A Novel Nonsense Pathogenic TTN Variant Identified in a Patient with Severe Dilated Cardiomyopathy

Both genetic and environmental factors contribute to the development of dilated cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain 25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman diagnosed with severe DCM and presenting relevant acquired risk factors for DCM (hypertension, diabetes, smoking habit, and/or previous alcohol and cocaine abuse) and with a family history of both DCM and sudden cardiac death. The left ventricular systolic function, as assessed by standard echocardiography, was 20%. The genetic analysis performed using TruSight Cardio panel, including 174 genes related to cardiac genetic diseases, revealed a novel nonsense TTN variant (TTN:c.103591A > T, p.Lys34531*), falling within the M-band region of the titin protein. This region is known for its important role in maintaining the structure of the sarcomere and in promoting sarcomerogenesis. The identified variant was classified as likely pathogenic based on ACMG criteria. The current results support the need of genetic analysis in the presence of a family history, even when relevant acquired risk factors for DCM may have contributed to the severity of the disease

The effects on bone cells of metal ions released from orthopaedic implants. A review

The increasing use of orthopedic implants and, in particular, of hip and knee joint replacements for young and active patients, has stimulated interest and concern regarding the chronic, long-term effects of the materials used. This review focuses on the current knowledge of the adverse biologic reactions to metal particles released from orthopaedic implants in vivo and in vitro. More specifically, the purpose of this article is to provide an overview of the current literature about the adverse effects of metal particles on bone cells and peri-implant bon

Ronc\ue0, Castello di Terrossa: prime indagini presso il sito

presentazione dei risultati preliminari relativo allo scavo del castello di Terrossa, presso Ronc\ue0 (Vr

Fracture-Related Infection in Bicolumnar Acetabular Fracture: A Case Report

Case: A 51-year-old man was affected by a fracture-related infection after a bicolumnar acetabular fracture. A significant alteration of the anatomy was present; thus, a 3D-printed model was useful for planning. A two-stage treatment was planned: in the first stage, implant removal with irrigation and debridement was performed, while in the second stage, a new osteosynthesis and implant of a THA were planned. During the second stage, the patient suffered a cardiogenic shock, so a third surgical procedure was necessary to implant THA. Targeted antibiotic therapy was administered eight weeks after the first stage, with the resolution of the infection. Conclusions: The infection was resolved following the recent guidelines and treating it like a periprosthetic infection with a two-stage revision. A collaboration between specialists in orthopaedics and infectious disease, respectively, and using multidisciplinary approach, were mandatory

Osteochondral repair by a novel interconnecting collagen-hydroxyapatite substitute: a large-animal study

A novel three-dimensional bicomponent substitute made of collagen type I and hydroxyapatite was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase. Thirty-six osteochondral lesions were created in the trochlea of six pigs; in each pig, two lesions were treated with scaffolds seeded with autologous chondrocytes (cell+group), two lesions were treated with unseeded scaffolds (cell- group), and the two remaining lesions were left untreated (untreated group). After 3 months, the animals were sacrificed and the newly formed tissue was analyzed to evaluate the degree of maturation. The International Cartilage Repair Society (ICRS) macroscopic assessment showed significantly higher scores in the cell- and untreated groups when compared with the cell+ group. Histological evaluation showed the presence of repaired tissue, with fibroblast-like and hyaline-like areas in all groups; however, with respect to the other groups, the cell- group showed significantly higher values in the ICRS II histological scores for "cell morphology" and for the "surface/superficial assessment." While the scaffold seeded with autologous chondrocytes promoted the formation of a reparative tissue with high cellularity but low glycosaminoglycans (GAG) production, on the contrary, the reparative tissue observed with the unseeded scaffold presented lower cellularity but higher and uniform GAG distribution. Finally, in the lesions treated with scaffolds, the immunohistochemical analysis showed the presence of collagen type II in the peripheral part of the defect, indicating tissue maturation due to the migration of local cells from the surroundings. This study showed that the novel osteochondral scaffold was easy to handle for surgical implantation and was stable within the site of lesion; at the end of the experimental time, all implants were well integrated with the surrounding tissue and no signs of synovitis were observed. The quality of the reparative tissue seemed to be superior for the lesions treated with the unseeded scaffolds, indicating the promising potential of this novel biomaterial for use in a one-stage procedure for osteochondral repair

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services