Cost-Effectiveness of Cement Augmentation Versus No Augmentation for the Fixation of Unstable Trochanteric Fractures

Background:A previous randomized controlled trial (RCT) demonstrated a trend toward a reduced risk of implant-related revision surgery following fixation with use of a Proximal Femoral Nail Antirotation (PFNA) with TRAUMACEM V+ Injectable Bone Cement augmentation versus no augmentation in patients with unstable trochanteric fractures. To determine whether this reduced risk may result in long-term cost savings, the present study assessed the cost-effectiveness of TRAUMACEM V+ cement augmentation versus no augmentation for the fixation of unstable trochanteric fractures from the German health-care payer's perspective.Methods:The cost-effectiveness model comprised 2 stages: a decision tree simulating clinical events, costs, and utilities during the first year after the index procedure and a Markov model extrapolating clinical events, costs, and utilities over the patient's lifetime. Sources of model parameters included the previous RCT, current literature, and administrative claims data. Outcome measures were incremental costs (in 2020 Euros), incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model uncertainty was assessed with deterministic and probabilistic sensitivity analyses.Results:The base-case analysis showed that fixation with cement augmentation was the dominant strategy as it was associated with cost savings (50.3/patient) and QALY gains (0.01 QALY/patient). Major influential parameters for the ICER were the utility of revision, rates of revision surgery within the first year after fixation surgery, and the costs of augmentation and revision surgery. Probabilistic sensitivity analyses demonstrated that estimates of cost savings were more robust than those of increased QALYs (66.4% versus 52.7% of the simulations). For a range of willingness-to-pay thresholds from 0 to 50,000, the probability of fixation with cement augmentation being cost-effective versus no augmentation remained above 50%.Conclusions:Fixation with use of cement augmentation dominated fixation with no augmentation for unstable trochanteric fractures, resulting in cost savings and QALY gains. Given the input parameter uncertainties, future analyses are warranted when long-term costs and effectiveness data for cement augmentation are available.Level of Evidence:Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence

A new technique for seeding chondrocytes onto solvent-preserved human meniscus using the chemokinetic effect of recombinant human bone morphogenetic protein-2

Many investigators are currently studying the use of decellularized tissue allografts from human cadavers as scaffolds onto which patients’ cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. However, it is difficult to seed cells onto very dense regular connective tissue which has few interstitial spaces. Here, we discuss the development of a chemotactic cell seeding technique using solvent-preserved human meniscus. A chemokinetic response to recombinant human bone morphogenetic protein-2 (rhBMP-2) was observed in a monolayer culture of primary chondrocytes derived from femoral epiphyseal cartilage of 2-day-old rats. The rhBMP-2 significantly increased their migration upto 10 ng/ml in a dose-dependent manner. When tested with solvent-preserved human meniscus as a scaffold, which has few interstitial spaces, rhBMP-2 was able to induce chondrocytes to migrate into the meniscus. After a 3-week incubation, newly-formed cartilaginous extracellular matrix was synthesized by migrated chondrocytes throughout the meniscus, down to a depth of 3 mm. These findings demonstrate that rhBMP-2 may be a natural chemokinetic factor in vivo, which induces migration of proliferative chondrocytes into the narrow interfibrous spaces. Our results suggest a potential application of rhBMP-2 for the designed distribution of chondrocytes into a scaffold to be used for tissue engineering

Endothelial cells enhance the in vivo bone-forming ability of osteogenic cell sheets

Addressing the problem of vascularization is of vital importance when engineering three-dimensional (3D) tissues. Endothelial cells are increasingly used in tissue-engineered constructs to obtain prevascularization and to enhance in vivo neovascularization. Rat bone marrow stromal cells were cultured in thermoresponsive dishes under osteogenic conditions with human umbilical vein endothelial cells (HUVECs) to obtain homotypic or heterotypic cell sheets (CSs). Cells were retrieved as sheets from the dishes after incubation at 20 °C. Monoculture osteogenic CSs were stacked on top of homotypic or heterotypic CSs, and subcutaneously implanted in the dorsal flap of nude mice for 7 days. The implants showed mineralized tissue formation under both conditions. Transplanted osteogenic cells were found at the new tissue site, demonstrating CS bone-inductive effect. Perfused vessels, positive for human CD31, confirmed the contribution of HUVECs for the neovascularization of coculture CS constructs. Furthermore, calcium quantification and expression of osteocalcin and osterix genes were higher for the CS constructs, with HUVECs demonstrating the more robust osteogenic potential of these constructs. This work demonstrates the potential of using endothelial cells, combined with osteogenic CSs, to increase the in vivo vascularization of CS-based 3D constructs for bone tissue engineering purposes.We would like to acknowledge Mariana T Cerqueira for the illustration in Figure 1. This study was supported by Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology 'Cell Sheet Tissue Engineering Center (CSTEC)' and the Global CUE program, the Multidisciplinary Education and Research Center for Regenerative Medicine (MERCREM), from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Financial support to RP Pirraco by the Portuguese Foundation for Science and Technology (FCT) through the PhD Grant SFRH/BD/44893/2008 is also acknowledged

Kinetochore fiber formation in animal somatic cells : dueling mechanisms come to a draw

