International Interobserver Variability of Breast Density Assessment.

PURPOSE: The aim of this study was to determine variability in visually assessed mammographic breast density categorization among radiologists practicing in Indonesia, the Netherlands, South Africa, and the United States. METHODS: Two hundred consecutive 2-D full-field digital screening mammograms obtained from September to December 2017 were selected and retrospectively reviewed from four global locations, for a total of 800 mammograms. Three breast radiologists in each location (team) provided consensus density assessments of all 800 mammograms using BI-RADS® density categorization. Interreader agreement was compared using Gwet's AC2 with quadratic weighting across all four density categories and Gwet's AC1 for binary comparison of combined not dense versus dense categories. Variability of distribution among teams was calculated using the Stuart-Maxwell test of marginal homogeneity across all four categories and using the McNemar test for not dense versus dense categories. To compare readers from a particular country on their own 200 mammograms versus the other three teams, density distribution was calculated using conditional logistic regression. RESULTS: For all 800 mammograms, interreader weighted agreement for distribution among four density categories was 0.86 (Gwet's AC2 with quadratic weighting; 95% confidence interval, 0.85-0.88), and for not dense versus dense categories, it was 0.66 (Gwet's AC1; 95% confidence interval, 0.63-0.70). Density distribution across four density categories was significantly different when teams were compared with one another and one team versus the other three teams combined (P < .001). Overall, all readers placed the largest number of mammograms in the scattered and heterogeneous categories. CONCLUSIONS: Although reader teams from four different global locations had almost perfect interreader agreement in BI-RADS density categorization, variability in density distribution across four categories remained statistically significant.

[PERIOPERATIVE MANAGEMENT OF AN ADOLESCENT GIRL WITH SEVERE FACTOR XI DEFICIENCY AND INHIBITORS].

INTRODUCTION: Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by injury-related hemorrhage, mostly associated with surgical procedures at sites noted for high fibrinolytic activity. Severe FXI deficiency is defined when the FXI level is lower than 15-20 IU/dL. Perioperative prophylactic treatment for high-bleeding-risk surgery in patients with severe FXI deficiency is based on fresh frozen plasma (FFP) transfusions or FXI concentrate (where available). Exposure to FFP and to FXI concentrate may lead to the development of inhibitory antibodies against FXI. This phenomenon occurs mostly in patients with very severe FXI deficiency (baseline FXI <1IU/dL) and is associated with an increased risk of substantial perioperative bleeding, unresponsive to FXI replacement. Thus, in individuals with severe FXI deficiency, routine testing for the presence of inhibitory antibodies against FXI is recommended. We present a 17-year-old adolescent patient with very severe FXI deficiency, who developed an inhibitor to FXI following FFP exposure associated with neurosurgery for medulloblastoma. Prophylactic treatment for subsequent invasive procedures consisted of single low dose (10 mcg/kg) recombinant activated factor VII (rFVIIa) and tranexamic acid (Hexakapron). The procedures were performed uneventfully, with no hemorrhagic or thrombotic complications. In patients with very severe FXI deficiency, the development of inhibitory antibodies following plasma replacement therapy comprises a rare and challenging occurrence. The formulation of a safe and effective evidence-based protocol for hemostatic support in these patients requires multi-center collaboration.

Pediatric severe factor XI deficiency: A multicenter study.

BACKGROUND: Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study. OBJECTIVE: Some hemostatic challenges may be unique or more common in children, such as bleeding in the neonatal period or trauma-related injury. The current study was designed to explore the potential impact of these differences in children with severe FXI deficiency. METHODS: Medical files of all children with FXI level under 15% followed at five tertiary centers were evaluated. The retrieved data comprised demographic and clinical characteristics, including bleeding episodes, surgical interventions, treatment strategies, as well as laboratory features. RESULTS: Sixty children, whose median age at diagnosis was 4.2 years and their median FXI level was 4%, were included. Three children experienced triggered intracranial hemorrhage (ICH) and two children had major bleeds. No bleeding complications occurred in surgeries in which hemostatic treatment consisting mostly of tranexamic acid or fresh frozen plasma was applied (n = 45). In contrast, excessive bleeding was noted in 25% of surgical procedures performed without hemostatic preparation (p = .002). CONCLUSION: This study's findings confirm the generally favorable outcome of this rare bleeding disorder, with no spontaneous bleeds or cases of perinatal ICH. Nonetheless, proper diagnosis and adequate hemostasis in the surgical setting are imperative. Unlike previous studies in adults, our pediatric study suggests an association between the severity of FXI deficiency and bleeding tendency.