Quantitative biomarker analysis of synovial gene expression by real-time PCR

Synovial biomarker analysis in rheumatoid arthritis can be used to evaluate drug effect in clinical trials of novel therapeutic agents. Previous studies of synovial gene expression for these studies have mainly relied on histological methods including immunohistochemistry and in situ hybridization. To increase the reliability of mRNA measurements on small synovial tissue samples, we developed and validated real time quantitative PCR (Q-PCR) methods on biopsy specimens. RNA was isolated from synovial tissue and cDNA was prepared. Cell-based standards were prepared from mitogen-stimulated peripheral blood mononuclear cells. Real time PCR was performed using TaqMan chemistry to quantify gene expression relative to the cell-based standard. Application of the cellular standard curve method markedly reduced intra- and inter-assay variability and corrected amplification efficiency errors compared with the C(t) method. The inter-assay coefficient of variation was less than 25% over time. Q-PCR methods were validated by demonstrating increased expression of IL-1β and IL-6 expression in rheumatoid arthritis synovial samples compared with osteoarthritis synovium. Based on determinations of sampling error and coefficient of variation, twofold differences in gene expression in serial biopsies can be detected by assaying approximately six synovial tissue biopsies from 8 to 10 patients. These data indicate that Q-PCR is a reliable method for determining relative gene expression in small synovial tissue specimens. The technique can potentially be used in serial biopsy studies to provide insights into mechanism of action and therapeutic effect of new anti-inflammatory agents

Outcomes of Salvage Arthrodesis and Arthroplasty for Failed Osteochondral Allograft Transplantation of the Ankle

Background: Osteochondral allograft (OCA) transplantation is a useful treatment for posttraumatic ankle arthritis in young patients, but failure rates are high and reoperations are not uncommon. The aim of this study was to evaluate the outcomes of failed ankle OCA transplantation converted to ankle arthrodesis (AA) or total ankle arthroplasty (TAA). Methods: We evaluated 24 patients who underwent salvage procedures (13 AA and 11 TAA) after primary failed ankle OCA transplantation. Reoperations were assessed. Failure of the salvage procedure was defined as an additional surgery that required a revision AA/TAA or amputation. Evaluation among nonfailing ankles included the American Academy of Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM), pain, and satisfaction. Results: In the salvage AA cohort, 3 patients were classified as failures (2 revision AA and 1 amputation). The 10 nonfailing patients had a mean follow-up of 7.4 years. Eighty-eight percent were satisfied with the procedure, but 63% reported continued problems with their ankle (eg, pain, swelling, stiffness). Mean pain level was 1.9 and AAOS-FAM core score was 83±13. In the salvage TAA cohort, 2 patients were classified as failures (both revision TAA). The 9 nonfailing patients had a mean follow-up of 3.8 years. Fifty percent were satisfied with the procedure, but 40% reported continued problems with their ankle. The mean pain level was 1.3, and the median AAOS-FAM core score was 82±26. Conclusion: Revision and reoperation rates for salvage procedures following failed OCA transplantation of the ankle are higher compared to published data for primary AA and TAA procedures. However, we believe OCA transplantation can serve as an interim procedure for younger patients with advanced ankle joint disease who may not be ideal candidates for primary AA or TAA at the time of initial presentation. Level of Evidence: Level IV, case series

1861-11-02 D.M. Howard, David Bugbee, and William Arnold invite Governor Washburn to event for John Goddard

https://digitalmaine.com/cw_me_1st_cav/1168/thumbnail.jp

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint

© The Author(s) 2020. Background: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. Purpose: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. Study Design: Consensus statement. Methods: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. Results: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. Conclusion: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors

A robust high speed serial PHY architecture with feed-forward correction clock and data recovery

This paper describes a robust architecture for high speed serial links for embedded SoC applications, implemented to satisfy the 1.5 Gb/s and 3 Gb/s Serial-ATA PHY standards. To meet the primary design requirements of a sub-system that is very tolerant of device variability and is easy to port to smaller nanometre CMOS technologies, a minimum of precision analog functions are used. All digital functions are implemented in rail-to-rail CMOS with maximum use of synthesized library cells. A single fixed frequency low-jitter PLL serves the transmit and receive paths in both modes so that tracking and lock time issues are eliminated. A new oversampling CDR with a simple feed-forward error correction scheme is proposed which relaxes the requirements for the analog front-end as well as for the received signal quality. Measurements show that the error corrector can almost double the tolerance to incoming jitter and to DC offsets in the analog front-end. The design occupies less than 0.4 mm2 in 90 nm CMOS and consumes 75 m

Outliers in Osteoarthritic Knees Concerning Distal Femoral Valgus Angle and Femoral Rotation Angle Reply

Scripps Clin, Shiley Ctr Orthopaed Res & Educ, La Jolla, CA 92037 USABalikesir Univ, Dept Orthopaed Surg, Balikesir, TurkeyUniv Fed Sao Paulo, Dept Orthopaed Surg, Sao Paulo, BrazilUniv Calif San Diego, Dept Orthopaed Surg, Sch Med, La Jolla, CA 92093 USAScripps Clin, Dept Orthopaed Surg, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USAUniv Fed Sao Paulo, Dept Orthopaed Surg, Sao Paulo, BrazilWeb of Scienc