The cumulative incidence of and risk factors for morphometric severe vertebral fractures in Japanese men and women: the ROAD study third and fourth surveys.

This population-based cohort study with a 3-year follow-up revealed that the annual incidence rates of vertebral fracture (VF) and severe VF (sVF) were 5.9%/year and 1.7%/year, respectively. The presence of mild VF at the baseline was a significant risk factor for incident sVF in participants without prevalent sVF. INTRODUCTION: This study aimed to estimate the incidence of morphometric vertebral fracture (VF) and severe VF (sVF) in men and women and clarify whether the presence of a mild VF (mVF) increases the risk of incident sVF. METHODS: Data from the population-based cohort study, entitled the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, were analyzed. In total, 1190 participants aged ≥ 40 years (mean age, 65.0 ± 11.2) years completed whole-spine lateral radiography both at the third (2012-2013, baseline) and fourth surveys performed 3 years later (2015-2016, follow-up). VF was defined using Genant's semi-quantitative (SQ) method: VF as SQ ≥ 1, mVF as SQ = 1, and sVF as SQ ≥ 2. Cumulative incidence of VF and sVF was estimated. Multivariate logistic regression analyses were performed to evaluate risk factors for incident sVF. RESULTS: The baseline prevalence of mVF and sVF were 16.8% and 6.0%, respectively. The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The annual incidence rates of sVF in participants without prevalent VF, with prevalent mVF, and with prevalent sVF were 0.6%/year, 3.8%/year, and 11.7%/year (p < 0.001), respectively. Multivariate logistic regression analyses in participants without prevalent sVF showed that the adjusted odds ratios for incident sVF were 4.12 [95% confident interval 1.85-9.16] and 4.53 [1.49-13.77] if the number of prevalent mVF at the baseline was 1 and ≥ 2, respectively. CONCLUSIONS: The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The presence of prevalent mVF was an independent risk factor for incident sVF.

Possible involvement of regulatory T cell abnormalities and variational usage of TCR repertoire in children with autoimmune neutropenia.

Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti-neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs ) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting Tregs , activated Tregs and non-suppressive Tregs . The frequency of activated Tregs (CD4+ CD25+ FoxP3high CD45RA- T cells) as well as that of total Tregs (CD4+ CD25+ FoxP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vß repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vß families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vß family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR-Vß family was individually compared, different use was prominently observed in the TCR-Vß 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR-Vß repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.

Not Only Hypoxia- but Radiation-Induced Epithelial-Mesenchymal Transition Is Modulated by Hypoxia-Inducible Factor 1 in A549 Lung Cancer Cells.

Hypoxia leads to post-treatment metastasis and recurrences of cancer via the epithelial-mesenchymal transition (EMT). Radiotherapy itself may also contribute to the acquisition of EMT phenotypes. Despite extensive studies on the EMT driven by either hypoxia or radiation stimuli, the molecular mechanisms characterizing these EMT events remain unclear. Thus, we aimed to evaluate the differences in the molecular pathways between hypoxia-induced EMT (Hypo-EMT) and radiation-induced EMT (R-EMT). Further, we investigated the therapeutic effects of HIF-1α inhibitor (LW6) on Hypo-EMT and R-EMT cells. A549 cells, lung adenocarcinoma cell line, acquired enhanced wound-healing activity under both hypoxia and irradiation. Localization of E-cadherin was altered from the cell membrane to the cytoplasm in both hypoxia and irradiated conditions. Of note, the expression levels of vimentin, one of the major EMT markers, was enhanced in irradiated cells, while it decreased under hypoxia condition. Importantly, LW6 significantly blocked EMT-related malignant phenotypes in both Hypo-EMT cells and R-EMT cells with concomitant re-location of E-cadherin onto the cell membrane. Moreover, LW6 deflected stress responsive signalling, JNK, activated sustainably under hypoxic condition, and the blockage of JNK impaired EMT phenotypes. Together, this work demonstrated the molecular events underlying Hypo-EMT and R-EMT, and highlighted HIF-1α as a therapeutic target not only in Hypo- EMT, but also in R-EMT.

