Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

The effect of improving oral health literacy among teachers on the oral health condition of primary schoolchildren in Cambodia.

AIM: In Cambodia, civil unrest has led to insufficient and inaccessible dental health services. Oral health education and awareness are lacking, thus childhood dental caries is highly prevalent. This study aimed to examine the effects of an oral health education programme for public primary school teachers on the pupils' oral health. METHODS: Between 2011 and 2015, an oral health education workshop was presented annually to primary school educators employed at a public school in Siem Reap, Cambodia. Oral screenings of 2,637 pupils (grades 1-6; subdivided between the lower 1-3 and upper 4-6 grades) were undertaken and the prevalence of dental caries, mean number of DFT, and mean percentage of DFT rate were calculated. CONCLUSION: Despite the persistently high prevalence of dental caries, the oral health status of the schoolchildren improved every year. Participation in the workshops may have improved the teachers' ability to provide oral healthcare instructions, leading to the reduced dental caries prevalence among pupils.

Models to predict prognosis in older patients with heart failure complicated by pre-frailty and frailty: a pilot prospective cohort study.

INTRODUCTION: There are no clinical prediction models to predict the prognosis of pre-frailty or frailty in patients with heart failure. We aimed to develop prediction models for the prognosis of pre-frailty and frailty in older patients with heart failure using the classification and regression tree (CART) method; we then tested the predictive accuracies of the developed models. METHODS: Patients with pre-frailty or frailty at admission were divided into improved and non-improved groups. The CART method was used to establish two models: A, which predicted the presence or absence of pre-frailty improvement during hospitalisation; and B, which predicted the presence or absence of frailty improvement during hospitalisation. RESULTS: Patients with heart failure complicated by pre-frailty (n=28) or frailty (n=156) were included. In model A, the accuracy of predicting pre-frailty improvement was high; the best predictor was single-leg standing time at admission, followed by left ventricular ejection fraction at admission. In model B, the accuracy of predicting frailty improvement was moderate; the best predictor was hand grip strength at admission, followed by estimated glomerular filtration rate at admission, haemoglobin level at admission, and change in single-leg standing time during hospitalisation. The areas under the receiver operating characteristic curves of the CART models were 0.96 and 0.84 in models A and B, respectively. CONCLUSION: Although conditions at admission may predict the improvement of pre-frailty and frailty during hospitalisation, cardiac rehabilitation that improves single-leg standing time may help to improve frailty, particularly when conditions at admission are poor.

Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

Magneto-optical Dy2O3 ceramics with optical grade.

Optical grade Dy2O3 ceramics was successfully produced by adding a small amount of ZrO2 as a sintering aid and hot isostatic pressing treatment at 1500∘C after pre-sintering at 1550∘C. No residual pores, grain boundary phases, or second phases were detected inside the transparent ceramics. Since birefringence was not observed under the polarizer, the produced Dy2O3 ceramics is an optically isotropic body. There was almost no beam distortion during the laser irradiation test, and the optical loss was extremely small (<0.1%/cm). The Verdet constant was 422radT-1m-1 at a wavelength of 633 nm, and the extinction ratio was 34 dB.

Symmetric Peripheral Running Sutures are Superior to Asymmetric Peripheral Running Sutures for Increasing the Tendon Strength in Flexor Tendon Repair.

BACKGROUND: The fatigue strength of three peripheral suture techniques for flexor tendon repair was compared by cyclic loading of the repairs in the porcine flexor digitorum tendon. METHODS: Thirty-six tendons were sutured using only peripheral sutures with 6-0 Nylon. An initial cyclic load of 10 N for 500 cycles was applied and increased by 10 N for an additional 500 cycles at each new load until rupture. RESULTS: The fatigue strength of the symmetric running peripheral suture was 85.0% and 144.8% greater than that of the two kinds of the asymmetric running peripheral sutures. CONCLUSIONS: Symmetric running sutures can enhance the suture strength and appears to be a useful technique for increasing the strength of the peripheral suture.

Brodie's Abscess of the Radius in a Child.

