The VES?13 and G?8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single?center study

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ?70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy?seven consecutive patients aged ?70 diagnosed with non?metastatic hormone?responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES?13 score ?3 or G?8 score ?14) and fit (VES?13 score <3 or G?8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ?70.

Research progress of phytosterolemia and its laboratory diagnosis / 中华检验医学杂志

Phytosterolemia is a rare, severe autosomal recessive sterol storage disorder caused by homozygous or compound heterozygous mutations in one of the ABCG5 and/or ABCG8 adenosine triphosphate binding cassette (ABC) genes. The most prominent features of phytosterolemia are the significantly increased serum content of plant sterols. Present review focused on the laboratory diagnosis of phytosterolemia, briefly described the metabolism of phytosterols, and introduced the latest research progress on phytosterolemia diagnosis, its relationship with ASCVD and laboratory diagnostic methods (including the detection of serum concentrations of phytosterols, ABCG5/G8 gene mutation). We hope this article could improve readers′ awareness and attention on this disease.

Evaluación geriátrica guiada por G8 en la decisión del tratamiento de adultos mayores con cáncer: un estudio piloto / Geriatric evaluation guided by G8 in the decision to treat older adults with cancer: a pilot study / Avaliação geriátrica guiada pelo G8 na decisão de tratar idosos com câncer: um estudo piloto

Introducción: El cáncer es una enfermedad asociada al envejecimiento y tiene una alta prevalencia en los adultos mayores. La valoración geriátrica integral (VGI) mejora los cuidados de los adultos mayores (AM) con cáncer. En contextos sanitarios con recursos limitados, no todos los AM podrán ser evaluados por un geriatra. Un modelo en 2 pasos, incluyendo el test G8, en la consulta habitual del oncólogo, permite seleccionar aquellos pacientes que se beneficiarán de una VGI. Esta puede aportar en la toma de decisiones del tratamiento oncológico específico. Objetivo: Evaluar el beneficio del test G8 y la VGI en ≥ 70 años con cáncer candidatos a recibir quimioterapia. Material y Métodos: Estudio observacional, descriptivo, de corte transversal, de una muestra no probabilística de pacientes ≥ de 70 años con diagnóstico de cáncer y candidatos a recibir quimioterapia. Se aplicó el G8 por el oncólogo y se completó la VGI en los que presentaron alteración en algunas de las áreas evaluadas. Resultados: Se analizaron 32 pacientes. Se realizó G8 a todos, en 21 de ellos se completó la VGI. En estos, en reunión multidisciplinaria con oncólogo y geriatra se discutió el tratamiento. En el 38% de los pacientes se cambió la conducta oncológica tras contar con la valoración geriátrica integral. Conclusión: Creemos que la incorporación del G8 en la práctica clínica del oncólogo aporta una herramienta de cribado útil para identificar los pacientes ≥70 años que se benefician de una VGI previa al inicio de tratamiento oncoespecífico, optimizando de esta manera los recursos.

Introduction: Cancer is a disease associated with aging and has a high prevalence in older adults. Comprehensive geriatric assessment (CGA) improves the care of older adults (OA)with cancer. In healthcare settings with limited resources, not all OA may be evaluated by a geriatrician. A 2-step model, including the G8 test, in the usual oncologist consultation, allows selecting those patients who will benefit from CGA. This can contribute to decision-making regarding specific cancer treatment. Objective: To evaluate the benefit of the incorporation of the G8 test and CGA in the ≥ 70 years with cancer candidates for chemotherapy. Material and Methods: Observational, descriptive, cross-sectional study of a non-probability sample of patients ≥ 70 years of age with a diagnosis of cancer and candidates for chemotherapy. The G8 was applied by the oncologist and the CGA was completed in those who presented alteration in some of the evaluated areas. Results: 32 patients were analyzed. G8 was performed in all, in 21 of them the CGA was completed. In these, the treatment was discussed in a multidisciplinary meeting with an oncologist and a geriatrician. Oncological behavior was changed in 38% of patients after having a comprehensive geriatric evaluation. Conclusion: We believe that the incorporation of the G8 test in the clinical practice of the oncologist provides a useful screening tool to identify patients ≥70 years who benefit from CGA prior to the start of oncospecific treatment, thus optimizing resources.

