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Objectives: This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS)., Methods: We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein, erythrocyte sedimentation rate, ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal anti-inflammatory drugs, prednisolone, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, and spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group., Results: At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher C-reactive protein levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis., Conclusions: C-reactive protein was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: The mechanisms behind the onset of acute aortic dissection have not been fully elucidated. We developed dynamic synchrotron-based X-ray phase-contrast tomography to quantitatively study the dynamics of biological samples and applied it to the fresh aortic wall in acute type-A aortic dissection (ATAAD)., Methods: Fresh, ring-shaped aortas undergoing aortic repair in ATAAD were measured in a container filled with normal cold saline within 24 h of surgery. As a control, we obtained 5 formalin-fixed normal ascending aortas from autopsies (female: 2, 59.7 years) [standard deviation (SD): 5.5 years]. To evaluate the quantitative morphological change, we estimated the density at each step stretched by 2 mm per step. The fresh specimens were analysed pathologically using the area ratio of the elastic fibres., Results: Samples were obtained from 5 patients [1 man and 4 women, 59.4 (SD: 8.7) years]. The overall density of the tunica media (TM) in the fresh aorta was 1.062 (SD: 0.006) g/cm3 and differed significantly between the dissected and non-dissected portions [1.05 (SD: 0.004) vs 1.066 (SD: 0.004) g/cm3, respectively; P = 0.0122]. When the fresh aortic wall was stretched and became thinner, the density of the TM remained unchanged. Compared with the pathological findings, the area ratios of the elastic fibres of the TM were lower in the non-dissected portion than normal [48.6 (SD: 7.1)% vs 60.5 (SD: 5.7 %, P < 0.001]., Conclusions: Dynamic synchrotron-based X-ray phase-contrast tomography can trace the deformation process that occurs in situ in fresh aorta in ATAAD. We confirmed that the densitometric property of the aortic wall in ATAAD was unchanged during the stretching process., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background and Objective: Surgical site infection (SSI) is common in surgery for malignant musculoskeletal tumours, specifically those arising from the trunk. In this study, we investigated the risk factors for SSI after resection of musculoskeletal tumours of the trunk., Methods: This retrospective observational study included 125 patients (72 males, 53 females) with musculoskeletal tumours of the trunk in our hospital from 1 April 2008 to 31 August 2023. The incidence of SSI and its risk factors were investigated., Results: SSI was observed in 26% (32/125), and the median time to SSI was 22 days. On multivariate analysis, the following were identified as risk factors for SSI: tumours arising caudal to Jacoby's line (hazard ratio [HR] 4.04; P = .0107), soft tissue reconstruction (HR 3.43; P = .0131), and low Geriatric Nutritional Risk Index (GNRI) (HR 0.96; P = .0304). Patients were classified into two risk categories based on GNRI scores: the risk group (GNRI ≤98) and no risk group (>98). The risk group showed a significantly lower overall noninfection survival rate (P = .023)., Conclusion: Tumours arising caudal to Jacoby line, soft tissue reconstruction, and lower GNRI were risk factors for SSI. Preoperative and postoperative nutritional interventions should be considered to improve GNRI., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to determine the anti-inflammatory activities and bioactive compounds of soymilk yogurt prepared using Lactiplantibacillus plantarum TOKAI 17 or Pediococcus pentosaceus TOKAI 759 m. Mice were divided into five groups: normal diet (ND), soymilk, soymilk yogurt using L. plantarum TOKAI 17 (SY 17) or P. pentosaceus TOKAI 759 m (SY 759 m), and 0.5 × 109 cells of each starter strain (BC 17 or BC759m). In the SY 759 m group, the serum pro-inflammatory cytokine levels and the cytotoxicity of natural killer cells were attenuated compared to the ND group. In the cecum microbiota, the abundances of butyrate-producing bacteria increased in the SY 759 m and BC 17 groups. Furthermore, SY 759 m metabolites contained high levels of aglycone isoflavone, adenine and showed a significant decrease in CCL-2 and interleukin-6 production in lipopolysaccharide-induced macrophage. In conclusion, soymilk yogurt produced using P. pentosaceus TOKAI 759 m modulates the gut microbiota and can potentially prevent pro-inflammatory cytokine production., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Objectives: The current study compared the outcome after orthopaedic surgeries in patients with rheumatoid arthritis receiving Janus kinase inhibitors (JAKis) versus biologic disease-modifying anti-rheumatic drugs (bDMARDs)., Methods: This was a retrospective observational study of Japanese patients with rheumatoid arthritis. Sixty-two patients with rheumatoid arthritis using JAKi preoperatively underwent orthopaedic surgeries. Using propensity score matching, these 62 patients were matched with 62 patients using bDMARDs preoperatively. The number of adverse events was counted. We also examined whether the drug-withholding period in the JAKi-treated group was associated with the occurrence of major postoperative adverse events, namely inflammatory flares and delayed wound healing., Results: JAKi-treated patients had a higher incidence of postoperative flares than bDMARD-treated patients (29% versus 12.1%, P = .01). The incidences of postoperative complications other than flares were not significantly different between the two groups. Among the JAKi-treated group, a longer perioperative drug-withholding period (≥11 days) was associated with a higher incidence of postoperative flares (P = .04). The incidences of delayed wound healing and surgical site infection were not associated with the duration of the JAKi-withholding period., Conclusions: JAKi-treated patients had a higher incidence of postoperative flares than bDMARD-treated patients. A total of ≥11 days of drug withdrawal was associated with postoperative flares., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA., Methods: We extracted 190 hips over two periods, i.e. the early period (1998-2003) and the late period (2013-19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty., Results: A comparison of the two periods' data showed that the degree of inward migration (-3.44 vs. -7.45 mm; P < .001) and upward migration (+4.3 vs. +0.95 mm; P < .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P < .001)., Conclusions: The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The study aimed to comprehend the clinical features and outcomes of surgical treatments for spinal disorders in patients with ankylosing spondylitis (AS)., Methods: This retrospective study enrolled patients with AS who underwent spine surgery between 2000 and 2019 in our facility., Results: Thirteen patients with AS underwent spine surgeries. The mean age was 56.2 years, and the mean disease duration was 25.1 years at the time of surgery. Nine patients had vertebral fracture, two had kyphotic deformity, and two had myelopathy due to the spinal ligament ossification. Fracture cases included five patients with secondary pseudarthrosis/delayed palsy due to conservative treatment failure. Spinal fixation was performed in all patients. Pedicle subtraction osteotomy for kyphosis and laminectomy for myelopathy were also conducted. All patients improved after surgeries. One patient with kyphotic deformity underwent additional surgery of bilateral hip prosthesis, which resulted in better spine alignment. Four cases of perioperative complications were observed., Conclusion: Myelopathy was newly found as the aetiology requiring surgery in patients with AS. This summarized case series could help physicians to identify patients with surgically treatable spinal disorders among patients with AS., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to clarify the relationship between vitamin D status and complications after periacetabular osteotomy., Methods: A total of 46 hips of 39 patients (3 men and 36 women; mean age at surgery, 41.0 years; mean postoperative follow-up duration, 63 months) were reviewed to obtain the following information: patients' serum 25-hydroxyvitamin D [25(OH)D] status, prevalence of postoperative delayed union of osteotomy sites in the greater trochanter (DUGT) and ischiopubic stress fractures (IPSFs), and risk factors., Results: The mean serum 25(OH)D level was 11.9 ng/ml. DUGT and IPSF were found in four (10.3%) and three (7.7%) patients, respectively. Serum 25(OH)D levels ≤ 11 ng/ml were significantly associated with DUGT in female patients (p = .02). Serum 25(OH)D levels ≤ 9 ng/ml and smoking were significantly associated with IPSF (p = 0.01 and 0.02, respectively). Overall, 21.7% of patients with serum 25(OH)D levels ≤ 11 ng/ml developed at least one complication; no complications occurred when serum 25(OH)D levels were >11 ng/ml., Conclusion: Severe vitamin D deficiency was highly prevalent in relatively young patients. Vitamin D deficiency and smoking were independent risk factors for postoperative complications. Proactive supplementation is advisable to reduce postoperative complications, especially in patients with serum 25(OH)D levels ≤ 11 ng/ml., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Postpartum depression is experienced by approximately 10% of women and affects the health and development of their children. Although it is recommended that all mothers have the opportunity for early detection and intervention for postpartum depression, it is unclear whether early postpartum check-ups help to reduce postpartum depression., Objective: The aim of this study was to assess the effect of 2-week postpartum check-ups on screening positive for postpartum depression in Japan., Methods: This was a population-based cohort study that used the administrative database of Tsuyama, Japan. Participants were women who received postpartum home visits from a public health nurse in Tsuyama during the fiscal years 2017-2019. Data were obtained on participant's attendance at a 2-week postpartum check-up and their responses on the Edinburgh Postpartum Depression Scale. Owing to the initiation of a publicly funded postpartum check-up programme, participants were pseudo-randomly assigned to receive/not receive a 2-week postpartum check-up. We conducted instrumental variable estimation to assess the causal effects of the check-up on screening positive for postpartum depression., Results: The characteristics of the 1,382 participants did not differ by fiscal year of childbirth. We found a 6.7% (95% confidence interval 2.2-11.2) reduction in the prevalence of screening positive for postpartum depression as an effect of 2-week postpartum check-ups among women received 1-month postpartum home visits., Conclusion: The results suggest that 2-week postpartum check-ups are effective in reducing the prevalence of screening positive for postpartum depression among 1-month postpartum women. Despite some limitations, early postpartum care could reduce postpartum depression., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: The purpose of the present study was to evaluate improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) after open-wedge high tibial osteotomy (HTO) in comparison with total knee arthroplasty (TKA) in cohorts over age 60 matched by pre-operative age, gender, body mass index (BMI), hip-knee-ankle angle (HKAA), KOOS sub-scores, and osteoarthritis (OA) grade., Methods: Propensity score matching was performed between 162 HTO patients and 134 TKA patients. When calculating the propensity score by multivariate logistic regression analysis, the following pre-operative confounders were included: age, gender, BMI, HKAA, KOOS sub-scores, and OA grade. Consequently, a total of 55 patients were included in each group. The Student's t-test was used to analyse differences in the post-operative KOOS sub-scores between groups., Results: After propensity score matching, all matched pre-operative valuables were identical, with no significant differences between the HTO and TKA groups. None of the post-operative KOOS sub-scores at 1 year after surgery showed a significant difference between the HTO and TKA groups. Both groups demonstrated significant and comparable post-operative improvement in every KOOS sub-score., Conclusions: In patients over age 60, there was no significant difference in short-term pain relief and improvements in activity and quality of life between HTO and TKA after propensity score matching including pre-operative age, KOOS sub-scores, and OA grade. HTO is a joint preservation procedure that is valid for knee OA even in individuals over age 60., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The protamine-derived peptide arginine-proline-arginine (RPR) can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 m m oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium triglyceride (TG) level compared with the OA group. Stearoyl-CoA desaturase-1 (SCD1) or sterol regulatory element-binding protein 1 (SREBP1) protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared with the OA group. Moreover, the effect of RPR disappeared when the peptide transporter 1 (PepT1) was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