We herein report an unusual case of Brodie's abscess of the radius in a child. A 13-year-old boy presented with pain on his right distal forearm. A plain radiograph showed an 8 cm translucent lesion in the distal radius. MRI showed a penumbra sign on the T1-weighted image, hyperintensity on T2-weighted images, and ring enhancement on the contrast-enhanced T1 image. 18F-FDG PET/CT images showed an uptake at the margin of the radius. Curettage and iliac cancellous bone grafting were undertaken for Brodie's abscess. Bacteriological examinations were found to be negative, however, the pathologic diagnosis showed chronic osteomyelitis. Eight months after surgery, the patient was asymptomatic and there was no sign of recurrence of infection. For Brodie's abscess in a child, thorough debridement is mandatory in addition to cancellous bone grafting. Brodie's abscess should be considered in the differential diagnosis of a patient who presents with forearm pain and exhibit the radiolucent osteolytic lesion on simple radiography.

Mechanochemically induced sulfur doping in ZnO via oxygen vacancy formation.

Surface defects of ZnO nanoparticles were induced via mechanical stressing using a Turbula shaker mixer and a planetary ball mill, and the possibilities for surface modification and functionalization of the ZnO nanoparticles were exemplified by sulfur doping of activated ZnO. Raman spectroscopy reveals that the formation of oxygen vacancies (VO) does not only occur under high stressing conditions in a planetary ball mill but even upon rather 'mild stressing' in the shaker mixer. The temporal evolution of the vacancy concentration in ZnO stressed under different conditions can be described by a model that accounts for stress number and vacancy diffusion with diffusion coefficients of VO of 3.7 × 10-21 m2 s-1 and 2.4 × 10-20 m2 s-1 for stressing in the shaker and the planetary ball mill, respectively. The thickness of the VO layer was estimated to be about 1 nm. Thiourea was mixed with defective ZnO particles, and then heated at various temperatures for sulfur-doping. A linear relationship between the amount of induced VO and the level of sulfur doping was found. Remarkably, mechanical activation is indispensable in order to control the level of sulfur doping quantitatively. High-angle annular dark field scanning transmission electron microscopy (HAADF STEM) observations with energy dispersive X-ray spectroscopy (EDX) analysis clearly revealed that the doped sulfur atoms are concentrated at the particle surface. Thus, ZnO (core)/ZnS (shell) structures are obtained easily via mechanochemical activation and subsequent thermal treatment.

A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer.

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).

Relationship between baseline characteristics and response to risedronate treatment for osteoporosis: data from three Japanese phase III trials.

We evaluated the influence of baseline age, bone mineral density (BMD), and serum levels of vitamin D on the response to risedronate treatment. Risedronate consistently increased BMD, but our results suggest vitamin D supplementation may be necessary to achieve optimal treatment effect. Furthermore, early intervention may help prevent bone fractures. INTRODUCTION: We aimed to investigate the influence of baseline age, BMD, and vitamin D insufficiency on the response to risedronate treatment. METHODS: Data regarding 1447 patients was obtained from the registries of three phase III clinical trials of risedronate. The response to treatment was expressed in terms of BMD increase and occurrence of new vertebral fractures. The patients were stratified by baseline values for age (<65, 65-72, and ≥72 years), lumbar spine BMD T-score (osteoporotic, <-2.5; and non-osteoporotic, ≥- 2.5), and serum levels of 25-hydroxyvitamin D (deficient, <21 ng/mL; and non-deficient, ≥21 ng/mL). RESULTS: Risedronate consistently increased lumbar spine BMD in all the groups, with similar percentage and absolute increments in all the age tertiles. The percentage, but not absolute, increment in BMD was significantly higher (p = 0.0003) in the osteoporotic than that in the non-osteoporotic patients (baseline). Of the 1330 patients whose baseline serum levels of 25-hydroxyvitamin D were available, 44.7% had vitamin D deficiency (<20 ng/mL), while 89.2% had insufficiency (<30 ng/mL). The percentage and absolute increments in BMD were lower (p < 0.05 and p < 0.01, respectively) in the vitamin D-deficient than those in the non-deficient patients. New vertebral fractures occurred in 1.5 and 0.8% of the osteoporotic and non-osteoporotic patients, respectively (end of the treatment). CONCLUSIONS: Therapeutic response in elderly patients is consistent, but early initiation of risedronate treatment may help prevent fractures. Risedronate-induced increase in BMD is lower in patients with vitamin D deficiency, suggesting that vitamin D supplementation is important to achieve optimal treatment response.

