0.22%. Trends for claims and compensation rates decreased over the study period. In high volume procedures, a low compensation rate was detected for excision of tonsils and adenoids, Caesarean section and extracapsular cataract operations using the phacoemulsification technique. A high compensation rate was detected for primary prosthetic replacement of the hip and knee joints and decompression of spinal cord and nerve roots. Unreasonable injury (death or permanent deterioration of health) was compensated in 2.4 per 100,000 procedures. Conclusions Register data research in a no-fault patient insurance system revealed a claims rate of 6 per 1,000 procedures and compensation rate of 2 per 1,000 procedures. A decreasing trend in both rates over the study period was detected. Different surgical procedures exhibit varying claims and compensation rates.