A Unique Surgical Case of Ancient Calcified Intravascular Papillary Endothelial Hyperplasia in the Tibia with Knee Joint Osteoarthritis.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH) is a reactive lesion histopathologically characterized by papillary growth of vascular endothelial cells. IPEH is most commonly found in the skin and subcutaneous tissues of the head, neck, and extremities. Furthermore, it has been reported to occur in oral surgery, but its occurrence in bone is extremely rare. CASE PRESENTATION: We present the case of a 77-year-old man with a chief complaint of left knee arthralgia. The knee joint X-ray showed Kellgren-Lawrence grade 4 osteoarthritis and a mass lesion with decreased permeability within the bone in the medial part of the proximal tibia. Computerized tomography (CT) scan of the left knee showed a localized mass in the left proximal tibia with clear margins and granular internal calcification. The preoperative diagnosis was left knee osteoarthritis and a benign tumor of the left proximal tibia (enchondroma or hemangioma). The patient requested surgical treatment, so left total knee arthroplasty (TKA) and resection of the tumor were performed. The pathology revealed a rare intraosseous IPEH with marked calcification. CONCLUSIONS: Since intraosseous IPEH could not be considered from the clinical findings, the pathological diagnosis was the decisive factor. This report showed the world's first case of intraosseous IPEH with marked calcification. Similar to the calcification of intraosseous hemangiomas, we considered the possibility that, in IPEH, the thrombus may fibrosis and organize in concentric circles, causing necrosis at the center and resulting in calcification. TKA was performed on the degenerative knee joint with IPEH, and a good patient outcome was obtained.

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Bone formation at Ti-6Al-7Nb scaffolds consisting of 3D honeycomb frame and diamond-like carbon coating implanted into the femur of beagles.

We fabricated Ti-6Al-7Nb bone scaffolds with 5 mm diameter and 20 mm length comprise of a three-dimensional (3D) honeycomb frame structure of truncated octahedra created by selective laser sintering 3D printing. The honeycomb frame was then coated with 0.1 µm thick diamond-like carbon (DLC) to increase biocompatibility. A round rod of Ti-6Al-7Nb alloy (ASTM F1295) was as a control material. They were implanted into the femur bones of beagles to evaluate bone morphometrics and to investigate changes in the transcriptome of the new bone tissue using DNA microarray analysis and real-time polymerase chain reaction (PCR). In the present report, the 3D honeycomb material with and without DLC film consisting of a-C:H is referred to as 3D_a-C:H and 3D_non, respectively. At 3 weeks after implantation, the 3D_non had more contact between the new and artificial bones compared with the control, and the 3D_a-C:H had more contact between the new and artificial bones compared with the control and 3D_non. Furthermore, 3D_a-C:H showed even more new bone compared with the control and 3D_non. At 8 weeks after implantation, more appeared lamellar bone with the 3D_a-C:H implant than those with the control and 3D_non. The real-time PCR results at 1 week of implantation revealed higher expression levels of VEGF, RANKL, and NOTCH2 expression with 3D_a-C:H than with 3D_non and control. As a result of real-time PCR at 2 weeks of implantation, OPN and CTSK expressions were found to be higher with 3D_a-C:H and 3D_non than that with the control.

Catastrophic failure of cup revision hip arthroplasty due to undiagnosed Paget disease of bone: A case report.

INTRODUCTION: Paget's disease of bone (PDB) is a localized chronic osteopathy, apparently not genetic in origin, and frequently diagnosed from incidental radiographic images. The disease is characterized by deformation, hypervascularity, and structural weakness of the bone and by changes in joint biomechanics. Most cases of PDB can be easily diagnosed from radiographic findings, but monostotic cases may be problematic and require invasive procedures. PRESENTATION OF CASE: A 70-year-old woman had re-revision surgery for early catastrophic failure of an isolated cup revision hip arthroplasty because of undiagnosed PDB 21 years after the primary total hip arthroplasty. To identify the pathomechanism of early failure, we performed bone biopsy on the right iliac crest. Histopathological findings showed a mosaic pattern in the bone characteristic of PDB. Prior to the planned re-revision surgery, we treated the PDB with denosumab until the patient's serum level of alkaline phosphatase (ALP) was within the normal limits. Two months after denosumab treatment, we performed re-revision hip arthroplasty using a structural allograft and a Kerboull-type reinforcement device. DISCUSSION: The delay in correct diagnosis of PDB was associated with the rapid destruction of pelvic bone. The preoperative use of antipagetic medication could decrease the risk of implant loosening and may be warranted to mitigate that risk. CONCLUSION: In patients with a failed arthroplasty, thoughtful evaluation is warranted for preoperative antipagetic medication in order to reduce PDB activity and potentially decrease the risk of implant loosening. This paper offers some steps for such risk reduction in the workup before revision surgery.

