Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Silicate/zinc-substituted strontium apatite coating improves the osteoinductive properties of ß-tricalcium phosphate bone graft substitute.

BACKGROUND: ß-Tricalcium phosphate (ß-TCP) is a popular synthetic bone graft substitute with excellent osteoconductive properties and bioabsorbability. However, its osteoinductive properties are inferior to those of autologous or allogeneic bone. Trace elements such as strontium (Sr), silica (Si), and zinc (Zn) have been reported to promote osteogenesis in materials. In this study, we aimed to determine whether a Si/Zn-substituted Sr apatite coating of ß-TCP could enhance osteoinductive properties. METHODS: The apatite-coated ß-TCP disks were prepared using nanoparticle suspensions of silicate-substituted Sr apatite (SrSiP) or silicate- and Zn-co-substituted Sr apatite (SrZnSiP). Bone marrow mesenchymal cells (BMSCs) from rat femur were cultured and subsequently seeded at a density of 1.0 × 106/cm2 onto apatite-coated and non-coated ß-TCP disks. In vitro, the ß-TCP disks were then placed in osteogenic medium, and lactate dehydrogenase (LDH) activity was measured from supernatants after culture for 2 days. Additionally, after culture for 14 days, the mRNA expression of genes encoding osteocalcin (OC), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was evaluated by qRT-PCR. In vivo, the ß-TCP disks were transplanted subcutaneously into rats that were sacrificed after 4 weeks. Then, the harvested disks were evaluated biochemically (ALP activity, OC content, mRNA expression of OC, ALP, BMP-2, and VEGF measured by qRT-PCR), radiologically, and histologically. RESULTS: Significantly higher mRNA expression of almost all evaluated osteogenic and angiogenic genes was observed in the SrZnSiP and SrSiP groups than in the non-coated group, with no significant cytotoxicity elicited by the apatite coating in vitro. Moreover, in vivo, the SrZnSiP and SrSiP groups showed significantly higher osteogenic and angiogenic gene expression and higher ALP activity and OC content than the non-coated group (P < 0.05). Radiological and histopathological findings revealed abundant bone formation in the apatite-coated group. CONCLUSIONS: Our findings indicate that apatite coating of ß-TCP improves osteoinductive properties without inducing significant cytotoxicity.

In vitro osteogenesis of rat bone marrow mesenchymal cells on PEEK disks with heat-fixed apatite by CO2 laser bonding.

BACKGROUND: Polyether-ether-ketone (PEEK) is increasingly being used for spinal applications. However, because of its biologically inactive nature, there are risks of false joint loosening and sinking. PEEK materials are coated with apatite to enhance the osteoconductive properties. In this study, we aimed to evaluate whether strontium apatite stimulate osteogenesis on the surface of PEEK by using the CO2 laser technique. METHODS: We prepared non-coated disks, laser-exposed disks without apatite, and four types of apatite-coated by laser PEEK disks (hydroxyapatite (HAP), strontium hydroxyapatite (SrHAP), silicate-substituted strontium apatite (SrSiP), and silicate-zinc-substituted strontium apatite (SrZnSiP)). A part of the study objective was testing various types of apatite coatings. Bone marrow mesenchymal cells (BMSCs) of rats were seeded at a density of 2 × 104/cm2 onto each apatite-coated, non-coated, and laser-irradiated PEEK disks. The disks were then placed in osteogenic medium, and alkaline phosphatase (ALP) staining and Alizarin red staining of BMSCs grown on PEEK disks were performed after 14 days of culture. The concentrations of osteocalcin (OC) and calcium in the culture medium were measured on days 8 and 14 of cell culture. Furthermore, mRNA expression of osteocalcin, ALP, runt-related transcription factor 2 (Runx2), collagen type 1a1 (Col1a1), and collagen type 4a1 (Col4a1) was evaluated by qPCR. RESULTS: The staining for ALP and Alizarin red S was more strongly positive on the apatite-coated PEEK disks compared to that on non-coated or laser-exposed without coating PEEK disks. The concentration of osteocalcin secreted into the medium was also significantly higher in case of the SrHAP, SrSiP, and SrZnSiP disks than that in the case of the non-coated on day14. The calcium concentration in the PEEK disk was significantly lower in all apatite-coated disks than that in the pure PEEK disks on day 14. In qPCR, OC and ALP mRNA expression was significantly higher in the SrZnSiP disks than that in the pure PEEK disks. CONCLUSIONS: Our findings demonstrate that laser bonding of apatite-along with trace elements-on the PEEK disk surfaces might provide the material with surface property that enable better osteogenesis.

