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Purpose: Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Methods: PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. The inclusion criteria were as follows: prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints: progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs).Results: Twenty three prospective studies comprising 1,856 patients with advanced NSCLC were included. The pooled ORR, median PFS and estimated overall survival were 39%, 6.8 months [95% confidence interval (CI), 5.53–8.13], and 18.6 months in the overall group. Similar ORR and median PFS with A + I + chemo versus A + I were observed in patients treated in first-line setting [59% and 9.47 months (95% CI, 6.45–12.49) versus 52% and 10.9 months (95% CI, 1.81–19.98), respectively]. We also observed improved ORR and mPFS with A + I + chemo versus A + I in subsequent-line setting [56% and 8.1 months (95% CI, 5.00–11.26) versus 22% and 5.1 months (95% CI, 4.01–6.15), respectively]. Efficacy of A + I + chemo therapy was evident across different PD-L1 subgroups, especially in patients with EGFR mutations [ORR: 59%; mPFS: 8.13 months (95% CI: 5.00–11.26)] or baseline liver metastases. The incidence of AEs with a major grade of ≥3 in the overall, A + I, and A + I + chemo groups were 4.1% vs. 5.5% vs. 3.4% for proteinuria, 13.7% vs. 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis.Conclusion: Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.

Objective: To systematically review the efficacy and safety of oral Acetaminophen for premature infants with patent ductus arteriosus (PDA).Methods: Databases including Ovid, EMbase, Pubmed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINHAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), WanFang Data, China Science and Technology Journal Database were searched to collect the randomized controlled trials (RCTs) about Acetaminophen for premature infants with PDA from inception to January 1, 2021. Quality assessment was performed through bias risk evaluation according to the Cochrane Handbook 5.1.0, and then the homogeneous studies were analyzed using Revman 5.4 software.Results: A total of 16 RCTs were included, which were divided into for four subgroups: subgroup I (oral acetaminophen vs. oral ibuprofen, 13 RCTs), subgroup II (oral acetaminophen vs. intravenous indomethacin, 1 RCT), subgroup III (oral acetaminophen vs intravenous ibuprofen, 1 RCT), and subgroup IV (oral acetaminophen vs intravenous placebo, 1 RCT). In subgroup I, There was no significant difference in the ductal closure rate after the first course of drug administration [typical relative risk (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.05], the accumulated ductal closure rate after two course of treatment (RR 0.96, 95% CI 0.91–1.02), and mortality (RR 1.06, 95% CI 0.75–1.49) between treatment with oral acetaminophen versus oral ibuprofen (p > 0.05); compared with oral ibuprofen, oral acetaminophen was associated with a significant reduction in the incidence of gastrointestinal bleeding/stool occult blood positive (RR 0.51, 95% CI 0.32 to 0.82)and oliguria (RR 0.62, 95% CI 0.42–0.91) (p < 0.05).Conclusion: The meta analysis approves the facts that there is no significant difference in the efficacity in premature infants with PDA between oral acetaminophen and buprofen or indometacin, but compared to ibuprofen, oral acetaminophen may decrease the incidence of oliguria and gastrointestinal bleeding. More reliable conclusions should be made through large-size, multi-center, well-designed RCTs.