Introdução: O câncer é uma doença associada ao envelhecimento e tem alta prevalência em idosos. A avaliação geriátrica ampla (AGA) melhora o atendimento a idosos com câncer. Em ambientes de saúde com recursos limitados, nem todos eles podem ser avaliadas por um geriatra. Um modelo de duas etapas, incluindo o teste G8, na consulta oncológica usual, permite selecionar os pacientes que serão beneficiados pela AGA. Isso pode contribuir para a tomada de decisões em relação ao tratamento específico do câncer. Objetivo: Avaliar o benefício da incorporação do teste G8 e AGA nos ≥ 70 anos com câncer, candidatos à quimioterapia. Material e Métodos: Estudo observacional, descritivo e transversal de uma amostra não probabilística de pacientes com idade ≥ 70 anos com diagnóstico de câncer e candidatos à quimioterapia. O G8 foi aplicado pelo oncologista e a AGA foi realizada naqueles que apresentaram alteração em algumas das áreas avaliadas. Resultados: 32 pacientes foram analisados. O G8 foi realizado em todos, em 21 deles a AGA foi aplicada. Nesses, o tratamento foi discutido em reunião multidisciplinar com oncologista e geriatra. O tratamento oncológico foi alterado em 38% dos pacientes após uma avaliação geriátrica amplia. Conclusão: Acreditamos que a incorporação do teste G8 na prática clínica do oncologista fornece uma ferramenta de triagem útil para identificar pacientes com idade ≥70 anos que se beneficiam da AGA antes do início do tratamento oncoespecífico, otimizando recursos.

Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats / 中国实验方剂学杂志

Objective:To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats, in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia. Method:A total of 40 SD rats were selected, including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling, the rats were randomly divided into the model group (equivalent normal saline), the high and low-dose Shuangyu Tiaozhi groups (15.6, 7.8 g·kg-1), and the Simvastatin group (4 mg·kg-1), with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC), triglyceride (TG) in serum and total cholesterol (TTC), free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining, and the levels of expressions of NPC1L1, ABCG8 and liver X receptor-α (LXR-α) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry. Result:After successful replication of the hyperlipidemia model, the blood lipid level was abnormally increased, and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1, LXR-α and ABCG8 increased significantly (PPα were significantly down-regulated, but ABCG8 was obviously up-regulated in a dose-dependent manner (PPPPPPConclusion:Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.

Lessons from the Field Count more than Ever: The New Era of Global Health

For many years, Japan has been silent on the achievements of Japan’s Overseas Development Assistance program including the health improvement of foreign countries. Japan’s contribution to global health communities through G8 process including Hashimoto Initiative is steadfast. On the other hand, in the field activity level, experts involved in ODA have not disclosed their achievements. However, the article by Wada et al., which describes the contents of TEN MR (Minimum Requirement), shed light on Japan’s silent ODA community by disclosing Japan’s achievements in global health by drawing lessons that may be applicable to other countries. Our future challenge in the global health will be how to synthesize actions that reflect the lessons learnt from the field and which show scientific evidence using established methods.

La respuesta terapéutica a ezetimiba en ratones C57BL/6 es mediada por cambios en la expresión de NPC1L1, ABCG5 y ABCG8 en el enterocito / Therapeutic response to ezetimibe in C57BL/6 mice is mediated by changes in NPC1L1, ABCG5 and ABCG8 expression in the enterocyte

Las proteínas NPC1L1, ABCG5 y ABCG8 participan en la absorción intestinal de colesterol. Ezetimiba inhibe este proceso bloqueando a NPC1L1, sin embargo, su efecto sobre ABCG5 y ABCG8 aún no está claro. Así, el objetivo del presente trabajo fue evaluar en ratones C57BL/6 con hipercolesterolemia inducida por dieta y tratados con ezetimiba, la expresión de NPC1L1, ABCG5 y ABCG8 mediante PCR en tiempo real y Western blot, en 3 grupos de animales: 1, dieta hipercolesterolémica D12336; 2, dieta D12336 más 5 mg/kg/día de ezetimiba; 3, dieta control. El nivel sérico de colesterol total fue significativamente diferente entre los grupos estudiados (control: 1,85 +/- 0,49 mmol/L; dieta D12336: 3,11 +/- 0,73 mmol/L; ezetimiba: 2,11 +/- 0,50 mmol/L, P = 0,001). La expresión génica de NPC1L1 aumentó 5,4 veces en el grupo que recibió la dieta D12336 (P = 0,003). Por otro lado, la expresión génica de ABCG5 y ABCG8 no fue diferente en el grupo con hipercolesterolemia (P = 0,239 y P = 0,201, respectivamente). Después del tratamiento con ezetimiba, la expresión génica de ABCG5 se incrementó 15,6 veces (P = 0.038). No hubo diferencias significativas en la expresión génica de NPC1L1 (P = 0,134) y ABCG8 (P = 0,067). En relación a la expresión proteica, la dieta D12336 incrementó los niveles de expresión de NPC1L1 (P = 0,022) y ABCG5 (P = 0,008); el tratamiento con ezetimiba incrementó los niveles de NPC1L1 (P = 0,048) y redujo los niveles de ABCG5 (P = 0,036) y ABCG8 (P = 0,016). En conclusión, nuestros resultados sugieren que tanto la dieta hipercolesterolémica como el tratamiento con ezetimiba, en un modelo experimental, afectan los niveles de expresión de NPC1L1, ABCG5 y ABCG8, sugiriendo que ABCG5 y ABCG8 están involucrados en la respuesta hipolipemiante a este fármaco. No obstante, el mecanismo mediante el cual se explica esta interacción requiere de un futuro estudio.