Silicate-substituted strontium apatite nano coating improves osteogenesis around artificial ligament.

BACKGROUND: Treatment of anterior cruciate ligament injuries commonly involves the use of polyethylene terephthalate (PET) artificial ligaments for reconstruction. However, the currently available methods require long fixation periods, thereby necessitating the development of alternative methods to accelerate the healing process between tendons and bones. Thus, we developed and evaluated a novel technique that utilizes silicate-substituted strontium (SrSiP). METHODS: PET films, nano-coated with SrSiP, were prepared. Bone marrow mesenchymal cells (BMSCs) from femurs of male rats were cultured and seeded at a density of 1.0 × 104/cm2 onto the SrSiP-coated and non-coated PET film, and subsequently placed in an osteogenic medium. The osteocalcin concentration secreted into the medium was compared in each case. Next, PET artificial ligament, nano-coated with SrSiP, were prepared. BMSCs were seeded at a density of 4.5 × 105/cm2 onto the SrSiP-coated, and non-coated artificial ligament, and then placed in osteogenic medium. The osteocalcin and calcium concentrations in the culture medium were measured on the 8th, 10th, 12th, and 14th day of culture. Furthermore, mRNA expression of osteocalcin, alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (Runx2) was evaluated by qPCR. We transplanted the SrSiP-coated and non-coated artificial ligament to the tibiae of mature New Zealand white rabbits. Two months later, we sacrificed them and histologically evaluated them. RESULTS: The secretory osteocalcin concentration in the medium on the film was significantly higher for the SrSiP group than for the non-coated group. Secretory osteocalcin concentration in the medium on the artificial ligament was also significantly higher in the SrSiP group than in the non-coated group on the 14th day. Calcium concentration on the artificial ligament was significantly lower in the SrSiP group than in the non-coated group on the 8th, 10th, 12th, and 14th day. In qPCR as well, OC, ALP, BMP2, and Runx2 mRNA expression were significantly higher in the SrSiP group than in the non-coated group. Newly formed bone was histologically found around the artificial ligament in the SrSiP group. CONCLUSIONS: Our findings demonstrate that artificial ligaments using SrSiP display high osteogenic potential and thus may be efficiently used in future clinical applications.

Lifestyle factors are significantly associated with the locomotive syndrome: a cross-sectional study.

BACKGROUND: The Japanese Orthopedic Association first proposed the concept of "locomotive syndrome" in 2007. It refers to circumstances in which elderly people need nursing care services or are at high risk of requiring such services within a short time. Recently, the public health burden of providing nursing care for elderly individuals has increased. Therefore, locomotive syndrome, and the means of preventing it, are a major public health focus in Japan. The purpose of this study was to investigate the relationships of lifestyle factors, such as smoking, alcohol consumption, sleep duration, and dental health, with locomotive syndrome. METHODS: We conducted a cross-sectional study using an internet panel survey. The participants comprised 747 individuals aged 30-90 years. Factors related to demographics (age, sex), general health (number of teeth, presence of periodontal disease), and lifestyle (smoking, alcohol consumption, sleep duration) were assessed. We also used the 25-question Geriatric Locomotive Function Scale to determine whether each participant had locomotive syndrome. Multivariate analysis was conducted using logistic regression to investigate the independent relationships between locomotive syndrome and lifestyle factors after adjusting for sex and age. RESULTS: A greater proportion of women (17.7%) than men (11.2%) had locomotive syndrome (p < 0.05). Participants aged ≥65 years showed significantly higher percentages (men: 21.4%, women: 75.7%) of locomotive syndrome compared with those aged <65 years (p < 0.05). Logistic regression analysis revealed that older age (≥ 65 years), sex, current smoking status, number of existing teeth, and presence of periodontal disease were associated with locomotive syndrome, whereas sleep duration was not. The frequency of alcohol consumption, except for daily drinking, was also associated with locomotive syndrome. CONCLUSION: Our study indicates that lifestyle factors, such as smoking and number of existing teeth, may partly affect the prevalence of locomotive syndrome. Hence, lifestyle modifications, such as improving oral hygiene and promoting cessation of smoking, are important means to reduce the risk of locomotive syndrome and should be promoted by public health staff.

Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites.

PURPOSE: The treatment of giant cell tumor (GCT) of bone remains controversial. Intralesional surgery (curettage) results in a higher rate of local recurrence, but better functional results compared to resection. The aim of this study was to assess whether the use of curettage was successful in the treatment of GCT of long bones. We evaluated the influence of adjuvant treatment, local tumor presentation, and demographic factors on the risk of recurrence. METHODS: We retrospectively reviewed the records of patients treated for GCT of long bones between 1990 and 2013, using curettage. No patient had any treatment other than surgery. After detailed curettage, the bone cavity was filled with bone allografts and/or cement. Recurrence rates, risk factors for recurrence and the development of pulmonary metastases were determined. The minimum follow-up was 24 months. RESULTS: We enrolled 210 patients with GCT of long bones treated by curettage. The rate of local recurrence was 16.2% (34/210 patients). The median follow-up was 89.2 months. In the multivariate analysis, no significant statistical effect on the local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement versus bone allografts. The only independent risk factor related to the local recurrence was the site, with a statistically significant higher risk for patients with GCT of the proximal femur. CONCLUSIONS: Our observation on the correlation of tumor location and risk of local recurrence is new. We suggest that patients with GCT of bone in the proximal femur should be followed closely soon after surgery to identify any possible recurrence.

Impact of telephone dispatcher assistance on the outcomes of pediatric out-of-hospital cardiac arrest.

OBJECTIVE: Most previous studies of pediatric out-of-hospital cardiac arrest have typically examined relatively small datasets from small study regions. Although several studies have reported the impact on adult out-of-hospital cardiac arrest, little information is available on the impact of telephone dispatcher assistance on the outcomes of pediatric out-of-hospital cardiac arrest. We set out to examine the impact of cardiopulmonary resuscitation instruction by telephone dispatcher on the outcomes of pediatric out-of-hospital cardiac arrest. DESIGN: Population-based, observational study. SETTING: Japan-wide population-based setting. PATIENTS: We identified 1,780 pediatric out-of-hospital cardiac arrest patients (67.8% male) with witnessed collapse from a nationwide, population-based, out-of-hospital cardiac arrest database. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: We assessed the impact of telephone dispatcher assistance on the outcomes of 1-month survival rates and favorable neurologic status among the groups. The overall rate of bystander-performed chest compression and mouth-to-mouth ventilation among the witnessed pediatric out-of-hospital cardiac arrests were 39.5% and 25.6%, respectively. Telephone dispatcher assistance was offered in 28.4% of the witnessed pediatric out-of-hospital cardiac arrest cases and resulted in a significant increase in both chest compression (adjusted odds ratio 6.04; 95% confidence interval 4.72-7.72) and mouth-to-mouth ventilation (adjusted odds ratio 3.10; 95% confidence interval 2.44-3.95), and a significant improvement in 1-month survival rate (adjusted odds ratio 1.46; 95% confidence interval 1.05-2.03), but no significant effect on favorable neurologic outcomes at 1 month (adjusted odds ratio 1.15; 95% confidence interval 0.70-1.88). Potential confounding factors included age categories, sex, bystander type, cause of cardiac arrest, bystander cardiopulmonary resuscitation, and attempted defibrillation. CONCLUSIONS: Telephone dispatcher assistance could significantly increase bystander cardiopulmonary resuscitation among witnessed pediatric out-of-hospital cardiac arrests. Although there was only a small, nonsignificant effect on the improvement in favorable neurologic outcome at 1 month, the improved survival associated with telephone dispatcher assistance in pediatric out-of-hospital cardiac arrest is clinically important, and is of major public health importance. In cases where cardiac arrest was uncertain from the bystander's replies during the call to emergency medical services, telephone dispatcher assistance was not offered, which could affect the adjusted odds ratio of the present study.

[Differential correlation of medical/laboratory examinations with blood levels of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran in Yusho patients from 2001 to 2004].