To our knowledge, only one previous report described the treatment of osteochondral autograft for steroid-induced osteonecrosis of the humeral head (ONHH) in a middle-aged patient. The present report describes a 20-year-old man who was found to have avascular osteonecrosis of the right humeral head after corticosteroid pulse treatment, followed by oral corticosteroid therapy. The patient complained of serious right shoulder pain and limited range of motion (ROM). Anteroposterior (AP) radiographs of the right shoulder revealed a crescent sign at the humeral head, indicating subchondral bone collapse with a linear sclerotic change and normal articular surface of the glenoid. The case was categorized as Stage 3 according to the Cruess classification. In general, Cruess classification Stage 3 is treated with humeral head replacement and shoulder arthroplasty. The patient underwent surgical treatment involving osteochondral autograft transplantation. Autografts were harvested from the right knee. At the 1.5-year follow-up, the patient was pain-free and showed an improved active ROM. Furthermore, AP radiographs demonstrated that the glenohumeral joint space was maintained, and no progression of humeral head collapse was observed. This case may be helpful in decision-making if young patients with ONHH require surgical treatment. Furthermore, osteochondral autograft transplantation may be an effective treatment for ONHH., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a spectrum of heterogeneous diseases commonly recognised by skin and osteoarticular lesions. There have been reports of some surgical cases of the progressive, destructive spondylitis associated with SAPHO syndrome, wherein the destructive spondylitis was considered to have developed due to the progression of spondylitis with SAPHO syndrome as the pathogenic bacteria were not isolated. We herein report a surgical case of destructive cervical spondylitis associated with SAPHO syndrome. A 54-year-old woman with a history of palmoplantar pustulosis suffered severe neck pain for 6 months. Radiography and computeed tomography showed sclerosed and collapsed cervical vertebrae, and the patient was referred to our hospital for further evaluation and management upon suspicion of infection or spondylitis with SAPHO syndrome. For the severe neck pain and progressive destruction of cervical vertebrae, we performed posterior fusion surgery with subsequent anterior fusion. Cutibacterium acnes (C. acnes) was isolated by enrichment culture with thioglycolate broth from both the anterior and the posterior tissue samples. We diagnosed pyogenic spondylitis secondary to C. acnes infection and administered doxycycline for 6 weeks after the first surgery. The neck pain was resolved and cervical fusion was achieved one year postoperatively. C. acnes infection could elicit destructive spondylitis. An enrichment culture should be performed to isolate the pathogenic bacteria in cases of destructive spondylitis with SAPHO syndrome., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To decrease hip abductor dysfunction after periacetabular osteotomy using a lateral/trochanteric approach, we aimed to modify transposition osteotomy of the acetabulum (TOA) to not cut the greater trochanter and abductor-iliac crest detachment. We subsequently compared abductor muscle strength recovery between TOAs with [conventional TOA (C-TOA)] and without [modified TOA (M-TOA)] trochanteric osteotomy. C-TOA and M-TOA were performed in 27 and 34 hips, respectively. Hip abduction, flexion and knee extension muscle strength were measured preoperatively and at 3, 5, 10, 24 and 52 weeks postoperatively. The muscle strength ratio of the affected and contralateral lower limbs was compared between the C-TOA and M-TOA groups. Neither the mean Merle d'Aubigné-Postel score at the final follow-up nor the postoperative center-edge angle showed significant differences between the M-TOA and C-TOA groups (15.7 versus 16.4 points; P  = 0.25 and 38.5° versus P  = 0.62 and 39.8°, respectively). The mean muscle strength ratios of hip abduction at 5, 12 and 24 weeks postoperatively were significantly higher in the M-TOA group than in the C-TOA group (0.62 versus 0.39, 0.76 versus 0.59 and 0.94 versus 0.70; P  = 0.03, 0.04 and 0.01, respectively). There were no significant differences between groups at Postoperative Week 52 ( P  = 0.36). Discomfort at the greater trochanter was observed in 18 hips (66.7%) in the C-TOA group but only in 4 hips (11.2%) in the M-TOA group. In conclusion, M-TOA is less invasive than C-TOA and allows an earlier recovery of abductor muscle strength without significant correction loss., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: The aim of this study was to investigate the efficacy and safety of tranexamic acid in patients undergoing surgery for bone and soft tissue tumors., Methods: Data were retrospectively collected from 454 consecutive patients with bone and soft tissue tumors who underwent open biopsy, marginal resection, curettage or wide resection between January 2017 and December 2018. We performed propensity score matching of patients who received tranexamic acid with those who did not. The primary outcome variables were intra-operative, peri-operative and estimated blood loss (IBL, PBL and EBL, respectively)., Results: Tranexamic acid (+) and tranexamic acid (-) groups were defined according to whether patients received tranexamic acid or not. Among the 454 patients, open biopsy was performed in 102, marginal resection in 175, curettage in 54 and wide resection in 123. Intra-operative blood loss was significantly lower in the tranexamic acid (+) group than in the tranexamic acid (-) group for both marginal and wide resection (marginal resection: 17.3 vs. 70.3 g, respectively, P = 0.045; wide resection: 128.8 vs. 273.1 g, respectively, P = 0.023). Peri-operative blood loss and estimated blood loss were also significantly lower in the tranexamic acid (+) group for wide resection (peri-operative blood loss: 341.5 vs. 686.5 g, respectively, P = 0.0039; estimated blood loss: 320.7 vs. 550.6 ml, respectively, P = 0.030). No venous thromboembolism occurred in either group., Conclusion: This study suggests that TXA administration safely and effectively reduces blood loss, in particular for wide resection, with no increase in the rate of adverse events., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan., Methods: The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features., Results: The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400-3900) and 800 (530-1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing., Conclusion: This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

