Immunogenicity of the BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis Is Associated with Medical Conditions.

BACKGROUND AND OBJECTIVES: Patients undergoing maintenance hemodialysis have an attenuated immune response to vaccination. The aim of our study was to determine the predictive factors for humoral response to vaccination with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In this retrospective, single-center study, we included patients on maintenance hemodialysis already vaccinated with two doses of the BNT162b2 vaccine (Pfizer-BioNTech) and with a post-vaccination serological follow-up. RESULTS: 252 patients were included for study with a mean age of 71.9 (±14.4) years. Twelve patients (4.7%) were under immunosuppressive therapy (calcineurin inhibitors: n = 4; chemotherapy for myeloma: n = 3; last infusion of rituximab over the previous 4 years: n = 2; abatacept: n = 2; adalimumab n = 1). Three of these patients were under immunosuppressive therapy for nonrenal solid organ transplantation. Multivariate analysis identified immunosuppressive therapy (OR 4.73 [1.38-16.17], p = 0.013) and lower baseline albumin levels (OR 1.23 [1.09-1.38], p < 0.001) as independent predictive factors of nonresponse to vaccination. Older age (ß = -0.59 ± 0.21, p = 0.006) and immunosuppressive therapy (ß = 40.33 ± 13.33, p = 0.003) were significantly associated with lower humoral response to vaccination. CONCLUSIONS: Approximately 90% of patients under maintenance hemodialysis developed specific antibodies to the BNT162b2 mRNA vaccine. Immunosuppressive therapy, malnutrition, and older age were associated with a higher risk of nonseroconversion or lower humoral response to mRNA-based vaccination against SARS-CoV-2. We strongly recommend serological monitoring after vaccination to determine booster timing, especially for patients with malnutrition or on immunosuppressive therapy.

Evaluation of reconstructive surgery using artificial ligaments in 71 acute knee dislocations.

This retrospective study assessed the results of 71 patients with knee dislocations who underwent acute combined repair and reconstruction using Ligament Advancement Reinforcement System (LARS) artificial ligaments between June 1996 and May 2008 with a follow-up between two and eight years. The outcome measures used were the Lysholm score, the International Knee Documentation Committee form (IKDC 2000), the Tegner activity level score, the Meyers ratings, Telos stress radiography, range of motion and clinical knee stability testing. When comparing high- versus low-energy dislocations and knee dislocation (KD) II/III versus KD IV injuries, a better Lysholm score for the knee dislocation (KD) II/III group was found compared with the KD IV group. The subjective and objective findings from our study are satisfactory and comparable with the results of other studies of knee dislocations. Our findings suggest that with a mean follow-up of 54 months, acute combined repair and reconstruction with LARS ligaments is a valid alternative for treating knee dislocations.

PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor.

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder associated with KIT germline mutations. In sporadic forms of the disease, somatic mutations target either KIT or PDGFRA genes. In a kindred in which 5 individuals had GIST, no germline mutation in KIT coding sequence has been detected. We hypothesized that the PDGFRA gene could be a predisposing gene in familial GIST. We sequenced PDGFRA exons 12 and 18 because several somatic mutations were identified within this region. We detected a germline PDGFRA missense mutation, 2675G > T, resulting in a tyrosine substitution for the highly conserved aspartic acid at codon 846. This mutation showed perfect cosegregation with the GIST phenotype among the 7 family members tested. Interestingly, PDGFRA Asp846 is homologous to codon 820, which is located in the KIT tyrosine kinase II domain. In a previous study, a KIT germline Asp820Tyr mutation was detected in a Japanese kindred in which 6 individuals had GIST. Transfection of a KIT820Tyr complementary DNA in nude mice was found to be tumorigenic confirming the oncogenic potential of this mutation. The present study shows that PDGFRA is a second familial GIST predisposing gene. These results indicate a further example of involvement of structurally related genes in familial cancer syndromes.