DNA Damage Sensor γ

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC

Evaluation of a Rapid Immunochromatographic ODK-0901 Test for Detection of Pneumococcal Antigen in Middle Ear Fluids and Nasopharyngeal Secretions

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs

Role of surgery for optic pathway/hypothalamic astrocytomas in children

Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated with chemotherapy following a surgical biopsy. In this report, we retrospectively considered the role of surgical intervention. In a series of 25 patients without neurofibromatosis type 1, the median age at initial treatment was 3.1 years (range, 0–15 years). Twenty cases were verified by histology, and five cases were diagnosed by MRI findings. Twenty-three patients received chemotherapy. All patients were alive at median follow-up of 66 months. Aims of surgery at the initiation of treatment were biopsy in 12 cases (1 stereotactic and 11 craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic astrocytoma; however, noticeable complications occurred in five children after the biopsies. Review of preoperative MRIs showed that all had typical findings indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit for the patients despite surgical risk and delay of chemotherapy. The extent of the seven resection surgeries was 70% or less removal, and postoperative adjuvant therapy was needed for six of the seven patients. The remaining six children who did not undergo surgery obtained remission with chemotherapy alone. After relapse in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection was not curative in any patient. In five patients, mostly older children, cystic expansion of tumor was partially resected, resulting in additional remission. In conclusion, considering the risk of open surgery and the effectiveness of chemotherapy, the role of surgical intervention is restricted to bulk-reduction surgery only when it is inevitable, especially at relapse after chemotherapy

Drug-Coated Balloon versus Plain Balloon Angioplasty in the Treatment of Infrainguinal Vein Bypass Stenosis: A Systematic Review and Meta-Analysis

The optimal endovascular therapy for vein graft stenosis (VGS) following infrainguinal arterial bypass is yet to be established. Drug-coated balloons (DCB) have rapidly improved the inferior patency outcomes of angioplasty using a conventional plain balloon (PB). This study compares the efficacy of DCBs and PBs for the treatment of infrainguinal VGS. This systematic review and meta-analysis was performed according to the PRISMA statement. Multiple electronic searches were conducted in consultation with a health science librarian in September 2022. Studies describing the comparative outcomes of angioplasty using DCBs and PBs in the treatment of infrainguinal VGS were eligible. Datasets from one randomized controlled trial and two cohort studies with a total of 179 patients were identified. The results indicated no significant difference in target lesion revascularization between DCBs and PBs (OR, 0.64; 95% CI, 0.32–1.28; p = 0.21), with no significant heterogeneity between studies. Additionally, differences in primary patency, assisted primary patency, secondary patency, and graft occlusion were not significant. Subgroup analysis showed similar effects for different DCB devices. In conclusion, DCBs showed no significant benefit in the treatment of VGS compared to PBs. Given the small population size of this meta-analysis, future trials with a larger population are desired

Plasma metabolite biomarkers for multiple system atrophy and progressive supranuclear palsy.

Radiological biomarkers have been reported for multiple system atrophy and progressive supranuclear palsy, but serum/plasma biomarkers for each disorder have not been established. In this context, we performed a pilot study to identify disease-specific plasma biomarkers for multiple system atrophy and progressive supranuclear palsy. Plasma samples collected from 20 progressive supranuclear palsy patients, 16 multiple system atrophy patients and 20 controls were investigated by comprehensive metabolome analysis using capillary electrophoresis mass spectrometry and liquid chromatography mass spectrometry. Medication data were obtained from patients with multiple system atrophy and progressive supranuclear palsy, and correlations with associated metabolites were examined. Receiver operating characteristics curve analyses were used to investigate diagnostic values for each disorder. The levels of 15 and eight metabolites were significantly changed in multiple system atrophy and progressive supranuclear palsy, respectively. Multiple system atrophy was mainly characterized by elevation of long-chain fatty acids and neurosteroids, whereas progressive supranuclear palsy was characterized by changes in the level of oxidative stress-associated metabolites. Receiver operating characteristic curve analyses revealed that patients with multiple system atrophy or progressive supranuclear palsy were effectively differentiated from controls by 15 or 7 metabolites, respectively. Disease-specific metabolic changes of multiple system atrophy and progressive supranuclear palsy were identified. These biomarker sets should be replicated in a larger sample