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

Incidence rate and risk factors for radiographic hip osteoarthritis in Japanese men and women: a 10-year follow-up of the ROAD study.

OBJECTIVE: To investigate the incidence and progression rate of radiographic hip osteoarthritis (OA) and its risk factors in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2,975 participants (1,043 men and 1,932 women) aged 23-94 years (mean, 70.2 years) living in urban, mountainous, and coastal communities were followed up with hip radiography at 3, 7, and 10 years (mean follow-up, 7.1 years). Radiographs were scored using the Kellgren/Lawrence (K/L) grading system, and radiographic hip OA was defined as K/L ≥ 2. The incidence and progression rate of hip OA were examined. Acetabular dysplasia was defined as a central-edge angle <20°. Cox's proportional hazard model was used to assess risk factors for incident and progressive radiographic hip OA. RESULTS: The incidence rate of radiographic hip OA was 5.6/1,000 person-years and 8.4/1,000 person-years in men and women, respectively. The progression rate of hip OA was 2.2/1,000 person-years and 6.0/1,000 person-years in men and women, respectively. The significant risk factors for incident hip OA were age, obesity, and acetabular dysplasia at baseline (hazard risk [HR] 1.05, 95% confidence interval [CI] 1.03-1.08; 1.78, 1.10-2.75; 2.06, 1.30-3.17, respectively). The significant risk factors for progressive hip OA were baseline hip pain and acetabular dysplasia (HR 5.68, 95%CI 1.07-22.61; 14.78, 3.66-56.06, respectively). CONCLUSION: Continued longitudinal surveys of the ROAD study will contribute to knowledge about and potential prevention of incident and progressive hip OA.

Retention among full-time occupational physicians in Japan.

BACKGROUND: To secure human resources for occupational medicine, it is important to analyse occupational physician retention trends and the factors associated with retention. However, little is currently known about this topic. AIMS: To identify occupational physician retention trends, to identify factors associated with this retention and to discuss the policy implications of the findings. METHODS: We analysed data from the biannual national physician census surveys conducted by the government of Japan from 2002 to 2014. In this study, those who chose 'working as an occupational physician' as their workplace/type of work from a pre-determined list in the survey questionnaire were considered full-time occupational physicians. We presented retention trends by calculating the annual retention rate for each set of two consecutive surveys. We then used logistic regression to identify factors associated with retention among occupational physicians. RESULTS: The annual retention rate of full-time occupational physicians from 2012 to 2014 was estimated as 76%, which represents a 6% improvement in retention over the study period. The odds of continuing to practise as an occupational physician were higher for occupational physicians working in cities compared with those working in towns or villages. CONCLUSIONS: Improving and facilitating smooth transitions between clinical practice and occupational medicine would help to secure human resources in occupational medicine, even if the current trend of low retention continues.

Clinical and functional significance of STEAP4-splice variant in CD14+ monocytes in patients with rheumatoid arthritis.

Tumour necrosis factor alpha (TNF)-α-induced adipose-related protein (TIARP) is a negative regulator of inflammation in arthritis model mice. In humans, six-transmembrane epithelial antigen of prostate 4 (STEAP4) (human counterpart of TIARP) is also expressed in CD14+ monocytes from patients with rheumatoid arthritis (RA). Recently, highly levels of exon 3-spliced variant STEAP4 (v-STEAP4) expression have been observed in porcine lung. The aim of this study is to elucidate the expression and functional role of v-STEAP4, comparing it with that of STEAP4, in the pathogenesis of arthritis. We identified v-STEAP4 in CD14+ cells. The expression of STEAP4 and v-STEAP4 was higher in patients with RA than in healthy participants. We also found that STEAP4 and v-STEAP4 were correlated positively with C-reactive protein and that their expression was decreased after treatment with an interleukin (IL)-6 antagonist in patients with RA. To investigate further the role of STEAP4 and v-STEAP4, we produced STEAP4 and v-STEAP4 over-expressing human monocytic cell lines (THP-1) for functional analysis. In the v-STEAP4 over-expressing cells, the production of IL-6 was suppressed significantly, but TNF-α was increased significantly through lipopolysaccharide (LPS) stimulation. Immunoblot analysis revealed that phosphorylated (p-)nuclear factor kappa B (NF-κB) was increased after LPS stimulation and degradation of nuclear factor kappa B inhibitor alpha (IκBα) was sustained, whereas p-signal transducer and activator of transcription 3 (STAT-3) was decreased with v-STEAP4. We identified specific up-regulation of v-STEAP4 in RA monocytes. V-STEAP4 might play a crucial role in the production of TNF-α and IL-6 through NF-κB and STAT-3 pathways, resulting in the generation of RA.