Proteins NPC1L1, ABCG5 and ABCG8 are involved in the intestinal absorption of cholesterol. Ezetimibe inhibits this process by blocking NPC1L1, however, its effect on ABCG5 and ABCG8 is not yet clear. Thus, the objective of this study was to evaluate in C57BL / 6 mice with diet-induced hypercholesterolemia treated with ezetimibe, the expression of NPC1L1, ABCG5 and ABCG8 by real time PCR and Western blot, in 3 groups of animals: 1, diet hypercholesterolemic D12336, 2, D12336 diet plus 5 mg/kg/ day of ezetimibe, 3, diet control. The serum level of total cholesterol was significantly different between groups (control: 1.85 +/- 0.49 mmol / L; diet D12336: 3.11 +/- 0.73 mmol / L; ezetimibe: 2.11 +/- 0.50 mmol / L, P = 0.001). NPC1L1 gene expression increased 5.4-fold in the group receiving the diet D12336 (P = 0.003). Furthermore, the gene expression of ABCG5 and ABCG8 was not different in the group with hypercholesterolemia (P = 0.239 and P = 0.201, respectively). After treatment with ezetimibe, ABCG5 gene expression was increased 15.6 times (P = 0.038). No significant differences in gene expression of NPC1L1 (P = 0.134) and ABCG8 (P = 0.067). Regarding protein expression, the D12336 diet increased the levels of expression of NPC1L1 (P = 0.022) and ABCG5 (P = 0.008), treatment with ezetimibe increased the levels of NPC1L1 (P = 0.048) and reduced levels of ABCG5 (P = 0.036) and ABCG8 (P = 0.016). In conclusion, our results suggest that both hypercholesterolemic diet as treatment with ezetimibe, in an experimental model, affect the expression levels of NPC1L1, ABCG5 and ABCG8, suggesting that ABCG5 and ABCG8 are involved in lipid-lowering response to this drug. However, the mechanism by which this interaction is explained requires further study.

Effect of five single nucleotide polymorphisms of ABCG5 and ABCG8 genes on eLipid-lowering response / Efecto de cinco polimorfismos de los genes ABCG5 y ABCG8 sobre la respuesta hipolipemiante a ezetimiba

In this study we evaluated the possible association between five single nucleotide polymorphisms in ABCG5 (rs6720173) and ABCG8 (rs11887534, rs4148211, rs4148217 and rs6544718) genes and ezetimibe response in Chilean hypercholesterolemic subjects. A total of 60 non-related hypercholesterolemic subjects, aged 18 to 65 years old were included in this study. These subjects were treated with ezetimibe (10mg/day) during one month. The ABCG5 and ABCG8 genotypes were assessed by PCR-RFLP. The genotype distribution of the ABCG5/ABCG8 polymorphisms was in Hardy-Weinberg equilibrium. Our results showed that the investigated polymorphisms were not associated with the response to ezetimibe. Nevertheless, the T allele of rs6544718 polymorphism was related to higher baseline levels of LDL-cholesterol (p<0.001). In addition, the G allele for the rs4148211 polymorphism was associated with greater baseline concentrations of triglycerides (P=0.019). This allele was also associated with lower concentrations of HDL-cholesterol (P=0.027), after ezetimibe treatment. Our results suggest that the studied polymorphisms do not affect the therapeutic response to ezetimibe in the evaluated subjects.

