Belatacept as a Treatment Option in Patients with Severe BK Polyomavirus Infection and High Immunological Risk-Walking a Tightrope between Viral Control and Prevention of Rejection.

Balancing the immune system with immunosuppressive treatment is essential in kidney transplant recipients to avoid allograft rejection on the one hand and infectious complications on the other. BK polyomavirus nephropathy (BKPyVAN) is a viral complication that seriously threatens kidney allograft survival. Therefore, the main treatment strategy is to reduce immunosuppression, but this is associated with an increased rejection risk. Belatacept is an immunosuppressant that acts by blocking the CD80/86-CD28 co-stimulatory pathway of effector T-cells with marked effects on the humoral response. However, when compared with calcineurin-inhibitors (CNI), the cellular rejection rate is higher. With this in mind, we hypothesized that belatacept could be used as rescue therapy in severely BKPyV-affected patients with high immunological risk. We present three cases of patients with BKPyVAN-associated complications and donor-specific antibodies (DSA) and one patient who developed T-cell-mediated rejection after a reduction in immunosuppression in response to BKPyVAN. Patients were switched to a belatacept-based immunosuppressive regimen and showed significantly improved viral control and stabilized graft function. The cases presented here suggest that belatacept is a potential treatment option in the complicated situation of refractory BKPyV infection in patients with high immunological risk.

Case Report: Management of a Multidrug-Resistant CMV-Strain in a Renal Transplant Recipient by High-Dose CMV-Specific Immunoglobulins, Modulation in Immunosuppression, and Induction of CMV-Specific Cellular Immunity.

The management of multidrug-resistant strains of cytomegalovirus after solid organ transplantation is challenging. This case report demonstrates the successful treatment of a multidrug-resistant strain of cytomegalovirus that may represent a valuable option for problematic cases. This report illustrates the emergence of a multidrug-resistant cytomegalovirus (CMV) UL54 mutant strain in a renal transplant recipient with severe lymphopenia and thrombocytopenia. We show that the combined treatment with high-dose intravenous cytomegalovirus-specific immunoglobulins (CMV-IVIG) after the switch to a mammalian target of rapamycin (mTOR)-inhibitor and cyclosporine A was a successful treatment alternative to direct antiviral treatment with high-dose ganciclovir and foscarnet. This treatment was associated with a quantitative induction of CMV-specific CD4 and CD8 T cells that showed maturation in phenotype and functionality with decreasing viral load. Our case report illustrates that high-dose CMV-IVIG and conversion of immunosuppressive drugs to mTOR inhibitors and cyclosporine A can be a successful treatment in a situation where the use of direct antiviral drugs was considered insufficient.

Strategies for repair of radial tears close to the meniscal rim--biomechanical analysis with a cyclic loading protocol.

BACKGROUND: Lateral meniscectomy contributes to early-onset osteoarthritis. Biomechanical properties of sutures repairs for complete radial meniscal tears remain unknown. HYPOTHESIS: Double horizontal suture techniques for repair of radial meniscal tears with a shorter distance from the meniscal rim provide significantly higher structural properties than do comparable single-suture techniques with a wider distance from the meniscal rim. STUDY DESIGN: Controlled laboratory study. METHODS: In 55 fresh-frozen porcine menisci, standardized complete radial meniscal tears were repaired with different distances from the meniscal rim and tear edges and with different numbers of sutures. In group A, the suture was 4 mm from the tear and 8 mm from the meniscal rim; group B, 2 mm from tear; group C, 2 mm from tear, 12 mm from rim; group D, double-loop technique, 2 mm from tear, 5 mm and 10 mm from rim; group E, longitudinal tear sutured with 1 loop, 8 mm from rim, and 4 mm between stitches. The specimens were cyclically loaded 1000 times between 5 and 20 N and loaded to failure. RESULTS: All repaired constructs survived the cyclic loading protocol. Compared with the single-loop techniques, the double-loop technique (group D) showed a significantly higher maximum load and yield load and significantly lower displacement after 1000 cycles. Compared with group B, group C had a higher displacement after 1000 cycles (P < .05), and its stiffness showed a descriptive negative trend (P = .09). Displacement after cycling testing in group C was higher than in groups B and D (P < .05). CONCLUSION: Repair of radial meniscal tears with a second suture and shorter distance from the meniscal rim has a positive influence on primary stability. Different distances from tear edges apparently have no influence on structural properties. CLINICAL RELEVANCE: Horizontal sutures for repair of radial meniscal tears provide high stability and can be enhanced with a second horizontal suture and shorter distance from the meniscal rim.