Taste detection ability of elderly nursing home residents.

Due to the rapid rise of aged populations throughout the world, it is essential to elucidate the cause of taste dysfunction, because it may reduce appetite, leading to inadequate dietary intake. We aimed to compare taste detection ability between dependently and independently living geriatric individuals of nearly the same age with oral status. Forty-three elderly individuals considered to be cognitively eligible and residing in nursing homes in Japan were enrolled (n = 43, 82·3 ± 8·5 years) and were compared with an independently living elderly group (n = 949, 79·9 ± 0·8 years), aiming to compare taste detection ability between dependently and independently living elders of nearly the same age. Information regarding comorbidity and medication was obtained as general health status, and oral status including number of present teeth, denture usage and maximal occlusal force was also noted. In the dependently living group, 69·4%, 14·3%, 16·3% and 8·2% of participants could detect sweet, sour, salty and bitter tastes, respectively, which was significantly lower than the independently living group for each taste (97·9%, 70·8%, 89·6% and 43·8% for sweet, sour, salty and bitter tastes, respectively). The multivariate logistic regression analysis revealed that residing in nursing homes was associated with reduced sensitivity for four different tastes. The diseases and the situation of dependent elders were more likely the cause of the decreased taste sensitivity.

Results of the Sugioka transtrochanteric rotational osteotomy for osteonecrosis: Frequency and role of a defect of the quadratus femoris muscle in osteonecrosis progression.

BACKGROUND: During transtrochanteric rotational osteotomy (RO), it is important to preserve the posterior column artery (PCA), which is generally located in the adipose tissue underneath the quadratus femoris muscle (QF). If there is a defect in the QF, the risk of injuring the PCA, subsequently resulting in total necrosis of the femoral head, may increase. Therefore, we investigated: (1) the frequency of defects of the QF at the time of RO, and (2) clinical outcome of RO based upon a defect of the QF. HYPOTHESIS: The presence of defects of the QF at the time of RO could be detected pre-operatively by magnetic resonance imaging. METHODS: RO was performed in 124 hips between 2001 and 2010. In all, 95 of the hips were in male patients and 29 in female patients. The mean age was 45.4 years (range: 11-61 years) at the time of surgery and MRI was performed before RO in all cases. We retrospectively evaluated the progression of a collapse through 3 years after RO. RESULTS: MRI showed a defect in the QF in four hips (3.2%) (2 males, 2 females), all of which were confirmed intra-operatively. Among the four patients, one (25%) underwent total hip arthroplasty because of varus deformity of the osteotomy site due to total necrosis of the femoral head 1 year after RO. The 120 hips with a normal QF showed no evidence of total necrosis or progression of necrosis of the femoral head, indicating that the presence of defects of the QF may increase the risk of poor survivorship of this procedure. CONCLUSIONS: Defects of the QF have been reported to occur in 1-2% of all patients, whereas in our study the incidence in ON was approximately 3%. In ON patients with QF defects, pre-operative MRI evaluation of the QF appears to be important when planning RO, followed by a carefully performed surgical procedure. LEVEL OF EVIDENCE: IV; retrospective case series without control group.

Asymmetric six-strand core sutures enhance tendon fatigue strength and the optimal asymmetry.

Under cyclic loading, we recorded the fatigue strength of a six-strand tendon repair with different symmetry in the lengths of suture purchase in two stumps of 120 dental rolls and in 30 porcine tendons. First, the strengths of the repairs with 1, 2, 3, 4 and 5 mm asymmetry were screened using the dental rolls. The asymmetric core suture repairs were then made with a Kessler repair of equal suture purchase (10 mm) in two tendon stumps, and shifting two other Kessler repairs by 1, 3 or 5 mm, respectively, along the longitudinal axis of the tendon in relation to the first (symmetric) Kessler repair. The core repairs with 3 mm or more asymmetry in suture purchases in two tendon ends showed significantly greater fatigue strength and significantly smaller gaps compared with 1 mm asymmetry in core suture repair. Our results support that asymmetric placement of core sutures in two tendon ends favour resisting gapping at the repair site and 3 mm or more asymmetry is needed to produce such beneficial effects.

