Feasibility of a self‐assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self‐assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full‐thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model.     

Association between central sensitivity syndrome and psychological factors in people with presurgical low back pain: A cross-sectional study

BackgroundLow back pain (LBP) is a major problem; it causes significant burden, incurs considerable economic and human costs, and adversely affects the quality of life (QoL). Central sensitivity syndrome (CSS) is known as a group of overlapping conditions that share a common pathophysiological mechanism of central sensitization. Previous studies have shown that CSS is present in several disorders. However, it has been studied for people with presurgical LBP. The purpose of the study was to investigate the proportion of patients with CSS for presurgical LBP and to analyse the association of CSS with clinical symptoms and psychological factors.MethodsData of demographics, the central sensitization inventory (CSI), psychological measures, clinical symptoms of 238 patients with presurgical LBP were evaluated. The patients were divided into two groups depending on the CSI scores (≥40 and < 40). The two groups were compared, and the correlation between the CSI scores and other outcomes was analysed. Furthermore, multiple regression analysis was performed to identify factors contributing to the CSI scores.Results13.0% of participants were CSS. All outcomes were significantly different between the groups and significant associations were found between the CSI scores and all other outcomes. In addition, Pain Catastrophizing Scale (PCS) was most significant associated scale for the CSI scores.ConclusionWe found that certain patients had CSS with presurgical LBP. The CSI scores were significantly associated with the majority of the factors. The PCS was the factor with the most influence on the CSI scores.     

Characteristics affecting cervical sagittal alignment in patients with chronic low back pain

BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ     

ASO Author Reflections: Perspectives of Laparoscopic Hepatectomy with Venous Tumor Thrombectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

ASO Author Reflections: Laparoscopic Arantius’ Approach as Shortcut Access for Major Hepatic Veins

Annals of Surgical Oncology -     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Analysis of Cdc2 and Cyclin D1 expression in breast cancer by immunoblotting

Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3% and 75.0% of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-double negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.     

Prevalence of second generation antibody to hepatitis C virus among voluntary blood donors in Osaka,Japan

To clarify the demographic characteristics of the prevalence of hepatitis C virus (HCV) infection in Osaka, Japan, where hepatocellular carcinoma is common, we investigated the screening data of antibody to HCV (anti-HCV, DAINABOTHCVPHA, second generation assay) in 197,600 voluntary blood donors residing in Osaka. The study found that age-standardized prevalence of anti-HCV was significantly higher than that of HBsAg (2.25cf 0.86 percent among males,P<0.001; 2.17cf 0.55 percent among females,P<0.001. It was much higher in the blood donors aged 55–64 years than in those aged 16–54 years (8.49cf 1.32 percent among males,P<10^–5; 7.26cf 1.42 percent among females,P<10^–5). The prevalence of anti-HCV among males was significantly higher than that of females in the younger (25–34 years) generations (1.02 to 1.49 percentcf 0.71 to 1.13 percent,P<0.05). A similar tendency was observed in the prevalence of high-titer (2¹²) anti-HCV. The number of coinfection (both HBsAg and anti-HCV seropositive) was very small, and it was not statistically different from the expected number.     

Effect of the XIAP inhibitor Embelin on TRAIL-induced apoptosis of pancreatic cancer cells

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in a wide variety of tumor cells, while it has no toxicity for the majority of normal cells.Therefore, TRAIL may be a suitable agent for anticancer therapy. We previously reported that a number of pancreatic cancer cell lines show resistance to TRAIL-induced apoptosis via overexpression of XIAP and FLIP. The present study was conducted to further examine TRAIL-based therapeutic strategies by aiming to restore functional apoptotic pathways in resistant pancreatic cancer cells. METHODS: In various pancreatic cancer cell lines, TRAIL-induced apoptosis was evaluated in the presence or absence of an XIAP-inhibitor (Smac peptide). Second, TRAIL-induced apoptosis was evaluated in TRAIL-resistant AsPC-1 cells with or without FLIP antisense. Third, the combined effect of Smac peptide and FLIP antisense was tested, and the activation of apoptosis-related caspases and poly (ADP-ribose) polymerase was evaluated. Finally, TRAIL-induced apoptosis was evaluated in the presence or absence of FLIP antisense and an XIAP inhibitor (embelin). RESULTS: Smac peptide enhanced TRAIL-induced apoptosis in a dose-dependent manner for several pancreatic cancer cell lines, but showed no effect on TRAIL-resistant AsPC-1 cells. Smac peptide alone had no influence on cell viability. TRAIL-induced apoptosis was restored in TRAIL-resistant AsPC-1 cells by exposure to FLIP antisense, which suppressed the expression of FLIP. The effect of TRAIL was augmented by the combination of FLIP antisense and Smac peptide. Similarly, TRAIL-induced apoptosis was restored by the combination of FLIP antisense and embelin. Activation of apoptotic caspases and cleavage of poly (ADP-ribose) polymerase was observed after sensitization of TRAIL-resistant pancreatic cancer cells. CONCLUSIONS: Pancreatic cancer cells gain resistance to TRAIL-induced apoptosis via expression of the antiapoptotic proteins XIAP and FLIP. Smac peptide and FLIP antisense could restore the apoptotic effect of TRAIL. An XIAP inhibitor, embelin, enhanced the effect of TRAIL in the presence of FLIP antisense. These findings may provide useful information for the development of TRAIL-based therapeutic strategies by restoring functional apoptotic pathways in resistant pancreatic cancer cells. In addition, a low molecular weight XIAP inhibitor like embelin could be a lead compound for the development of effective XIAP inhibitors.     

Efficacy of an artificial pancreas device for achieving tight perioperative glycemic control in living donor liver transplantation

Intraoperative hyperglycemia during liver transplantation can induce infectious bacterial complications after surgery. The aim of this study was to evaluate the efficacy of the artificial endocrine pancreas in achieving perioperative blood glucose control and preventing infection in patients undergoing living donor liver transplantation (LDLT). We compared 14 patients with an artificial endocrine pancreas device to 14 patients who underwent glycemic control using the sliding scale method with respect to perioperative blood glucose level and postoperative infection. In this study, we aimed to control the perioperative glucose levels consecutively for 24 hours from the induction of anesthesia. The average blood glucose level in the artificial pancreas group was significantly lower than that in the sliding scale group (118 vs. 141 mg/dL, P < 0.05). The postoperative bacterial infection rate of the artificial pancreas group was significantly lower than that of the sliding scale group within one month after LDLT (35.7% vs. 78.6%, P < 0.05). Multiple regression analysis showed non‐application of artificial endocrine pancreas as a significant risk factor of posttransplant infection. The artificial endocrine pancreas enabled the perioperative glucose level to be stably controlled without hypoglycemia. Artificial pancreas may reduce the incidence of postoperative infection after LDLT.