High in-vivo accuracy of a novel robotic-arm-assisted system for total knee arthroplasty.

PURPOSE: Robotic-assisted total knee arthroplasty (TKA) has been shown to improve the accuracy and precision of bony resections and implant position. However, the in vivo accuracy of the full surgical workflow has not been widely reported. The primary objective of this study is to determine the accuracy and precision of a robotic-arm-assisted system throughout the intraoperative workflow. METHODS: This was a retrospective cohort study of adult patients who underwent primary TKA with various workflows and alignment targets by three arthroplasty-trained surgeons with previous experience using the ROSA® Knee System (Zimmer Biomet) over a 3-month follow-up period. Accuracy and precision were determined by measuring the difference between various workflow time points, including the final preoperative plan (PP), robot-validated (RV) resection angle and postoperative radiographs (PR). The absolute mean difference between the measurements determined accuracy, and the standard deviation represented precision. The lateral distal femoral angle, medial proximal tibial angle, femoral flexion angle and tibial slope were measured on postoperative coronal long-leg radiographs and true short-leg lateral radiographs. RESULTS: A total of 77 patients were included in the final analyses. The accuracy for the coronal femoral angle was 1.62 ± 1.11°, 0.75 ± 0.79° and 1.96 ± 1.29° for the differences between PP and PR, PP and RV and RV and PR. The tibial coronal accuracy was 1.44 ± 1.03°, 0.81 ± 0.67° and 1.57 ± 1.14° for PP/PR, PP/RV and RV/PR, respectively. Femoral flexion accuracy was 1.39 ± 1.05°, 0.83 ± 0.59° and 1.81 ± 1.21° for PP/PR, PP/RV and RV/PR, respectively. Tibial slope accuracy was 0.99 ± 0.72°, 1.19 ± 0.87° and 1.63 ± 1.11°, respectively. The proportion of patients within 3° was 93.2%, 95.3%, 97.3% and 94.6% for the distal femur, proximal tibia, femoral flexion and tibial slope angles when the final intraoperative plan was compared to PRs. No patients had a postoperative complication at the final follow-up. CONCLUSIONS: The ROSA Knee System has acceptable accuracy and precision of coronal and sagittal plane resections with few outliers at various steps throughout the platform's entire workflow in vivo. LEVEL OF EVIDENCE: Level III.

Identification of protective and 'at risk' HLA genotypes for the development of pseudotumours around metal-on-metal hip resurfacings.

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. 'Controls' were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two 'at risk' alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.

Computable Guidelines and Clinical Decision Support for Cervical Cancer Screening and Management to Improve Outcomes and Health Equity.

Cervical cancer is highly preventable when precancerous lesions are detected early and appropriately managed. However, the complexity of and frequent updates to existing evidence-based clinical guidelines make it challenging for clinicians to stay abreast of the latest recommendations. In addition, limited availability and accessibility to information technology (IT) decision supports make it difficult for groups who are medically underserved to receive screening or receive the appropriate follow-up care. The Centers for Disease Control and Prevention (CDC), Division of Cancer Prevention and Control (DCPC), is leading a multiyear initiative to develop computer-interpretable ("computable") version of already existing evidence-based guidelines to support clinician awareness and adoption of the most up-to-date cervical cancer screening and management guidelines. DCPC is collaborating with the MITRE Corporation, leading scientists from the National Cancer Institute, and other CDC subject matter experts to translate existing narrative guidelines into computable format and develop clinical decision support tools for integration into health IT systems such as electronic health records with the ultimate goal of improving patient outcomes and decreasing disparities in cervical cancer outcomes among populations that are medically underserved. This initiative meets the challenges and opportunities highlighted by the President's Cancer Panel and the President's Cancer Moonshot 2.0 to nearly eliminate cervical cancer.

Arthroscopic correction of femoroacetabular impingement improves athletic performance in male athletes.

PURPOSE: To measure the changes in athletic performance in athletes treated arthroscopically for femoroacetabular impingement and compare results to a matched controlled athletic cohort, over a 1-year period. METHODS: Male athletes scheduled for arthroscopic correction of symptomatic FAI were recruited and tested (pre-operatively and 1-year postsurgery) for measures of athletic performance which included acceleration (10-m sprint), change of direction speed (CODS), squatting depth, and reactive strength index (RSI). The FAI group was compared to a matched, healthy, control group who were tested at baseline and 1 year later with no disruption to their regular training or competition status; the prevalence of anterior groin pain during testing in either group was recorded. Hip range of motion (ROM) was also measured for both groups at baseline and at 1 year in the FAI group to look for change following intervention. RESULTS: Prior to surgery, the FAI group were slower than the control group (p < 0.001) for acceleration (3% slower) and CODS (10% slower). At 1 year, 91% of the FAI group returned to full competition at an average time of 17 weeks, while substantial reductions in pain were also noted during acceleration (51-6%, p = 0.004), CODS (62-8%, p = 0.001), and squat test (38-8%, p = 0.003). Significant improvements were seen in the FAI group for CODS (7%, p < 0.001) and squat depth measures (6%, p = 0.004) from baseline to 1 year (significant time × group interaction effects were noted for these also). The changes in performance in the control group over time were non-significant across all of the measures (n.s.). At 1-year postsurgery, there were no statistically significant differences between the groups for any of the athletic measures. There was a significant and clinically important improvement in range of hip motion in the FAI group at 1-year postsurgery (p < 0.05). CONCLUSION: Symptomatic FAI causes substantial reductions in athletic performance compared to healthy competitors placing these athletes at a distinct performance disadvantage. The results from the current study demonstrate that arthroscopic correction (including labral repair) in athletes with symptomatic FAI, reduces pain and restores athletic performance to a level which is comparable to healthy athletes, at 1 year. LEVEL OF EVIDENCE: II.

