Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.     

The hypereosinophilic syndromes: current concepts and treatments

The hypereosinophilic syndromes (HES) encompass a spectrum of diseases that have increased blood eosinophils and tissue damage in common. The clinical manifestations are protean and may involve any organ system, but especially the skin. Our understanding of these diseases has drastically changed over the past 15 years, along with new classifications that characterize patients with marked eosinophilia. One HES variant, myeloproliferative, is actually chronic eosinophilic leukaemia with a unique genetic marker, FIP1L1-PDGFRA . Such patients are well-controlled by administration of the kinase inhibitor, imatinib, and remissions appear durable with continued imatinib therapy. FIP1L1-PDGFRA is expressed in several cell lineages, thus explaining increases in neutrophils and mast cells in HES. The lymphocytic HES variant is associated with T-cell clones producing interleukin-5 (IL-5) and can evolve into lymphoma. While myeloproliferative and lymphocytic HES are well established and permit elimination of the term, idiopathic, to these varieties, most HES patients do not fall into these categories and are classified as complex (using the 2006 Workshop Report). A recent study showed that a monoclonal antibody to IL-5, mepolizumab, reduced glucocorticoid therapy in HES patients who did not possess the FIP1L1-PDGFRA mutation while controlling eosinophilia and preventing recurrence or progression of tissue damage. These advances augur well for continued progress in the understanding and treatment of HES.     

Anthelmintic activity of cyclotides: In vitro studies with canine and human hookworms

Hookworm infection is a leading cause of maternal and child morbidity in countries of the tropics and subtropics, as well as being an important parasite in companion-animal medicine. The cyclotides are a novel family of cyclic cystine knot containing peptides from plants that have been shown to possess anthelmintic activity against Haemonchus contortus and Trichostrongylus colubriformis, two important gastrointestinal nematodes of sheep. In the current study we demonstrated the in vitro effects of three representative cyclotides, kalata B1, kalata B6 and cycloviolacin O14, on the viability of larval and adult life stages of the dog hookworm Ancylostoma caninum, and larvae of the human hookworm Necator americanus. The cyclotides showed significant anthelmintic activity towards both hookworm species. The different cyclotides showed similar patterns of relative activity as that seen previously with the livestock nematode species. This study demonstrates that cyclotides have promising activity in vitro against important parasites of companion animals and humans.     

Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepal-6 cells and its relationship with collagen type Ⅳ

AIM: To investigate the regulation of activin receptor-interacting protein 2 (ARIP2) expression and its possible relationships with collagen type Ⅳ (collagen Ⅳ) in mouse hepatoma cell line Hepal-6 cells.METHODS: The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation factors were analyzed by treatment with signal transduction activators such as phorbol 12-myristate 13-acetate (PMA), forskolin and A23187. After pcDNA3-ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type Ⅱ receptor (ActRII)and collagen Ⅳ expression were evaluated.RESULTS: The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation (2 or 4 h). TheARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 (25.3% ± 5.7% vS 48.1% ± 3.6%, P ＜ 0.01). ARIP2 overexpression could remarkably suppress the expression of ActRIIA mRNA in dose-dependent manner, but has no effect on ActRIIB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen Ⅳ mRNA and protein expressions induced by activin A in Hapel-6 cells.CONCLUSION: These findings suggest that ARIP2 expression can be influenced by various factors. ARIP2 may participate in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA and play an important role in regulation of development of liver fibrosis induced by activin.     

Case of Chronic Lymphocytic Leukemia with Unusual Chromosome Aberrations

Chronic lymphocytic leukemia is one of the most common leukemias in the western world and consists of many chromosome aberrations. We report the case of a 74-year-old male patient with chronic lymphocytic leukemia with complex variant translocations t(8;22)(q24;q11) and der(8)t(6;8)(p21;p21) identified by chromosome banding analysis and confirmed by fluorescence in situ hybridization analysis of interphase cells. Because of the rarity of these changes, possible molecular mechanisms associated with this karyotype are discussed.     

尘螨变应性鼻炎全血细胞IL-4、IL-13的表达及临床意义

目的探讨IL-4、IL-13在变应性鼻炎发病机制中的作用及IL-4、IL-13拮抗剂治疗变应性鼻炎的临床意义。方法取52例变应性鼻炎（实验组）及25例无过敏性疾病（对照组）患者的外周血，用PMA（phorbol 12-myristate 13-acetate佛波酯）＋inomycin（离子霉素）及标准化尘螨抗原刺激后经细胞内染色，流式细胞仪检测IL-4、IL-13、IFN-γ的表达细胞百分数，ELISA检测血清IL-4、IL-13含量。结果对照组经标准化尘螨变应原刺激后细胞内测出IFN-γ为0．3％-0．4％，但检测不到IL-4与IL-13，经PMA＋inomycin刺激后IFN-γ为5．0％-12．4％、IL-4为0．5％-0．8％、IL-13为0％-0．2％；实验组经标准化尘螨变应原刺激后IFN-γ为0．3％-0．5％、IL-4为0．9％-1．3％、IL-13为0．5％-0．9％，经PMA＋inomycin刺激后IFN-γ为17.3％-24．0％、IL-4为2．1％-3．5％、IL-13为0．8％-2．0％。实验组血清中IL-4含量为（1．768±0．485）pg／ml、IL-13为（5．427±1．263）pg／ml，对照组IL-4与IL-13含量均低于敏感度。结论IL-4、IL-13在变应性鼻炎患者中表达升高，参与了变态反应过程，为临床应用IL-4、IL-13拮抗剂治疗变应性鼻炎提供了依据。     

The emerging role of the epigenetic enzyme Sirtuin-1 and high mobility group Box 1 in patients with diabetic foot ulceration

Background

Diabetic foot ulceration (DFU) is a serious diabetic complication that can progress to amputation and since SIRT1 regulates glucose metabolism, inflammation, and oxidative stress which are the major contributors in diabetic complications, So we aimed to discuss its role as an epigenetic biomarker in DFU and highlight its link to oxidative stress and inflammatory cytokines.