Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to enhance the efficacy of anti-VEGF monotherapies in nAMD. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa (code: IBI302), which is capable of neutralizing both VEGF isoforms and C3b/C4b. Efdamrofusp alfa showed superior efficacy over anti-VEGF monotherapy in a mouse laser-induced choroidal neovascularization (CNV) model after intravitreal delivery. Dual inhibition of VEGF and the complement activation was found to further inhibit macrophage infiltration and M2 macrophage polarization. Intravitreal efdamrofusp alfa demonstrated favorable safety profiles and exhibited antiangiogenetic efficacy in a nonhuman primate laser-induced CNV model. A phase 1 dose-escalating clinical trial (NCT03814291) was thus conducted on the basis of the preclinical data. Preliminary results showed that efdamrofusp alfa was well tolerated in patients with nAMD. These data suggest that efdamrofusp alfa might be effective for treating nAMD and possibly other complement-related ocular conditions.

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). Therapeutic efficacy of nCRT is significantly affected by treatment-induced diarrhea and hematologic toxicities. Metabolic alternations in cancer therapy are key determinants to therapeutic toxicities and responses, but exploration in large-scale clinical studies remains limited. Here, we analyze 743 serum samples from 165 LARC patients recruited in a phase III clinical study using untargeted metabolomics and identify responsive metabolic traits over the course of nCRT. Pre-therapeutic serum metabolites successfully predict the chances of diarrhea and hematologic toxicities during nCRT. Particularly, levels of acyl carnitines are linked to sex disparity in nCRT-induced diarrhea. Finally, we show that differences in phenylalanine metabolism and essential amino acid metabolism may underlie distinct therapeutic responses of nCRT. This study illustrates the metabolic dynamics over the course of nCRT and provides potential to guide personalized nCRT treatment using responsive metabolic traits.

The impact of rising ambient temperatures on sleep and its phases under climate change is becoming increasingly concerning but remains underexplored. Sleep, consisting of non-rapid eye movement and rapid eye movement phases, is crucial for health, and insufficient sleep in either phase could have significant implications. Based on sleep monitoring data of 23 million days from 214,445 participants across mainland China, we investigated how daily average temperature affected sleep. For each 10 °C increase in ambient temperature, the odds of sleep insufficiency increased by 20.1%, while total sleep duration decreased by 9.67 minutes, with deep sleep declining the most (by 2.82%). Projections under the unrestricted (SSP5-8.5) greenhouse gas emission scenario suggest that by the end of the century, sleep insufficiency could rise by 10.50%, with an annual loss of 33.28 hours of sleep per person. These findings highlight the potential of climate warming to exacerbate sleep deprivation and degrade sleep quality, especially for the elderly, women, individuals with obesity, and regions of South, Centre and East.

Jiang R, et al. J Gynecol Oncol. 2019 Jun;31:e86. https://doi.org/10.3802/jgo.2020.31.e86

Previous studies have shown that industry funded trials are associated with pro-industry conclusions and publication bias. Less is known about the role of industry funders and their influence on trial conclusions and time to publication. We identified all industry funded RCTs published in six high-impact clinical journals between 2014 and 2016 to estimate the prevalence of the role of industry funders in trial design, data collection, data analyses, data interpretation and manuscript writing. Ordinal logistic regression was used to assess the association between the role of industry funders and trial conclusions, which was classified on a five-point scale. Cox proportional-hazards were used to examine the effect of role of funder on time to publication. Of the 255 eligible RCTs, industry funders had a role in trial design in 179 (70.2%) trials, data collection in 160 (62.7%) trials, data analyses in 173 (67.8%) trials, data interpretation in 135 (52.9%) trials and manuscript writing in 168 (65.9%) trials. Trials with any role of industry funders had 3.6 times (95% CI 2.0-6.6) higher odds of having positive conclusions compared with those without role of industry funders. In trials with any role of industry funders, positive trials were published more rapidly than negative trials (hazard ratio = 4.3; 95% CI 2.7-6.7, P < 0.001), while for trials without role of industry funders, there was no association (hazard ratio = 1.07; 95% CI 0.57-1.99, P = 0.84). The involvement of industry funders is common in all stages of clinical trials and was associated with more positive conclusions and more rapid publication of RCTs with positive results.