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Aim: Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model., Methods: A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders., Results: Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population., Limitations: Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison., Conclusions: The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Purpose: We examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan., Methods: 87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model., Results: A heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06-1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51-0.94, Q3: HR, 0.68; 95%CIs, 0.50-0.95, Q4: HR, 0.66; 95%CIs, 0.44-0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02-1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11-2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men., Conclusions: Heavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women., Competing Interests: The authors have declared that no competing interests exist.

Background: In the current literature, for adult lumbar spondylolisthesis, the direct comparison of clinical outcomes and perioperative complications between transforaminal lumbar interbody fusion (TLIF) and posterior lumbar interbody fusion (PLIF) is limited. Whether the therapeutic effect of TLIF is better than that of PLIF is still controversial. In this retrospective controlled study, our aim was to compare their clinical outcomes and radiological results of the above two stabilization approaches after 1-year follow-up period., Methods: This investigation was approved via the Institutional Review committee of China-Japan friendship hospital. This was a retrospective single-center analysis of subjects. We reviewed the patients with spondylolisthesis treated with TLIF or PLIF between July 2016 and February 2019 in our hospital. Patients with these conditions will be included: with the radiological evidence of degenerative lumbar spondylolismia with leg pain and/or low back pain, or the neurogenic claudication after failure of conventional conservative treatment for more than 6 months. The patients who received 3 levels or more intervertebral fusion levels were excluded. Patients without a completed medical history were excluded. Patients who had a history of lumbar spine surgery were also excluded. Clinical outcomes in our follow-up included functional outcomes, complications, and radiographic such as spondylolisthesis degree. The radiographs were obtained at 1, 3, 6, and 12 months during the outpatient follow-up., Results: This protocol will provide a solid theoretical basis for exploring which technique is better in treatment of spondylolisthesis., Trial Registration: This study protocol was registered in Research Registry (number: researchregistry6032).

Purpose: This study aimed to identify the 100 most cited research articles on cervical cancer brachytherapy., Methods and Materials: The Institute for Scientific Information Web of Science was used to identify the 100 most cited articles in cervical cancer brachytherapy as of July 5, 2019. The following important information was extracted: journal, year and month, country of region, author, type of article, type of dose rate, type of radionuclide, and image modality for brachytherapy planning., Results: The 100 most cited articles in cervical cancer brachytherapy were published between 1981 and 2016, and the citations ranged from 858 to 49, which collectively had been cited 11,372 times at the time of searching. The index of citations per year ranged from 63.56 to 1.43. These articles were from 16 countries or regions, with most publications being from the United States (n = 27), followed by Austria (n = 26), Japan (n = 10), France (n = 7), and the Netherlands (n = 7). The International Journal of Radiation Oncology, Biology, Physics produced the most articles (n = 46), followed by Radiotherapy and Oncology (n = 39) and Gynecologic Oncology (n = 5). These articles were categorized as original studies (n = 75), reviews (n = 2), editorials (n = 2), surveys (n = 2), guidelines (n = 3), and recommendations (n = 6). A high dose rate (n = 69) was the most widely used, dose rate followed by a low dose rate (n = 20) and pulsed dose rate (n = 16)., Conclusions: The bibliometric analysis presents a detailed list of the 100 most cited articles in cervical cancer brachytherapy. This analysis provides an insight into historical developments and enables the important advances in this field to be recognized., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

B cells have recently been proven to have phagocytic activities, but few studies have explored the relevant regulation mechanisms. In this study, we showed that the Japanese flounder ( Paralichthys olivaceus ) membrane-bound (m)IgM + B lymphocyte population could phagocytose inactivated Lactococcus lactis with a mean phagocytic rate of 25%. High-purity mIgM + B lymphocytes were subsequently sorted to investigate the cellular response to L. lactis stimulation in vitro . Transcriptome analysis identified 1,375 differentially expressed genes (DEGs) after L. lactis stimulation, including 975 upregulated and 400 downregulated genes. Many of these DEGs were enriched in multiple pathways associated with phagocytosis such as focal adhesion, the phagosome, and actin cytoskeleton regulation. Moreover, many genes involved in phagolysosomal function and antigen presentation were also upregulated after stimulation, indicating that mIgM + B lymphocytes may degrade the internalized bacteria and present processed antigenic peptides to other immune cells. Interestingly, the type I interferon 3 ( IFN I-3) gene was upregulated after L. lactis stimulation, and further analysis showed that the recombinant (r)IFN I-3 significantly enhanced phagocytosis of L. lactis and Edwardsiella tarda by mIgM + B lymphocytes. In addition, significantly higher intracellular reactive oxygen species (ROS) levels were detected in mIgM + B lymphocytes following rIFN I-3 treatment. We also found that IFN I-3 significantly upregulated Stat1 expression in mIgM + B lymphocytes, and the enhancing effect of IFN I-3 on mIgM + B lymphocyte-mediated phagocytosis was suppressed by fludarabine treatment. Collectively, these results demonstrate that mIgM + B cell-mediated phagocytosis in the Japanese flounder is effectively triggered by bacterial stimulation, and further enhanced by IFN I-3, which itself may be regulated by Stat1.

Objectives: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors., Methods: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption., Results: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC)., Conclusion: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.

Background: Human papillomavirus (HPV) plays a role in the development of oral carcinoma. However, the reported prevalence of HPV in oral carcinoma has varied widely., Methods: The prevalence of HPV 16, 18 and 33 was investigated in Japanese and North-east Chinese oral squamous cell carcinomas (OSCCs) with polymerase chain reaction (PCR). The expression of p53 protein was examined immunohistochemically., Results: HPV 16 and 18 were detected in 7 (23.3%) and 10 (33.3%) of 30 Japanese and 11 (36.7%) and 5 (16.7%) of 30 Chinese samples, respectively. HPV 16 and 18 coinfection was detected in 3/30 Japanese and 2/30 Chinese samples. HPV 33 was not detected. There was no significant correlation between HPV 16 and 18 and the sites, gender, age and histological grade. The prevalence of both HPV 16 and 18 was similar and higher in the Japanese and North-east Chinese samples (46.7% each). HPV 16 or/and 18 infection or/and p53 overexpression were in 22 (73.3%) of 30 Japanese samples and 24 (80.0%) of 30 North-east Chinese samples, respectively., Conclusions: HPV 16/18 infection or/and p53 overexpression may play an important role in developing some OSCCs. and the presence of HPV sequences and mutant p53 are not necessarily mutually exclusive.