High Mortality After Total Knee Arthroplasty Periprosthetic Joint Infection is Related to Preoperative Morbidity and the Disease Process but Not Treatment.

BACKGROUND: Periprosthetic joint infection (PJI) mortality rate is approximately 20%. The etiology for high mortality remains unknown. The objective of this study was to determine whether mortality was associated with preoperative morbidity (frailty), sequalae of treatment, or the PJI disease process itself. METHODS: A multicenter observational study was completed comparing 184 patients treated with septic revision total knee arthroplasty (TKA) to a control group of 38 patients treated with aseptic revision TKA. Primary outcomes included time and the cause of death. Secondary outcomes included preoperative comorbidities and Charlson Comorbidity Index (CCMI) measured preoperatively and at various postoperative timepoints. RESULTS: The septic revision TKA cohort experienced earlier mortality compared to the aseptic cohort, with a higher mortality rate at 90 days, 1, 2, and 3 years after index revision surgery (P = .01). There was no significant difference for any single cause of death (P > .05 for each). The mean preoperative CCMI was higher (P = .005) in the septic revision TKA cohort. Both septic and aseptic cohorts experienced a significant increase in CCMI from the preoperative to 3 years postoperative (P < .0001 and P = .002) and time of death (P < .0001 both) timepoints. The septic revision TKA cohort had a higher CCMI 3 years postoperatively (P = .001) and at time of death (P = .046), but not one year postoperatively (P = .119). CONCLUSION: Compared to mortality from aseptic revision surgery, septic revision TKA is associated with earlier mortality, but there is no single specific etiology. As quantified by changes in CCMI, PJI mortality was associated with both frailty and the PJI disease process, but not treatment.

Administration of Tranexamic Acid Improves Long-Term Outcomes in Total Knee Arthroplasty.

BACKGROUND: Blood transfusion in total knee arthroplasty (TKA) is associated with increased morbidity, including periprosthetic joint infection (PJI). Tranexamic acid (TXA) reduces blood transfusion rates, but there is limited evidence demonstrating improved outcomes in TKA resulting from TXA administration. The objectives of this study are determining whether TXA is associated with decreased rate of PJI, decreased rate of outcomes associated with PJI, and whether there are differences in rates of adverse events. METHODS: A multicenter cohort study comprising 23,421 TKA compared 4423 patients receiving TXA to 18,998 patients not receiving TXA. Primary outcome was PJI within 2 years of TKA. Secondary outcomes included revision surgery, irrigation and debridement, transfusion, and length of stay. Adverse events included readmission, deep vein thrombosis, pulmonary emboli, myocardial infarction, or stroke. Adjusted odds ratios were determined using linear mixed models controlling for age, sex, thromboembolic prophylaxis, Charlson comorbidity index, year of TKA, and surgeon. RESULTS: TXA administration reduced incidence of PJI by approximately 50% (odds ratio [OR], 0.55; P = .03). Additionally, there was decreased incidence of revision surgery at 2 years (OR, 0.66; P = .02). Patients receiving TXA had reductions in transfusion rate (OR, 0.15; P < .0001) and length of stay (P < .0001). There was no difference in the rate of pulmonary emboli (OR, 1.20; P = .39), myocardial infarction (OR, 0.78; P = .55), or stroke (OR, 1.17; P = .77). CONCLUSION: Administration of TXA in TKA resulted in reduced rate of PJI and overall revision surgery. No difference in thromboembolic events were observed. The use of TXA is safe and improves outcomes in TKA. LEVEL OF EVIDENCE: Level III, Observational Cohort Study.

The Dual PI3K/mToR Inhibitor Omipalisib/GSK2126458 Inhibits Clonogenic Growth in Oncogenically-transformed Cells from Neurocutaneous Melanocytosis.

BACKGROUND: Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. MATERIALS AND METHODS: Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors. Activation of MEK and Akt was determined by immunoblots. Colony formation and cell viability were assessed upon pharmacological inhibition of MEK, Akt and mToR. RESULTS: Clonogenicity appeared to depend on bFGF and IGF1signaling through ERK and Akt. Omipalisib treatment prevented colony formation and induced autophagic cell death. CONCLUSION: Signaling through Akt is important for survival of clonogenic cells in NCM, and omipalisib treatment as a monotherapy or in combination with MEK162 could be an effective therapeutic strategy to inhibit clonogenic growth.