Spatial transcriptomics reveals novel genes during the remodelling of the embryonic human arterial valves.

Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST). We show that ST can be used to investigate the transcriptome of the developing arterial valves, circumventing the problems of accurately dissecting out these tiny structures from the developing embryo. We show that the transcriptome of CS16 and CS19 arterial valves overlap considerably, despite being several days apart in terms of human gestation, and that expression data confirm that the great majority of the most differentially expressed genes are valve-specific. Moreover, we show that the transcriptome of the human arterial valves overlaps with that of mouse atrioventricular valves from a range of gestations, validating our dataset but also highlighting novel genes, including four that are not found in the mouse genome and have not previously been linked to valve development. Importantly, our data suggests that valve transcriptomes are under-represented when using commonly used databases to filter for genes important in cardiac development; this means that causative variants in valve-related genes may be excluded during filtering for genomic data analyses for, for example, BAV. Finally, we highlight "novel" pathways that likely play important roles in arterial valve development, showing that mouse knockouts of RBP1 have arterial valve defects. Thus, this study has confirmed the utility of ST for studies of the developing heart valves and broadens our knowledge of the genes and signalling pathways important in human valve development.

Efficacy of Prophylactic Anti-VEGF in Preventing Radiation Retinopathy: A Systematic Review and Meta-Analysis.

Background: In patients predisposed to radiation retinopathy (RR), administration of therapy after apparent clinical signs and symptoms are considered too late, resulting in substantial vision loss and blindness. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) might serve as a strategy to slow disease progression and prolong good eyesight. Objective: To evaluate the efficacy of prophylactic anti-VEGF in preventing RR and preserving vision in patients at high risk of radiation-induced vision loss. Methods: A systematic literature search was performed from inception to 4 June 2023 using Cochrane Library, EMBASE, PubMed (MEDLINE), and Scopus. Eligible studies were clinical trials and observational studies investigating the incidence of radiation maculopathy (RM), radiation optic neuropathy (RON), moderate vision loss (loss of more than or equal to 3 lines of baseline visual acuity [VA]) and final VA, whether good (20/40 or better) or poor (20/200 or worse), following prophylactic anti-VEGF. Three reviewers independently conducted article screening, data extraction and risk of bias assessment. Random effects models were used to determine the cumulative effects of each outcome. Results: Four studies (one clinical trial and three observational studies), involving 2109 patients, were included in our analysis. Across all studies, there were significant reductions in the events of RM (pooled odds ratio [OR] 0.50; 95% CI, 0.34-0.74; p = 0.001), RON (pooled OR 0.62; 95% CI, 0.42-0.90; p = 0.012) and poor final VA (pooled OR 0.50; 95% CI, 0.37-0.68; p = 0.003). The association of moderate vision loss and good final VA with the use of prophylactic anti-VEGF between the groups was unclear owing to the high level of heterogeneity. Conclusion: Prophylactic anti-VEGF therapy might delay RM and RON, preventing high-risk patients from developing poor VA by approximately 50%. However, this evidence should be interpreted with caution because of its low level of certainty. Future robust studies are warranted to confirm this finding.

Impact of Estimated Plasma Volume Status on Mortality in Right Heart Failure Patients: A Retrospective Cohort Study in Indonesia.

Background: Plasma volume (PV) expansion hallmarks the syndrome of heart failure (HF) but is difficult to be quantified noninvasively. Estimated plasma volume status (ePVS) has marked prognostic utility in the failing left heart, however its use in right heart failure (RHF) remains unknown. This study aims to investigate the prognostic value of ePVS among isolated RHF patients. Methods: We retrospectively collected 208 patients admitted for RHF in our hospital from the electronic database from 2017 to 2019. ePVS was calculated using the Hakim formula. Patients were divided into low and high groups based on their PV value. Logistic regression was used to compare the odds of in-hospital mortality between these groups. Results: The overall in-hospital mortality was 12.5%, tripled from the low group to the high group (6.7% vs. 18.3%), within a median of 6 (3-19) days. High ePVS significantly predicted mortality in RHF, even after being adjusted for demographic, hemodynamic, chemistry, and medication variables (adjusted OR: 5.83, 95% CI: 1.62-20.95, p < 0.01). Conclusion: ePVS is associated with in-hospital mortality among isolated RHF patients. Given not only the wide accessibility of hemogram but also the low cost and the rapid quantification of relative PV, this simple tool can potentially aid in optimizing RHF management, especially in rural area, although further evaluation is warranted.