Cost-effectiveness of camrelizumab combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma in China.

OBJECTIVE: This study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective of Chinese healthcare system. DESIGN: A Markov model consisting of four health states, progression-free survival, first progression survival, second progression survival and death, was built to simulate 3-week patient transitions over a 20-year horizon. A direct comparison between first-line camrelizumab in combination with gemcitabine plus cisplatin and gemcitabine plus cisplatin was performed by calculating transition probabilities from the CAPTAIN-1st trial. Costs and utilities were collected from the local public database and literature. One-way and probabilistic sensitivity analyses were employed to evaluate the robustness of the model. SETTING: The Chinese healthcare system perspective. PARTICIPANTS: A hypothetical cohort of Chinese patients with pathologically diagnosed L/M NPC who had an Eastern Cooperative Oncology Group performance status of 0 or 1. INTERVENTIONS: First-line camrelizumab in combination with camrelizumab and gemcitabine plus cisplatin (CGP) versus gemcitabine plus cisplatin (GP). PRIMARY OUTCOME MEASURE: Cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER). RESULTS: The baseline analysis demonstrated that, compared with first-line GP, first-line CGP yields an effectiveness increase of 0.26 QALY, accompanied by an increment of US$6137.59 in healthcare cost. This results in an ICER of US$23 482.32/QALY. With the willingness-to-pay (WTP) threshold for a QALY set at US$37 654.50, first-line CGP proves to be cost-effective in 97.20% of the iterations. Deterministic sensitivity analyses indicated that the uncertainty in model parameters had no substantial effect on our results. Probability sensitivity analysis indicated that CGP was cost-effective at the assumed WTP threshold. CONCLUSION: For Chinese patients with L/M NPC, adding Chinese-developed anti-PD-1 antibody camrelizumab to the first-line GP chemotherapy may be cost-effective.

Percutaneous closure of ventricular septal rupture after myocardial infarction: A retrospective study of 81 cases.

OBJECTIVE: To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI). METHODS: This retrospective study included 81 patients who underwent transcatheter closure for postinfarction VSR. We analyzed clinical data from hospitalization and the 30-day follow-up, compared clinical data from the survival and death groups, and explored the best closure time and the safety and efficacy of occlusion. The risk factors for death at 30 days were analyzed by logistic regression. RESULTS: C-reactive protein (CRP), white blood cell counts, N-terminal pro brain natriuretic peptide (NT-ProBNP), and aspartate aminotransferase were higher in the death group than in the survival group (p < .01), with a higher rate of application of vasoactive drugs, and a shorter time from AMI to operation (p < .05). At 30 days postocclusion, 19 patients (23.5%) had died. The mortality rate was significantly lower for operation performed 3 weeks after AMI than for operation performed within 3 weeks of AMI (12.5% vs. 48%, p < .001). Devices were successfully implanted in 76 patients, with 16 (21.1%) operation-related complications and 12 (15.8%) valve injuries. Cardiac function improved significantly (p < .001) at discharge (N = 66) and 30 days after procedure (N = 62). Qp/Qs and pulmonary artery systolic pressure decreased significantly, while aortic systolic pressure increased significantly (p < .001). Additionally, EF and LVDd improved (p < .05) after occlusion. Increases in CRP and NT-ProBNP were risk factors for death at 30 days after closure (p < .05). CONCLUSION: Percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR.

Comparison between Cardiac CTA and Echocardiography for Assessment of Ventricular Septal Rupture Diameter and Its Effect on Transcatheter Closure.

Objective: This study is aimed at comparing cardiac computed tomographic angiography (CTA) with echocardiography in the assessment of ventricular septal perforation diameter. Methods: A total of 44 ventricular septal rupture (VSR) patients undertaking transcatheter occlusion were included and randomly divided into the CTA group and echocardiography group with a 1 : 1 ratio. Clinical data, operation-related data, and 30 d follow-up data were collected and analyzed. Results: Incidence of closure failure, occluder displacement, poor occluder molding, and occluder waist diameter shrinkage between the two groups were not statistically different. The mean residual shunt volume in the echocardiography group (4.2 (3.1, 5.9) mm) was significantly higher than that in the CTA group (2.1 (0, 4.0) mm) with a p value of 0.005. However, no significant differences were found in all-cause mortality and incidence of operative complications within 30 days after surgery. Within the CTA group, the correlation was strongest between postoperative occluder diameter and long diameter measured by CTA with a correlation coefficient of 0.799 and p < 0.001, followed by the correlation between postoperative occluder diameter and mean diameter measured by CTA with a correlation coefficient of 0.740 and p < 0.001. The diameter measured by echocardiography was not correlated to postoperative occlude diameter. Conclusion: Assessment of VSR diameter by cardiac CTA is more accurate than by echocardiography.

Activation of GPR81 by lactate inhibits oscillatory shear stress-induced endothelial inflammation by activating the expression of KLF2.

Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellular-regulated kinase 5 (ERK5) pathway. These findings demonstrate a potential protective role of GPR81 against atherogenesis and that targeted activation of GPR81 may inhibit endothelial inflammation and dysfunction induced by OSS.