Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Na?ve Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study)

ObjectiveTo explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients.MethodsConsecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab (n = 57) or tocilizumab (n = 70) treatment were included in our prospective cohort study. Our cohort started in February 2010, and the patients observed for at least 1 year as of April 2013 were analysed. We assessed baseline variables including patients'' characteristics (age, sex, disease duration, prednisolone dose, methotrexate dose, other disease-modifying antirheumatic drug use, Clinical Disease Activity Index [CDAI]) and serum biomarker levels (C-reactive protein, immunoglobulin M-rheumatoid factor, anti-cyclic citrullinated protein/peptide antibodies, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, bone alkaline phosphatase, osteonectin, osteopontin) to extract factors associated with clinical remission (CDAI≤2.8) at 1 year using univariate analyses, and the extracted factors were entered into a multivariate logistic regression model. Similar analyses were also performed for Simplified Disease Activity Index (SDAI) remission (≤3.3) and Disease Activity Score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) remission (<2.6).ResultsThere were no significant differences in the baseline characteristics except for methotrexate use between the groups. In the multivariate analyses, the low baseline osteopontin levels (OR 0.9145, 95% CI 0.8399–0.9857) were identified as predictors of CDAI remission in the tocilizumab group, whereas no predictors of CDAI remission were found in the infliximab group. Similar results were obtained when using SDAI and DAS28-ESR remission criteria.ConclusionBaseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis. Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts.     

Assessment of Cancer-Related Fatigue,Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09)

Introduction

Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams.

Materials and Methods

Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative.

Results

Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0–1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients’ fatigue severity was classified as none (score 0), mild (1–3), moderate (4–6), and severe (7–10), respectively.

Discussion

Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.     

Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome

West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50 % of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22 %, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36 %, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21 %, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14 %, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome.     

Effect of maturation on muscle quality of the lower limb muscles in adolescent boys

Background

The purpose of this study was to clarify the effect of maturation on the muscle quality of the lower limb muscles around puberty.

Methods

Subjects were 117 Japanese boys age 12 to 15 years. The maturity status was assessed by using a self-assessment of stage of pubic hair development based on the criteria of Tanner. On the basis of the criteria, subjects were divided into the prepubescent or pubescent group. Muscle thickness of knee extensors and plantar flexors were measured by a B-mode ultrasound. Muscle volume index (MV) was calculated from muscle thickness and limb length. Maximal voluntary isometric joint toques (TQ) of knee extension and ankle plantar flexion were measured using a myometer. Muscle quality was derived from dividing TQ by MV (TQ/MV).

Results

In both muscles, TQ-MV relationships were also similar between the prepubescent and pubescent groups, and there was no significant difference in TQ/MV between the two groups when chronological age was statistically adjusted.

Conclusion

The current results indicate that, for adolescent boys, the muscle quality of the lower limb muscles is not significantly influenced by maturation.     

Genome-Wide DNA Polymorphisms in Seven Rice Cultivars of Temperate and Tropical Japonica Groups

Elucidation of the rice genome is expected to broaden our understanding of genes related to the agronomic characteristics and the genetic relationship among cultivars. In this study, we conducted whole-genome sequencings of 6 cultivars, including 5 temperate japonica cultivars and 1 tropical japonica cultivar (Moroberekan), by using next-generation sequencing (NGS) with Nipponbare genome as a reference. The temperate japonica cultivars contained 2 sake brewing (Yamadanishiki and Gohyakumangoku), 1 landrace (Kameji), and 2 modern cultivars (Koshihikari and Norin 8). Almost >83% of the whole genome sequences of the Nipponbare genome could be covered by sequenced short-reads of each cultivar, including Omachi, which has previously been reported to be a temperate japonica cultivar. Numerous single nucleotide polymorphisms (SNPs), insertions, and deletions were detected among the various cultivars and the Nipponbare genomes. Comparison of SNPs detected in each cultivar suggested that Moroberekan had 5-fold more SNPs than the temperate japonica cultivars. Success of the 2 approaches to improve the efficacy of sequence data by using NGS revealed that sequencing depth was directly related to sequencing coverage of coding DNA sequences: in excess of 30× genome sequencing was required to cover approximately 80% of the genes in the rice genome. Further, the contigs prepared using the assembly of unmapped reads could increase the value of NGS short-reads and, consequently, cover previously unavailable sequences. These approaches facilitated the identification of new genes in coding DNA sequences and the increase of mapping efficiency in different regions. The DNA polymorphism information between the 7 cultivars and Nipponbare are available at NGRC_Rices_Build1.0 (http://www.nodai-genome.org/oryza_sativa_en.html).     

A Cross-Sectional Analytic Study of Postpartum Health Care Service Utilization in the Philippines

Background

The maternal mortality ratio in the Philippines remains high; thus, it will be difficult to achieve the Millennium Development Goals 5 by 2015. Approximately two-thirds of all maternal deaths occur during the postpartum period. Therefore, we conducted the present study to examine the current state of postpartum health care service utilization in the Philippines, and identify challenges to accessing postpartum care.

Methods

A questionnaire and knowledge test were distributed to postpartum women in the Philippines. The questionnaire collected demographical characteristics and information about their utilization of health care services during pregnancy and the postpartum period. The knowledge test consisted of 11 questions regarding 6 topics related to possible physical and mental symptoms after delivery. Sixty-four questionnaires and knowledge tests were analyzed.

Results

The mean time of first postpartum health care visit was 5.1±5.2 days after delivery. Postpartum utilization of health care services was significantly correlated with delivery location (P<0.01). Women who delivered at home had a lower rate of postpartum health care service utilization than women who delivered at medical facilities. The majority of participants scored low on the knowledge test.

Conclusion

We found inadequate postpartum health care service utilization, especially for women who delivered at home. Our results also suggest that postpartum women lack knowledge about postpartum health concerns. In the Philippines, Barangay health workers may play a role in educating postpartum women regarding health care service utilization to improve their knowledge of possible concerns and their overall utilization of health care services.     

Prognostic Value of FDG PET Imaging in Patients with Laryngeal Cancer

Background and Purpose

To investigate the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer.

Materials and Methods

The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method.

Results

The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧4) had a significantly lower progression-free survival rate than those with a low SUVmax (<4; p<0.0001).

Conclusions

The pretreatment SUVmax of nodal disease in patients with laryngeal cancer is prognostic for recurrence.     

Cytological,genetic, and biochemical characteristics of an unusual non‐Chlorella photobiont of Stentor polymorphus collected from an artificial pond close to the shore of Lake Biwa,Japan

Stentor polymorphus (Müller) Ehrenberg (Heterotrichea, Ciliophora) is a trumpet‐form ciliate with endosymbiotic green algae (photobionts). Previous reports have indicated that this photobiont has a form typical of Chlorella Beijerinck (Trebouxiophyceae), with one chloroplast and a distinct pyrenoid. We collected S. polymorphus from an artificial pond on the shore of Lake Biwa in Japan. Microscopic examination demonstrated that there was no pyrenoid in the photobiont, and thus we analyzed the cytological, genetic, and biochemical characteristics of these algal cells. Cultured photobionts were smaller than those in hospite. Phylogenetic analyses placed the photobiont within the genus Mychonastes Simpson and Van Valkenburg, a chlorophycean alga occurring in fresh/brackish waters that lacks pyrenoids. Mychonastes provided little photosynthate to its host; the quantity of carbohydrate amounted to only 2% of that provided to Paramecium bursaria (Ehrenberg) Focker by its photobiont.