Evaluation of Antibacterial and Cytotoxic Properties of a Fluorinated Diamond-Like Carbon Coating for the Development of Antibacterial Medical Implants.

Peri-implant infection is a serious complication in surgical procedures involving implants. We conducted an in vitro study to determine whether the use of a fluorinated diamond-like carbon (F-DLC) coating on a titanium alloy surface can prevent peri-implant infection. After applying the F-DLC, we evaluated its antibacterial and cytotoxic properties. The coating groups, containing controlled fluorine concentrations of 5.44%, 17.43%, 24.09%, and 30%, were examined for the presence of Staphylococcus aureus and Escherichia coli according to ISO 22196 for the measurement of antibacterial activity on plastics and other nonporous surfaces. Biological toxicity was evaluated using Chinese hamster V79 cells according to ISO 10993-5 for the biological evaluation of medical devices. In the control group, populations of S. aureus and E. coli substantially increased from 2.4 × 104 to (1.45 ± 1.11) × 106 colony-forming units (CFUs) and from 2.54 × 104 to (4.04 ± 0.44) × 106 CFUs, respectively. However, no bacteria colonies were detected in any F-DLC group with a fluorine concentration of ≥ 17.43%. In the biological toxicity study, an F-DLC coating with a fluorine concentration of 30% showed a colony formation rate of 105.8 ± 24.1%, which did not differ significantly from the colony formation rate of 107.5 ± 31.1% in the nontoxic control group. An F-DLC coating on titanium alloy discs showed excellent in vitro antibacterial activity with no biological toxicity.

Subchondral fracture caused by unevenly stiffened meniscus after radiofrequency-assisted arthroscopic knee meniscectomy: A case report and review of the literature.

INTRODUCTION: Causality for postarthroscopic osteonecrosis of the knee is unknown, and related mechanisms have been poorly characterized. PRESENTATION OF CASE: This report describes a case of a 69-year-old man with subchondral fracture occurring after arthroscopic meniscectomy using a radiofrequency assisted shaver. The patient experienced increasingly intense knee pain 10 months after the meniscectomy. MR imaging revealed postarthroscopic osteonecrosis of the knee in the femoral medial condyle, requiring unicompartmental knee arthroplasty. A mid-coronal cut section of the resected medial femoral condyle showed a linear fracture line parallel to the subchondral bone endplate. Histopathological examination showed prominent callus formation on both sides of the fracture, comprised of reactive woven bone and granulation tissue. The middle portion of the resected medial meniscus was of uneven height, with significant stiffening of the higher side. The stiffened region of the medial meniscus corresponded to the subchondral fracture in the medial femoral condyle. DISCUSSION: The etiology of post-arthroscopic osteonecrosis of the knee is controversial, but it seems possible that altered knee biomechanics after meniscectomy may predispose patients to osteonecrosis. The findings of the current case suggested that uneven stiffening of the meniscus caused concentration of stress that resulted in postarthroscopic subchondral fracture. CONCLUSION: Subchondral insufficiency fracture following arthroscopy may be underdiagnosed. Surgeons need to carefully consider the risk of subchondral fracture following uneven stiffening of the meniscus when to use radiofrequency in the debridement of a torn meniscus.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. METHODS AND ANALYSIS: The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). ETHICS AND DISSEMINATION: The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. TRIAL REGISTRATION NUMBER: UMIN000018752.