On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O₂ ratio (PaO₂/FiO₂) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO₂/FiO₂ ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.

Background: Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Definitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation. Results: A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30–1.63), 1.39 (1.25–1.54) and 1.40 (1.17–1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P < 0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR = 1.59, 95% CI 1.30–1.82), and the mortality was not significantly different at 70 months after the last delivery (HR = 1.14, 95% CI 0.99–1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum (70 months after the last delivery) to capture the increased risk. Conclusion: This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum.

Background: To assess the spatiotemporal variation in female breast cancer attributable to low physical activity (LPA) at a global scale from 1990 to 2019, which is essential to promote physical activity, as well as prevent and control breast cancer. Methods: The number of deaths and disability-adjusted life years (DALYs), and the corresponding age-standardized rates (ASMR and ASDR) of LPA-related breast cancer in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019 to measure the related breast cancer burden by age and region. The estimated annual percentage change (EAPC) was calculated to quantify the secular trend in breast cancer burden rates. Results: From 1990 to 2019, globally, both breast cancer deaths and DALYs attributable to LPA nearly doubled, although the corresponding ASMR and ASDR decreased slightly, with EAPC of -0.46 (95% confidence interval: -0.52, -0.40) and -0.44 (95% confidence interval: -0.49, -0.39), respectively. The LPA-related breast cancer burden varied considerably across the world, with the highest-burden rates in Oceania, Tropical Latin America and Caribbean, and the fastest growth in North Africa and Middle East. The ASMR and ASDR showed a logarithmic association with the Socio-demographic Index, and a temporally upward trend in most of 204 countries regardless of the Socio-demographic Index or the ASMR in 1990. Conclusions: Despite a decline in LPA-related breast cancer burden achieved in many countries during the last 3 decades like Bermuda, Myanmar, USA and China, an increase still occurred in most of 204 countries and territories, such as Solomon Islands, Equatorial Guinea, Japan and India. The findings can bring greater awareness to the importance of promoting physical activity for the local government to control the attributable breast cancer burden.

Recent studies highlighted the clinicopathologic importance of the tumor microenvironment (TME) in delineating molecular attributes and therapeutic potentials. However, the overall TME cell infiltration landscape in nonsquamous non–small cell lung cancer (NSCLC) has not been comprehensively characterized. In this study, we used consensus non-negative matrix factorization molecular subtyping to determine TME cell infiltration patterns and identified 3 TME clusters (TME-C1, -C2, -C3) characterized by distinct clinicopathologic features, infiltrating cells, and biological processes. Proteomics analyses revealed that cyclic GMP-AMP–stimulator of interferon genes immune signaling–mediated protein and phosphorylation levels were significantly upregulated in inflammation-related TME-C2 clusters. The score extracted from the TME-related signature (TMEsig-score) divided patients with NSCLC into high- and low-score subgroups, where a high score was associated with favorable prognosis and immune infiltration. The genomic landscape revealed that patients with low TMEsig-score harbored more somatic copy number alterations and higher mutation frequency of driver genes involving STK11 , KEAP1 , SMARCA4 , and others. Drug sensitivity analyses suggested that tumors with high TMEsig-score were responsible for favorable clinical response to immune checkpoint inhibitor treatment. In summary, this study highlights that comprehensive recognizing of the TME cell infiltration landscape will contribute to enhancing our understanding of TME immune regulation and promote effectiveness of precision biotherapy strategies.

Background: Understanding the spatiotemporal trends of colorectal cancer (CRC) deaths caused by low physical activity (LPA) and high body mass index (BMI) is essential for the prevention and control of CRC. We assessed patterns of LPA and high BMI-induced CRC deaths from 1990 to 2019 at global, regional, and national levels.Methods: Data on CRC deaths due to LPA and high BMI was downloaded from the Global Burden of Disease 2019 Study. We calculated estimated annual percentage change (EAPC) to quantify spatiotemporal trends in the CRC age-standardized mortality rate (ASMR) due to LPA and high BMI.Results: In 2019, CRC deaths due to LPA and high BMI were estimated as 58.66 thousand and 85.88 thousand, and the corresponding ASMRs were 0.77/100,000 and 1.07/100,000, with EAPCs of−0.39 [95% confidence interval (CI):−0.49,−0.29] and 0.64[95% CI: 0.57, 0.71] from 1990 to 2019 respectively. Since 1990, the ASMR of CRC attributable to LPA and high BMI has been on the rise in many geographic regions, especially in low middle and middle sociodemographic index (SDI) regions. Thirteen countries had a significant downward trend in CRC ASMR attributed to LPA, with EAPCs < −1. And, only 4 countries had a significant downward trend in CRC ASMR attributable to high BMI, with EAPCs < −1. Countries with a higher baseline burden in 1990 and a higher SDI in 2019 had a faster decline in ASMR due to high BMI and LPA.Conclusions: The burden of CRC caused by LPA and high BMI is on the rise in many countries. Countries should adopt a series of measures to control the local prevalence of obesity and LPA in order to reduce disease burden, including CRC.