Purpose: Immunotherapy combined with chemotherapy have synergistic effects in multiple malignancies. We aimed to compare the efficacy and safety of toripalimab plus hepatic arterial infusion ...chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib in advanced hepatocellular carcinoma (HCC). Materials and Methods: We conducted this retrospective study at 3 hospitals in China and eligible patients were 18 years or older and had a primary diagnosis of unresectable HCC with macroscopic vascular invasion and/or extrahepatic spread. These patients were treated with toripalimab plus HAIC or lenvatinib monotherapy. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), disease control rate per response evaluation criteria in solid tumors (RECIST) 1.1, and objective response rate (ORR) per RECIST 1.1. The results were compared by Student's test or the chi-square test, and the survival curves were calculated by the Kaplan–Meier method, and propensity-score matching (PSM) was used to reduce bias. Results: A total of 118 patients were recruited for this study: 53 in the TorHAIC group and 65 in the lenvatinib group. We found that the TorHAIC group showed a longer PFS (9.3 95% CI, 7.81-10.8 vs 4.8 months 95% CI, 3.31−6.29; hazard ratio HR = 0.57, 95% CI, 0.38-0.85; p = .006), a longer OS (17.13 95% CI, 13.99−20.27 vs 10.1 months 95% CI, 8.14−12.06; HR = 0.5, 95% CI, 0.31 − 0.81; p = .005), a higher disease control rate (86.8% vs 69.2%, p = .002) and a higher ORR (47.2% vs 9.2%, p < .001) by RECIST criteria than the lenvatinib group. Both toripalimab plus HAIC and lenvatinib had acceptable safety profiles. No treatment-related deaths occurred in this study. In the propensity score-matched cohorts (47 pairs), the outcomes in the TorHAIC group were also better than those in the lenvatinib group (p < .05). Conclusion: Toripalimab plus HAIC was tolerable and effective in advanced HCC and the result needs to be confirmed in the phase III trial.
Summary Background Afatinib—an oral irreversible ErbB family blocker—improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR ...mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin—a chemotherapy regimen widely used in Asia—for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. Methods This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer American Joint Committee on Cancer version 6, performance status 0–1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m2 on day 1 and day 8 plus cisplatin 75 mg/m2 on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov , NCT01121393. Findings 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7–13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1–6·7; hazard ratio 0·28, 95% CI 0·20–0·39; p<0·0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 14·6% of 239 patients), diarrhoea (13 5·4%), and stomatitis or mucositis (13 5·4%), compared with neutropenia (30 26·5% of 113 patients), vomiting (22 19·5%), and leucopenia (17 15·0%) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6·3%) patients in the afatinib group and nine (8·0%) patients in the gemcitabine and cisplatin group. Interpretation First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. Funding Boehringer Ingelheim.
To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC).
Chinese patients ...with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort.
The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo 95% confidence interval (CI), 17.4-28.4 vs 8.9 mo 95% CI, 7.5-10.3 in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria.
In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.
Background The aim of the present study was to investigate NLRP3 inflammasome expression in human carotid atherosclerotic plaques and its relationship to plaque vulnerability. Methods Carotid ...atherosclerotic plaques collected from 30 patients scheduled for carotid endarterectomy (CEA) were subjected to immunohistochemical, mRNA, and protein expression studies. Ten mesenteric arteries from intestinal cancer patients served as controls for the immunohistochemical studies. Twenty individuals who had no carotid stenosis or coronary artery stenosis served as controls for analyzing atherosclerotic risk factors and for enzyme-linked immunosorbent assay (ELISA) studies. Serum samples were collected from all patients to determine interleukin-1β (IL-1β) and IL-18 levels. Results The NLRP3 inflammasome signaling pathway components NLRP3, ASC, caspase-1, IL-1β, and IL-18 were strongly expressed in carotid atherosclerotic plaques, but not in healthy mesenteric arteries. Immunohistochemical, mRNA, and protein expression studies revealed higher expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in unstable compared to stable plaques. The NLRP3 inflammasome was localized in the cytoplasm of macrophages and foam cells and was associated with cholesterol crystal clefts inside and outside of cells. ELISA showed that the serum levels of the cytokines IL-1β and IL-18 were higher in the CEA group compared to controls. Conclusions These results demonstrated for the first time the close relationship between the expression of NLRP3 signaling pathway and human carotid atherosclerotic plaques. NLRP3, ASC, caspase-1, IL-1β, and IL-18 were associated with plaque vulnerability and atherogenesis. The serum levels of IL-1β and IL-18 may be useful predictors of atherosclerosis.