In this study, the spatial counting statistics of free electron beams, which were released via field emission from cold metal and propagated through a vacuum region, were investigated to examine the normal functioning of the counting equipment for electron correlation spectroscopy. The beam electrons were recorded separately according to the locations of individual events as they reached the direct detection transmission Complementary Metal Oxide Semiconductor (CMOS) sensor. We examined the spatial point patterns arising from the locations of the individual events of each primary electron being detected in the case of electrons in a state in which the wave function is constant on the sensor. The quadrat method, which compares the observed frequencies of the number of electron counts in the subsets of the study region with the predicted frequencies from a Poisson distribution, indicates a clustering-type departure from complete spatial randomness. To explore some of the basic principles governing the location of coherent electrons being counted, Ripley's K-function and the corresponding L-function of a stationary spatial point process were used to test the complete spatial randomness from the data. The maximum peak in the average of the L-functions was sensitive only to the mean counts per frame. Thus, clustering of spatial point patterns may result from abnormalities in the direct detection camera. When the interaction of the beam electrons with the sensor is included in the simulation, there is a reasonable match between the average of the L-functions and the experimental curves with the theoretically simulated curves., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term., Methods: Of the 663 patients enrolled in the 2 studies, 559 patients' follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed., Results: Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively., Conclusions: VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes., Subj Collection: 152, 1542., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients., Methods: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle., Results: Median follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation., Conclusions: This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Long working hours in Japan is a social concern. This is also true for the working hours of physicians, who often do side work in addition to working at their main hospital. New physician work regulations to be implemented in Japan require work-hour management, including side work. This study examined the association between physicians' overtime and side work hours and their health outcomes., Methods: We conducted a cross-sectional study using data from a survey of working physicians conducted by the Japan Medical Association from 2021 to 2022. Questionnaires completed by 2906 full-time working physicians aged 24-69, excluding junior resident doctors, were analyzed. Depressive symptoms and the presence of thoughts of death or suicide using the Quick Inventory of Depressive Symptomatology - Japanese version was used to assess health outcomes. Logistic regression analysis was performed using overtime at the main place of employment and side work hours as exposure factors., Results: Both depressive symptoms and thoughts of death or suicide increased in the group with longer overtime hours at the main place of work. A similar tendency was observed for side work but adjusting for overtime hours eliminated the association. In other words, total working hours had an impact on health, regardless of whether overtime work at the main place of employment or side work., Conclusions: Despite the existence of multiple hurdles to managing working hours, including side work, the working environment for physicians needs to be improved to protect their health and quality of medical care., (© 2022 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Potential health benefits of melatonin have been suggested. Although melatonin is present in various foods, little is known about the health effects of dietary melatonin intake. We estimated habitual dietary melatonin intake and examined its association with total and cause-specific mortality in a population-based cohort study in Japan. Study subjects included 13,355 men and 15,724 women aged ≥35 years who responded to a self-administered questionnaire in 1992. Their diets were assessed via a food frequency questionnaire at baseline. The melatonin content in various foods on the questionnaire was measured to estimate melatonin intake. Mortality was ascertained during 16 years of follow-up (1992-2008). Hazard ratios (HRs) and 95% confidence intervals (CIs) for total and cause-specific mortality were calculated according to melatonin quartiles. A total of 5,339 deaths occurred during follow-up. Melatonin intake was significantly associated with decreased risks of total mortality, cardiovascular mortality, and noncancer, noncardiovascular mortality after controlling for covariates; HRs for the highest quartile of melatonin intake versus the lowest were 0.90 (95% CI: 0.82, 0.98; P for trend = 0.05), 0.85 (95% CI: 0.72, 0.99; P for trend = 0.10), and 0.77 (95% CI: 0.67, 0.90; P for trend = 0.003), respectively. The data suggest a potential benefit of dietary melatonin with regard to mortality rates., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Movement is a fundamental characteristic of animals, but challenging to measure noninvasively. Noninvasive methods for measuring travel have different weaknesses, so multiple techniques need to be applied multiple techniques for reliable inferences. We used two methods, direct tracking and camera trapping, to examine the variation in time and seasonal differences in movement rates of mandrills ( Mandrillus sphinx ), an elusive primate that lives in large groups in central Africa. In a 400-km 2 rainforest area in Moukalaba-Doudou National Park, Gabon, we tracked unidentified groups 46 times from 2009 to 2013. We systematically placed 157 terrestrial camera traps in the same area from 2012 to 2014 and recorded groups 309 times. Generalized additive mixed models (GAMMs) of the tracking data indicated that the group travel speed varied with time and season. In the fruiting season, the movement rate fluctuated with time in a bimodal pattern, whereas in the nonfruiting season, it increased monotonously with time. The predicted day range was longer in the fruiting season (6.98 km) than in the nonfruiting season (6.06 km). These seasonal differences suggest responses to changes in food resources and temperature. Camera-trap detection rates showed similar temporal and seasonal patterns to the tracking data, allowing us to generalize our findings to the population level. Moreover, cameras never detected mandrills at night, and we observed that they slept high in trees and hardly moved until the next morning, all suggesting their strict avoidance of nighttime movement. This study demonstrated the significance of the multiple-method approach in drawing robust conclusions on temporal patterns of animal movement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Mammalogists.)

