surgical-perfusion-isolation-porcine-pancreas-for-islet

Surgical Perfusion and Isolation of the Porcine Pancreas for Islet Isolation

Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet ...

Washington University School of Medicine

Particle-induced periprosthetic osteolysis is the major cause for orthopedic implant failure. This failure is mediated mainly by the action of osteoclasts, the principal cells responsible for bone resorption and osteolysis. Therapeutic interventions to alleviate osteolysis have been focused on understanding and targeting mechanisms of osteoclastogenesis. The nuclear transcription factor NFAT is an essential terminal differentiation factor of osteoclastogenesis. This transcription factor is known to cooperate with c-jun/AP-1 in mediating RANKL-induced osteoclastogenesis. We have previously determined that RANKL is an essential cytokine mediator of particle-induced osteoclastogenesis, and that PMMA particles activate JNK and c-jun/AP-1 in bone marrow macrophages (osteoclast precursors). In the current study, we investigated the effect of PMMA particles on the NFAT signaling pathway in osteoclast precursor cells. Our findings point out that PMMA particles stimulate nuclear translocation of NFAT2 in wild-type osteoclast precursors, which is associated with increased osteoclastogenesis. More importantly, induction of osteoclastogenesis was selectively blocked in a dose-dependent fashion by the calcineurin inhibitors, Cyclosporine-A and FK506. Further, this activation was also blocked in a time-dependent fashion by the NFAT inhibitor VIVIT. Finally, we provide novel evidence that PMMA particles induce binding of NFAT2 and AP-1 proteins. Thus, our findings demonstrate that activation of the NFAT pathway in conjunction with MAP kinases is essential for basal and PMMA-stimulated osteoclastogenesis.

NFAT2 is an essential mediator of orthopedic particle-induced osteoclastogenesis.

Cytokines and growth factors mediate inflammatory osteolysis in response to particles released from bone implants. However, the mechanism by which this process develops is not entirely clear. Blood vessels and related factors may be required to deliver immune cells and soluble factors to the injury site. Therefore, in the current study we investigated if, vascular endothelial growth factor (VEGF), which is required for angiogenesis, mediates polymethylmethacrylate (PMMA) particles-induced osteolysis. Using bone marrow derived macrophages (BMMs) and ST2 stromal cell line, we show that PMMA particles increase VEGF expression. Further, using a murine calvarial osteolysis model, we found that PMMA injection over calvaria induce significant increase in VEGF expression as well as new vessel formation, represented by von Willebrand factor (vWF) staining. Co-treatment using a VEGF-neutralizing antibody abrogated expression of vWF, indicating decreased angiogenesis. Finally, VEGF neutralizing antibody reduced expression of Tumor necrosis factor (TNF) and decreased osteoclastogenesis induced by PMMA particles in calvariae. This work highlights the significance of angiogenesis, specifically VEGF, as key driver of PMMA particle-induced inflammatory osteolysis, inhibition of which attenuates this response.

Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria.

The Patient-Reported Outcomes Measurement Information System (PROMIS) is increasingly used to assess patient health. The Bundled Payment for Care Improvement (BPCI) initiative for total hip arthroplasty (THA) was introduced to decrease costs and improve clinical care. We investigated differences between BPCI and non-BPCI THA patients and their PROMIS scores, along with its feasibility and responsiveness in these populations.

Is the Patient-Reported Outcome Measurement Information System Feasible in Bundled Payment for Care Improvement in Total Hip Arthroplasty Patients?

Routine surveillance of primary hip and knee arthroplasties has traditionally been performed with office follow-up visits at one year postoperatively. The value of these visits is unclear. The present study aims to determine the utility and burden of routine clinical follow-up at one year after primary arthroplasty to patients and providers.

The burden and utility of routine follow-up at one year after primary arthroplasty.

Several bundled payment plans, like the Bundled Payment for Care Improvement (BPCI) initiative for total joint arthroplasty, have been introduced to decrease costs and improve clinical care. Measuring clinical outcomes with efficient, standardized methodologies is essential to determine the relative value of total joint arthroplasty care. We investigated feasibility and responsiveness of the recently developed Patient-Reported Outcomes Measurement Information System (PROMIS) in total knee arthroplasty (TKA) patients.

Is the Patient-Reported Outcome Measurement Information System Feasible in Bundled Payment for Care Improvement Total Knee Arthroplasty Patients?

