A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee.

BACKGROUND: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. PURPOSE: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. RESULTS: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, -1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, -0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). CONCLUSION: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. REGISTRATION: International Standard Randomised Controlled Trial Number: 48911177.

AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture.

The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require data management plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices.

Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.

OBJECTIVE: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. METHODS: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. RESULTS: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). CONCLUSIONS: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. CLASSIFICATION OF EVIDENCE: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.

In vivo roughening of retrieved total knee arthroplasty femoral components.

BACKGROUND: Joint registry data highlights the higher rates of cumulative revision for younger patients undergoing TKR. One of the reasons associated with this higher revision rate may be due to the wear of the UHMWPE leading to loosening. Alternate bearing surfaces have been developed to address this problem; however, roughening of the metal bearing surface has not been demonstrated in vivo. METHOD: We recorded roughness measurements of retrieved femoral components. RESULTS: Average lateral condyle roughness was 0.032 µm, compared to control values of 0.020 µm, p=0.002; average medial condyle roughness was 0.028 µm, compared to a control value of 0.019, p<0.001. CONCLUSION: There was a small but statistically significant roughening of femoral components in vivo compared to controls. This may have important implications for aseptic loosening of knee arthroplasty components and the decision to use scratch resistant components.

ß-Catenin stabilization in skeletal muscles, but not in motor neurons, leads to aberrant motor innervation of the muscle during neuromuscular development in mice.

ß-Catenin, a key component of the Wnt signaling pathway, has been implicated in the development of the neuromuscular junction (NMJ) in mice, but its precise role in this process remains unclear. Here we use a ß-catenin gain-of-function mouse model to stabilize ß-catenin selectively in either skeletal muscles or motor neurons. We found that ß-catenin stabilization in skeletal muscles resulted in increased motor axon number and excessive intramuscular nerve defasciculation and branching. In contrast, ß-catenin stabilization in motor neurons had no adverse effect on motor innervation pattern. Furthermore, stabilization of ß-catenin, either in skeletal muscles or in motor neurons, had no adverse effect on the formation and function of the NMJ. Our findings demonstrate that ß-catenin levels in developing muscles in mice are crucial for proper muscle innervation, rather than specifically affecting synapse formation at the NMJ, and that the regulation of muscle innervation by ß-catenin is mediated by a non-cell autonomous mechanism.

The Stanmore knee arthrodesis prosthesis.

Knee arthrodesis is most commonly performed for failed total knee arthroplasty. Conventional arthrodesis techniques are associated with a high incidence of complications and are unsuitable in cases with extensive bone loss. We report our medium-term results using a custom-made cemented knee arthrodesis prosthesis in 10 patients with a mean follow-up of 56.4 months (range, 15-199 months). The prosthesis was implanted as a 1- or 2-stage procedure for infected revision knee arthroplasty or tumor endoprosthesis in 9 patients and as a primary procedure in 1 patient with angiosarcoma involving the knee extensor mechanism. The average combined femoral and tibial bone deficit was 170 mm (range, 56-220 mm). Implant survivorship was 90%. All patients with retained prosthesis had no evidence of residual infection or loosening and were able to mobilize independently. One prosthesis was revised though retained following a prosthetic fracture, and 1 patient underwent above-knee amputation for uncontrolled infection. We conclude that the Stanmore knee arthrodesis prosthesis provides reliable fusion in an otherwise difficult-to-treat group of patients.

Pre-operative Embolization of Primary and Secondary Bone Tumours is Safe and Effective: a Retrospective Study.

BACKGROUND: The surgical treatment of bone tumours can result in large peri-operative blood loss, due to their large sizes and hypervascularity. Pre-operative embolisation has been successfully used to downgrade vascularity, thus reducing peri-operative blood loss and its associated complications. METHODS: Pre-operative embolisation was successfully undertaken on twenty-six patients with a variety of primary and secondary bone tumours. RESULTS: Mean blood loss was 796 mL and we experienced no complications. CONCLUSION: Pre-operative arterial embolisation of large, richly vascular bone tumours in anatomically difficult positions, is a safe and effective method of downstaging vascularity and reducing blood loss.

Use of endoprosthetic diaphyseal replacement: a novel approach to management of extensive metastatic tumor of the midshaft radius.

We report the first use of an endoprosthetic diaphyseal replacement after the excision of a midshaft radial tumor. We present a rare case of a solitary midshaft radial metastasis in a 72-year-old gentleman who was treated 8 years earlier for primary renal cell carcinoma by radical nephrectomy. Follow-up for this patient was 25 months after implant insertion and at the latest review was pain-free. Functional scores for the elbow (using the Mayo Elbow Performance Score) and the wrist (using the Mayo Wrist Score) were 80 and 60, respectively, both out of 100. Use of a midshaft radial endoprosthesis provides a good functional outcome and symptom relief after extensive tumor resection, with regard to functional outcome and symptom relief.