Do sarcopenia and/or osteoporosis increase the risk of frailty? A 4-year observation of the second and third ROAD study surveys.

In this 4-year follow-up study including 1083 subjects (≥ 60 years), the prevalence of frailty was estimated to be 5.6%; osteoporosis was found to be significantly associated with frailty. Moreover, the presence of both osteoporosis and sarcopenia increased the risk of frailty compared to the presence of osteoporosis or sarcopenia alone. INTRODUCTION: This study aims to examine the contribution of sarcopenia and osteoporosis to the occurrence of frailty using 4-year follow-up information of a population-based cohort study. METHODS: The second survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted between 2008 and 2010; 1083 subjects (aged ≥ 60 years, 372 men, 711 women) completed all examinations on frailty, sarcopenia, and osteoporosis, which were defined using Fried's definition, Asian Working Group for Sarcopenia criteria, and WHO criteria, respectively. The third survey was conducted between 2012 and 2013; 749 of 1083 individuals enrolled from the second survey (69.2%, 248 men, 501 women) completed assessments identical to those in the second survey. RESULTS: The prevalence of frailty in the second survey was 5.6% (men, 3.8%; women, 6.6%). The cumulative incidence of frailty was 1.2%/year (men, 0.8%/year; women, 1.3%/year). After adjustment for confounding factors, logistic regression analysis indicated that osteoporosis was significantly associated with the occurrence of frailty (odds ratio, 3.07; 95% confidence interval, 1.26-7.36; p = 0.012). Moreover, the occurrence of frailty significantly increased according to the presence of osteoporosis and sarcopenia (odds ratio vs. neither osteoporosis nor sarcopenia: osteoporosis alone, 2.50; osteoporosis and sarcopenia, 5.80). CONCLUSIONS: Preventing osteoporosis and coexistence of osteoporosis and sarcopenia may help reduce the risk of frailty.

Outcomes of fulvestrant therapy among japanese women with advanced breast cancer: a retrospective multicenter cohort study (JBCRG-C06; Safari).

PURPOSE: This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). METHODS: Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan-Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. RESULTS: Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74-0.86; P < 0.001), longer period from AMBC diagnosis to F500 use (≥3 vs. <3 years; HR 0.60, 95% CI 0.51-0.70; P < 0.001), and no prior palliative chemotherapy administered for unresectable or metastatic breast cancer (no vs. yes; HR 0.69, 95% CI 0.60-0.80; P < 0.001) were associated with significantly longer TTF. Among 691 patients, where information on histologic/nuclear grade was available, a low grade was also associated with a longer TTF, but this finding was not maintained among patients with recurrent breast cancer (N = 558). Among women with recurrent breast cancer, a longer DFI between a patient's initial breast cancer diagnosis and their recurrence was associated with a longer TTF on F500 therapy. CONCLUSIONS: Our study showed that treatment period of F500 was longer when used in earlier-line treatment. For patients on F500, TTF was also longer for patients who had not received prior palliative chemotherapy and for those who had a longer period from their AMBC diagnosis to F500 use.

Radiographic measurements of the hip joint and their associations with hip pain in Japanese men and women: the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study.