Background: Soft tissue sarcomas arise in the deep sites of the buttocks and lower extremities. Since a tourniquet is not applied during surgery for soft tissue sarcomas at such sites, excessive intraoperative blood loss may occur. Various devices, including LigaSure™ (Medtronic, Dublin, Ireland), are used as electrothermal bipolar vessel sealers. However, its clinical relevance in soft tissue sarcomas surgery remains unclear. This study aimed to assess the effectiveness of LigaSure™ in soft tissue sarcomas surgery., Methods: This study included 168 patients who underwent surgeries for soft tissue sarcomas in the deep sites in the buttocks and lower extremities between January 2004 and March 2018. The primary outcome was intraoperative blood loss, and secondary outcomes were surgery duration, wound complications, perioperative haemoglobin concentrations and intraoperative blood transfusion. To reduce selection biases, propensity score matching was applied. We defined the matched cases wherein LigaSure™ was used as the 'using group' and the other matched cases as the 'non-using group'. Outcomes were compared between both groups., Results: From each group, 35 cases were selected using propensity score matching. The intraoperative blood loss was significantly smaller statistically in the using group (181.5 ± 240.4 ml vs. 394.7 ± 547.3 ml, respectively; P = 0.041). The duration of operation was longer in the using group (189.9 ± 97.6 min vs. 140.6 ± 75.7 min, respectively; P = 0.007). There were no significant differences in other outcomes., Conclusion: By using LigaSure™ for soft tissue sarcomas occurring in the buttocks and lower extremities, we observed a trade-off between reduced intraoperative blood loss and longer operative time., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: This study aimed to report the mid-term radiological outcomes of patients with bipolar hemiarthroplasty (BHA) for stage 3 osteonecrosis of the femoral head (ONFH), and to identify the risk factors for postoperative radiological changes., Methods: We retrospectively investigated 62 patients (38 men and 24 women; mean age, 50.1 years) aged <70 years who underwent primary BHA for Association Research Circulation Osseous stage 3 ONFH between 1998 and 2010. The mean follow-up period after BHA was 12.8 years. The following changes were assessed on follow-up radiographs: outer head migration, polyethylene wear, and femoral osteolysis. The association between demographic data and the development of postoperative radiological changes was evaluated., Results: Radiological changes were found in 20 hips (32.3%) at a mean of 8.1 years after BHA; of these, three hips (4.8%) underwent total hip arthroplasty conversion at a mean of 10.9 years after BHA. Both univariate and multivariate analysis revealed that younger age and female sex were independent risk factors for the development of postoperative radiological changes., Conclusion: The current results suggest that the indication of BHA should be carefully determined in young or female patients with ONFH, even when the disease is in the early stage.