Nonbacterial osteitis: a clinical, histopathological, and imaging study with a proposal for protocol-based management of patients with this diagnosis.

BACKGROUND: Nonbacterial osteitis (NBO), a term referring to sterile bone lesions with nonspecific histopathological features of inflammation, may be either unifocal or multifocal, acute (< or =6 months) or chronic, and recurrent. Only when the condition is chronic, recurrent, and multifocal is it appropriate to use the term chronic recurrent multifocal osteomyelitis (CRMO). We present our clinical experience as the largest reported series of children with NBO to date. METHODS: We report a retrospective clinical, histopathological, and radiological study of 41 children with nonbacterial osteitis. RESULTS: Of 41 children (2-16 years of age) diagnosed with NBO in our institution over the last 6 years, 21 (51%) had recurrent disease and 18 (44%) had multifocal disease. The most common bones affected were the clavicle, femur, and tibia (in order of decreasing prevalence) accounting for 44 (63%) of a total of 70 lesions. Only one individual had SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) and no other patients had evidence of bowel or skin disease. In the absence of evidence for an infective etiology, we recommend nonsteroidal anti-inflammatory agents as the firstline therapy and bisphosphonates only in cases of resistant disease. CONCLUSIONS: On the basis of our findings, we propose using a patient questionnaire and protocol for investigating and managing patients who present with NBO to orthopedic surgeons. We predict that this will benefit patients with this disorder by improving our knowledge of the presenting signs and symptoms and related disorders, rationalizing the therapeutic approach, and allowing us to learn about the natural history of the disease.

Bone remodeling around the tibial component of distal femoral expandable endoprosthesis.

Radiographs of 33 patients who had an expandable prosthesis inserted after tumor resection in the distal femur were evaluated. We hypothesized that, when a sleeve was present, there was greater stem migration and cortical reaction. The thickness of medial and lateral cortices of the tibia was measured at 6 months and on the last follow-up radiograph. The distance from the edge of the prosthesis to the cortical edge was also compared. When a sleeve was present, there was greater stem migration (P < .001) and a greater increase in lateral cortical thickness (P < .001). There was a higher revision rate when a sleeve was used, but this was not statistically significant. There was no difference in function according to the Toronto Extremity Salvage Score (TESS) between the 2 groups. This is the first study to demonstrate that the presence of a polyethylene sleeve is associated with a tendency for the tibial prosthesis to migrate laterally and cause a greater sclerotic reaction.

Use of a distal radius endoprosthesis following resection of a bone tumour: a case report.

Limited literature is available on the reconstruction of the distal radius using prosthetic replacement following resection of a bone tumour. We present the first reported case, in the English literature, of the use of an entirely metal endoprosthesis for the reconstruction of the distal radius. This case involves a 66-year-old male who was treated for giant cell tumour of the distal radius with surgical excision of the lesion and replacement of the defect using a predominantly titanium endoprosthesis. He was followed-up for 56 months following surgery and had a good functional outcome with no associated pain or complications. We propose that the use of a primarily titanium endoprosthesis for the reconstruction of a bone defect of the distal radius is a suitable alternative, providing good function of the forearm with satisfactory range of movement at the wrist and adequate pain relief.

Post-radiation sciatic neuropathy: a case report and review of the literature.

BACKGROUND: Post-radiation peripheral neuropathy has been reported in brachial and cervical plexuses and the femoral nerve. CASE PRESENTATION: We describe a patient who developed post-radiation sciatic neuropathy after approximately 3 years and discuss the pathophysiology, clinical course and treatment options available for the deleterious effects of radiation to peripheral nerves. CONCLUSION: This is the first case of post-radiation involvement of the sciatic nerve reported in the literature.

"Pseudosarcoma" in a pregnant woman.

BACKGROUND: Intravascular fasciitis (IVF) is a rare benign condition characterised by reactive myofibroblastic proliferation arising from the superficial or deep fascia and involving arteries and/or veins. It is a distinct variant of the more common condition of nodular fasciitis, which possesses similar clinical and histological features to IVF, but lacks vascular invasion. A thorough review of the literature revealed 26 reported cases of IVF. CASE PRESENTATION: We report a case of IVF in a 16-week pregnant lady affecting the hypothenar eminence of the hand associated with the ulnar artery. CONCLUSION: The characteristic involvement of muscular arteries and veins by reactive myofibroblastic proliferation in IVF suggests a malignant component and often leads to an inappropriate diagnosis for this benign condition. We propose that hormone-related changes associated with pregnancy may play an important role in the aetiopathogenesis of this myofibroblastic lesion.