Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

Human fluids alter DNA-acquisition in Acinetobacter baumannii

Transformation is one of the mechanisms of acquisition of foreign genetic material leading to the emergence of multidrug resistant (MDR) bacteria. Recently, human serum albumin (HSA) was shown to specifically increase transformation frequency in the nosocomial pathogen Acinetobacter baumannii. To further assess the relevance of HSA as a possible modulator of A. baumannii transformation in host-pathogen interactions, in this work we examined the effect of different human fluids. We observed a significant increase in transformation frequencies in the presence of pleural fluid, whole blood cells and liquid ascites, and to a lesser extent with urine. The observed effects correlate with both HSA and bacterial content found in the assayed patient fluids. Taken together, these results are in agreement with our previous findings that highlight HSA as a possible host signal with the ability to trigger natural transformation in A. baumannii.     

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

纤维蛋白原/白蛋白比值比对可手术乳腺癌患者预后的影响

目的探讨纤维蛋白原/白蛋白比值比(FAR)对可手术乳腺癌患者预后的影响。 方法依据纳入、排除标准，收集中国医学科学院北京协和医院2013年1～12月收治的520例Ⅰ～Ⅲ期可手术乳腺癌患者临床资料进行回顾性研究。在术前检测血浆纤维蛋白原和白蛋白水平。将纤维蛋白原与白蛋白质量浓度比值乘以100定义为FAR。根据受试者工作特征曲线确定FAR最佳临界值，并依据最佳临界值将受试者分为高FAR组(FAR>6.99)147例和低FAR组(FAR≤6.99)343例。采用Kaplan-Meier法和log-rank检验评估2组患者的DFS和OS，用Cox比例风险回归模型分析患者DFS和OS的影响因素。 结果log-rank检验显示，高FAR组患者的DFS和OS均比低FAR组差(χ²＝32.885、16.320，P均<0.001)。Cox比例风险回归模型单因素分析和多因素分析均显示：高FAR为患者DFS的独立危险因素(HR＝4.092，95%CI：2.425～6.903，P<0.001；HR＝4.226，95%CI：2.476～7.212，P<0.001);高FAR为患者OS的独立危险因素(HR＝3.907，95%CI：1.913～7.978，P<0.001；HR＝4.320，95%CI：2.087～8.942，P<0.001)。 结论术前高FAR患者的无疾病进展时间更短，OS率更低。术前FAR水平有望成为预测乳腺癌患者预后的有效指标。     

Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases

PurposeTo evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (¹⁶⁶Ho)-radioembolization.Materials and MethodsThis was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on ¹⁶⁶Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded.ResultsOne hundred five of 120 scheduled patients completed the same-day treatment with ¹⁶⁶Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58–9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28).Conclusion¹⁶⁶Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.     

Same-Day Repeat Hepatopulmonary Shunt Measurement during Planning Angiography for Hepatic Radioembolization

This report describes a technique for measuring lung shunt fraction (LSF) twice in a single session during planning arteriography for radioembolization using low and standard dose technetium-99m macroaggregated albumin (^99mTc-MAA). A patient with a 16.0 cm hepatocellular carcinoma and LSF of 70% was treated with lenvatinib for 4 weeks. Planning arteriography with administration of 0.5 millicuries of ^99mTc-MAA was then performed. Arterial access was maintained while the LSF was calculated, which was persistently elevated at 54%. Embolization of arteriovenous shunts was performed during the same session and 5.0 millicuries of ^99mTc-MAA were administered. The repeat LSF was 29%. Successful radioembolization was subsequently performed.     

Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.