Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus.

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

Factors influencing caregiver burden in chronic pain patients: A retrospective study.

Chronic pain coexists with disability, anxiety, depression, and sleep disturbances, which are factors of pain chronicity in the fear-avoidance model. Self-efficacy for managing pain plays a protective role against pain chronicity. For chronic pain sufferers, social support from caregivers is important. However, such caregivers face enormous physical and mental burdens. This study aimed to assess how self-efficacy and factors related to the fear-avoidance model affect caregiver burden. Participants were 135 chronic pain patients and their caregivers who visited our outpatient pain special clinic. In clinical assessments, numeric rating scale (NRS), pain catastrophizing scale (PCS), hospital anxiety and depression scale (HADS), Athens insomnia scale (AIS), pain disability assessment scale (PDAS), pain self-efficacy questionnaire (PSEQ) for the patients and Zarit Burden Interview (ZBI) for their caregivers were evaluated. Participants were divided into 2 groups (L group ZBI < 24 points and H group ZBI ≥ 24 points) and compared. Regression analyses were conducted to identify factors correlated with the ZBI scores. Compared to L group, H group showed significantly higher NRS and HADs depression scores, and lower PSEQ scores. In univariate regression analysis, ZBI scores were significantly correlated with NRS, PCS, HADS anxiety, HADS depression, PDAS and PSEQ. Multiple linear regression analysis revealed that ZBI scores were significantly correlated with PSEQ. The caregivers who perceived high caregiver burden had significantly higher patients' pain intensity, depression, and lower self-efficacy than those who perceived low caregiver burden. Caregiver burden correlated with the pain intensity, pain catastrophizing, anxiety, depression, disability, and self-efficacy of chronic pain patients. Among these factors, self-efficacy was the most negatively correlated with caregiver burden. Treatments focused on increasing self-efficacy for managing pain have the potential to reduce caregiver burden.

Postoperative computed tomography assessment of anteromedial cortex reduction is a predictor for reoperation after intramedullary nail fixation for pertrochanteric fractures.

PURPOSE: Postoperative radiographs are routinely used to assess fracture reduction following intramedullary nail fixation for pertrochanteric fractures, even though computed tomography (CT) is a superior modality. We aimed to determine the association between reduction quality assessed by CT and rates of reoperation and to evaluate the association of reoperation and reduction quality according to the assessment modality (plain radiographs vs. CT). METHODS: A retrospective analysis of 299 consecutive patients treated with intramedullary nail fixation for pertrochanteric fractures was conducted. Fracture reduction measured by postoperative radiographs and CT was categorized as anatomical type, extramedullary type, or intramedullary type. Postoperative data for analysis included reduction status, tip-apex distance (TAD), screw position in the femoral head, sliding distance, and conditions associated with reoperation. RESULTS: Of the 299 patients included with a mean age of 83.1 ± 8.2 years, there were six patients who required reoperation (2.0%). According to the CT assessments, there were 42 intramedullary reductions (14.0%). Patients with a non-intramedullary reduction based on postoperative CT images were significantly more likely to have proper placement of the screw, a reduced TAD, a reduced sliding distance, and a lower reoperation rate than those with an intramedullary reduction (P < 0.05). The reduction quality assessed by postoperative CT was significantly associated with reoperation (95% CI, 1.45-29.31). CONCLUSIONS: Intramedullary reduction assessed by CT was associated with reoperation. The reduction quality based on CT findings was more predictive for reoperation than that from plain radiographs.

Assessment of the Concordance Rate between Intraoperative Pathological Diagnosis and the Final Pathological Diagnosis of Spinal Cord Tumors.

The intraoperative pathological diagnosis (IPD) plays an important role in determining the optimal surgical treatment for spinal cord tumors. The final pathological diagnosis (FPD) is sometimes different from the IPD. Here, we sought to identify the accuracy of the IPD of spinal cord tumors compared to the FPD. We retrospec-tively analyzed the cases of 108 patients with spinal cord tumors treated surgically in our institute; the IPD, FPD, mismatched cases, and concordance rate between the IPD and FPD were investigated. Five cases involved a mismatch between the IPD and FPD. The overall concordance rate was 95.4%, with 90.9% for extra-dural lesions, 98.5% for intradural extramedullary lesions, 84.2% for intramedullary lesions, and 100% for dumbbell-type tumors. The concordance rate of intramedullary lesions tended to be lower than that of other lesions (p = 0.096). A lower concordance rate was revealed for intramedullary lesions compared to the other lesions. Despite the IPD clearly remaining a valuable tool during operative procedures, surgeons should recog-nize the limitations of IPDs and make comprehensive decisions about surgical treatments.

Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors.

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases.

BACKGROUND: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. METHODS: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). RESULTS: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). CONCLUSIONS: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

Early response assessment of palliative conventional radiotherapy for painful uncomplicated vertebral bone metastases.

BACKGROUND: Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis. METHODS: Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR. RESULTS: Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P < 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS < 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002). CONCLUSIONS: Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

Bony landmark between the attachment of the medial meniscus posterior root and the posterior cruciate ligament: CT and MR imaging assessment.