Periacetabular osteotomy (PAO) is a well-accepted treatment for acetabular dysplasia, but treatment success is not uniform. Concurrent hip arthroscopy has been proposed for select patients to address intraarticular abnormalities. The patient-reported outcomes, complications, and reoperations for concurrent arthroscopy and PAO to treat acetabular dysplasia remain unclear.

What Mid-term Patient-reported Outcome Measure Scores, Reoperations, and Complications Are Associated with Concurrent Hip Arthroscopy and Periacetabular Osteotomy to Treat Dysplasia with Associated Intraarticular Abnormalities?

The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed by the National Institutes of Health to collect outcome data in rapid dynamic fashion on electronic platforms. The potential role of PROMIS in monitoring pain and function in young total hip arthroplasty (THA) patients has been under-investigated. The purpose of this study is to investigate correlation between PROMIS Physical Function (PF) and PROMIS Pain Interference (PI) and legacy scores with similar considerations.

Does the Patient-Reported Outcomes Measurement Information System Correlate to Legacy Scores in Measuring Physical Health in Young Total Hip Arthroplasty Patients?

Hip microinstability remains poorly-defined but increasingly diagnosed in the setting of borderline dysplasia (LCEA 20-25°), soft tissue laxity, or following unrepaired arthroscopic capsulotomy. While hip microinstability is com-monly treated with arthroscopic capsular plication with short-term outcomes reported, this procedure has been performed open for some time. The purpose of current study was to assess the durability of outcomes of combined arthroscopy and open capsular plication in treating symptomatic hip microinstability at mid-term follow-up.

Mid-Term Outcomes of Combined Hip Arthroscopy and Limited Open Capsular Plication in the Non-Dysplastic Hip.

Femoroacetabular impingement (FAI) is one of the most common causes of hip osteoarthritis, yet the factors controlling disease progression are poorly understood.

Factors Associated With Disease Progression in the Contralateral Hip of Patients With Symptomatic Femoroacetabular Impingement: A Minimum 5-Year Analysis.

Mental health is becoming increasingly important in patient outcomes. The patient reported outcome measurement information system (PROMIS) was developed by the NIH to collect outcome data in rapid dynamic fashion on electronic platforms. The potential role of PROMIS in monitoring young total hip arthroplasty (THA) patients is under-investigated. The purpose of this study is to investigate correlations between PROMIS Depression or Anxiety with SF-12 mental component score.

Does the Patient-Reported Outcomes Measurement Information System Correlate to Legacy Scores in Measuring Mental Health in Young Total Hip Arthroplasty Patients?

Article	Year
NFAT2 is an essential mediator of orthopedic particle-induced osteoclastogenesis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society\| PubMed ID: 18655139	2008
Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria. Bone\| PubMed ID: 30904629	2019
Is the Patient-Reported Outcome Measurement Information System Feasible in Bundled Payment for Care Improvement in Total Hip Arthroplasty Patients? The Journal of arthroplasty\| PubMed ID: 31932103	2020
The burden and utility of routine follow-up at one year after primary arthroplasty. The bone & joint journal\| PubMed ID: 32600196	2020
Is the Patient-Reported Outcome Measurement Information System Feasible in Bundled Payment for Care Improvement Total Knee Arthroplasty Patients? The Journal of arthroplasty\| PubMed ID: 32933798	2021
What Mid-term Patient-reported Outcome Measure Scores, Reoperations, and Complications Are Associated with Concurrent Hip Arthroscopy and Periacetabular Osteotomy to Treat Dysplasia with Ass... Clinical orthopaedics and related research\| PubMed ID: 33300755	2021
Does the Patient-Reported Outcomes Measurement Information System Correlate to Legacy Scores in Measuring Physical Health in Young Total Hip Arthroplasty Patients? The Journal of arthroplasty\| PubMed ID: 34332792	2021
Mid-Term Outcomes of Combined Hip Arthroscopy and Limited Open Capsular Plication in the Non-Dysplastic Hip. The Iowa orthopaedic journal\| PubMed ID: 34552415	2021
Factors Associated With Disease Progression in the Contralateral Hip of Patients With Symptomatic Femoroacetabular Impingement: A Minimum 5-Year Analysis. The American journal of sports medicine\| PubMed ID: 36018805	2022
Does the Patient-Reported Outcomes Measurement Information System Correlate to Legacy Scores in Measuring Mental Health in Young Total Hip Arthroplasty Patients? The Iowa orthopaedic journal\| PubMed ID: 36601225	2022

Wahid Abu-Amer

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