Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1ß-induced inflammation.

We recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21-/-) (n = 16) and wild type C57BL/6 (p21+/+) mice (n = 16) served as in vivo models of collagen antibody-induced arthritis (CAIA). Arthritis severity was evaluated by immunological and histological analyses. The response of p21 small-interfering RNA (siRNA)-treated human RA FLSs (n = 5 per group) to interleukin (IL)-1ß stimulation was determined in vitro. Arthritis scores were higher in p21-/- mice than in p21+/+ mice. More severe synovitis, earlier loss of Safranin-O staining, and cartilage destruction were observed in p21-/- mice compared to p21+/+ mice. p21-/- mice expressed higher levels of IL-1ß, TNF-α, F4/80, CD86, p-IKKα/ß, and matrix metalloproteinases (MMPs) in cartilage and synovial tissues via IL-1ß-induced NF-kB signaling. IL-1ß stimulation significantly increased IL-6, IL-8, and MMP expression, and enhanced IKKα/ß and IκBα phosphorylation in human FLSs. p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1ß, IL-6, and TNF-α.

BNCT for primary synovial sarcoma.

Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.

Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model.

Eicosapentanoic acid (EPA) is an antioxidant and omega-3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of ~3 weeks. Therefore, this study aimed to clarify the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten-week-old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 µL corn oil, EPA injection alone (EPA-I): DMM + 2 µL corn oil + 125 µg/µL EPA, Gel: DMM + gelatin hydrogels, and EPA-G: DMM + 125 µg/µL EPA-incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix-metalloproteinases-3 (MMP-3), MMP-13, interleukin-1ß (IL-1ß), p-IKK α/ß, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA-G than in EPA-I. MMP-3-, MMP-13-, IL-1ß-, and p-IKK α/ß-positive cell ratio was significantly lower in EPA-G than in EPA-I. However, CD86- and CD163-positive cell ratio was not significantly different between EPA-I and EPA-G. The average-sum F4/80 score of macrophage in EPA-G was significantly lower than that in EPA-I. EPA-incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra-articular administration of controlled-release EPA can be a new therapeutic approach for treating OA.

[Prolonged Disturbance of Consciousness following Preoperative Glycerin Enema in an Elderly Patient].

A 94-year-old female patient with femoral neck fracture received 60 ml glycerin enema prior to surgery, according to the preoperative preparation protocol. She was found unconscious and unresponsive 60 minutes after the treatment. Vital signs were checked and ECG monitoring was started. The results were unremarkable and similar to those recorded at the time of admission. A neurologist was consulted, and a thorough evaluation was performed. None of physical and neurological examination, laboratory testing and urgent intracranial imaging revealed significant abnormalities or lesion responsible for the depressed consciousness. Vasovagal reflex triggered by enema and the consequent hypotension was thought to be the most likely cause of transient cerebral hypoperfusion resulting in loss of consciousness. The patient remained unresponsive for the next 2 hours, and came to open her eyes with tapping stimuli. She took another hour to fully regain consciousness without any residual neurologic deficit. Her surgery was cancelled. Vasovagal reflex is known to be one of the potential complications associated with enema. Our experience suggests that the necessity of glycerin enema for preoperative bowel preparation in elderly patients should be cautiously determined and it should be given, if necessary, under adequate vigilance.

Backout of the helical blade of proximal femoral nail antirotation and accompanying fracture nonunion.

This article describes a case of backout of the helical blade, a rare complication of proximal femoral nail antirotation. A 31-year-old man had sustained a trochanteric fracture of his right femur. Fracture fixation using proximal femoral nail antirotation and autologous bone grafting 7 months later were performed at another hospital. However, bony union was not obtained, and the patient's pain and limp persisted. Therefore, he presented to the current authors. A radiograph taken at presentation revealed backout of the helical blade and fracture nonunion. A radiograph taken 1 month later showed a more advanced backout of the helical blade. The authors performed exchange nailing supplemented with transplantation of peripheral blood CD34-positive cells and autologous bone grafting. The proximal femoral nail antirotation was revised to a long gamma 3 nail, and a U-lag screw was used to obtain better stability. The postoperative course was uneventful. The patient regained ambulation without pain or support at 12 weeks postoperatively. Radiographic bony union was completed 9 months postoperatively. At 1-year follow-up, he could run and stand on the previously injured leg and had returned to work. Backout of the helical blade should be considered as a possible complication of proximal femoral nail antirotation. Incomplete fixation of the helical blade is the possible reason for backout. The use of a helical blade in young patients may cause difficulty in insertion and result in incomplete fixation.