OBJECTIVES: (1) To reveal the prevalence of the bony recess (posterior dimple) and (2) to determine the position of the posterior dimple on the tibial plateau using three-dimensional computed tomography (3DCT). MATERIALS AND METHODS: In this study, a retrospective review of 112 patients was performed to identify the posterior dimple and to evaluate its position on 3DCT. Magnetic resonance images (MRIs) were also used to determine the positional relationship among the posterior cruciate ligament (PCL), medial meniscus posterior insertion (MMPI), and posterior dimple. RESULTS: The posterior dimple was observed in 100 of 112 knees (89.3%) on 3DCT. The center of the posterior dimple was 13.6 ± 0.8 mm from the medial tibial eminence apex. MRI showed that the posterior dimple separated the tibial attachment of the PCL and MMPI. CONCLUSION: This is the first study to discuss the prevalence and position of the bony recess in the posterior intercondylar fossa.

MRI of rheumatoid arthritis:comparing the outcome measures in rheumatology clinical trials (OMERACT) scoring and volume of synovitis for the assessment of biologic therapy.

The outcome measures in rheumatology clinical trials (OMERACT) scores are the most mature quantitation system for rheumatoid arthritis (RA) on magnetic resonance imaging (MRI). Direct measuring techniques of synovial volume have been reported with good reproducibility, although few reports have demonstrated the changes of these measures in response to treatment. To assess these clinical responses, we evaluated the correlation of the changes of clinical activity score 28-joints disease activity score (DAS28-CRP) with the changes of OMERACT scores and with synovial volume measurements. Eight RA patients who were treated by biologic agents were examined with MRI of the dominant affected wrist and finger joints before and one year after the treatment. The total OMERACT score was reduced from 48.0 to 41.3, and synovial volume was reduced from 15.4 to 8.8 milliliters. Positive correlations were seen between the changes of DAS28-CRP and the changes of OMERACT synovitis score (r＝0.27), OMERACT total score (r＝0.43) and synovial volume (r＝0.30). Limited to synovium assessment, synovial volume showed a better correlation with DAS28-CRP than the OMERACT synovitis score. On the other hand, the OMERACT total score showed a higher correlation with DAS28-CRP than synovial volume, probably because the OMERACT total score includes scores for bone erosion and bone edema as well.

Two-directional arthrographic assessment for treating bilateral development dislocation of the hips in children after walking age.

We reviewed the treatment outcome in 14 hips of 7 patients who were diagnosed as having bilateral developmental dislocation of the hip (DDH) after walking age and could be followed up until they were at least 14 years of age. Based on the results of two-directional arthrography of the hip, closed reduction was performed in 2 hips, and open reduction was performed without osteotomy in 12 hips. The final radiographic evaluations were made according to the Kalamchi and MacEwen classification and Severin classification. The mean age at the initial visit was 1 year and 9 months (range, 1 year and 5 months to 3 years). The outcome was satisfactory for one hip in Group Ⅰ and 2 hips in Group Ⅱ according to the Kalamchi and MacEwen classification, and in 83% of the Severin Class Ⅰ and Ⅱ hips. Arthrography was useful for identifying asymmetry, demonstrating the usefulness of a treatment strategy based on arthrography of the hip.

Multiple regression analysis for grading and prognosis of cubital tunnel syndrome: assessment of Akahori's classification.

The purpose of this study was to quantitatively evaluate Akahori's preoperative classification of cubital tunnel syndrome. We analyzed the results for 57 elbows that were treated by a simple decompression procedure from 1997 to 2004. The relationship between each item of Akahori's preoperative classification and clinical stage was investigated based on the parameter distribution. We evaluated Akahori's classification system using multiple regression analysis, and investigated the association between the stage and treatment results. The usefulness of the regression equation was evaluated by analysis of variance of the expected and observed scores. In the parameter distribution, each item of Akahori's classification was mostly associated with the stage, but it was difficult to judge the severity of palsy. In the mathematical evaluation, the most effective item in determining the stage was sensory conduction velocity. It was demonstrated that the established regression equation was highly reliable (R = 0.922). Akahori's preoperative classification can also be used in postoperative classification, and this classification was correlated with postoperative prognosis. Our results indicate that Akahori's preoperative classification is a suitable system. It is reliable, reproducible and well-correlated with the postoperative prognosis. In addition, the established prediction formula is useful to reduce the diagnostic complexity of Akahori's classification.

Assessment of head wear more than ten years after total hip arthroplasty: 22-mm zirconia vs. metal heads.

The present retrospective study assessed radiographs to determine socket wear in total hip arthroplasty (THA) with 22-mm zirconia or COP (Cobalt-Chrome alloy rich in Cobalt and Phosphorous) heads, and in cemented stems at more than 10 years after operation. Sockets of ultra high molecular weight polyethylene were used in each of two THA groups (13 hips each) in a clinical trial in our hospital between 1989 and 1990. Three observers carried out masked assessments of the radiographs. Upon final examination, there was no remarkable loosening in the zirconia or COP group, and no case had required revision surgery as of 2005. There was a statistically significant difference between the 2 groups in average annual linear wear, at 0.093 mm/year and 0.046 mm/year in the zirconia and COP groups, respectively. Volume wear and average annual volume wear were also significantly greater in the zirconia group despite its superior mechanical strength and toughness in vitro. Our present findings do not confirm early expectations of lower wear in long-term results of 22-mm zirconia femoral heads used in THA.