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Introduction: In 2021, KEYNOTE-590 (NCT03189719) showed that pembrolizumab plus 5-fluorouracil and cisplatin (PPF) has more benefits than 5-fluorouracil and cisplatin (PF) as a first-line regimen to treat individuals with advanced esophageal cancer. However, given that it is expensive, controversies over the value of using this compared to competitive strategies remain. Hence, we conducted a cost-effectiveness evaluation of pembrolizumab plus chemotherapy. Methods: A Markov model was applied in evaluating the efficacy and cost of PPF and PF over a 7-year horizon and measured the health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The economic data included were relevant to patients in the USA and China. We also performed one-way and probabilistic sensitivity analyses to determine the uncertainties relevant to the model. Willingness to pay thresholds (WTP) of $150,000/QALY (USA) and $35,673/QALY (China) were used to calculate a probability for the cost-effectiveness of PPF. Results: PPF yielded 0.386–0.607 QALYs (0.781–1.195 LYs) compared with PF. In our analysis, compared with receiving PF, patients with advanced esophageal cancer receiving PPF had an ICER of $577,461/QALY in the USA and $258,261/QALY in China, those for esophageal squamous cell carcinoma were $550,211/QALY in the USA and $244,580/QALY in China, and a programmed cell death ligand 1 combined positive score (PD-L1 CPS) ≥ 10 was associated with a cost of $479,119/QALY in the USA and $201,355/QALY in China. Sensitivity analysis found the price of pembrolizumab to be the biggest influence. Conclusion: From the economic perspectives of the USA and China, a first-line regimen of PPF for esophageal cancer therapy may not be as cost-effective as PF. However, patients with esophageal cancer and PD-L1 CPS ≥ 10 may gain the most LYs from initial PPF treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the roles of miR-149 in the progression of human osteosarcoma (OS).Results: miR-149 level was upregulated in tissues from OS patients more than in normal subjects. Cell proliferation and apoptosis assays revealed that miR-149 increased cell proliferation and inhibited cell apoptosis in OS cell line (MG63). An increase of Bcl-2 gene expression and a decrease of cleaved-caspase-3, and cleaved-PARP expression were observed in MG63 cells with transfection of miR-149. Additionally, bone morphogenetic protein 9 (BMP9) was identified as a target of miR-149 in MG63 cells, and BMP9 expression was negatively correlated with miR149 level in OS clinical samples. Co-overexpression of BMP9 with miR-149 in MG63 cells prohibited miR-149-mediated promotive effects on OS progression. Importantly, overexpression of miR-149 conferred chemoresistance in MG63 cells.Conclusions: miR-149 promotes OS progression via targeting BMP9. [ABSTRACT FROM AUTHOR]

Background: Due to the adverse effects of cemented hip arthroplasty, uncemented stems with hydroxyapatite (HA) coating reduces these risks and enhanced integration. The concept of an extensive HA coating for the fixation of a tapered femoral stem (Corail) was introduced, which can achieve durable biological fixation and preserve normal periprosthetic bone activity. Here we describe the clinical and radiological outcome in patients with the Corail stem. Methods: 92 total hip replacements in 81 patients using the Corail stem were followed-up. 47 patients were women, and the mean age at surgery was 62.9 ± 8.7 (34-71) years. The indications included: osteoarthritis of the hip (71.1%), avascular necrosis (13.6%), femur neck fractures in elderly (9.7%) and post-traumatic osteoarthritis (6.8%). Findings: Eight patients died during follow-up. The revision was only found in two patients due to line wear and resulted in an 10-year Kaplan-Meier estimated overall survival rate of 97.83%. The clinical results were good, with a mean Harris hip score of 92.3 ± 5.6 (72-100). The mean total Merle d'Aubigné and Postel score was 6.8 ± 0.5 pre-operatively and 16.1 ± 1.4 at latest follow-up. All unrevised implants were radiographically stable, with a mean liner wear of 0.07 mm/year. Conclusion: This long-term analysis confirmed the durability of the functional and radiographic results. Our findings suggest the long-term results of Corail HA-coated stem are more satisfactory which is preferable to any other system. [ABSTRACT FROM AUTHOR]

Erythropoietin-producing hepatocyte (Eph) receptor family constitutes the largest family of tyrosine kinase receptors in the human genome. Loss of EphB6, a kinase-deficient receptor, correlated with a negative outcome in several carcinomas. This study aimed to investigate the expression of EphB6 protein and mRNA levels in colorectal cancers (CRCs) and possible correlations with clinicopathological variables and prognosis. To assess protein expression level, 124 CRCs and 57 colorectal adenomas samples were examined by immunostaining, the mRNA level of 43 paired CRC and the adjacent normal tissues were detected by using SYBR Green real-time PCR method. Decreased expression of EphB6 protein was found in CRC as compared with adenoma and normal tissues (χ = 10.146, P = 0.001 and χ = 45.333, P < 0.001, respectively). Low EphB6 mRNA expression was detected in 83.8 % of cancers with negative or low EphB6 protein expression. The loss of EphB6 protein in CRC was positively associated with poorly differentiation ( P < 0.001), lymph node metastasis ( P = 0.006), Dukes stage ( P = 0.002) and depth of invasion ( P = 0.016). The patients with lymph node metastasis had a worse prognosis independently of gender, age, tumor site, stage and differentiation (RR = 0.404, CI 0.267-0.213, P < 0.001). Low levels of EphB6 protein expression are associated with a shorter mean duration of survival in colorectal cancer. Our results demonstrated that EphB6 may represent a novel, useful tissue biomarker for the prediction of survival rate in CRC. [ABSTRACT FROM AUTHOR]