OBJECTIVE: To investigate radiographic measurements of the hip joint and their associations with hip pain, and the prevalence of acetabular dysplasia defined by radiographic measurements of the hip joint in Japanese men and women using the large-scale population-based cohort of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. METHODS: From the baseline survey of the ROAD study (cross-sectional study), 2963 participants (1040 men, 1923 women; mean age, 70.2 years) were analyzed. All participants underwent radiographic examinations of both hips using an anteroposterior view under weight-bearing. Minimum joint space width (mJSW), central-edge (CE) angle, acetabular depth-to-width ratio (ADR), and acetabular head index (AHI) were measured. Associations between these radiographic measurements and hip pain were assessed by calculating odds ratios (ORs) using multivariable logistic-regression analysis. Acetabular dysplasia was defined as a CE angle <20°. RESULTS: Mean radiographic measurements of the hip joint for men were: mJSW, 3.8 mm; CE angle, 30.6°; ADR, 262.1 per 1000; and AHI, 81.4%. For women, these values were: mJSW, 3.4 mm; CE angle, 29.9°; ADR, 262.7 per 1000; and AHI, 81.2%. Associations were seen between hip pain and each of mJSW, CE angle, ADR, and AHI (OR 4.52, 95% confidence interval 3.45-5.97; 1.14, 1.11-1.18; 1.31, 1.24-1.40; and 1.15, 1.12-1.18, respectively). Acetabular dysplasia showed an overall prevalence of 13.9%, and was significantly more prevalent in women than in men (P = 0.012). CONCLUSION: The present study of radiographic measurements of the hip joint showed that mJSW, CE angle, ADR, and AHI were associated with hip pain.

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

OBJECTIVE: The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. METHODS: We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. RESULTS: DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). CONCLUSION: This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort.

Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year observations between the second and third ROAD study surveys.

In a 4-year follow-up study that enrolled 1099 subjects aged ≥60 years, sarcopenia prevalence was estimated at 8.2%. Moreover, the presence of osteoporosis was significantly associated with short-term sarcopenia occurrence, but the reciprocal relationship was not observed, suggesting that osteoporosis would increase the risk of osteoporotic fracture and sarcopenia occurrence. INTRODUCTION: The present 4-year follow-up study was performed to clarify the prevalence, incidence, and relationships between sarcopenia (SP) and osteoporosis (OP) in older Japanese men and women. METHODS: We enrolled 1099 participants (aged, ≥60 years; 377 men) from the second survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study (2008-2010) and followed them up for 4 years. Handgrip strength, gait speed, skeletal muscle mass, and bone mineral density were assessed. SP was defined according to the Asian Working Group for Sarcopenia. OP was defined based on the World Health Organization criteria. RESULTS: SP prevalence was 8.2% (men, 8.5%; women, 8.0%) in the second survey. In those with SP, 57.8% (21.9%; 77.6%) had OP at the lumbar spine L2-4 and/or femoral neck. SP cumulative incidence was 2.0%/year (2.2%/year; 1.9%/year). Multivariate regression analysis revealed that OP was significantly associated with SP occurrence within 4 years (odds ratio, 2.99; 95% confidence interval, 1.46-6.12; p < 0.01), but the reciprocal relationship was not significantly observed (2.11; 0.59-7.59; p = 0.25). CONCLUSIONS: OP might raise the short-term risk of SP incidence. Therefore, OP would not only increase the risk for osteoporotic fracture but may also increase the risk for SP occurrence.

Angular Momentum of Twisted Radiation from an Electron in Spiral Motion.

We theoretically demonstrate for the first time that a single free electron in circular or spiral motion emits twisted photons carrying well-defined orbital angular momentum along the axis of the electron circulation, in adding to spin angular momentum. We show that, when the electron velocity is relativistic, the radiation field contains harmonic components and the photons of lth harmonic carry lℏ total angular momentum for each. This work indicates that twisted photons are naturally emitted by free electrons and are more ubiquitous in laboratories and in nature than ever thought.

Clinical results of accelerated hypofractionated radiotherapy for central-type small lung tumours.

PURPOSE: We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. METHODS: Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5-3 Gy. A total dose of 69-75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan-Meier method. RESULTS: The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60-87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11-49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. CONCLUSIONS: Accelerated hypofractionated radiotherapy using a fraction size of 2.5-3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.

Prevalence of radiographic hip osteoarthritis and its association with hip pain in Japanese men and women: the ROAD study.