Objectives: Delayed wound healing is one of the most common complications following forefoot surgery in patients with rheumatoid arthritis. We aimed to identify the risk factors for delayed wound healing following rheumatoid forefoot surgery., Methods: Consecutive patients who underwent primary rheumatoid forefoot surgery (86 feet; 53 patients) between April 2008 and February 2019 were retrospectively evaluated. Clinical data, including smoking history, duration of the disease, presence of diabetes mellitus, medication, white blood cell count, erythrocyte sedimentation rate (ESR), C-reactive protein, the surgical procedure performed, and the Japanese Society for Surgery of the Foot (JSSF) scores, were collected., Results: Delayed wound healing was identified in 20 of 86 (23.3%) feet. In univariate analysis, participants showing delayed healing were older at the time of surgery ( p  = .04), their ESR was higher ( p  = .0006), and their total ( p  = .019) and pain ( p  = .016) scores on the JSSF Lesser toe scale were lower than those showing normal healing. In multivariable analysis, both the total preoperative JSSF Lesser toe scale score ( p  = .0239) and ESR ( p  = .0126) remained significant risk factors for delayed wound healing., Conclusions: After rheumatoid forefoot surgery, surgeons should pay more attention to wound care in patients with lower preoperative JSSF Lesser toe score and high ESR.

Small RNAs (sRNA) are non-cording RNAs composed of 50∼400 nt responsible for coordinating the adaption of Escherichia coli and other bacteria to changing environmental conditions, including pH and temperature. However, the role of sRNAs in lactic acid bacteria (LAB) has not yet been clarified. In this study, we used the Lactobacillus casei-Pediococcus group to evaluate the function of sRNAs in LAB, using RNA sequencing in the exponential growth phase and stationary phase to map and analyze sRNA fragments, which were categorized as Pediococcus pentosaceus and Lactobacillus paracasei. We evaluated the role of sRNAs in nutrient synthesis for cell growth in exponential growth phase and in protein and biofilm biosynthesis for cell body durability. During exponential growth, the sRNA fragments were found to be involved in the stress response in Pediococcus pentosaceus and in environmental adaption in Lactobacillus paracasei. The results suggest that the function of sRNA can be characterized from sRNA fragments using RNA sequencing during the exponential growth and stationary phases in Lactobacillus casei-Pediococcus group., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting. Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI). Results: At baseline, the patients' mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were naïve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to -0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified. Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period.

Objectives: This retrospective study aimed to assess long-term hip survival after transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) and identify factors influencing patient-reported outcome measures (PROMs) in patients with preserved joints. Methods: Altogether, 95 consecutive hips in 85 ONFH patients who underwent ARO during 2000-2007 (86.7% follow-up) were studied. Controls were 35 patients with 41 hips with ONFH managed conservatively for >1 year after collapse. We analyzed hip survival using the Kaplan-Meier method, with the endpoint defined as any therapeutic surgery related to ONFH. We also evaluated PROMs for both groups in patients with surviving hips and available radiographs at the final follow-up. Results: The 10-year hip survival rate after ARO was 85.4%, which was significantly higher than the 5-year rate in the control group (50.4%). Multiple regression analyses showed that the presence of osteoarthritic change after ARO was significantly associated with poor scores for both the Oxford Hip Score and the Short Form-12 Health Survey Physical Component Summary. Conclusions: ARO could effectively preserve hip joints with post-collapse ONFH, although the presence of osteoarthritic change could lead to lower satisfaction even among patients with long-term hip survival after ARO.

Objectives: This study retrospectively investigated the mid-term outcome of Legacy constrained condylar knee (LCCK) prosthesis in patients with rheumatoid arthritis (RA) having severe varus/valgus deformity, instability, and/or bone loss. Methods: Between January 2000 and December 2015, LCCK prostheses had been performed in 32 knees of 25 patients with RA, and 23 knees of 17 patients of the postoperative follow-up minimum 2 years were analyzed in this study (Primary: 14 knees, Revision: 9 knees). The average of follow-up duration was 6.9 ± 2.7 years, all were female, and the average of age and RA duration at the surgery was 59.0 ± 9.5 years and 26.6 ± 13.5 years, respectively. Clinical result was analyzed by Knee Society Score (KSS) knee and function at preoperative time and final visit. Imaging outcome was investigated by femoral tibial angle (FTA), four component alignment angles, and radiolucent line at pre-/postoperative time. Results: KSS knee/function scores and radiographic FTAs were improved after operation. Radiolucent lines around components were seen in 17 knees (73.9%), of which only one knee (4.3%) has shown aseptic loosening. The seven-year Kaplan-Meier survivorship analysis resulted in 91.7%. Conclusion: LCCK prosthesis in RA patients was achieved to the excellent mid-term clinical and radiographic result.

