The closure of the neural tube (NT) in the human embryo has generally been described as a continuous process that begins at the level of the future cervical region and proceeds both rostrally and caudally. On the other hand, multiple initiation sites of NT closure have been demonstrated in mice and other animals. In humans, based on the study of neural tube defects (NTD) in clinical cases, van Allen et al. (1993) proposed a multisite NT closure model in which five closure sites exist in the NT of human embryos. In the present study, we examined human embryos in which the NT was closing (Congenital Anomaly Research Center, Kyoto University) grossly and histologically, and found that NT closure in human embryos initiates at multiple sites but that the mode of NT closure in humans is different from that in many other animal species. In addition to the future cervical region that is widely accepted as an initiation site of NT closure (Site A), the mesencephalic-rhombencephalic boundary was found to be another initiation site (Site B). The second closure initiating at Site B proceeds bidirectionally and its caudal extension meets the first closure from Site A over the rhombencephalon, and the rostral extension of the second closure meets another closure extending from the rostral end of the neural groove (Site C) over the prosencephalon, where the anterior neuropore closes. The caudal extension of the first closure initiating at Site A was found to proceed all the way down to the caudal end of the neural groove where the posterior neuropore is formed, indicating that in humans, NT closure does not initiate at the caudal end of the neural groove to proceed rostrally. Since there is a considerable species difference in the mode of NT closure, we should be careful when extrapolating the data from other animals to the human. It seems that the type of NTD affects the intrauterine survival of abnormal embryos. Almost all the embryos with total dysraphism appear to die by 5 weeks of gestation, those with an opening over the rhombencephalon by 6.5 weeks, and those with a defect at the frontal and parietal regions survive beyond 7 weeks.

This study found that 22% of dialysis patients had hemorrhagic events after valve replacement, and approximately half of them died. Particularly, cerebral hemorrhage was fatal and two thirds of the patients died. So we should meditate the methods to reduce hemorrhage. Therefore, new methods to reduce the risk of hemorrhage are urgently needed.

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Objective: To investigate the influence of choice of prosthesis (bioprosthetic valves or mechanical valves) on intermediate-term outcomes in patients on hemodialysis undergoing aortic valve replacement (AVR).Methods: A multi-institutional retrospective cohort study was conducted in 18 Japanese centers. All adult patients on chronic hemodialysis who underwent AVR from 2008 and 2015 were included (n ¼ 491). The early and late results were compared between groups. The hazard ratios were calculated using Cox regression and Fine-Gray models with adjustment for propensity score based on 41 confounders. The mean follow-up period was 2.5 AE 2.1 years (up to 8.3 years) with 98% completeness.Results: There were 323 patients who received a bioprosthetic valve (group B), and 168 patients who received a mechanical valve (group M). There was no significant difference for in-hospital death rate between groups (group B: 12.1%; group M: 8.9%; P ¼ .29). The overall survival rate at 5 years after surgery was 39.3% in group B and 50.4% in group M (P ¼ .42). Freedom from reoperation at 5 years was 97.1% in group B and 97.8% in group M (P ¼ .88). On propensity-score adjusted analyses, there were no significant differences in overall survival between groups.Conclusions: There were no significant differences in overall survival between bioprosthetic valves and mechanical valves in patients on hemodialysis undergoing AVR.

The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.