Insulin degludec versus insulin glargine, both once daily as add-on to existing orally administered antidiabetic drugs in insulin-naive Japanese patients with uncontrolled type 2 diabetes: subgroup analysis of a pan-Asian, treat-to-target phase 3 trial.

Insulin degludec (IDeg) is a novel basal insulin analogue with an ultralong duration of action that provides flat and stable reductions in blood glucose. The BEGIN ONCE ASIA trial was a phase 3 pan-Asian study examining the efficacy and safety of IDeg once daily (OD) versus insulin glargine (IGlar) OD in insulin-naive patients with type 2 diabetes (T2D). In this multinational, 26-week, open-label, treat-to-target trial, participants were randomised (2:1) to IDeg OD or IGlar OD, administered with one or more antidiabetic drugs (OAD) per os. Here we report the results from a post hoc analysis of Japanese patients enrolled in the trial [n = 133; 63.2 % male; mean age 61.0 years; mean body mass index 24.1 kg/m2; mean glycosylated haemoglobin (HbA1c) 8.5 %]. After 26 weeks, mean HbA1c levels were similar between the two groups [estimated mean treatment difference 0.11 %; 95 % confidence interval (CI) -0.09, 0.31]. Confirmed hypoglycaemia was reported in 53.4 and 61.4 % of patients in the IDeg OD and IGlar OD groups [rate ratio (IDeg/IGlar) 0.87; 95 % CI 0.51, 1.48]. Confirmed nocturnal hypoglycaemia was reported in 17.0 and 22.7 % of patients in the IDeg OD and IGlar OD groups, respectively [rate ratio (IDeg/IGlar) 0.50; 95 % CI 0.19, 1.32]. Adverse event rates were similar between treatment groups. Initiating insulin treatment with IDeg OD in Japanese patients with T2D, inadequately maintained on OADs and requiring treatment intensification, provided effective glycaemic control with low rates of confirmed and nocturnal confirmed hypoglycaemia.

Non-anatomical reconstruction of lateral ulnar collateral ligament of the elbow after tumor resection.

We present the case of an 80-year-old man with a tumor recurrence on his right arm 6 years after initial treatment. The lateral aspect of the elbow joint, involving overlaying skin, muscles, tendons, joint capsule, lateral collateral ligament complex, the lateral 1/3 of the capitellum, and lateral epicondyle of humerus were excised in the tumor resection. Intraoperative assessment revealed multidirectional instability of the elbow, and joint stabilization was needed. Because the lateral epicondyle was resected, graft placement in an anatomical position was impossible to carry out. Therefore, non-anatomical reconstruction of lateral ulnar collateral ligament with palmaris longus tendon graft was performed. The skin was reconstructed using an antegrade pedicled radial forearm flap. For wrist extension reconstruction, the pronator quadratus tendon was transferred to the extensor carpi radialis brevis tendon. One year after the operation, elbow range of motion was 5-130°. The patient remains symptom free. The Mayo elbow performance score is good. The Musculoskeletal Tumor Society rating score is excellent. To our knowledge, this is the first report of an elbow lateral ulnar collateral ligament reconstruction after tumor resection.

Correction of coronal alignment correlates with reconstruction of joint height in unicompartmental knee arthroplasty.