Radiofrequency ablation of osteoid osteoma: Aiming for excellent outcomes in an Australasian context.

INTRODUCTION: To report a series of patients with osteoid osteoma treated by radiofrequency ablation in whom no complications or recurrences occurred. METHODS: Over a 13-year period, 32 consecutive patients with osteoid osteoma were treated by radiofrequency ablation in an Australasian teaching centre. RESULTS: All patients had resolution of symptoms with no complication or recurrence. CONCLUSIONS: This series is further evidence for the use of radiofrequency ablation as the primary treatment for osteoid osteoma.

Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency.

Parathyroid hormone (PTH) anabolic osteoporosis therapy is intrinsically limited by unknown mechanisms. We previously showed that disabling the transcription factor Nmp4/CIZ in mice expanded this anabolic window while modestly elevating bone resorption. This enhanced bone formation requires a lag period to materialize. Wild-type (WT) and Nmp4-knockout (KO) mice exhibited equivalent PTH-induced increases in bone at 2 weeks of treatment, but by 7 weeks, the null mice showed more new bone. At 3-week treatment, serum osteocalcin, a bone formation marker, peaked in WT mice, but continued to increase in null mice. To determine if 3 weeks is the time when the addition of new bone diverges and to investigate its cellular basis, we treated 10-week-old null and WT animals with human PTH (1-34) (30 µg/kg/day) or vehicle before analyzing femoral trabecular architecture and bone marrow (BM) and peripheral blood phenotypic cell profiles. PTH-treated Nmp4-KO mice gained over 2-fold more femoral trabecular bone than WT by 3 weeks. There was no difference between genotypes in BM cellularity or profiles of several blood elements. However, the KO mice exhibited a significant elevation in CFU-F cells, CFU-F(Alk)(Phos+) cells (osteoprogenitors), and a higher percentage of CFU-F(Alk)(Phos+) cells/CFU-F cells consistent with an increase in CD45-/CD146+/CD105+/nestin+ mesenchymal stem cell frequency. Null BM exhibited a 2-fold enhancement in CD8+ T cells known to support osteoprogenitor differentiation and a 1.6-fold increase in CFU-GM colonies (osteoclast progenitors). We propose that Nmp4/CIZ limits the PTH anabolic window by restricting the number of BM stem, progenitor, and blood cells that support anabolic bone remodeling.

Immortalization and characterization of osteoblast cell lines generated from wild-type and Nmp4-null mouse bone marrow stromal cells using murine telomerase reverse transcriptase (mTERT).

Intermittent parathyroid hormone (PTH) adds new bone to the osteoporotic skeleton; the transcription factor Nmp4/CIZ represses PTH-induced bone formation in mice and as a consequence is a potential drug target for improving hormone clinical efficacy. To explore the impact of Nmp4/CIZ on osteoblast phenotype, we immortalized bone marrow stromal cells from wildtype (WT) and Nmp4-knockout (KO) mice using murine telomerase reverse transcriptase. Clonal lines were initially chosen based on their positive staining for alkaline phosphatase and capacity for mineralization. Disabling Nmp4/CIZ had no gross impact on osteoblast phenotype development. WT and KO clones exhibited identical sustained growth, reduced population doubling times, extended maintenance of the mature osteoblast phenotype, and competency for differentiating toward the osteoblast and adipocyte lineages. Additional screening of the immortalized cells for PTH-responsiveness permitted further studies with single WT and KO clones. We recently demonstrated that PTH-induced c-fos femoral mRNA expression is enhanced in Nmp4-KO mice and in the present study we observed that hormone stimulated either an equivalent or modestly enhanced increase in c-fos mRNA expression in both primary null and KO clone cells depending on PTH concentration. The null primary osteoblasts and KO clone cells exhibited a transiently enhanced response to bone morphogenetic protein 2 (BMP2). The clones exhibited lower and higher expressions of the PTH receptor (Pthr1) and the BMP2 receptor (Bmpr1a, Alk3), respectively, as compared to primary cells. These immortalized cell lines will provide a valuable tool for disentangling the complex functional roles underlying Nmp4/CIZ regulation of bone anabolism.