Study protocol of a multicenter registry of patients with rheumatoid arthritis starting biologic therapy in Japan: Tsurumai Biologics Communication Registry (TBCR) Study

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.     

Atrial fibrillation occurring early after cardiovascular surgery: impact of the surgical procedure

Purpose

Postoperative atrial fibrillation/flutter (AF) is still the most common complication after cardiovascular surgery, and it is important to determine the risk factors in order to establish effective management for recent postoperative AF. This study investigated the clinical predictors of postoperative AF using a prospectively collected database.

Methods

A total of 418 patients underwent cardiovascular surgery and were enrolled in this study. The relationship between postoperative AF and perioperative factors was examined.

Results

Postoperative AF occurred in 134 patients (32.1 %). A univariate analysis showed that an older age, hypertension, perioperative transfusion, use of cardiopulmonary bypass and thoracic aortic surgery were significantly associated with postoperative AF. The incidence of fibrillation was 49.4 % (39/79) in patients having aortic surgery. A multivariate analysis revealed that an older age, transfusion, and aortic surgery were all independent predictors of postoperative AF.

Conclusions

An older age, transfusion, and aortic surgery are strong independent predictors of postoperative AF. These findings help to identify high-risk patients for AF after cardiovascular surgery. Careful perioperative management is required for older patients undergoing aortic surgery with cardiopulmonary bypass.     

Degree of biological apatite c‐axis orientation rather than bone mineral density controls mechanical function in bone regenerated using recombinant bone morphogenetic protein‐2

The aim of the present study was to assess the bone regeneration process in defects introduced into rabbit long bones, which were regenerated with controlled release of recombinant bone morphogenetic protein‐2 (rBMP‐2). The orientation of the biological apatite (BAp) c‐axis and bone mineral density (BMD) were compared as predictors of bone mechanical function. A 20‐mm‐long defect was introduced in rabbit ulnas, and 17 µg of rBMP‐2 was controlled‐released into the defect using a biodegradable gelatin hydrogel as the carrier. In the bone regeneration process, two characteristic phases may have been governed by different factors. First, new bone formation actively occurred, filling the bone defect with newly formed bone tissue and increasing the BMD. This process was regulated by the strong osteoinductive capacity of rBMP‐2. Second, after filling of the defect and moderate BMD restoration, preferential BAp c‐axis orientation began to increase, coincident with initiation of remodeling. In addition, the BAp c‐axis orientation, rather than BMD, was strongly correlated with Young's modulus, an important index of bone mechanical function, particularly in the later stage of bone regeneration. Thus, preferential BAp c‐axis orientation is a strong determinant and predictor of the mechanical function of tissue‐engineered bone. Therefore, analysis of BAp preferential c‐axis orientation in addition to measurement of BMD is crucial in assessment of bone mechanical function. © 2013 American Society for Bone and Mineral Research © 2013 American Society for Bone and Mineral Research     

Design and optimization of the oriented groove on the hip implant surface to promote bone microstructure integrity

We proposed a novel surface modification for an artificial hip joint stem from the viewpoint of maintenance and establishment of appropriate bone function and microstructure, represented by the preferred alignment of biological apatite (BAp) and collagen (Col). Oriented grooves were introduced into the proximal medial region of the femoral stem to control the principal stress applied to the bone inside the grooves, which is a dominant factor contributing to the promotion of Col/BAp alignment. The groove angle and the stem material were optimized based on the stress inside the grooves through a finite element analysis (FEA). Only the groove oriented proximally by 60° from the normal direction of the stem surface generated the healthy maximum principal stress distribution. The magnitude of the maximum principal stress inside the groove decreased with increasing the stem Young's modulus, while the direction of the stress did not largely changed. An in vivo implantation experiment showed that this groove was effective in inducing the new bone with preferential Col/BAp alignment along the groove depth direction which corresponded to the direction of maximum principal stress inside the groove. The anisotropic principal stress distribution and the oriented microstructure inside the groove are similar to those found in the femoral trabeculae; therefore, the creation of the oriented groove is a potent surface modification for optimizing implant design for a long-term fixation.     

Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate

Quantitative analysis of the orientational distribution of biological apatite (BAp) crystals is proposed as a new index of bone quality. This study aimed to analyze BAp c-axis orientation in ovariectomized (OVX) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. Sixty female monkeys aged 9–17 years were divided into five groups: one sham group and four OVX groups. The sham group and one OVX group were treated daily with vehicle for 17 months. The other three groups were treated daily with minodronic acid at doses of 0.015 and 0.15 mg/kg, and alendronate at 0.5 mg/kg orally, respectively. The seventh lumbar vertebrae were subjected to analysis of the preferential BAp c-axis orientation in the ventral cortical bone. The BAp c-axis orientation along the craniocaudal axis was significantly increased in the OVX monkeys. The high dose of minodronic acid suppressed the OVX-induced increase in the BAp c-axis orientation, whereas alendronate showed a non-significant tendency to suppress the increase in the orientation. In analysis with other parameters, the BAp c-axis orientation was positively correlated with bone formation indices in biochemical markers and bone histomorphometry and negatively correlated with the increase in lumbar bone mineral density. On the other hand, the BAp c-axis orientation was not correlated with bone resorption indices, except for the eroded surface. These results indicate that the increase in BAp c-axis orientation was ameliorated by minodronic acid treatment in OVX monkeys, mainly by suppression of bone formation increase.     

Is left upper lobectomy for lung cancer a risk factor for cerebral infarction?

Purpose

Cerebral infarction is a rare complication of lung resection that can result in severe sequelae. Our aim was to investigate the characteristics of patients who suffer from cerebral infarction after surgery for lung cancer.

Methods

We retrospectively reviewed all patients who underwent resection of at least a single lobe for lung cancer at our institution between January 2008 and October 2013. We compared the patients who presented with cerebral infarction with those patients who did not within 30 days of surgery.

Results

A total of 562 patients underwent surgery, with five males and one female subsequently experiencing cerebral infarction. Five patients underwent left upper lobectomy and one underwent left lower lobectomy. Patient age, sex, body mass index, smoking index, and operative time were not significantly different between the six patients with postoperative cerebral infarction and the other 556 patients; only the type of operative procedure was significantly different (p < 0.001). Contrast-enhanced computed tomography revealed thrombosis in the stump of the left superior pulmonary vein in patients with postoperative cerebral infarction.

Conclusions

Cerebral infarction occurs at a high frequency in patients who undergo left upper lobectomy for lung cancer. Thrombosis in the left superior pulmonary-vein stump might cause cerebral infarction.

     

Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning,Disability and Health Core Set for Diabetes Mellitus

Background

We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM.

Methods

A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including “Body functions”, “Body structures”, “Activities and participation”, and “Environmental factors”.

Results

The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes.

Conclusion

The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy.

     

Multiple gastrointestinal stromal tumors in neurofibromatosis type 1 treated with laparoscopic surgery

Gastrointestinal stromal tumors (GISTs) have been reported to occasionally occur in patients with neurofibromatosis type 1 (NF-1), and many cases have had multiple lesions predominantly involving the small intestine. We report herein a case of multiple GISTs associated with NF-1 from whom laparoscopic surgery was beneficial. In a 79-year-old female admitted with anemia and melena, the abdominal computed tomography revealed a tumor arising from the small intestine. Laparoscopic surgery was performed, and another small tumor was revealed during laparoscopic observation. Extracorporeal partial and wedge resection of the small intestine were undertaken. Both lesions were diagnosed as typical GISTs of low risk. Laparoscopic surgery would be useful for examination and a minimally invasive approach to tumors of the small intestine, especially on cases with the possibility of multiple tumors.