Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.

Systems immunology approaches were employed to investigate innate and adaptive immune responses to influenza and pneumococcal vaccines. These two non-live vaccines show different magnitudes of transcriptional responses at different time points after vaccination. Software solutions were developed to explore correlates of vaccine efficacy measured as antibody titers at day 28. These enabled a further dissection of transcriptional responses. Thus, the innate response, measured within hours in the peripheral blood, was dominated by an interferon transcriptional signature after influenza vaccination and by an inflammation signature after pneumococcal vaccination. Day 7 plasmablast responses induced by both vaccines was more pronounced after pneumococcal vaccination. Together, these results suggest that comparing global immune responses elicited by different vaccines will be critical to our understanding of the immune mechanisms underpinning successful vaccination.

Modern Day Bicruciate-Retaining Total Knee Arthroplasty: A Short-Term Review of 146 Knees.

BACKGROUND: Bicruciate retaining (BCR) implants were first proposed in the 1960s with the polycentric knee. Given the technical difficulty of implanting these devices, and the mixed results at the time, the BCR concept had stalled, until recently. This study seeks to provide a short-term review of the BCR implant design, describe patient-reported outcomes, and discuss key aspects to ensure successful implantation of the modern-day BCR implant design. METHODS: Between October 2014 and December 2016, the senior author performed 146 primary total knee arthroplasties using BCR implants. Arthritic knees, with minimal soft tissue damage and an intact anterior cruciate ligament, were the general indications used for this cohort. All patients implanted with the BCR device were included in this analysis. One hundred forty-six (100%) BCR knees were available for follow-up at an average of 12 months (range, 1-33 months) postoperatively. RESULTS: Ninety-one percent of respondents reported their knee always or sometime feels normal, with only 9% of respondents reporting their knee never feels normal. Our study reports 94% of patients reported neutral satisfaction or higher, with only 6% of patients reporting dissatisfaction and 1% reported being very dissatisfied. Of all 146 BCR devices implanted, there were 2 (1.4%) revisions and 1 (0.7%) reoperation, a manipulation under anesthesia. CONCLUSION: This is the largest consecutive series of BCR total knee arthroplasties using the modern-day implant design with 1-year follow-up in the United States. The results of our study show great patient-reported satisfaction, function, and short-term outcomes for patients implanted with the new BCR design.

A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis.

The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1ß after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.