Reliability and validity of D-dimer monitoring for pulmonary thromboembolism in patients with unresectable, advanced or recurrent colorectal cancer treated with bevacizumab.

Pulmonary thromboembolism (PTE) is one of the leading causes of death among cancer outpatients. The aim of the present study was to investigate the reliability and validity of D-dimer monitoring for PTE in patients with unresectable, advanced or recurrent colorectal cancer treated with bevacizumab. A total of 25 patients with advanced colorectal cancer who received bevacizumab combination chemotherapy as primary treatment were retrospectively reviewed. The selection criteria included that D-dimer tests were performed repetitively, and that chest and abdominal contrast-enhanced CT scans were completed. The D-dimer levels and the presence or absence of PTE on CT images were retrospectively examined. Four cases (16%) were detected as having asymptomatic PTE. The D-dimer values at the onset of PTE were 14.2, 4.6, 1.1 and 0.9 µg/ml. The negative predictive value was 90.5% when 3.0 µg/ml was set as the D-dimer level cutoff value. The incidence of PTE, including asymptomatic PTE, in the present study was higher compared with that reported in previous studies on various types of cancer, of various stages and treated with different chemotherapy regimens. In patients with bevacizumab-treated unresectable, advanced or recurrent colorectal cancer, the D-dimer test was found to be less useful for exclusion diagnosis; however, along with chest CT, it may be useful in the detection and diagnosis of PTE. However, the determination of the optimal reference values and appropriate measurement timing of D-dimer testing requires further study.

Effect of different shielding conditions on the stability of Cisplatin.

BACKGROUND: Because cisplatin (CDDP) decreases upon light exposure, it is necessary to prevent such exposure during administration. However, the shielding conditions employed are not uniform. Therefore, in this study, we examined the shielding effects of four shading covers, which are commonly used to ensure the stability of CDDP in clinical settings. METHODS: Four shielding conditions, along with a control, were tested under a 1000-Lux white fluorescent lamp at room temperature: aluminum foil (Al), brown shading cover (BSC), yellow shading cover (YSC), milky-white anti-exposure cover (MAC), and no shading cover (NSC). Under each shielding condition, the relationship between the wavelength and transmittance was monitored in the range of 200-800 nm. CDDP was diluted to three concentration levels: 50, 100, and 250 µg/mL. Furthermore, the amount of remaining CDDP and the pH in the solutions were measured for 120 h. RESULTS: We found that BSC, YSC, and MAC conditions allowed various levels of transmittance; however, Al could not completely transmit light at all wavelengths. Moreover, we showed that the CDDP decreased under MAC and NSC conditions in a time-dependent manner, whereas this decrease was prevented under Al, BSC, and YSC conditions till 120 h. We also demonstrated increases in pH under MAC and NSC conditions in a time-dependent manner, which was prevented under Al, BSC, and YSC conditions till 120 h. Similar results were observed for all three CDDP concentration levels. The results also indicated the approximate relationship between the amount of remaining CDDP and the pH increase. CONCLUSIONS: Considering the opacity of each cover, our results suggest that BSC and YSC are useful and effective for minimizing CDDP degradation in clinical settings. Our results also indicate the alternatives for preparing, storing, and administering CDDP in clinical facilities, making the treatment schedule more flexible. Cumulatively, these findings indicate that the use of the appropriate shading covers, such as BSC or YSC, prevents the decrease in CDDP under fluorescent lighting, potentially contributing to achieving its full therapeutic effect.

Relationship between Low Pretreatment Geriatric Nutritional Risk Index and Poor Tolerability of Azacitidine in Patients with Myelodysplastic Syndromes.

BACKGROUND: Predicting tolerability and treatment-related risks associated with azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) before the initiation of therapy is required for appropriate treatment. Thus, in this study, the nutritional status of patients with MDS prior to AZA treatment was evaluated using the geriatric nutritional risk index (GNRI). Tolerability and overall survival (OS) after AZA initiation were also investigated. METHODS: This was a single-center retrospective observational study. A total of 59 patients with MDS treated with AZA were assessed using GNRI, and a comparison of undernourished (GNRI <92, n = 27) and non-undernourished (GNRI ≥92, n = 32) patients was performed. RESULTS: The undernourished group had a significant reduction in the number of patients that successfully completed 4 cycles of AZA treatment compared with the non-undernourished group (undernourished group, 11/27 patients, 40.7% vs. non-undernourished group, 24/32 patients, 75.0%; p = 0.009). Factors associated with the difference included karyotype and GNRI. There was also a significant increase in the rate of infectious complications in the undernourished group compared with the non-undernourished group (undernourished group, 33/60 cycles, 55.0% vs. non-undernourished group, 31/92 cycles, 33.7%; p = 0.012). Lastly, a significant reduction in OS was observed in the undernourished group compared with the non-undernourished group (undernourished group, 11.5 months; 95% CI, 5.2-16.7 vs. non-undernourished group, 21.9 months; 95% CI, 13.8-24.0; p = 0.026). Factors associated with OS included both the revised International Prognostic Scoring System (IPSS-R) and GNRI. CONCLUSIONS: These results indicate that predicting treatment completion and adverse events in patients with MDS prior to AZA treatment is important. This study suggests GNRI may be a valuable nutritional assessment tool for determining tolerability and OS of AZA treatment.

Trichostatin A, an HDAC class I/II inhibitor, promotes Pi-induced vascular calcification via up-regulation of the expression of alkaline phosphatase.

AIM: Vascular calcification, a major complication of chronic kidney disease (CKD), refers to the mineralization of vascular smooth muscle cells (VSMCs), resulting from a phenotypic change towards osteoblast-like cells. Histone deacetylase inhibitors (HDIs), potential therapeutic agents for CKD, are known to promote the differentiation and mineralization of osteoblasts. In this study, we aimed to determine the effects of an HDI on the phenotypic change of VSMCs and the development of vascular calcification. METHODS: The effect of trichostatin A (TSA), an HDI, on human aortic smooth muscle cells (HASMCs) was determined. The mineralization of HASMCs was induced by inorganic phosphorus (Pi), and was confirmed by quantitation of Ca levels and by von Kossa staining. Furthermore, we examined the effect of alkaline phosphatase (ALP) suppression using siRNA on Pi-induced vascular calcification in the presence or absence of TSA. RESULTS: TSA increased the expression and activity of ALP in HASMCs at a concentration which showed an inhibitory effect of histone deacetylase (HDAC) activity but not on cell viability. Moreover, TSA promoted the Pi-induced mineralization of HASMCs. In addition, both phosphonoformic acid (PFA), which is a sodium-dependent phosphate transporter inhibitor, and suppression of ALP expression by siRNA markedly inhibited the TSA-promoted mineralization of HASMCs. CONCLUSION: These data show that inhibition of HDAC activity promotes Pi-induced vascular calcification via the up-regulation of ALP expression. Taken together, HDIs may increase the risk of vascular calcification in CKD patients.