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Chromosoma 114 (2005): 310-318, doi:10.1007/s00412-005-0028-2.The attachment to and movement of a chromosome on the mitotic spindle is mediated by the formation of a bundle of microtubules (MTs) that tethers the kinetochore on the chromosome to a spindle pole. The origin of these “kinetochore fibers” (K-fibers) has been investigated for over 125 years. As noted in 1944 by Schrader, there are only three possible ways to form a K-fiber: either it a) grows from the pole until it contacts the kinetochore; b) grows directly from the kinetochore; or c) it forms as a result of an interaction between the pole and the chromosome. Since Schrader’s time it has been firmly established that K-fibers in centrosome-containing animal somatic cells form as kinetochores capture MTs growing from the spindle pole (route a). It is now similarly clear that in cells lacking centrosomes, including plants and many animal oocytes, K-fibers “self-assemble” from MTs generated by the chromosomes (route b). Can animal somatic cells form K-fibers in the absence of centrosomes by the “self-assembly” pathway? In 2000 the answer to this question was shown to be a resounding “yes”. With this result, the next question became whether the presence of a centrosome normally suppresses K-fiber self-assembly, or if this route works concurrently with centrosome-mediated K-fiber formation. This question, too, has recently been answered: observations on untreated live animal cells expressing GFP-tagged tubulin clearly show that kinetochores can nucleate the formation of their associated MTs in the presence of functional centrosomes. The concurrent operation of these two “dueling” routes for forming K-fibers in animals helps explain why the attachment of kinetochores and the maturation of K-fibers occur as quickly as it does on all chromosomes within a cell.The work is sponsored by NIH grant GMS 40198

A biomaterials approach to influence stem cell fate in injectable cell-based therapies

Background Numerous stem cell therapies use injection-based administration to deliver high-density cell preparations. However, cell retention rates as low as 1% have been observed within days of transplantation. This study investigated the effects of varying administration and formulation parameters of injection-based administration on cell dose recovery and differentiation fate choice of human mesenchymal stem cells. Methods The impact of ejection rate via clinically relevant Hamilton micro-syringes and biomaterial-assisted delivery was investigated. Cell viability, the percentage of cell dose delivered as viable cells, proliferation capacity as well as differentiation behaviour in bipotential media were assessed. Characterisation of the biomaterial-based cell carriers was also carried out. Results A significant improvement of in-vitro dose recovery in cells co-ejected with natural biomaterials was observed, with ejections within 2% (w/v) gelatin resulting in 87.5 ± 14% of the cell dose being delivered as viable cells, compared to 32.2 ± 19% of the dose ejected in the commonly used saline vehicle at 10 μl/min. Improvement in cell recovery was not associated with the rheological properties of biomaterials utilised, as suggested by previous studies. The extent of osteogenic differentiation was shown to be substantially altered by choice of ejection rate and cell carrier, despite limited contact time with cells during ejection. Collagen type I and bone-derived extracellular matrix cell carriers yielded significant increases in mineralised matrix deposited at day 21 relative to PBS. Conclusions An enhanced understanding of how administration protocols and biomaterials influence cell recovery, differentiation capacity and choice of fate will facilitate the development of improved administration and formulation approaches to achieve higher efficacy in stem cell transplantation

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Evaluation of Cost, Payments, Healthcare Utilization, and Perioperative and Post-Operative Outcomes of Patients Treated with Posterior Lumbar Spinal Surgery Using Open versus Minimally Invasive Surgical Approaches

Chantal E Holy,1,* Katherine A Corso,1,* Dawn E Bowden,2 Michael J Erb,2 Jill R Ruppenkamp,1 Sandra Coombs,3 John B Pracyk3 1Johnson & Johnson Medical Devices Companies, Medical Device Epidemiology and Real World Data Sciences, New Brunswick, NJ, USA; 2Johnson & Johnson Medical Devices Companies, Health Economics and Market Access, Raynham, MA, USA; 3DePuy Synthes, Raynham, MA, USA*These authors contributed equally to this workCorrespondence: Katherine A CorsoJohnson & Johnson Medical Devices Companies, Medical Device Epidemiology and Real World Data Sciences, 410 George Street, New Brunswick, NJ, 08901, USATel +1 508 977 6696Email [email protected]: Minimally invasive surgery (MIS) of the spine has been associated with favorable outcomes compared to open surgery. This study evaluated matched cohorts treated with MIS versus open posterior lumbar fusion for costs, payments, healthcare utilization and outcomes.Patients and Methods: This study used the Premier Healthcare and IBM® MarketScan® Commercial and Medicare Databases. Patients with posterior lumbar fusion from 2015 to 2018 were identified and categorized as “Open” or “MIS”. Cohorts were matched on patient and provider characteristics. Perioperative complications, hospital costs, healthcare utilization and post-operative outcomes and payments to providers were analyzed. Statistical significance was evaluated using T-tests and chi-square tests.Results: After matching, 2,388 Open and 796 MIS from PHD, and 415 Open and 83 MIS from MarketScan were included. Statistically significant differences between MIS versus Open were found for index hospital costs, $29,181 (SD:$14,363) versus $27,616 (SD:$13,822), p=0.01; length of stay, 2.94 (SD: 2.10) versus 3.15 (SD: 2.03) days, p=0.01; perioperative urinary tract infection, 1.01% and 2.09% (p=0.05); and 30-day risk of hematoma/hemorrhage, 19.28% versus 8.43%, p=0.02. There were observed, but statistically non-significant differences in additional perioperative or post-operative complications, home discharge, 90-day all-cause and spine-related readmission, and 90-day post-operative payments.Conclusion: Compared to Open, patients that underwent MIS had statistically significant lower length of stay, lower perioperative UTI, greater hospital costs, and higher 30-day risk of hematoma/hemorrhage. The differences observed in post-operative complications and payments and readmissions warrant further investigation in larger matched cohorts.Keywords: minimally invasive surgical procedures, database, spine, lumbar vertebrae, propensity score, health services research, health care cost