The aim of this study was to determine the expressions of Toll-like receptors (TLRs) 7-9 and type I interferon (IFN) signal in labial salivary glands (LSGs) and cultured salivary gland epithelial cells (SGECs) from primary Sjögren's syndrome (pSS) patients. We performed an immunohistochemistry analysis of LSGs from 11 patients with pSS as defined by American-European Consensus Group classification criteria and five healthy subjects. The pSS patients' SGECs were analyzed by immunofluorescence and western blotting. IFN-α expression was examined by immunosorbent assay and flow cytometry. Mononuclear cells (MNCs) from pSS patients' LSGs showed TLR-7-dominant expression. B cells, plasma cells and plasmacytoid dendritic cells (pDCs) co-expressed with TLR-7. Myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interferon regulatory factor 7 (IRF7) co-expressed with the pDC marker CD303 in LSGs. Ducts from pSS patients dominantly expressed TLR-7, and TLR-7 in the ducts co-expressed with MyD88, TRAF6 and IRF7. Type I IFNs including IFN-α and IFN-β were detected in MNCs and ducts in pSS patients' LSGs. Increased TRAF6 expression and the nuclear translocation of IRF7 in SGECs were detected by immunofluorescence following loxoribine (a TLR-7 ligand) stimulation despite IFN-β pretreatment. Western blotting showed increased TRAF6 expression in SGECs following IFN-β and loxoribine stimulation. Although no increase in IFN-α was detected in supernatant from stimulated SGECs, the IFN-α in supernatant from stimulated peripheral blood pDCs from pSS patients was significantly increased. Our findings suggest that TLR-7 is dominantly expressed in both MNCs and ducts with downstream signals for type I IFNs, indicating that TLR7-dominant innate immunity is related to the development of sialadenitis in pSS., (© 2018 British Society for Immunology.)

This study evaluated the immunostimulative effect on bone marrow-derived dendritic cells (DCs) of adjuvant-active exopolysaccharide (EPS) produced by Leuconostoc mesenteroides strain NTM048. EPS stimulation increased IL-6, IL-10, IL-12, and retinal dehydrogenase (RALDH) gene expression levels and induced retinoic acid-synthesizing RALDH-active DCs, which play a crucially important role in controlling adaptive immune responses in mucosa.

We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO.

Objective: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response., Methods: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of 'good clinical response' was a decrement of disease activity score (DAS) 28 ≧ 1.2 at three months with achievement of DAS28 remission through 6-12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS) > 0 was defined as 'radiographic progression'. Predictors of radiographic progression were determined by logistic regression analysis., Results: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p = .032)., Conclusions: Our data suggest that MRI bone erosion predicts poor radiographic outcome of early-stage RA even if it has been successfully treated.

Objectives: To determine the prevalence of ultrasonographic abnormalities of sternoclavicular joints (SCJ) and peripheral joints (PJ) in patients with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome., Methods: Thirteen patients with SAPHO syndrome who fulfilled diagnostic criteria proposed by Kahn for SAPHO syndrome 2003 and 13 healthy individuals age- and sex-matched were enrolled. Synovitis, defined by synovial hypertrophy with power Doppler (PD) signals, of the SCJ and the PJ including wrist, MCP, PIP, and the other symptomatic joints were evaluated by ultrasound (US)., Results: Synovitis with PD signals was detected in 16 (61.5%) of the 26 SCJ and 11 (84.6%) of the SAPHO syndrome patients, and none of the controls. Synovitis with PD signals in any PJ was detected in 4 (30.7%) of the SAPHO syndrome patients., Conclusions: Synovitis of the SCJ and PJ in SAPHO syndrome was detectable by US with a PD method. US can be useful for the diagnosis of SAPHO syndrome.

Objectives: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA., Methods: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan-Meier method, and the associated influencing factors were determined., Results: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals., Conclusions: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.

Objective: The purpose of this study was to clarify the minimum joint space width (MJSW) that leads to subchondral bone exposure (SBE) in patients with hip dysplasia., Methods: We included 82 subjects (86 hips) who had hip dysplasia with center-edge angle less than 20° and who underwent periacetabular osteotomy combined with hip arthroscopy. The acetabular and femoral cartilages were divided into three regions: anterosuperior, superior, and posterosuperior; for each region, we analyzed the correlation between the incidence of SBE and the MJSW measured on plain radiographs. The disease stage was defined according to the Kellgren and Lawrence grades (KL grade)., Results: SBE was found in 51 hips (59.3%) in total, involved the acetabulum in 49 hips (57.0%), and involved the femoral head in 26 hips (30.2%). SBE was more frequent in the acetabulum, with the highest incidence in the anterosuperior region, followed by the superior region. SBE was present in six hips (22.2%), 17 hips (56.7%), and 28 hips (96.5%), at KL-1, KL-2, and KL-3, respectively. MJSW of hips with SBE was significantly smaller than those without SBE (2.3 vs 4.0 mm, p < 0.001), and the cut-off value for MJSW that led to SBE was 3.7 mm (sensitivity: 0.902, 1 - specificity: 0.343). SBE was present in 23.3% in patients with MJSW ≥3.7 mm, whereas 76.7% in those <3.7 mm., Conclusions: Cartilage degeneration is more advanced than would be predicted on plain radiographs. The cut-off value of MJSW for SBE was 3.7 mm in patients with symptomatic hip dysplasia.

