Tomoyuki Ito

Tranexamic Acid for Reduction of Blood Loss During Total Hip Arthroplasty

In this study, we evaluated the hemostatic effects of tranexamic acid (TNA), an antifibrinolytic drug, by examining the timing of its administration during total hip arthroplasty. One hundred seven patients being treated for osteoarthritis of the hip joint were randomly divided into 5 groups based on the timing of TNA administration. The intraoperative blood loss, postoperative blood loss, and hemoglobin of these patients who received TNA at different times during the procedure were monitored. We found that the intraoperative blood loss in the preoperative TNA administration groups was significantly lower than both control and postoperative TNA administration groups. Furthermore, 1 g TNA 10 minutes before surgery and 6 hours after the first administration was most effective for the reduction of blood loss during total hip arthroplasty.

High-Level Expression of the Coxsackievirus and Adenovirus Receptor Messenger RNA in Osteosarcoma, Ewing’s Sarcoma, and Benign Neurogenic Tumors among Musculoskeletal Tumors

Purpose: The sensitivity of human tumor tissues to infection with recombinant adenoviruses correlates with the expression of the coxsackievirus and adenovirus receptor (CAR). CAR has been shown to function as the primary receptor for adenoviruses and to play a critical role in adenovirus entry into host cells. It is important for clinical gene therapy to determine the expression level of CAR in tumor tissues. Experimental Design: We analyzed the expression of CAR mRNA in 154 musculoskeletal tumor tissues from 154 patients and 10 normal mesenchymal tissues from 3 patients using reverse transcription-PCR and real-time quantitative PCR. An adenovirus infection assay was performed in two cell lines that were established from CAR-positive osteosarcoma tissue and CAR-negative malignant fibrous histiocytoma tissue. Results: Ninety-nine of 154 tumors were detected as CAR positive by reverse transcription-PCR. We found that the expression levels of CAR mRNA varied markedly between different tumors as determined by real-time quantitative PCR. CAR mRNA was expressed at high levels in osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma; at intermediate levels in exostosis, giant cell tumor, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and hemangioma; and at low levels in alveolar soft part sarcoma and desmoid. Whereas the osteosarcoma cell line that expressed a high level of CAR mRNA, like its parent tumor, had a high efficiency of adenovirus infection, the malignant fibrous histiocytoma cell line with almost undetectable expression of CAR mRNA, like its parent tumor, had a low efficiency of infection. Conclusions: Our data showed the great variations in CAR mRNA expression among human musculoskeletal tumors and mesenchymal tissues and implicated the potential usefulness of adenoviral vectors in gene therapy for osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma. Efficient transduction with adenovirus for gene therapy could be realized in appropriate, sensitive tumor types.

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (104–108 PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. β-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

A case of aseptic abscesses syndrome treated with corticosteroids and TNF-alpha blockade

Aseptic abscesses syndrome (AA) is an emerging clinicopathological entity characterized by visceral sterile collections of mature neutrophils that do not respond to antibiotics but regress quickly when treated with corticosteroids. Although most previous case reports of AA have been restricted to Europe, we present here a Japanese woman with AA showing recurrence of splenic abscesses, ileocolitis, pyoderma gangrenosum, and arthritis. Although both steroid therapy and tumor necrosis factor (TNF)-alpha blockade were effective, relapses remained frequent.

Tubulointerstitial nephritis and Fanconi syndrome in a patient with primary Sjögren's syndrome accompanied by antimitochondrial antibodies: A case report and review of the literature.

Abstract We describe a 53-year-old woman with primary Sjögrens syndrome and tubulointerstitial nephritis showing distal renal tubular acidosis and Fanconi syndrome. The patient showed high serum IgM levels and positivity for antimitochondrial antibodies, although her liver function was in normal range. According to our literature review, 75% of patients with tubulointerstitial nephritis who were positive for antimitochondrial antibodies showed Fanconi syndrome, suggesting that these antibodies may directly be associated with the pathophysiology of Fanconi syndrome.

Usefulness of a novel method for the screening of deep vein thrombosis by using a combined D-dimer- and age-based index before total hip arthroplasty

Plasma D-dimer level is clinically useful for diagnosing patients with suspected deep vein thrombosis (DVT). However, the cut-off value for the D-dimer level remains controversial and undetermined with regard to total hip arthroplasty (THA). The objective of this study was to estimate the efficacy of an age- and D-dimer-based index for diagnosing DVTs in asymptomatic cases before THA. We enrolled 224 patients with no symptoms associated with DVT before THA. All the patients underwent ultrasonography, and the plasma D-dimer level was recorded about 1 month preoperatively. The optimal cut-off value was calculated using multiple logistic regression and receiver operating curve analyses. DVTs were detected in 13 patients (5.8%) using ultrasonography. Multiple logistic regression analysis demonstrated that age (odds ratio [OR]: 1.13; p = 0.007) and D-dimer value (OR: 1.74; p = 0.003) were related to the existence of preoperative DVT. A DVT index (0.12 × age + 0.45 × the D-dimer value) of 8.15 was the most reasonable cut-off value according to the receiver operating curve analysis. This value caused 100% sensitivity and 70.1% specificity, with an area under the curve (AUC) of 0.905 (range, 0.836–0.975). For age and D-dimer value, the AUCs were 0.828 (0.749–0.907) and 0.716 (0.522–0.910), respectively. This study demonstrated that age and D-dimer index can be useful in screening patients for DVTs before THA. This DVT index is also easy to calculate and may be clinically significant.