BACKGROUND: Since 1968, when the Yusho poisoning incident occurred, annual physical, dermatological, dental, and ophthalmological and laboratory examinations, collectively called Yusho health checks, have been conducted for Yusho patients. The Yusho incident was a health hazard caused by intake of rice-bran oil contaminated with PCB and PeCDF; therefore, since 2001 the levels of dioxins such as PeCDF in the blood have been measured in applicants. Here, we investigated correlations among findings from various medical examinations and those between those findings and PeCDF, PCB, and PCQ. PATIENTS AND METHODS: Subjects were Yusho patients who underwent Yusho annual health checks and had their levels of PeCDF measured between 2001 and 2004. The results of 4 years of health checks of those who underwent the health checks for 2 years or longer were aggregated to extract representative inspection items by principal component analysis. We also investigated the presence or absence of correlations among these items and PeCDF, PCB, and PCQ levels in blood. RESULTS: Using 49 variables extracted by principal component analysis as objective variables, we determined that there were correlations between the following combinations: arthralgia, A/G ratio and PeCDF level, ophthalmological symptoms such as excessive eye discharge and PCB level, and total cholesterol, inferior gingival pigmentation and PCQ level.

Maxillofacial bone regeneration with osteogenic matrix cell sheets: An experimental study in rats.

OBJECTIVE: Regeneration of maxillofacial bone defects, characterized by relatively small but complicated shapes, poses a significant clinical challenge. Osteogenic matrix cell sheets (OMCSs) have osteogenic ability and good shaping properties and may be ideal graft materials. Here, we assessed whether implantation of OMCSs could be used to repair maxillofacial bone defects. DESIGN: We adopted a rat mandibular symphysis model. The rat mandible is formed by a paired bone and the central portion consisting of fibrous tissue. There is no bone tissue at the site; accordingly, this site was interpreted as a physiological bone gap and was used for evaluation. Rat bone marrow cells were cultured in medium containing dexamethasone and ascorbic acid phosphate to create OMCSs. The OMCSs were implanted into the rat mandibular symphysis without a scaffold. Microcomputed tomography and histological analyses were conducted after 2, 4, and 8 weeks. RESULTS: Two weeks after implantation, microcomputed tomography images and histological sections showed some sparse granular calcification tissue within the bone gap at the mandibular symphysis. At 4 weeks, the calcification tissue spread, and the gap of the mandibles were continued. At 8 weeks, this continuous new bone tissue was matured. The experimental group showed abundant new bone tissue in the group with OMCS implantation, but not in the group with sham implantation. CONCLUSIONS: Our present results indicated that use of OMCSs may be an optimal approach towards achieving maxillofacial regeneration.

Outcomes of chest compression only CPR versus conventional CPR conducted by lay people in patients with out of hospital cardiopulmonary arrest witnessed by bystanders: nationwide population based observational study.

OBJECTIVE: To compare the effectiveness of cardiopulmonary resuscitation (CPR) with chest compression only and conventional CPR on outcomes after cardiopulmonary arrest out of hospital. DESIGN: Nationwide population based observational study. SETTING: A nationwide emergency medical service system in Japan. Population All consecutive patients with out of hospital cardiopulmonary arrest, January 2005 to December 2007 in Japan, witnessed at the moment of collapse. Lay people attempted chest compression only CPR (n = 20,707) or conventional CPR (mouth to mouth ventilation and chest compression) (n = 19,328), and patients were transferred to hospital by ambulance. MAIN OUTCOME MEASURES: Factors associated with better outcomes (assessed with χ(2), multiple logistic regression analysis, odds ratios and their 95% confidence intervals): one month survival and neurologically favourable one month survival rates defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories. RESULTS: Conventional CPR was associated with better outcomes than chest compression only CPR, for both one month survival (adjusted odds ratio 1.17, 95% confidence interval 1.06 to 1.29) and neurologically favourable one month survival (1.17, 1.01 to 1.35). Neurologically favourable one month survival decreased with increasing age and with delays of up to 10 minutes in starting CPR for both conventional and chest compression only CPR. The benefit of conventional CPR over chest compression only CPR was significantly greater in younger people in non-cardiac cases (P = 0.025) and with a delay in start of CPR after the event was witnessed in non-cardiac cases (P = 0.015) and all cases combined (P = 0.037). CONCLUSIONS: Conventional CPR is associated with better outcomes than chest compression only CPR for selected patients with out of hospital cardiopulmonary arrest, such as those with arrests of non-cardiac origin and younger people, and people in whom there was delay in the start of CPR.

Twenty-year changes of penta-chlorodibenzofuran (PeCDF) level and symptoms in Yusho patients, using association analysis.