OBJECTIVES: Because there have been no standard methods to determine pre-operatively the thickness of resection of the proximal tibia in unicompartmental knee arthroplasty (UKA), information about the relationship between the change of limb alignment and the joint line elevation would be useful for pre-operative planning. The purpose of this study was to clarify the correlation between the change of limb alignment and the change of joint line height at the medial compartment after UKA. METHODS: A consecutive series of 42 medial UKAs was reviewed retrospectively. These patients were assessed radiographically both pre- and post-operatively with standing anteroposterior radiographs. The thickness of bone resection at the proximal tibia and the distal femur was measured radiographically. The relationship between the change of femorotibial angle (δFTA) and the change of joint line height, was analysed. RESULTS: The mean pre- and post-operative FTA was 180.5° (172.2° to 184.8°) and 175.0° (168.5° to 178.9°), respectively. The mean δFTA was 5.5° (2.3° to 10.1°). The joint line elevation of the tibia (JLET) was 4.4 mm (2.1 to 7.8). The δFTA was correlated with the JLET (correlation coefficient 0.494, p = 0.0009). CONCLUSIONS: This study indicated that there is a significant correlation between the change of limb alignment and joint line elevation. This observation suggests that it is possible to know the requirement of elevation of the joint line to obtain the desired correction of limb alignment, and to predict the requirement of bone resection of the proximal tibia pre-operatively. Cite this article: Bone Joint Res 2015;4:128-133.

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

Panoramic radiography measurements, osteoporosis diagnoses and fractures in Japanese men and women.

OBJECTIVES: The purpose of this study was to investigate the association of the shape of the mandibular cortex on panoramic radiographs with the risk of an osteoporosis diagnosis without prevalent fractures and with the risk of osteoporotic fractures in Japanese men and women. SUBJECTS AND METHODS: One thousand and twenty-one subjects aged 40-89 years, who visited our university hospital and underwent panoramic radiography between 2007 and 2013, participated in this study. Eighty-eight patients received a diagnosis of osteoporosis without prevalent fractures, and 55 were diagnosed with osteoporotic fractures. Blinded to the groupings, we classified the shape of the mandibular cortex on panoramic radiographs as normal, moderately eroded or severely eroded. RESULTS: After adjustment for confounding factors, the odds ratios for an osteoporosis diagnosis associated with moderately eroded and severely eroded mandibular cortices were 1.4 (95% CI, 0.8-2.6) and 2.6 (95% CI, 1.4-5.0), respectively. The odds ratios for an osteoporotic fracture associated with moderately eroded and severely eroded cortices were 0.8 (95% CI, 0.4-1.7) and 1.1 (95% CI, 0.5-2.5), respectively. CONCLUSIONS: Subjects in Japan with eroded mandibular cortices tended to be at increased risk of osteoporosis diagnoses but not of fractures.

A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.

BACKGROUND: Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. PATIENTS AND METHODS: The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. RESULTS: Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death. CONCLUSIONS: In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.

Dysregulated FOXO transcription factors in articular cartilage in aging and osteoarthritis.

OBJECTIVE: Aging is a major risk factor for osteoarthritis (OA). Forkhead-box class O (FoxO) transcription factors regulate mechanisms of cellular aging, including protein quality control, autophagy and defenses against oxidative stress. The objective of this study was to analyze FoxO transcription factors in normal, aging and OA cartilage. DESIGN: Knee joints from humans ages 23-90 and from mice at the age of 4-24 months and following surgically induced OA were analyzed for expression of FoxO proteins. Regulation of FoxO protein expression and activation was analyzed in cultured chondrocytes. RESULTS: Human cartilage expressed FOXO1 and FOXO3 but not FOXO4 proteins. FOXO1 and FOXO3 were more strongly expressed the superficial and mid zone as compared to the deep zone and were mainly localized in nuclei. During human joint aging, expression of FOXO1 and FOXO3 was markedly reduced in the superficial zone of cartilage regions exposed to maximal weight bearing. In OA cartilage, chondrocyte clusters showed strong FOXO phosphorylation and cytoplasmic localization. Similar patterns of FOXO expression in normal joints and changes in aging and OA were observed in mouse models. In cultured chondrocytes, IL-1ß and TNF-α suppressed FOXO1, while TGF-ß and PDGF increased FOXO1 and FOXO3 expression. FOXO1 and FOXO3 phosphorylation was increased by IL-1ß, PDGF, bFGF, IGF-1, and the oxidant t-BHP. CONCLUSIONS: Normal articular cartilage has a tissue specific signature of FoxO expression and activation and this is profoundly altered in aging and OA in humans and mice. Changes in FoxO expression and activation may be involved in cartilage aging and OA.