No abstract

Therapeutic study, Level V (expert opinion). See the Guidelines for Authors for a complete description of levels of evidence.

Aging or injury leads to degradation of the cartilage matrix and the development of osteoarthritis (OA). Because of a paucity of single-cell studies of OA cartilage, little is known about the interpatient variability in its cellular composition and, more importantly, about the cell subpopulations that drive the disease. Here, we profiled healthy and OA cartilage samples using mass cytometry to establish a single-cell atlas, revealing distinct chondrocyte progenitor and inflammation-modulating subpopulations. These rare populations include an inflammationamplifying (Inf-A) population, marked by interleukin-1 receptor 1 and tumor necrosis factor receptor II, whose inhibition decreased inflammation, and an inflammation-dampening (Inf-D) population, marked by CD24, which is resistant to inflammation. We devised a pharmacological strategy targeting Inf-A and Inf-D cells that significantly decreased inflammation in OA chondrocytes. Using our atlas, we stratified patients with OA in three groups that are distinguished by the relative proportions of inflammatory to regenerative cells, making it possible to devise precision therapeutic approaches. RESULTS High-dimensional mass cytometry-based profiling of normal and OA cartilageToward our goal of profiling rare stem/progenitor-like populations within normal and OA cartilage, we used cyTOF, a mass spectrometrybased high-dimensional method for single-cell detection of isotopelabeled antibodies (Fig. 1A) (8). While cyTOF panels have to be preselected for each experiment, this technique provides the advantage , Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage.

Purpose The Covid-19 pandemic has disrupted health care systems all over the world. Elective surgical procedures have been postponed and/or cancelled. Consensus is, therefore, required related to the factors that need to be in place before elective surgery, including hip and knee replacement surgery, which is restarted. Entirely new pathways and protocols need to be worked out. Methods A panel of experts from the European Hip Society and European Knee Association have agreed to a consensus statement on how to reintroduce elective arthroplasty surgery safely. The recommendations are based on the best available evidence and have been validated in a separate survey. Results The guidelines are based on five themes: modification and/or reorganisation of hospital wards. Restrictions on orthopaedic wards and in operation suite(s). Additional disinfection of the environment. The role of ultra-clean operation theatres. Personal protective equipment enhancement. Conclusion Apart from the following national and local guidance, protocols need to be put in place in the patient pathway for primary arthroplasty to allow for a safe return.

Purpose The COVID-19 pandemic has disrupted the health care system around the entire globe. A consensus is needed about resuming total hip and knee procedures. The European Hip Society (EHS) and the European Knee Association (EKA) formed a panel of experts that have produced a consensus statement on how the safe re-introduction of elective hip and knee arthroplasty should be undertaken. Methods A prospective online survey was done among members of EHS and EKA. The survey consisted of 27 questions. It includes basic information on demographics and details the participant's agreement with each recommendation. The participant could choose among three options (agree, disagree, abstain). Recommendations focussed on pre-operative, perioperative, and post-operative handling of patients and precautions. Results A total of 681 arthroplasty surgeons participated in the survey, with 479 fully completing the survey. The participants were from 44 countries and 6 continents. Apart from adhering to National and Local Guidelines, the recommendations concerned how to make elective arthroplasty safe for patients and staff. Conclusion The survey has shown good-to-excellent agreement of the participants with regards to the statements made in the recommendations for the safe return to elective arthroplasty following the first wave of the COVID-19 pandemic.

Total knee arthroplasty is a traditional surgical procedure aimed to restore function and relief pain in patients with severe knee osteoarthritis. Recently, many medial pivot knee systems were deigned to replicate the normal knee kinematic: a highly congruent medial compartment and a less conforming lateral tibial plateau characterize these devices. A slightly asymmetric soft tissue balancing is mandatory using medial pivot designs to obtain a correct and physiological knee biomechanics leading good outcomes and long survival rates. This article describes a new surgical technique using a modern third generation TKA design combined with wireless load-sensor tibial trials to improve the correct knee load balancing with a minimal conformity of the polyethylene insert. The use of wireless load-sensing tibial trials has several benefits: it is an intraoperative, objective and dynamic tool allowing surgeons to optimize in real time soft tissue balancing. The meaning of a "truly balanced knee" is still a controversial issue in the current literature.

Background The Infiltration between the Popliteal Artery and Capsule of the Knee (IPACK) block is a new anesthesiologist- administered analgesic technique for controlling posterior knee pain that has not yet been well studied in total knee arthroplasty (TKA) patients. We compared pain outcomes in TKA patients before and after implementation of the IPACK with the hypothesis that patients receiving IPACK blocks will report lower pain scores on postoperative day (POD) 0 than non-IPACK patients. Methods With Institutional Review Board approval, we retrospectively reviewed data for consecutive TKA patients by a single surgeon 4 months before (PRE) and after (POST) IPACK implementation. All TKA patients received adductor canal catheters and peri-operative multimodal analgesia. The primary outcome was pain on POD 0. Other outcomes were daily pain scores, opioid consumption, ambulation distance, length of stay, and adverse events within 30 days. Results Post-implementation, 48/50 (96%) of TKA patients received an IPACK block, and they were compared with 32 patients in the PRE group. On POD 0, the lowest pain score (median [10th–90th percentiles]) was significantly lower for the POST group compared to the PRE group (0 [0–4.3] vs. 2.5 [0–7]; P = 0.003). The highest patient-reported pain scores on any POD were similar between groups with no differences in other outcomes. Conclusions Within a multimodal analgesic protocol, addition of IPACK blocks decreased the lowest pain scores on POD 0. Although other outcomes were unchanged, there may be a role for new opioid-sparing analgesic techniques, and changing clinical practice change can occur rapidly.

Osteoarthritis (OA) is a degenerative disease of the joint, which results in pain, loss of mobility, and, eventually, joint replacement. Currently, no disease-modifying drugs exist, partly because of the multiple levels at which cartilage homeostasis is disrupted. Recent studies have highlighted the importance of epigenetic dysregulation in OA, sparking interest in the epigenetic modulation for this disease. In our previous work, we characterized a fivefold increase in cytosine hydroxymethylation (5hmC), an oxidized derivative of cytosine methylation (5mC) associated with gene activation, accumulating at OA-associated genes. To test the role of 5hmC in OA, here, we used a mouse model of surgically induced OA and found that OA onset was accompanied by a gain of ~40,000 differentially hydroxymethylated sites before the notable histological appearance of disease. We demonstrated that ten-eleven-translocation enzyme 1 (TET1) mediates the 5hmC deposition because 98% of sites enriched for 5hmC in OA were lost in Tet1−/− mice. Loss of TET1-mediated 5hmC protected the Tet1−/− mice from OA development, including degeneration of the cartilage surface and osteophyte formation, by directly preventing the activation of multiple OA pathways. Loss of TET1 in human OA chondrocytes reduced the expression of the matrix metalloproteinases MMP3 and MMP13 and multiple inflammatory cytokines. Intra-articular injections of a dioxygenases inhibitor, 2-hydroxyglutarate, on mice after surgical induction of OA stalled disease progression. Treatment of human OA chondrocytes with the same inhibitor also phenocopied TET1 loss. Collectively, these data demonstrate that TET1-mediated 5hmC deposition regulates multiple OA pathways and can be modulated for therapeutic intervention.