Adult-onset Chronic Recurrent Multifocal Osteomyelitis with High Intensity of Muscles Detected by Magnetic Resonance Imaging, Successfully Controlled with Tocilizumab

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that generally occurs in children and predominantly affects the long bones with marginal sclerosis. We herein report two cases of adult-onset CRMO involving the tibial diaphysis bilaterally, accompanied by polyarthritis. Magnetic resonance imaging (MRI) showed both tibial osteomyelitis and high intensity of the extensive lower leg muscles. Anti-interleukin-6 therapy with tocilizumab (TCZ) effectively controlled symptoms and inflammatory markers in both patients. High intensity of the lower leg muscles detected by MRI also improved. These cases demonstrate that CRMO should be included in the differential diagnosis of adult patients with bone pain, inflammation, and high intensity of the muscles detected by MRI. TCZ may therefore be an effective therapy for muscle inflammation of CRMO.

Comparison of clinical and laboratory features of patients with and without allergic conditions in IgG4-related disease: A single-center experience in Japan

Abstract Objective: The objective of this study is to compare the clinical and laboratory features of Japanese patients with IgG4-related disease, with and without allergic conditions. Methods: We retrospectively examined the clinical and laboratory features and clinical courses of 51 patients with definitively diagnosed IgG4-RD, collected from Nagaoka Red Cross Hospital between January 2004 and August 2017, with reference to the presence of allergic conditions. Results: Among these patients, 43% had allergic conditions. In the allergy group, the proportion of females was significantly higher, the age at diagnosis was significantly lower, and upper body organ involvement was predominant in comparison with the non-allergy group. There was no significant inter-group difference in the absolute number of peripheral blood eosinophils, the levels of serum IgG4 and IgE, the response to steroid, or the proportion of patients who relapsed. Conclusion: The present findings suggest that there may be some differences in the clinical features of IgG4-RD patients according to the allergic conditions that are present, although eosinophilia and high serum levels of IgE and IgG4 are common features regardless of allergy.

The anteroposterior axis of the tibia is approximately perpendicular to the anterior pelvic plane in the standing position in healthy Japanese subjects

BackgroundWe previously reported that the clinical epicondylar axis (CEA) was approximately parallel to the transverse axis of the anterior pelvic plane (APP) in the standing position in normal subjects. The purpose of this study was to investigate the rotational alignment between APP in the standing position and the anteroposterior (AP) axis of the tibia relative to pelvic coordination in normal subjects.MethodsThis study included 68 healthy Japanese, 24 males and 44 females, without lumbago and knee pain. Femoral neck anteversion (FNA), condylar twist angle, and knee rotation angle were measured in femoral coordination. The angle between the femoral neck axis and CEA transverse axis of APP was also measured, and the angle between the AP axis of the tibia and the transverse axis of APP was calculated. The mean value of knee rotation angle was 0.23° and 2.06° in male and female subjects, respectively.ResultsThere was a moderate positive correlation between FNA and the femoral axis angle relative to the transverse axis of APP. The knee rotation angle relative to APP was 0.33° and 1.56° in male and female subjects, respectively, and the tibia AP axis was approximately perpendicular to the transverse axis of APP in the standing position. Regarding validation, we obtained high interclass correlation coefficients for both intraobserver and interobserver reliability.ConclusionWe found that the knee rotation angle was almost 0° and that the tibia AP axis was approximately perpendicular to the CEA. The tibia AP axis was also approximately perpendicular to the transverse axis of the APP in standing position.

Recurrence of pelvic abscess from Panton–Valentine leukocidin‐positive community‐acquired ST30 methicillin‐resistant Staphylococcus aureus

A 17‐year‐old female patient (a basketball player) suffered from recurrent pelvic abscesses from methicillin‐resistant Staphylococcus aureus (MRSA). The first episode, from strain NN12, occurred in October 2004. Her cutaneous abscesses complicated into systemic progression to osteomyelitis and multifocal pelvic abscesses, adjacent to the sacroiliac joint. The second episode, abscesses at tissues adjacent to the sacroiliac joint from strain NN31A, occurred late in February 2005. The third episode, from strain NN31B, occurred on July 30, 2005, repeating the second episode. Three MRSA strains were identical in terms of genotypes (belonging to Panton‐Valentine leukocidin [PVL]‐positive ST30 community‐acquired MRSA, CA‐MRSA), pulsed‐field gel electrophoresis patterns, and peptide cytolysin gene (psmα) expression levels. The three MRSA strains exhibited superior THP‐1 cell invasion ability over hospital‐acquired MRSA (New York/Japan clone). The data suggest that PVL‐positive ST30 CA‐MRSA, with high levels of cell invasion and peptide cytolysins, causes recurrence of pelvic abscesses in a healthy adolescent.