Objectives: Tumours remain a serious threat to human life. Following rapid progress in oncology research, tyrosine kinase inhibitors have been used to treat multiple tumour types. Given the great influence of kidneys on pharmacokinetics, renal toxicities associated with TKIs have attracted attention. However, the TKIs with the lowest risks of renal impairment are unclear. In this study, we conducted a Bayesian network meta-analysis to compare the incidence of renal impairment among different TKIs in patients with tumours.Methods and analysis: Six databases (PubMed, EMBASE, The Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database) were electronically searched from inception to 1 November 2021 to identify randomized controlled trials on the incidence of renal impairment for different TKIs in patients with tumours. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Then, a pairwise meta-analysis was conducted using Stata version 13, and network meta-analysis within the Bayesian framework was conducted using R software version 3.5.3 with the package “gemtc 0.8–2” recalling JAGS (version 4.3.0).Results: Overall, 34 randomized controlled trials were included in this study. Although renal toxicity was common among patients receiving TKIs, the incidence and severity greatly differed among the drugs and studies. Elevated creatinine and protein levels were the most common nephrotoxic events, whereas haematuria was relatively rare. Among TKIs, nintedanib and ripretinib carried the lowest risks of renal impairment.Conclusion: TKIs displayed different profiles of renal toxicity because of their different targets and underlying mechanisms. Clinicians should be aware of the risks of renal impairment to select the optimal treatment and improve patient adherence to treatment.Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022295853].

Background Antiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs); however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs. Methods We retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method. Results Of the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval [CI], 33.0–59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5–9.3) and 47.0 months (95% CI, 35.4–58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0–9.0), compared with 8.0 months (95% CI, 2.7–13.3 months) for patients in the anlotinib group (P = 0.945). The most common grade 3 adverse events (AEs) were hypertension (n = 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n = 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation. Conclusion For refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.

Background Anemia is relatively common in cancer patients, and baseline anemia is associated with poor survival in patients with non-small cell lung cancer (NSCLC). However, there is a lack of large-sample studies of patients with NSCLC with epidermal growth factor receptor (EGFR) mutations. Methods We retrospectively analyzed anemia‑related data for patients with NSCLC and EGFR mutations who were admitted to Zhejiang Cancer Hospital from January 2013 to June 2019 and treated with targeted therapy. The patients’ clinicopathological features were evaluated by χ2 tests and the relationships between clinical characteristics and prognosis were investigated using Kaplan–Meier and multivariate Cox regression analyses. Results A total of 2,029 patients treated with EGFR-tyrosine kinase inhibitors (TKIs) were finally enrolled in this study, of whom 24.6% had baseline anemia. Patients without baseline anemia had longer median overall survival (OS) than patients with baseline anemia (36.10 vs. 29.10 months, P = 0.001), and patients with grade < 2 anemia had longer median OS than those with grade ≥ 2 anemia (35.00 vs. 25.10 months, P < 0.001). Multivariate analyses identified baseline anemia as a factor predicting a poor prognosis in terms of OS in patients with EGFR mutations. Conclusions Baseline anemia is a significant factor predicting a poor prognosis in terms of OS in patients with NSCLC and EGFR mutations treated with targeted therapy. A higher grade of baseline anemia may also be related to shorter OS. And a higher risk of EGFR-mutated patients who had received targeted therapy could also be observed.

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We aimed to explore the treatment efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung squamous cell carcinoma (SCC) patients and identify potential beneficial subgroups of EGFR-mutated lung SCC patients in this study. Between February 1 st , 2013 and December 1 st , 2021, 657 advanced lung SCC patients were enrolled at Zhejiang Cancer Hospital. Amplification refractory mutation system PCR or next-generation sequencing were used to detect gene abnormality. C linicopathological features were analyzed by chi-square test and the clinical results of lung SCC patients who received first-generation EGFR-TKI were analyzed by the Kaplan-Meier method. Lung SCC patients harboring EGFR mutation accounted for 11.0% in this study. Of 657 lung SCC patients, the median PFS and OS of 116 patients who received targeted therapy were 3.6 months and 16.2 months, patients treated with targeted therapy had similar OS to patients without targeted therapy (p = 0.839). Of 110 lung SCC patients who received first-generation EGFR-TKI, EGFR-mutated patients had long PFS (p = 0.000) but similar OS (p = 0.472) than patients with EGFR wide type. EGFR-mutated SCC patients who received first-generation EGFR-TKI as a first-line benefit are equal to patients who received first-generation EGFR-TKI as the second line or beyond according to similar PFS (p = 0.311) and OS (p = 0.721) between them. In addition, there was also no significant difference in PFS (p = 0.376) and OS (p = 0.205) between patients with exon 19 deletion and L858R point mutation.Lung SCC patients harboring EGFR mutation received first-generation EGFR-TKI had better clinical survival than patients with EGFR wide type.

BackgroundInfectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis.MethodsThe literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3).ResultsIn total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections.ConclusionThis study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research.

Contributions: (I) Conception and design: Z Song, J Wei; (II) Administrative support: Z Song; (III) Provision of study materials and patients: Z Song;

Background We aimed to determine the clinical. outcomes of various immune checkpoint inhibitor (ICI) combinations for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The results predicted the treatment efficacy of these combinations. Methods From July 15, 2016 to March 22, 2022, 85 NSCLC patients with EGFR mutations, enrolled at the Zhejiang Cancer Hospital, received ICI combinations after resistance to prior EGFR-tyrosine kinase inhibitors (EGFR-TKIs). These patients were diagnosed with EGFR mutations using an amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS). Survival times were analyzed using the Kaplan–Meier method and log-rank test. Results Patients who received ICIs combined with anti-angiogenic therapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received ICIs combined with chemotherapy. There was no significant difference in survival time between patients who received ICIs combined with chemotherapy and anti-angiogenic therapy and patients who received ICIs combined with anti-angiogenic therapy or ICIs combined with chemotherapy, which was due to the limitation sample size of patients who received ICIs combined with chemotherapy and anti-angiogenic therapy. Patients with L858R mutations had a longer PFS and OS than patients with exon 19 deletions. T790M negative patients benefited more from ICI combinations, compared with T790M positive patients. In addition, there was no significant difference in PFS and OS between patients with TP53 co-mutations and patients without a TP53 co-mutation. We also found that patients with prior first-generation EGFR-TKI resistance had longer PFS and OS than prior third-generation EGFR-TKI resistance patients. There was no new adverse event in this study. Conclusions EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.