Objective: We evaluated whether the early responsiveness of ultrasound synovitis can predict the clinical response in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs)., Methods: Articular synovitis was assessed by ultrasound at 22 bilateral wrist and finger joints in 39 RA patients treated with bDMARDs. Each joint was assigned a gray-scale (GS) and power Doppler (PD) score from 0 to 3, and the sum of the GS or PD scores was considered to represent the ultrasound disease activity. We investigated the correlation of the change in ultrasound disease activity at three months with the EULAR response criteria at six months., Results: GS and PD scores were significantly decreased at three months (p < 0.0001). The % changes of the GS and PD scores at three months were significantly higher at six months in moderate and good responders compared with non-responders (p < 0.05). These tendencies were numerically more prominent if clinical response was set as good responder or Disease Activity Score 28 remission. Poor improvement of ultrasound synovitis scores had good predictive value for non-responders at six months., Conclusions: The responsiveness of ultrasound disease activity is considered to predict further clinical response in RA patients treated with bDMARDs.

The predominant histological types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. Since these two histological types present as different diseases in terms of their epidemiology, pathologenesis, and tumor biology, separate therapeutic approaches should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), their high rates of tumor recurrence have prompted investigation of multimodality therapies that combine surgery with chemotherapy, radiotherapy, and chemoradiotherapy. In Japan, preoperative chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) followed by radical esophagectomy has been accepted as the standard therapeutic approach for resactable clinical Stage II/III ESCC. Similarly, the CDDP and 5-FU regimen has been accepted as the first-line treatment for metastatic and unresectable ESCCs in Japan. Thus, in Japan chemotherapy is an indispensable component of therapy for both resectable and unresectable ESCCs. This review discusses the current knowledge, rationale, and available data regarding chemotherapy for resectable and unresectable ESCCs., (© 2016 International Society for Diseases of the Esophagus.)

Objective: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice., Method: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria., Results: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%)., Conclusions: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.

Kawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person-to-person and does not occur in clusters within households, schools or nurseries. KD is a self-limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen-associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD-specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe-associated molecular patterns (MAMPs), as shown by liquid chromatography-tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe-derived innate immune stimulants and that it is not a typical infectious disease., (© 2016 British Society for Immunology.)

Objective: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response., Methods: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC., Results: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60 kg) as compared with the groups with body weight <60 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC., Conclusions: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV.

Objectives: The aim of this study was to clarify the molecular mechanisms elicited by toll-like receptor (TLR)3 in salivary gland cell death in patients with SS., Methods: Expression of TLR3 and its downstream molecules was examined by immunohistochemical analysis, immunofluorescence, Western blot (WB), and antibody dot-blot array in labial salivary glands (LSGs), and cultured primary salivary gland epithelial cells (SGECs) obtained from patients with SS. We also investigated the difference of expression between ducts/alveoli of LSGs and cultured SGECs., Results: Phosphorylated Fas-associated protein with death domain (p-FADD) or caspase-8 was not found in ducts or alveoli of LSGs from SS patients and controls. Weak expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) was found in SS patients, whereas no staining was observed in LSGs of controls. In contrast to LSGs, stimulation of SGECs with polyinosinic:cytidylic acid (poly I:C) significantly induced the expression of RIPK3, p-FADD, and cleaved caspase-8 by immunofluorescence and RIPK3, p-FADD, and cleaved caspase-3 by WB. However, it was counteracted by epidermal growth factor (EGF). Co-localization of anti-apoptotic molecules hemeoxygenase-2, heat shock protein 27, and p-protein kinase B or p-Akt was induced in EGF-stimulated SGECs., Conclusions: We observed that poly I:C induced apoptosis of SGECs in vitro compared with a relatively low prevalence of apoptosis found in the ducts and alveoli of LSGs in vivo. Thus, we speculate that other counter-regulatory mechanisms, including those induced by EGF, might exist to protect against TLR3-mediated apoptosis of ductal and acinar epithelial cells in vivo.

Objectives: The aim of this study is to identify variables at diagnosis to predict the subsequent relapse in patients with Takayasu arteritis (TA)., Methods: We retrospectively analyzed 33 patients with TA in our hospitals from April 2000 to July 2015. We collected baseline variables at diagnosis including clinical symptoms and laboratory data using medical records and investigated associations of these indices with subsequent relapses., Results: The patients included two males and 31 females (94%). The median age at diagnosis was 39 years old, and the median follow-up duration was 90 months. Relapse was noted in 18 patients (55%). Only lower total cholesterol (Tcho) [median, 117 mg/dL (relapse) vs. 182 mg/dL (nonrelapse)] was preferentially distributed in the relapse group as compared with the non-relapse group. Multivariable logistic analysis showed that hypocholesterolemia (<150 mg/dL) at diagnosis was the only predictor of subsequent relapse (odds ratio: 5.43, 95% confidence interval: 1.13-30.19; p = 0.035). The nonrelapse survival rate was significantly lower in the group with a Tcho level <150 mg/dL by Kaplan-Meier estimate (p < 0.001)., Conclusions: We found that hypocholesterolemia at diagnosis is a predictor of subsequent relapse in patients with TA.

Objectives: This study was conducted to evaluate the period from symptom onset to diagnosis of ankylosing spondylitis (AS) in Japanese patients and to examine possible reasons for delayed diagnosis., Methods: Seventy-two consecutive patients with AS were studied. Diagnostic delay was defined as the gap between the first spondyloarthropathic symptom and diagnosis of AS according to the modified New York criteria., Results: The mean patient ages at disease onset and diagnosis were 25.6 ± 11.3 and 33.3 ± 13.2 years old, respectively, resulting in diagnostic delay of 6.7 years. The number of medical institutions to which patients were referred before diagnosis was 2.4, and orthopedic surgeons were most commonly visited (62%). Non-specific low back pain or lumbar spondylitis (33%) and degenerative arthritis (28%) were the primary diagnoses preceding that of AS. Absence of articular symptoms significantly correlated with diagnostic delay. The patients with disease onset on year 2000 or later had significantly shorter periods until diagnosis than those before 2000 (3.6 vs. 7.5 years)., Conclusions: The present study showed a marked diagnostic delay among Japanese patients with AS. Although it has been improved, continuing medical education focusing on inflammatory back pain in adolescent is required for early diagnosis of AS.