OBJECTIVE: Although hip osteoarthritis (OA) is a major cause of hip pain and disability in elderly people, few epidemiologic studies have been performed. We investigated the prevalence of radiographic hip OA and its association with hip pain in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2975 participants (1043 men and 1932 women), aged 23-94 years (mean 70.2 years), living in urban, mountainous, and coastal communities were analyzed. The radiographic severity at both hips was determined by the Kellgren/Lawrence (K/L) grading system. Radiographic hip OA was defined as K/L ≥ 2, and severe radiographic hip OA as K/L ≥ 3. RESULTS: The crude prevalence of radiographic hip OA was 18.2% and 14.3% in men and women, respectively, that of severe radiographic hip OA was 1.34% and 2.54%, and that of symptomatic K/L ≥ 2 OA was 0.29% and 0.99%, respectively. The crude prevalence of hip OA, including severe OA, was not age-dependent in men or women. Male sex was a risk factor for radiographic hip OA, whereas female sex was a risk factor for severe radiographic hip OA and hip pain. Compared with K/L = 0/1, hip pain was significantly associated with K/L ≥ 3, but not with K/L = 2. CONCLUSION: The present cross-sectional study revealed the prevalence of radiographic hip OA and severe hip OA in Japanese men and women. Hip pain was strongly associated with K/L ≥ 3.

Joint space narrowing, body mass index, and knee pain: the ROAD study (OAC1839R1).

OBJECTIVE: The objective of the present study was to clarify the association of joint space narrowing with knee pain in Japanese men and women using a large-scale population-based cohort of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. METHODS: This study examined the association between minimum joint space width (mJSW) in the medial compartment and pain at the knee. mJSW was measured in the medial and lateral compartments of the knee using a knee osteoarthritis (OA) computer-aided diagnosis system. RESULTS: From the 3040 participants in the ROAD study, the present study analyzed 2733 participants who completed the radiographic examinations and questionnaires regarding knee pain (975 men and 1758 women; mean age, 69.9 ± 11.2 years). Subjects with lateral knee OA were excluded. After adjustment for age and Body mass index (BMI), medial mJSW, as well as medial mJSW/lateral mJSW, was significantly associated with knee pain. Sex and BMI affected the association of medial mJSW with knee pain. The threshold of medial mJSW was approximately 3 mm in men and 2 mm in women, while that of medial mJSW/lateral mJSW was approximately 60% in both men and women. BMI was found to have a distinct effect on the association of mJSW with pain. CONCLUSION: The present cross-sectional study using a large-scale population from the ROAD study showed that joint space narrowing had a significant association with knee pain. The thresholds of joint space narrowing for knee pain were also established.

Factors affecting changes in the serum levels of 25-hydroxyvitamin D: a 3-year follow-up of the ROAD study.

UNLABELLED: In this 3-year population-based cohort study, among 1346 subjects, the mean annual change in the serum 25-hydroxyvitamin D levels was 7.6 %/year, which tended to increase during the 3-year period. Multivariate regression analysis indicated that the L2-4 bone mineral density and total daily energy intake were significant independent associated factors. INTRODUCTION: The aim of this study was to clarify the change rate of the serum levels of 25-hydroxyvitamin D (25D) and the associated factors in a general Japanese population during a 3-year period. METHODS: The baseline survey of Research on Osteoarthritis/osteoporosis Against Disability study (ROAD), a large-scale population-based cohort study, was performed between 2005 and 2007, and a follow-up survey was repeated 3 years later. Among 1690 participants at baseline, the change rate of the serum 25D levels were assessed in 1346 individuals (79.6 %; 458 men and 888 women) who completed measurements of 25D at both the baseline and follow-up examinations. The change rate was calculated, and the factors associated with the changes in the 25D levels were determined using multivariate regression analysis after adjustment for age, gender, body mass index, participated month, and regional differences at baseline. RESULTS: The mean (standard deviation) change rate of the 25D levels in all subjects was 7.6 (13.3) %/year (men, 8.2 [12.4] %/year; women, 7.3 [13.7] %/year). Multivariate regression analysis indicated that higher bone mineral density at lumbar spine L2-4 (p = 0.05) and total daily energy intake (p = 0.04) were significantly associated with the change rate of the 25D levels. CONCLUSIONS: The serum levels of 25D tended to increase over the 3-year period, and higher lumbar bone mineral density and daily energy intake were found to be associated with increases in the 25D levels over time.

