Validation of a Free Phenytoin Assay on Cobas c501 Analyzer Using Calibrators From Cobas Integra Free Phenytoin Assay by Comparing its Performance With Fluorescence Polarization Immunoassay for Free Phenytoin on the TDx Analyzer

For many years, fluorescence polarization immunoassay (FPIA) on the TDx analyzer has been used for determination of free phenytoin concentration. Recently Abbott Laboratories decided to discontinue the TDx analyzer and related assays on this analyzer. Free phenytoin assay is also available from Roche Diagnostics for application on the Cobas Integra analyzer (fluorescence polarization assay) but not on Cobas c510 analyzer. Free phenytoin calibrators from the Cobas Integra free phenytoin assay and the reagents from the KIMSphenytoin assay were used for the determination of free phenytoin on the Cobas c501 analyzer. The intra‐run and inter‐run precisions were both <7.2%. The assay was linear from 0.2 to 4 μg/ml. The free phenytoin assay on the Cobas c501 was compared with the FPIAassay on the TDx analyzer using sera from 25 patients receiving phenytoin (phenytoin concentration between 0.3 and 3.7 μg/ml). The following regression equation was observed: y = 0.9899 x + 0.0408 (r = 0.98, n = 25). In conclusion, the free phenytoin assay on the Cobas c501 analyzer is a valid alternative to free phenytoin assay on the TDx analyzer. J. Clin. Lab. Anal. 27:1–4, 2013. © 2012 Wiley Periodicals, Inc.     

52例青少年骨性安氏Ⅱ类高角病例切牙区牙槽骨开窗和骨开裂的锥形束CT特点

目的 应用锥形束CT(CBCT）探讨52例青少年骨性安氏Ⅱ类高角错畸形切牙区骨开窗和骨开裂的发生率及分布情况，为临床正畸治疗提供一定的依据。 方法 自2013年7月至2018年1月于承德市口腔医院进行CBCT检查的患者中，随机选取临床诊断为骨性Ⅱ类高角错畸形青少年病例52例，将其扫描数据导入SIDEXIS XG 2.56软件，在测量平面上根据定义诊断上下切牙区牙槽骨骨开窗和骨开裂，并采用χ²检验的方法对其分布在性别、上下颌骨、牙位间的差异进行数据分析。 结果 在样本人群中牙槽骨缺损的发生率高达86.53%。其中骨开窗和骨开裂的发生率分别为65.38%和67.30%。416颗纳入牙中82颗牙齿出现骨开窗,107颗牙齿出现骨开裂。骨开裂发生率在牙位间差异显著（P<0.05)。骨开窗发生率上下颌骨差异无统计学意义（P>0.05）,骨开裂则主要发生于下颌骨（P<0.05)。男性与女性切牙区牙槽骨骨开窗与骨开裂的发生率差异无显著性。 结论 青少年骨性安氏Ⅱ类高角错畸形患者在正畸治疗前切牙区即存在广泛的牙槽骨缺损，正畸治疗开始前及过程中医师应密切关注患者牙槽骨解剖形态。     

Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4 translocation in adipocytes of rats fed a high fat diet

Summary JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57 % lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58 % decrease in insulin receptor substrate-1 (IRS-1) content with a 58 % decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56 % and 73 % respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46 % reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance. [Diabetologia (1998) 41: 400–409] Received: 23 June 1997 and in revised form: 29 November 1997     

Use and acceptance of the International Study Group for Pancreatic Fistula (ISGPF) definition and criteria in the surgical literature

Background

The level of utilization and acceptance of the 2005 International Study Group for Pancreatic Fistula (ISGPF) definition for postoperative pancreatic fistula (POPF) has not be quantified. The aim of this study was to determine the uptake of the ISGPF definition and evaluate its use in the surgical literature.

Inferring the Association between the Risk of COVID-19 Case Fatality and N501Y Substitution in SARS-CoV-2

As COVID-19 is posing a serious threat to global health, the emerging mutation in SARS-CoV-2 genomes, for example, N501Y substitution, is one of the major challenges against control of the pandemic. Characterizing the relationship between mutation activities and the risk of severe clinical outcomes is of public health importance for informing the healthcare decision-making process. Using a likelihood-based approach, we developed a statistical framework to reconstruct a time-varying and variant-specific case fatality ratio (CFR), and to estimate changes in CFR associated with a single mutation empirically. For illustration, the statistical framework is implemented to the COVID-19 surveillance data in the United Kingdom (UK). The reconstructed instantaneous CFR gradually increased from 1.0% in September to 2.2% in November 2020 and stabilized at this level thereafter, which monitors the mortality risk of COVID-19 on a real-time basis. We identified a link between the SARS-CoV-2 mutation activity at molecular scale and COVID-19 mortality risk at population scale, and found that the 501Y variants may slightly but not significantly increase 18% of fatality risk than the preceding 501N variants. We found no statistically significant evidence of change in COVID-19 mortality risk associated with 501Y variants, and highlighted the real-time estimating potentials of the modelling framework.     

Dynamically monitoring tissue factor and tissue factor pathway inhibitor following secondary brain injury

Objective: To study the altering rule of coagulation function at molecular level in patients with secondary brain injury (SBI). Methods: Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were studied in 32 patients 1, 2,3 and 7 days after craniocerebral injury. Repeated cranial CT scans and platelet counts were made simultaneously.Same measurements were done in 30 normal adults except CT scan. Results: No obvious difference was found in age, sex and platelet count between the injured and the normal groups. TFPI/TF decreased markedly in the first week after injury in patients with SBI, but only decreased on the 7th day in the patients without obvious SBI. For the patients who developed delayed intracranial hematoma (DIH) or hematoma enlargement, TF rose only 1 and 2 days after injury, but TFPI had a tendency to rise again after a fall on the 3rd day. For those patients who developed no DIH, TF rose all the time within the 1st week. Conclusions: Decrease of TFPI/TF for a long time,especially within 3 days after injury, may be one of the most important reasons for SBI. High expression of TF for a relative short time and increase of TFPI after a fall within 3 days may be one of the important reasons for DIH or hematoma enlargement.     

Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma

Background

CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin.

Methods

Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25 mg/m² IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months.

Results

65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS ≥ 4 mo; the median PFS was 5.1 mo (95% CI, 3.9, 6.5) vs 3.4 mo (2.5, 6.7). Median OS was 13.3 mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501.

Conclusions

While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.