Objective: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). Methods: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. Results: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. Conclusion These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.

Methods: We examined the computed tomography scans from the thoracic vertebra to the sacrum used to diagnose DISH in 140 patients (98 men and 42 women; average age, 78.6 years). We compared patients who did (n=52) and did not have (n=88) fractures at the continuous vertebral bodies fused by bone bridges. The relationship between the vertebral fractures and the maximum number of vertebrae that are bony cross-linked with contiguous adjacent vertebrae (max VB) from the thoracic vertebra to the sacrum or from the lumbar vertebra to the sacrum and proximal femur BMD were analyzed using a logistic regression model. Results: We found that after adjusting for the confounding factors, higher max VB, both from the thoracic vertebrae to the sacrum and the lumbar vertebrae to the sacrum, was associated with a higher risk of vertebral fractures. This difference was statistically significant. The risk was higher when only the lumbar vertebrae to the sacrum was considered (thoracic vertebrae to the sacrum: odds ratio, 1.21; p<0.05; lumbar vertebrae to the sacrum: odds ratio, 2.78; p<0.01). Moreover, low proximal femur BMD in DISH patients raises the fracture risk (odds ratio, 0.47; p<0.01). Conclusions Many continuous vertebral bone bridges, especially those that extend to the lumbar spine and low proximal femur BMD, are risk factors for fracture in DISH patients.

Methods: For this prospective multicenter study, 40 patients were followed up through radiologic and clinical examinations for at least 1 year postoperatively. All surgical procedures were either single- or double-level LLIF using bioactive porous titanium spacers without bone grafts. Results: Four patients were excluded from the study owing to aggravation from other comorbidities. Another 36 patients, including 26 and 10 with single- and double-level LLIFs, respectively, participated in the follow-up. The mean age at the time of surgery was 63.7 years. The mean operating time was 50.5 minutes per level. The mean estimated intraoperative blood loss was 11.6 mL per level. Clinical scores improved in all cases and were maintained throughout the follow-up period. The intervertebral bony union rates were 67.4% and 84.8% at 6 and 12 months, respectively. Endplate cyst signs were observed in 13.0% and 8.7% of patients at 6 and 12 months, respectively. Fused segmental angles were maintained throughout the follow-up period, indicating no cage subsidence. Conclusions Single- and double-level LLIFs using bioactive porous titanium spacers without bone grafts were found to be minimally invasive, resulting in clinical and imaging results comparable with conventional procedures. Therefore, this type of implant may be an option for minimally invasive spinal fusion surgery.

Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers. Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. Conclusions The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers. Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. Conclusions The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

A 14-year-old women who had a history of aortic root replacement at 7 years old admitted our hospital due to dilatation of aortic arch aneurysm. Loeys-Dietz syndrome was diagnosed when she was 10 years old. Computed tomography showed 70 mm proximal arch aneurysm. Operative findings revealed brachiocephalic artery and left common carotid artery branched from aneurysm. Partial arch replacement was performed and distal anastomosis was made between left common carotid artery and left subclavian artery. Close observation by CT regularly is necessary and undergo aortic repair not to miss the timing of surgery.

OBJECTIVE: To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. METHODS: We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). RESULTS: More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade > or =2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade > or =2 vaginal stenosis rate at 3 years at 100% (p=0.001). CONCLUSION: High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.
Adult ; Aged ; Aged, 80 and over ; Brachytherapy/*adverse effects/methods ; Constriction, Pathologic/etiology/pathology ; Female ; Humans ; Iridium Radioisotopes/therapeutic use ; Middle Aged ; *Pallor ; Prognosis ; Prospective Studies ; Radiopharmaceuticals/therapeutic use ; Retrospective Studies ; Uterine Cervical Neoplasms/*radiotherapy ; Vaginal Diseases/*etiology/pathology

A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.
1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities
2．How to select Safety Specification (SS) and describe its characteristics
・Selection of SS
・Characterization of SS
・Association with Research Questions (RQ)
3．How to define and describe RQ
・What is RQ ?
・RQ interpretation in other relevant guidelines
・Methodology to develop RQ for PVP with examples
・Best approach to integrating PVP for whole aspects of safety concern
4．How to optimize PVP for specific RQ
・Routine PVP or additional PVP ?
・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)
・Checklist to help develop PVP
5．Epilogue:
・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.
・Significance of background incidence rate and needs for comparator group
・Infrastructure for the future PVP activities
6．Appendix: Checklist to help develop PVP activities in RMP
The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.

Objective : Although dissection extending to the aortic root is a common finding, it is potentially fatal in patients with acute type A aortic dissection. The purpose of this study was to evaluate surgical results of acute type A aortic dissection with proximal involvement. The proximal extension of dissection, types of aortic root procedure and its feasibility were investigated. Methods : Between 1997 and 2011, 80 patients with acute type A aortic dissection underwent emergent operation. Results : Dissection reaching around the coronary artery orifice was observed in 28 patients. In 11 patients, both left and right coronary arteries were involved with aortic dissection. Aortic root replacement was performed in 4 patients. In 7 patients, the dissected aortic root was reinforced by GRF glue and proximal aorta was replaced with a graft. Among these patients, postoperative aortic root redissection with severe aortic regurgitation was observed in 5 patients during postoperative long-term periods. All of them required surgical re-intervention of the aortic root. In 17 patients, dissection was extended to the right coronary artery. Aortic root reconstruction was performed in 2 patients due to pre-existing annulo-aortic ectasia. The remaining 15 patients underwent proximal reinforcement with GRF glue. No patient showed dissection extending to the left coronary artery alone. Operative mortality was 11% and other types of complications concerning the aortic root was not observed. Conclusion : An acceptable outcome was demonstrated with our surgical strategy of proximal aortic dissection. For patients, in particular, with proximal involvement to both the left and right coronary arteries, redissection of the aortic root should be noticed as a late complication with considerable frequency. Special care should be taken for precise recognition of the proximal extension of dissection and appropriate surgical procedure including simultaneous aortic root replacement.