Purpose:Sorafenib is recommended for patients with hepatocellular carcinoma refractory to transarterial chemoembolization but with unsatisfactory overall survival and tumor response rate. Previously ...published studies showed hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin was an effective and safe treatment. The aims of this study were to compare the clinical efficacy and safety of oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy with sorafenib in patients with hepatocellular carcinoma refractory to transarterial chemoembolization. Methods: This was a retrospective subgroup analysis of 2 prospective clinical trials, including 114 patients with hepatocellular carcinoma who were confirmed to be transarterial chemoembolization refractoriness. Of these, 55 patients received hepatic arterial infusion chemotherapy of fluorouracil, and leucovorin (FOLFOX-HAIC group, oxaliplatin 85 or 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, and 2400 mg/m2 for 23 or 46 h, every 3 weeks), and 59 patients were treated with sorafenib (sorafenib group, 400 mg sorafenib twice daily). Overall survival, progression-free survival, objective response rate, and treatment-related adverse events were compared between the 2 groups. Results: The FOLFOX-HAIC group showed a longer overall survival (17.1 months 95% confidence interval 13.4-20.8 vs 9.1 months 95% confidence interval 7.5-10.6; hazard ratio 0.35 95% confidence interval 0.23-0.53; P < .001), a higher objective response rate (RECIST: 18 32.7% vs 1 1.7%, P < .001), and a longer progression-free survival (7.6 months 95% confidence interval 5.6-9.6 vs 3.9 months 95% confidence interval 2.3-5.4; hazard ratio 0.49 95% confidence interval 0.33-0.72; P < .001) than the sorafenib group. The safety results suggested that both oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy and sorafenib had acceptable treatment-related toxic effects. No significant difference was observed in the overall occurrence of any grade, grade 3/4, or serious adverse events between the 2 groups. Conclusions: Oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy might be a better choice than sorafenib for patients with hepatocellular carcinoma refractory to transarterial chemoembolization.
Severe acute respiratory disease coronavirus 2 is currently causing the coronavirus disease 2019 (COVID-19) pandemic, placing extreme strain on the global health system. Vaccination is the main ...measure for preventing the COVID-19 epidemic, especially for high-risk groups including patients with chronic kidney disease (CKD). However, CKD patients receiving dialysis or kidney transplant may be characterized by decreased renal function and immune disorders, which may have uncertainties in their health. This overview aims to introduce the possible impact of the COVID-19 vaccine on kidney disease and its application in patients with CKD to provide evidence for the COVID-19 vaccine in patients with CKD. The data for this study were collected from PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI). The following keywords were used: “COVID-19”, “COVID-19 vaccine,” and “CKD”. The publication time of the papers was set from the establishment of the databases to September 2021. A total of 47 studies were included, and patients with CKD are a high-risk group for COVID-19 infection and severe illness. Vaccination is a powerful tool for preventing CKD patients from COVID-19. Because of possible side effects, the recurrence or deterioration of kidney disease may occur in CKD patients after vaccination. Although vaccination for patients with CKD remains a problem, with the advantages outweighing the disadvantages, stable CKD patients should complete a vaccination plan, and doctors should be aware of the recurrence or deterioration of kidney disease and close monitoring. Data access statement:. Research data supporting this publication are available from the electronic databases of PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and the China Knowledge Resource Integrated Database (CNKI).
Objectives This study sought to evaluate the prognostic value of coronary artery calcium score (CACS) and coronary computed tomography angiography (CTA) for major adverse cardiac events (MACE). ...Background The prognostic value of CACS has been well described. Few studies use the rich information of coronary CTA to predict future clinical outcomes and compare CACS with coronary CTA. Methods We followed up 5,007 outpatients who were suspected of having coronary artery disease (CAD) and who underwent cardiac CTA. Cardiac CT was assessed for CACS and the extent, the location, the stenosis severity, and the composition of the plaque in coronary CTA. The endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. Results Follow-up was completed in 4,425 patients (88.4%), with a median follow-up period of 1,081 days. At the end of the follow-up period, 363 (8.2%) patients had experienced MACE. Cumulative probability of 3-year MACE increased across CT strata for CACS (CACS 0, 2.1%; CACS 1 to 100, 12.9%; CACS 101 to 400, 16.3%; and CACS >400, 33.8%; log-rank p < 0.001); for coronary CTA (no plaque 0.8%, nonobstructive disease 3.7%, 1-vessel disease 27.6%, 2-vessel disease 35.5%, and 3-vessel disease 57.7%; log-rank p < 0.001); and for characteristics of the plaques (5.5% for calcified plaque, 22.7% for noncalcified plaque, and 37.7% for mixed plaque; log-rank p < 0.001). The area under the receiver-operating characteristic curves showed the incremental value of CACS and coronary CTA for predicting MACE: 0.71 for clinical risk factors, which improved to 0.82 by adding CACS and further improved to 0.93 by adding coronary CTA (both p < 0.001). Conclusions The CACS and coronary CTA findings have prognostic value and have incremental value over routine risk factors for MACE, and coronary CTA is superior to CACS. Cardiac CT seems to be a promising noninvasive modality with significant prognostic value.
Background Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography ...(EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL ) and healthy never-smokers. Methods We recruited 48 patients with COPD (stage I, n = 14; stage II, n = 15; stage, III-IV, n = 19), 21 SNL , and 17 healthy never-smokers. A smoking history inquiry, as well as spirometry, chest CT, bronchoscopy, and EB-OCT were performed. Mean luminal diameter (Dmean ), inner luminal area (Ai), and airway wall area (Aw) of third- to ninth-generation bronchi were measured using EB-OCT. Results Patients with more advanced COPD demonstrated greater abnormality of airway architecture in both large and medium to small airways, followed by SNL and never-smokers. Abnormality of airway architecture and EB-OCT parameters in SNL were comparable to those in stage I COPD. FEV1 % predicted correlated with Dmean and Ai of seventh- to ninth-generation bronchi in COPD; however, neither Dmean nor Ai of third- to sixth-generation bronchi correlated with FEV1 % in stage I and stage II COPD and in SNL. Conclusions FEV1 -based COPD staging partially correlates with small airway disorders in stage II-IV COPD. Small airway abnormalities detected by EB-OCT correlate with FEV1 -based staging in COPD and identify early pathologic changes in healthy heavy smokers.
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