The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Intrapleural Administration With Rh-Endostatin and Chemical Irritants in the Control of Malignant Pleural Effusion: A Systematic Review and Meta-Analysis.

INTRODUCTION: A modified and recombinant human endostatin (Rh-endostatin) is often used in the control of malignant pleural effusion (MPE) through intrapleural infusion. OBJECTIVES: To demonstrate the clinical response, survival, and safety of Rh-endostatin plus chemical irritants, their optimal combinations, treatment threshold, and optimal usage, we performed a new systematic review and meta-analysis. METHODOLOGY: All randomized controlled trials (RCTs) were collected from Chinese and English electronic databases (from inception until August 2020). We pooled the data using a series of meta-analyses and summarized the evidence quality following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 75 RCTs recruiting 4,678 patients, which reported six combinations for Rh-endostatin plus chemical irritants. Among the six combinations, only Rh-endostatin plus cisplatin (DDP) with enough trials might improve the complete response [2.29 (1.93, 2.71)] and quality of life [3.01 (2.49, 3.63)] and reduce treatment failure [0.29 (0.25, 0.33)] and progressive disease [0.27 (0.22, 0.34)]. It might not increase the risk of adverse drug reactions. For patients with lung cancer, moderate to massive effusion, initial treatment, Karnofsky Performance Status (KPS) score ≥60, or anticipated survival time ≥3 months, Rh-endostatin (30-45 mg each time, once or twice a week 3-4 times) plus DDP (30-60 mg/m2) obtained a significant improvement in clinical response and a reduction of failure and progressive disease. Most results had good robustness and moderate quality. CONCLUSIONS: Current evidence suggests that Rh-endostatin with DDP may be an optimal combination, which may improve clinical response and reduce failure and progressive disease with good safety. Rh-endostatin (30-40 mg each time, once or twice a week 3-4 times) with DDP (30-40 mg/m2) may be an optimal usage for achieving an ideal response.

The Optimal Adjuvant Strategy of Aidi Injection With Gemcitabine and Cisplatin in Advanced Non-small Cell Lung Cancer: A Meta-analysis of 70 Randomized Controlled Trials.

Introduction: Aidi injection (Aidi) is composed of cantharidin, astragaloside, ginsenoside, and elentheroside E. As an important adjuvant therapy, Aidi in combination with gemcitabine and cisplatin (GP) is often used in the treatment of non-small cell lung cancer (NSCLC). Objectives: We performed a new evaluation to demonstrate the clinical efficacy and safety of the Aidi and GP combination and further explored an optimal strategy for achieving an ideal response and safety level in advanced NSCLC. Methodology: We collected all the related trials from Chinese and English-language databases, analyzed their methodological bias risk using the Cochrane evaluation Handbook for Systematic Reviews of Interventions Version 5.1.0, extracted all the data using a predefined data extraction form, pooled the data using a series of meta-analyses, and finally summarized the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 70 trials with 5,509 patients. Compared with GP alone, the Aidi and GP combination showed a significant improvement in the objective response rate (ORR) [1.82 (1.62-2.04)], disease control rate (DCR) [2.29 (1.97-2.67)], and quality of life (QOL) [3.03 (2.55-3.60)] and a low incidence of hematotoxicity and gastrointestinal and hepatorenal toxicity. Aidi might be more suitable for patients who are first-treated, elderly, or patients with a Karnofsky Performance Status (KPS) score ≥ 60 or anticipated survival time (AST) ≥3 months. An Aidi (50 ml/day, 7-14 days/cycle for one to two cycles), gemcitabine (1000 mg/m2), and cisplatin (20-30 mg/m2, 40-50 mg/m2, or 60-80 mg/m2) might be an optimal regimen for realizing an ideal response and safety level. Most results were robust and of moderate quality. Conclusion: Current evidence indicates that Aidi's value in adjuvant chemotherapy may be broad-spectrum, not just for some regimens. The Aidi and GP combination may show a good short-term response, antitumor immunity, and safety level in patients with NSCLC. Aidi (50 ml/day, 7-14 days/cycle for one and two cycles) with GEM (1000 mg/m2) and DDP (20-30 mg/m2 or 40-50 mg/m2) may be an optimal regimen for realizing an ideal goal in patients who are first-treatment, elderly, or have a KPS score ≥ 60 or AST≥3 months.

Intrathoracic infusion therapy with Lentinan and chemical irritants for malignant pleural effusion: a systematic review and meta-analysis of 65 randomized controlled trials.

BACKGROUND: Aderivative of Shiitake mushrooms, Lentinan is used to control malignant pleural effusion (MPE) through intrathoracic infusion. PURPOSE: To determine the clinical response, survival and safety of Lentinan plus chemical irritants, and the optimal combinations with chemical irritants, indication, threshold and optimal regimen for achieving the desired responses. STUDY DESIGN: We performed a new systematic review and meta-analysis following the PRISMA guidelines. METHODS: We collected all randomized controlled trials (RCTs) regarding Lentinan plus chemical irritants from Chinese and English electronic databases (from inception until March 2019). We evaluated their bias risk, synthesized data using meta-analysis, and summarized evidence quality following the Grades of Recommendation Assessment, Development and Evaluation approach. RESULTS: We included 65 RCTs involving 4,080 patients and nine chemical irritants. Most trials had unclear bias risk. Lentinan with cisplatin significantly improved complete response [Risk ratio (RR) = 1.68, 95% confidence intervals (CI) (1.51 to 1.87), p < 0.00001, Fig.3a] and quality of life [RR = 1.51 95% CI (1.41 to 1.62), p < 0.00001, Fig.4], and decreased the risk of treatment failure, myelosuppression, gastrointestinal reaction, and chest pain. For patients with moderate to large volume of the pleural effusion, primary treatment, KPS score ≥ 50-60, or anticipated survival time ≥ 3months, Lentinan (3-4 mg/time, once a week for three to four times) withcisplatin (30-40 mg/m2 or 50-60 mg/m2) significantly improved complete response and decreased failure. Most results were robust and moderate quality. CONCLUSION: The results suggest that Lentinan with chemical irritants, especially cisplatin is beneficial to the patient with MPE, and provide evidence for the indication, threshold, and optimal regimen that may achieve success and decrease failure.

Evolutions of volatile sulfur compounds of Cabernet Sauvignon wines during aging in different oak barrels.

The evolution of volatile sulfur compounds (VSCs) in Cabernet Sauvignon wines from seven regions of China during maturation in oak barrels was investigated. The barrels were made of different wood grains (fine and medium) and toasting levels (light and medium). Twelve VSCs were quantified by GC/FPD, with dimethyl sulfide (DMS) and methionol exceeding their sensory thresholds. Most VSCs tended to decline during the aging, while DMS was found to increase. After one year aging, the levels of DMS, 2-methyltetrahy-drothiophen-3-one and sulfur-containing esters were lower in the wines aged in oak barrels than in stainless steel tanks. The wood grain and toasting level of oak barrels significantly influenced the concentration of S-methyl thioacetate and 2-methyltetrahy-drothiophen-3-one. This study reported the evolution of VSCs in wines during oak barrel aging for the first time and evaluated the influence of barrel types, which would provide wine-makers with references in making proposals about wine aging.