Objectives: Total hip arthroplasty (THA) is often performed in the lateral decubitus (lateral) position. In this position, the pelvis may have various degrees of tilt leading to implant malposition. We sought to quantify the pelvic tilt in lateral position and further pelvic movement during surgery., Methods: In 95 cases with primary THA, three-dimensional pelvic tilts were quantified by superimposing images reconstructed from CT data onto antero-posterior radiographs taken in lateral position at set-up and after cup placement. Pelvises were fixed with a device compressing anterior superior iliac spines and sacrum., Results: Various degrees of pelvic tilt occurred compared to the supine position; sagittal: -3.1° (-25.5° to 10.2°), axial: 3.9° (-8.4° to 17°), coronal: 0.9° (-11.9° to 13.2°). Absolute changes more than 5° were observed 43%, 47%, and 12% in the sagittal, axial, and coronal planes, respectively. The more preoperative posterior pelvic tilt resulted in the more change in the sagittal plane. Further pelvic movement of about 3° in three planes were observed ranging from -11° to 20° after cup placement., Conclusion: This study showed various pelvic tilt and movement during THA. As pelvic tilt directly alters the cup orientation, its changes should be well understood. Improved tools for positioning and holding the pelvis are required.

A 63-year-old man with enlargement of the bilateral submandibular glands visited with elevated serum IgG4. A biopsy specimen showed plasma cell infiltration with more than 50% IgG4/IgG staining, suggesting the existence of IgG4-related disease (IgG4-RD). Positive anti-SS-A/Ro antibody and the labial salivary gland's biopsy suggested existence of primary Sjögren's syndrome (pSS). Administration of glucocorticoid improved the serum IgG4 level while reducing the submandibular gland lesions. Positive TUNEL staining suggested the coexistence of IgG4-RD and pSS.

Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in 2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI.

Objective: We have tried to clarify the clinical importance of the measurement of serum type-I interferon (IFN) in patients with anti-melanoma differentiation-associated gene 5 Ab (MDA5 Ab)-positive dermatomyositis (DM)., Methods: We studied 30 patients with DM: 10 were anti-MDA5 Ab-positive and 20 were anti-MDA5 Ab-negative. At each patient's initial visit, serum IFN-α, IFN-β, interleukin 18 (IL-18), ferritin, and the titer of anti-MDA5 Ab were measured using enzyme-linked immunosorbent assays (ELISAs). The associations between the IFNs and with the other variables were examined., Results: Rapidly progressive interstitial lung disease (RPILD) was confirmed in 10 patients, most of whom were complicated in the anti-MDA5 Ab-positive DM patients. The presence of clinically amyopathic dermatomyositis (CADM) as well as the serum concentrations of IFN-α and ferritin was significantly higher in the anti-MDA5 Ab-positive DM patients. Serum concentration of IL-18 did not differ between anti-MDA5 Ab-positive and anti-MDA5 Ab-negative groups; however, a positive correlation was found between IFN-α and IL-18 in the anti-MDA5 Ab-positive DM patients (r = 0.8139, p = 0.0146)., Conclusion: Serum IFN-α can be used as a useful biomarker in patients with anti-MDA5 Ab-positive DM, which may reflect the presence of RPILD.

Objective: To explore the clinical application of automated scanning of wrist and finger joints by an Automated Breast Volume Scanner (ABVS) in patients with rheumatoid arthritis (RA)., Methods: A total of 140 metacarpophalangeal (MCP) joints and 28 wrist joints from the 14 active RA patients were examined by both an ABVS system (the ACUSON S2000) from dorsal sites and by conventional ultrasonography (US) from multiple directions on the same day. We used a semiquantitative scale from 0 to 3 of synovial hypertrophy and the presence of bone erosion by grayscale for both methods; the efficacy of the two methods for identifying synovial hypertrophy and bone erosion were evaluated by kappa coefficient., Results: The scanning time of the ABVS was 2 min per patient and that of conventional US was 15 min per patient. The kappa coefficients of synovial hypertrophy in the MCP joints were 0.60 and 0.79 in wrist joints. These values were increased in the joints where synovial hypertrophy was moderate to severe (scores greater than 2). The kappa coefficients for the presence of bone erosion in the MCP joints were 0.74 and 0.93 in wrist joints., Conclusion: The present data showed a substantial agreement between ABVS and conventional US for assessments of the synovial hypertrophy and bone erosion of wrist and finger joints in patients with RA. Since ABVS can scan the wrist and finger joints automatically in a short time, ABVS is a helpful new ultrasonic method to examine joint injuries in patients with RA.

Esophagectomy, one of the most invasive of all gastrointestinal operations, is associated with a high frequency of postoperative complications and in-hospital mortality. The purpose of the present study was to determine whether exposure to the atomic bomb explosion at Hiroshima in 1945 might be a preoperative risk factor for in-hospital mortality after esophagectomy in esophageal cancer patients. We thus reviewed the outcomes of esophagectomy in 31 atomic bomb survivors with esophageal cancer and 96 controls (also with cancer but without atomic bomb exposure). We compared the incidences of postoperative complications and in-hospital mortality. Of the clinicopathological features studied, mean patient age was significantly higher in atomic bomb survivors than in controls. Of the postoperative complications noted, atomic bomb survivors experienced a longer mean period of endotracheal intubation and higher incidences of severe pulmonary complications, severe anastomotic leakage, and surgical site infection. The factors associated with in-hospital mortality were exposure to the atomic bomb explosion, pulmonary comorbidities, and electrocardiographic abnormalities. Multivariate analysis revealed that exposure to the atomic bomb explosion was an independent significant preoperative risk factor for in-hospital mortality. Exposure to the atomic bomb explosion is thus a preoperative risk factor for in-hospital death after esophagectomy to treat esophageal cancer., (© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)