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Our model appears to predict somewhat more female bias than is observed empirically; we discuss a number of possible model extensions that would improve realism and that would be expected to result in a closer quantitative fit with experimental data.Although nivolumab, a programmed cell death 1 (PD-1) inhibitor, is a standard therapy for platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), no definitive biomarkers have been reported thus far. This study aimed to select promising prognostic markers in nivolumab therapy and to create a novel prognostic scoring system. In this retrospective cohort study, we reviewed patients with R/M HNSCC who were treated with nivolumab from April 2017 to April 2019. We developed a prognostic score for immune checkpoint inhibitor (ICI) therapy that was weighed using hazard ratio-based scoring algorithms. Significant variables were selected from the multivariate Cox proportional hazard analyses on overall survival (OS). A total of 85 patients with HNSCC were analyzed in the present study. The relative eosinophil count (REC), the ratio of eosinophil increase (REI), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were selected as variables affecting the prognostic score. The patients were divided into four groups very good (score = 0), good (score = 1), intermediate (score = 2), and poor (score = 3). PF-04418948 supplier The OS hazard ratios were 2.77, 10.18, and 33.21 for the good, intermediate, and poor risk groups compared with the very good risk group, respectively. The Eosinophil Prognostic Score is a novel prognostic score that is effective for predicting the prognosis of HNSCC patients treated with nivolumab. This score is more precise as it includes changes in biomarkers before and after the treatment.Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP-based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment-triggered release. 5′-Deoxy-5-fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co-imprinted nanoparticles were prepared as a smart carrier. Prodrug-loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in-liver bioconversion, this MIP-based prodrug delivery is liver-independent but tumor-dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms.Withdrawal from opioid painkillers can produce short-lived physical symptoms and protracted psychological symptoms including anxiety and depressive-like states that often lead to opioid misuse and opioid use disorder (OUD). Studies testing the hypothesis that opioid withdrawal potentiates the reinforcing effects of opioid self-administration (SA) are largely inconclusive and have focused on males. Although some clinical evidence indicates that women are more likely than men to misuse opioids to self-medicate, preclinical studies in both sexes are lacking. Based on clinical reports, we hypothesized that withdrawal from escalating-dose morphine injections that approximates a prescription painkiller regimen would lead to increased oxycodone SA to a greater extent in female compared to male rats. After escalating-dose morphine (5-30 mg/kg or vehicle, twice/day for 12 days), rats underwent a 2-week abstinence period during which withdrawal signs were measured. The impact of this treatment was assessed on oxycodone SA acquisition, maintenance, dose response, and progressive ratio responding, with additional analyses to compare sexes. We found that both sexes expressed somatic withdrawal, whereas only males demonstrated hyperalgesia in the warm water tail flick assay. During SA acquisition, males with prior morphine exposure took significantly more oxycodone than females. Finally, females with prior morphine exposure demonstrated the lowest motivation to SA oxycodone in the progressive ratio test. Contrary to our initial hypothesis, our findings suggest that prior opioid exposure increases vulnerability to initiate misuse more in males and decreases the reinforcing efficacy of oxycodone in females.Essentials Increase in serum uric acid (SUA) levels has been widely associated with higher risk of cardiovascular disease. We investigated the link between SUA levels and the risk of venous thromboembolism (VTE) recurrence. Patients with SUA levels ≥ 4.38 mg/dL showed a three-fold increase in the risk of VTE recurrence. Elevated SUA levels are associated with increased risk of recurrent VTE independently from traditional risk factors. ABSTRACT Background The link between serum uric acid (SUA) and the risk of cardiovascular disease is well established. However, the impact of SUA levels on the risk of venous thromboembolism (VTE) recurrence is unknown. Objectives To investigate the association between SUA and the risk of VTE recurrence. Patients and Methods We performed a monocenter, prospective study on 280 patients with a previous episode of VTE that completed the oral anticoagulant period. SUA levels at enrollment were correlated with the risk of VTE recurrence (mean follow-up 71.1 ± 29.2 months). Results PaTE recurrence independently from traditional risk factors.Essentials An optimal therapeutic strategy has yet to be established to prevent early shunt thrombosis. A phase 1 study of cangrelor was performed in neonates after palliation of congenital heart disease. PD endpoint of >90% platelet inhibition in 60% of patients was achieved at 0.5 µg/kg/min dosing. No serious adverse events related to drug administration were observed, including bleeding. ABSTRACT Background Systemic-to-pulmonary artery shunt thrombosis is a significant cause of early postoperative mortality in neonates after palliation of congenital heart disease. In the context of thromboprophylaxis, an optimal therapeutic strategy has yet to be established before aspirin administration. Cangrelor, a fast-acting, reversible P2Y12 inhibitor, may fill this unmet need. Objectives To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of cangrelor in neonates undergoing stage 1 palliation. Methods This prospective, open-label, single-arm study evaluated two cangrelor dosing cohorts following placement of a systemic-to-pulmonary artery shunt, right ventricle-to-pulmonary artery shunt, or ductal stent.