Comprehensive phenotypic and genomic characterization of venous malformations

Hirose K., Hori Y., Ozeki M., et al. Comprehensive phenotypic and genomic characterization of venous malformations. Human Pathology 145, 48 (2024); https://doi.org/10.1016/j.humpath.2024.02.004.Venous malformations (VMs) are the most common vascular malformations. TEK and PIK3CA are the causal genes of VMs, and may be involved in the PI3K/AKT pathway. However, the downstream mechanisms underlying the TEK or PIK3CA mutations in VMs are not completely understood. This study aimed to identify a possible association between genetic mutations and clinicopathological features. A retrospective clinical, pathological, and genetic study of 114 patients with VMs was performed. TEK, PIK3CA, and combined TEK/PIK3CA mutations were identified in 49 (43%), 13 (11.4%), and 2 (1.75%) patients, respectively. TEK-mutant VMs more commonly occurred in younger patients than TEK and PIK3CA mutation-negative VMs (other-mutant VMs), and showed more frequent skin involvement and no lymphocytic aggregates. No significant differences were observed in sex, location of occurrence, malformed vessel size, vessel density, or thickness of the vascular smooth muscle among the VM genotypes. Immunohistochemical analysis revealed that the expression levels of phosphorylated AKT (p-AKT) were higher in the TEK-mutant VMs than those in PIK3CA-mutant and other-mutant VMs. The expression levels of p-mTOR and its downstream effectors were higher in all the VM genotypes than those in normal vessels. Spatial transcriptomics revealed that the genes involved in “blood vessel development”, “positive regulation of cell migration”, and “extracellular matrix organization” were up-regulated in a TEK-mutant VM. Significant genotype-phenotype correlations in clinical and pathological features were observed among the VM genotypes, indicating gene-specific effects. Detailed analysis of gene-specific effects in VMs may offer insights into the underlying molecular pathways and implications for targeted therapies

Mortality risk associated with nuclear disasters depends on the time during and following evacuation of hospitals near nuclear power plants: An observational and qualitative study

This study aimed to examine the factors correlated with emergency evacuations on patients’ prognosis in hospitals severely affected by the Fukushima Daiichi nuclear power plant (FDNPP) accident in March 2011, and to recommend measures mitigating potential health risks among them in future disasters. Seven hospitals within a 20-km radius of the FDNPP were designated as the evacuation zone, of which three hospitals located within a 5-km radius were examined. Information regarding hospital emergency evacuation among the three hospitals from previous literature and official reports were integrated and interview outcomes of staff at each hospital were qualitatively analyzed using thematic analysis. Our thematic analysis identified four themes: insufficient preparedness for disaster, difficulty of patient evacuation, insufficient materials, and insufficient information. Comparison of the three hospitals located within a 5-km radius of the FDNPP revealed that hospitals with several patients or those with a high proportion of bedridden or critically ill patients faced more difficulty in emergency evacuation and experienced higher fatalities. In addition to individual evacuation plans, for future preparedness, external and public organizations should prepare disaster responses such as procedures to integrate information on the status of each medical facility and measures to support them individually