BACKGROUND: Recently, methods for measurement of dioxins in the blood have improved. Also, techniques for analyzing large quantities of data have been developed, such as data mining. Even in subjects with elusive characteristics, it is becoming possible to find previously unknown characteristics by checking all combinations of symptoms. FINDINGS: Using association analysis of the data mining technique, we extracted and compared combinations with a strong relationship between recent symptoms (2001-2004) and recent blood PeCDF levels, and between past symptoms (1986-1989) and recent PeCDF levels, in physical, blood, dermatological, dental and ophthalmological examinations.Patients with a higher PeCDF level were more likely to present with symptoms included in the diagnostic criteria, such as pigmentation. In addition, we obtained evidence that recent PeCDF levels had a stronger relationship with recent than past symptoms. CONCLUSIONS: Recent PeCDF levels should not be compared directly with past symptoms. However, as the excretion rate of PeCDF has been constant, it is probable that PeCDF levels were higher in the past if recent PeCDF levels were also high. The study confirmed a relationship between past PeCDF levels and past clinical symptoms. For symptoms included in the diagnostic criteria, there was a stronger relationship between PeCDF levels and past symptoms than recent symptoms. Alleviation of symptoms in each patient or aging weakened the relationship between PeCDF levels and symptoms.

Cutaneous symptoms such as acneform eruption and pigmentation are closely associated with blood levels of 2,3,4,7,8-penta-chlorodibenzofurans in Yusho patients, using data mining analysis.

BACKGROUND: Yusho an intoxication caused by oral dioxins and polychlorinated biphenyls occurred in 1968. Patients suffered from various systemic symptoms, including general fatigue, nausea, muscular and articular pain, acneform eruptions, black comedones, cutaneous and oral pigmentation, and increased eye discharge. The major causative factor was the contamination of rice oil with 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF). Recent technical advances have allowed us to measure blood levels of PeCDF. However, there is little information on which symptoms and laboratory data are directly associated with PeCDF levels. METHODS: Yusho patients underwent annual medical check-ups from 2001 to 2003. Blood PeCDF levels were correlated with the presence or absence of symptoms in medical, hematological, dermatological, dental and ophthalmological examinations. This study analyzed all combinations by using the association analysis. This is the most suitable method to evaluate all combinations of the data comprehensively. This method was used to determine the rate of patients with high PeCDF level in the population with each symptom, and to extract combinations of three symptoms which were strongly associated with high PeCDF level. RESULTS AND CONCLUSION: The rate of the patients with high PeCDF level was high in populations with high uric acid, black comedones (face), second highest quartile of age, or high urea nitrogen. The combination of three symptoms associated with the highest rate of patients with high PeCDF level was "high uric acid, female sexuality, and history of acneform eruptions", followed by "history of Yusho in and after 1968, high cholesterol level, and subjective symptoms." This analysis newly suggested that PeCDF concentration may be associated with history of dermatological symptoms, high uric acid, and elevated erythrocyte sedimentation rate.

Hydroxyapatite ceramics as a carrier of gene-transduced bone marrow cells.

The aim of this study was to develop an efficient exogenous gene delivery system using cultured marrow cells and porous hydroxyapatite ceramics. Bone marrow cells were obtained from the femoral shaft of a Fischer 344 rat and cultured in a medium containing 15% fetal bovine serum until confluent. After trypsinization, cells were subcultured at a cell density of 1 x 10(4) cells/cm2 in the presence of fetal bovine serum. The subcultured bone marrow cells were infected with recombinant retroviruses carrying the lacZ gene. The retrovirus infection was performed seven times from day 1 to day 7 during the culturing procedure. Cells expressing the lacZ gene were stained blue with the X-gal staining and represented approximately 80%. Composites of virus-infected bone marrow cells and hydroxyapatite ceramics were implanted at the subcutaneous site of recipient Fischer 344 rats. Four weeks after the implantation the ceramics were harvested. The histological sections of the ceramics showed abundant bone formation in the pores of the ceramics and obviously blue-stained osteoblasts and osteocytes. Other cell types that were stained blue were some fibroblastic cells and endothelial cells in the newly formed capillaries. These findings indicate that osteoblasts and osteocytes in the newly formed bone were derived from the cultured bone marrow cells, and therefore gene transfection by retroviruses did not disturb the bone formation process. Because of the durability of the newly formed bone tissue, creating composites of cultured bone marrow cells and hydroxyapatite ceramics might be an ideal method for exogenous gene transfection.