Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions

Purpose Treatment of large cartilage lesions of the knee in weight-bearing areas is still a controversy and challenging topic. Autologous osteochondral mosaicplasty has proven to be a valid option for treatment but donor site morbidity with most frequently used autografts remains a source of concern. This study aims to assess clinical results and safety profile of autologous osteochondral graft from the upper tibio-fibular joint applied to reconstruct symptomatic osteochondral lesions of the knee. Methods Thirty-one patients (22 men and 9 women) with grade 4 cartilage lesions in the knee were operated by mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint, between 1998 and 2006. Clinical assessment included visual analog scale (VAS) for pain and Lysholm score. All patients were evaluated by MRI pre- and post-operatively regarding joint congruency as good, fair (inferior to 1 mm incongruence), and poor (incongruence higher than 1 mm registered in any frame). Donor zone status was evaluated according to specific protocol considering upper tibio-fibular joint instability, pain, neurological complications, lateral collateral ligament insufficiency, or ankle complaints. Results Mean age at surgery was 30.1 years (SD 12.2). In respect to lesion sites, 22 were located in weight-bearing area of medial femoral condyle, 7 in lateral femoral condyle, 1 in trochlea, and 1 in patella. Mean follow-up was 110.1 months (SD 23.2). Mean area of lesion was 3.3 cm 2 (SD 1.7), and a variable number of cylinders were used, mean 2.5 (SD 1.3). Mean VAS score improved from 47.1 (SD 10.1) to 20.0 (SD 11.5); p = 0.00. Similarly, mean Lysholm score increased from 45.7 (SD 4.5) to 85.3 (SD 7.0); p = 0.00. The level of patient satisfaction was evaluated, and 28 patients declared to be satisfied/very satisfied and would do surgery again, while 3 declared as unsatisfied with the procedure and would not submit to surgery again. These three patients had lower clinical scores and kept complaints related to the original problem but unrelated to donor zone. MRI score significantly improved at 18–24 months comparing with pre-operative (p = 0.004). No radiographic or clinical complications related to donor zone with implication in activity were registered. Conclusions This work corroborates that mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint is effective to treat osteochondral defects in the knee joint. No relevant complications related to donor zone were registered

Characterization of MTAP gene expression in breast cancer patients and cell lines

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors\ub4 MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNB

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p