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BACKGROUND: Regional citrate anticoagulation (RCA) is the preferred continuous kidney replacement therapy (CKRT) anticoagulation strategy for children in the USA. Nafamostat mesilate (NM), a synthetic serine protease, is used widely for CKRT anticoagulation in Japan and Korea. We compared the safety and efficacy of NM to RCA for pediatric CKRT. METHODS: Starting June 2019, the most recent 100 medical records of children receiving CKRT with either RCA or NM were reviewed retrospectively, at one children's hospital in Japan (NM) and one in the USA (RCA). The number of hours a single CKRT filter was in use, was the primary outcome. Safety was assessed by bleeding complications for the NM group and citrate toxicity leading to RCA discontinuation or electrolyte imbalance in the RCA group. RESULTS: Eighty patients received NM and 78 patients received RCA. Median filter life was longer for the NM group (NM: 38 [22, 74] vs. RCA: 36 [17, 66] h, p = 0.02). When filter life was censored for discontinuation other than clotting, the 60-h survival rate was higher for RCA (71% vs. 54%). The hazard ratio comparing NM over RCA varied over time (HR 0.7; 0.2-1.5, p = 0.33 at 0 h to HR 5.5; 1.3-23.7, p = 0.334 at 72 h). The lack of difference in filter survival persisted controlling for filter surface area, catheter diameter, and pre-CKRT platelet count. Major bleeding rates did not differ between groups (NM: 5% vs. RCA: 9%). CONCLUSIONS: RCA and NM provide satisfactory anticoagulation for CKRT in children with no difference in major bleeding rates. A higher resolution version of the Graphical abstract is available as Supplementary information.

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To help reduce the number of pedestrians lying on the road suffering fatal or severe injuries as a result of vehicle collisions, we investigated the influencing factors. We conducted an analysis of the records of the Institute for Traffic Accident Research and Data Analysis Japan between 2012 and 2018; we found that 2452 pedestrians lying on the road were involved in collisions (797 fatalities, 784 severely injured, 871 mildly injured). Multivariate logistic regression analysis identified the following as major factors that positively influenced the fatalities: head or neck injuries (odds ratio [OR], 90.221); trunk injuries (OR, 71.040); trucks as offending vehicle (OR, 2.741); collision velocity of 10-20 km/h (OR, 31.794), 20-30 km/h (OR, 2.982), 30-40 km/h (OR, 8.394), 40-50 km/h (OR, 16.831), and >50 km/h (OR, 18.639); and hit-and-run cases (OR, 1.967). The following had a positive influence on severe injuries: trunk injuries (OR, 4.060); collision velocity of 10-20 km/h (OR, 2.540), 20-30 km/h (OR, 3.700), 30-40 km/h (OR, 5.297), 40-50 km/h (OR, 5.719), and ≥50 km/h (OR, 5.244); and hit-and-run cases (OR, 2.628). Decreasing the collision velocity, avoiding collisions to the head and neck or trunk, and preventing hit-and-run cases would be effective in reducing fatal or severe injuries to pedestrians lying on the road.

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Objective: Recent studies have suggested that aPS-PT antibody is one of the most relevant autoantibodies to APS. This study aimed to demonstrate the pathogenicity of aPS-PT antibody in vivo . Methods: At first, cultured rat vascular endothelial cells (RECs) were exposed to calf thymus-derived histones. Two hours later, lactate dehydrogenase release from the RECs and expression of PS on the cell surface were assessed. Next, we administered an i.v. injection of calf thymus-derived histones into Wistar rats (12.5 µg/g weight of 8-week-old female rats), and 2 h later they were given an i.v. injection of aPS-PT mAb (1.25 mg/g weight, n = 6) or an equal dose of rat IgM as controls (n = 5). Three days later, histological examination was conducted. Results: Calf thymus-derived histones (>12.5 µg/ml) could injure RECs in vitro . Simultaneously, annexin V could bind to the RECs; thereby, this result indicated that cell-free histone exposure of vascular endothelial cells induced cell surface expression of PS, which is naturally present inside the plasma membrane. Thrombosis developed with higher frequency in the rats given an i.v. injection of aPS-PT mAb than in controls. Conclusion: We established a rat model of thrombosis induced by i.v. injection of aPS-PT mAb.

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