Risk factors for fracture-related infection after open reduction and internal fixation of proximal humerus fractures: A multicenter retrospective study of 496 fractures (TRON group study).

INTRODUCTION: One of the complications of the surgical therapy for proximal humerus fractures is fracture-related infection (FRI). This multicenter study aimed to investigate the incidence of FRI and clarify the risk factors associated with FRI in patients receiving open reduction and internal fixation for proximal humerus fracture. MATERIAL AND METHODS: Among 684 patients diagnosed as having proximal humerus fracture and who were treated by surgical therapy in 13 institutions (named TRON group) from 2015 through 2020, 496 patients (men, n = 134, women, n = 362; mean [SD] age, 68.5 [14.5] years; mean [SD] body mass index [BMI], 23.0 [4.4] kg/m2) were included as subjects. Excluded were 188 patients due to less than 12 month's follow-up, patients who underwent osteosynthesis using neither plate nor nail and those with open fracture. We extracted the following as risk factors of FRI: sex, BMI, smoking status, diabetes, glenohumeral fracture dislocation, fracture classification, approach, implant, waiting period, type of anesthesia, operative time and blood loss during surgery. We conducted logistic regression analysis to investigate the risk factors of FRI using these extracted items as explanatory variables and the presence or absence of FRI as the response variable. RESULT: FRI occurred after surgery for proximal humerus fracture in 9 of the 496 patients (1.8%). The causative organism was methicillin-susceptible Staphylococcus aureus in 4 patients, Pseudomonas aeruginosa in one patient and Enterococcus faecalis in one patient. In the other 3 patients, causative organisms were not detected. The univariate analysis showed significant differences for present of glenohumeral fracture dislocation (p = 0.004). Logistic regression analysis showed glenohumeral fracture dislocation to be the significant explanatory factor for FRI (odds ratio 12.3, p = 0.0375). CONCLUSION: This study revealed an infection rate following open reduction and internal fixation of proximal humerus fracture of 1.8% (9 patients) and that Staphylococcus was the most frequent causative organism. Glenohumeral fracture dislocation is a significant risk for postoperative FRI.

Displaced humeral head after intramedullary nailing for proximal humeral fracture is associated with worse short-term outcomes-a multicenter TRON study.

Background: In recent years, complex and unstable proximal humeral fractures (PHFs) are treated with intramedullary nails (IMNs) in the elderly; however, the postoperative radiographic findings related to the clinical outcome are not clear. This study evaluated the association of clinical outcomes with the radiographic findings of PHFs treated with IMNs. Methods: We collected data of patients aged >60 years with PHFs treated with IMNs from 2015 to 2019 in 13 associated centers' database (named TRON). We excluded patients lost to follow-up of <6 months postoperatively (PO6M). We evaluated clinical outcomes with the University of California at Los Angeles (UCLA) score at PO6M and defined a score of <27 as poor. We assessed the radiographic findings on the anteroposterior view of the humeral head postoperatively, and each radiographic finding such as humeral head height (HHH), head shaft angle, and cranialization of the greater tuberosity was divided into two groups: poor and good. Factors associated with poor UCLA at PO6M were extracted by logistic regression analysis, and the factors were divided into two groups (poor and good) and matched for age, sex, and fracture type. The UCLA score at PO6M between the groups was examined by the Mann-Whitney U test, and the significance level was set at 0.05. The minimal clinical important difference in the UCLA score was set 2 points. Results: The study included 243 patients (mean age, 76 years; range, 60-95 years). The mean follow-up period was 12 months (range, 6-56 months). The correlation coefficients indicated that there was either no or only a weak correlation between HHH, head shaft angle, and cranialization of the greater tuberosity. A poor HHH (HHH <0 or >10 mm) was extracted as a factor associated with a poor UCLA score at PO6M by logistic regression analysis (odds ratio: 5.78, 95% confidence interval = 1.2-27.7, P = .0287). In matched pair analysis, the UCLA score at PO6M was significantly lower in the poor HHH group (26 [range: 9-33] vs. 24 [range: 10-35], P = .0458). Conclusion: We revealed that the HHH was an independent risk factor for poor short-term outcomes. There was a significant difference in the UCLA score between groups divided by the HHH in cases treated with IMNs. The HHH can be used intraoperatively or postoperatively as a reliable parameter to predict clinical outcomes in PHFs treated with IMNs.

Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T- and NK-cell lymphoproliferative diseases.

PURPOSE: Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells, and T- and NK-cell lymphoproliferative diseases (T/NK-LPD) that are refractory to conventional chemotherapies may develop. To identify a molecular-targeted therapy for EBV-associated T/NK-LPDs, we investigated whether CC chemokine receptor 4 (CCR4) was expressed on EBV-infected T and/or NK cells and whether a humanized anti-CCR4 monoclonal antibody, mogamulizumab, was effective. EXPERIMENTAL DESIGN: CCR4 expression was examined in various cell lines. In vitro, the effects of mogamulizumab on cell lines were evaluated in the presence of peripheral blood mononuclear cells from volunteers. In vivo, the effects of mogamulizumab were evaluated using a murine xenograft model. CCR4 expression was examined on EBV-infected cells from patients with EBV-associated T/NK-LPDs. Ex vivo, the effects of mogamulizumab were evaluated using patient lymphocytes. RESULTS: CCR4 expression was confirmed in most EBV-positive T and NK cell lines. Mogamulizumab induced antibody-dependent cellular cytotoxicity (ADCC) activity against CCR4-positive cell lines, and inhibited the growth of EBV-positive NK-cell lymphomas in a murine xenograft model. Furthermore, CCR4 was expressed on EBV-infected cells in 8 of 17 patients with EBV-associated T/NK-LPDs. Interestingly, CCR4 was positive in 5 of 5 patients with hydroa vacciniforme, a photodermatosis caused by the clonal expansion of EBV-infected γδT cells. EBV-positive γδT cells were obtained from a patient with hydroa vacciniforme and subjected to an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The γδT cells that were positive for CCR4 were killed by mogamulizumab via ADCC. CONCLUSIONS: These results indicate that mogamulizumab may be a therapeutic option against EBV-associated T/NK-LPDs.