Serum levels of 25-hydroxyvitamin D and the occurrence of musculoskeletal diseases: a 3-year follow-up to the road study.

UNLABELLED: Assessment of serum 25-hydroxyvitamin D levels in association with the occurrence of musculoskeletal diseases using a population-based cohort study design revealed that serum 25-hydroxyvitamin D levels could predict the occurrence of osteoporosis at the femoral neck within 3 years, but not the occurrence of knee osteoarthritis or lumbar spondylosis. INTRODUCTION: The aim of this study is to clarify the association between serum 25-hydroxyvitamin D (25D) levels and occurrence of osteoporosis and osteoarthritis in the general population. METHODS: The Research on Osteoarthritis/Osteoporosis Against Disability study, a large-scale population-based cohort study, was performed during 2005-2007. Serum 25D levels were measured in 1,683 participants. Of these, 1,384 individuals (81.9%) completed a second follow-up survey 3 years later. Osteoporosis was defined according to World Health Organization criteria, in which osteoporosis is diagnosed by T-scores of bone mineral density (BMD) that are 2.5 standard deviations (SD) less than normal BMD. Knee osteoarthritis and lumbar spondylosis were defined as Kellgren-Lawrence grade ≥2, using paired X-ray films. Cumulative incidences were determined according to changes in measurements using World Health Organization criteria for osteoporosis or Kellgren-Lawrence grades for osteoarthritis between the baseline and second survey. RESULTS: The mean (SD) serum 25D level of the 1,384 participants in both surveys was 23.4 ng/mL (6.5). The annual cumulative incidences of osteoporosis at L2-4 and the femoral neck were 0.76 and 1.83%/year, respectively. The incidences of knee osteoarthritis and lumbar spondylosis were 3.3 and 11.4%/year, respectively. After adjusting for potential associated factors, logistic regression analyses revealed that the odds ratio for the occurrence of femoral neck osteoporosis significantly decreased as serum 25D levels increased (+1 SD; odds ratio 0.67; 95% confidence interval 0.49-0.92; p = 0.014). CONCLUSIONS: Higher serum 25D levels may prevent the occurrence of osteoporosis at the femoral neck, but not knee osteoarthritis, lumbar spondylosis, or osteoporosis at L2-4.

Predictors of the response to treatment in acute lupus hemophagocytic syndrome.

OBJECTIVE: The objective of this paper is to identify predictors for the response to treatment of acute lupus hemophagocytic syndrome (ALHS). METHODS: We reviewed seven cases with ALHS admitted to our hospital and published ALHS cases identified in the 2001-2014 Medline database, and then conducted univariate and multivariate analyses to identify predictors for the response to treatment. RESULTS: Review of our cases showed a significant and negative correlation between serum ferritin and anti-DNA antibody (p = 0.0025). All three patients treated with cyclosporine A (CsA) were considered responders despite high serum ferritin and corticosteroid resistance. We also reviewed 93 patients with ALHS identified in 46 articles. Multiple logistic regression analysis identified C-reactive protein (CRP) (OR 0.83, p = 0.042) and hemoglobin (OR 1.53, p = 0.026) measured at diagnosis of ALHS as significant predictors of the response to corticosteroid monotherapy. Moreover, among 32 patients treated with CsA, serum ferritin was significantly higher in CsA responders (12163 ± 16864 µg/l, n = 22) than in non-responders (3456 ± 6267/µg/l, p = 0.020, n = 10). Leukocyte count was significantly lower in the CsA responders (1940.0 ± 972.3/µl) than in the non-responders (3253 ± 2198/µl, p = 0.034). CONCLUSION: Low CRP and high hemoglobin can predict a positive response to corticosteroid monotherapy while high serum ferritin and low leukocyte count can predict a positive response to CsA in patients with ALHS and therefore, when corticosteroid monotherapy is not effective in such cases, CsA could be the first choice of an additional immunosuppressive agent.

OARSI guidelines for the non-surgical management of knee osteoarthritis.

OBJECTIVE: To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. METHOD: Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS: Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). CONCLUSION: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.