En este estudio se evaluó la posible asociación entre cinco polimorfismos de nucleótido único en los genes ABCG5 (rs6720173) y ABCG8 (rs11887534, rs4148211, rs4148217 y rs6544718) y la respuesta a ezetimiba en pacientes hipercolesterolémicos chilenos. Un total de 60 individuos hipercolesterolemicos, no relacionados, con edades entre 18 y 65 años fueron incluidos. Estos sujetos fueron tratados con ezetimiba (10mg/día) durante un mes. Los genotipos de ABCG5 y ABCG8 fueron evaluados por PCR-RFLP. La distribución de genotipos de los polimorfismos de ABCG5/ABCG8 se encontraba en equilibrio de Hardy-Weinberg. Nuestros resultados mostraron que los polimorfismos estudiados no se asociaron con la respuesta a la ezetimiba. Sin embargo, el alelo T del polimorfismo rs6544718 fue relacionado con niveles basales elevados de LDL-colesterol (p <0,001). Además, el alelo G para el polimorfismo rs4148211 se asoció con una mayor concentración basal de triglicéridos (p = 0,019). Este alelo también se asoció con concentraciones más bajas de HDL-colesterol (p = 0,027), después del tratamiento con ezetimiba. Nuestros resultados sugieren que los polimorfismos estudiados no afectan a la respuesta terapéutica a la ezetimiba en los sujetos evaluados.

Evaluation of Hemoglobin A1c on the Cobas Integra 800 Immunoassay and Tosoh HLC-723 G8 HPLC Analyzer / 임상검사와정도관리

BACKGROUND: Hemoglobin A1c (HbA1c) is a good marker for the monitoring of glycemic control in patients with diabetes mellitus and various methods are used for determination of HbA1c. We evaluated the analytical performance of ion-exchange high-performance liquid chromatography system, standard mode (G8 SM) and variant mode (G8 VM) of Tosoh HLC-723 G8 (Tosoh Corporation, Japan) and Cobas Integra 800 (Roche Diagnostics, Germany) using new reagent (Tina-quant Hemoglobin A1c Gen.2, Roche Diagnostics) for immunoassay. METHODS: G8 SM, G8 VM, and Cobas Integra 800 were evaluated for linearity, precision, comparison of method, and speed. Variant II Turbo (Bio-Rad Laboratories, USA) was used for comparison test for above three analyzers. RESULTS: Three instruments showed within-run precision (CVs) of 0.52-1.12% in low level and 0.39-0.90% in high level control material. Total run precision (CVs) were in 0.95-1.26% in low level and 0.60-0.94% in high level control material. The linearity was good for the range of 4-15% and comparison with Variant II turbo was excellent with 0.9878-0.9977 of correlation coefficient. Analytical speed was 2 min/1 min in G8 SM, 3.5 min/1.5 min in G8 VM, and 14.7 min/18 sec in Cobas Integra 800, respectively. CONCLUSIONS: HLC-723 G8 SM and VM, and Cobas Integra 800 were showed excellent linearity, precision, and comparison with other instrument. We should consider the characteristics including analytical method and speed in each instrument when clinical laboratory is planning to introduce different equipment for HbA1c determination.

Evaluation of the Tosoh HLC-723 G8 HbA1c Autoanalyzer / 임상검사와정도관리

BACKGROUND: We evaluated overall performance and analysis time of newly developed HLC-723 G8 (Tosoh corp., Tokyo, Japan) HbA1c autoanalyzerwhich utilizes cation-exchange HPLC method. METHODS: Linearity, precision, correlation with Variant II Turbo (Bio-Rad Laboratories, Hercules, CA, USA), analysis time, labile HbA1c (L-A1c) separation ability and stability of refrigerated sample at 4degrees C were evaluated. RESULTS: HLC-723 G8 showed good linearity between HbA1c 4.9-12.0% range (R2=0.9995). Within-run and total imprecision (CVs) were less than 1.0%. Correlation with Variant II Turbo and L-A1c separation ability were excellent. Analysis time per sample took 1.0 min. Stability of refrigerated sample at 4degrees C for at least 21 days was good. CONCLUSIONS: HLC-723 G8 showed good analytical performance and its rapid analysis time enables us to support outpatient diagnosis of diabetic patients efficiently.

Study on development of DNA probe for identification of Prevotella intermedia G8-9K-3 / 대한치주과학회지

The purpose of this study is to develop species-specific DNA probe for detection and identification of Prevotella intermedia (P. intermedia) G8-9K-3. This study procedure includes (1) whole-genomic DNA extraction of P. intermedia G8-9K-3 (2) construction of the genomic DNA library, (3) screening of strain-specific DNA probe by reverse dot hybridization, (4) confirmation of strain-specific DNA probe by Southern blot hybridization, (5) determination of nucleotide sequences of strain-specific DNA probe. Twenty-eight recombinant plasmids containing Hind III-digested DNA fragments of P. intermedia G8-9K-3 were obtained. Reverse dot Hybridization and Southern blot analysis data showed that one of them, Pig3, could be P. intermedia G8-9K-3-specific DNA probe. This datum indicates that this Pig3 DNA probe could be useful in detection and identification of the P. intermedia G8-9K-3 strain.