Cord Blood Transplantation in 2 Infants Presenting Monosomy 7 Clonal Hematopoiesis: SAMD9 / SAMD9L Germline Mutation.

Recently, germline mutations in SAMD9 and SAMD9L were increasingly found in children with monosomy 7. We report the outcomes in 2 infants with the SAMD9/SAMD9L variant, who presented with anemia and thrombocytopenia (patient 1), and neutropenia and nonsymptomatic white-matter-encephalopathy (patient 2). Both patients received cord blood transplantation and experienced critical post-cord blood transplantation adverse events; patients 1 and 2 developed fulminant engraftment syndrome and life-threatening graft-versus-host disease, respectively. Of note, selective loss of chromosome 7 in bone marrow-derived CD34 + cells was inferred.

Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution.

Treatment of children with refractory immune thrombocytopenic purpura (ITP) is challenging and poorly established. We retrospectively reviewed the clinical data of 87 patients under the age of 16 years who were diagnosed with ITP from April 1998 to March 2017 in our institution. Refractory ITP was defined as a platelet count of < 50 × 109/L at 14 days after receiving intravenous immunoglobulin (IVIG) and prednisolone. We presumed that there was a pathophysiological overlap between refractory ITP and refractory thrombocytopenia (RT): a subtype of refractory cytopenia of childhood (RCC). Immunosuppressive therapies including anti-thymocyte globulin and cyclosporine (CsA) have been adopted for children with RCC in Japan. Thus, from 2009 onwards, we changed the diagnosis from refractory ITP to RT and introduced CsA for refractory ITP/RT. Nine of 42 patients developed refractory ITP in the 1998-2008 group, who received conventional treatments such as IVIG and steroid therapy. Eight of 45 patients developed refractory ITP in the 2009-2017 group, who received CsA with or without IVIG therapy. The response rate at three years after diagnosis was significantly higher in the 2009-2017 group (98%) than in the 1998-2008 group (83%) (p = 0.019). In conclusion, our strategy of introducing CsA for refractory ITP/RT contributed to better outcomes.

Age-Specific Differences in Foreign Bodies Ingested by Children: A Cohort Study of 252 Japanese Cases.

Background and Objectives: When children accidentally ingest foreign bodies, they may be unable to communicate adequately; it is often difficult to identify the causative foreign body unless someone is watching over them. In such instances, to identify the causative foreign body during clinical practice, we aimed to determine if it varies according to age. Materials and Methods: From April 2013 to June 2018, 252 records of pediatric patients with a confirmed diagnosis of foreign-body ingestion were retrospectively examined in a Japanese university hospital. Comparisons among multiple age groups, according to type of ingested foreign body, were analyzed using Kruskal‒Wallis tests. The differences between the individual data were tested using the Steel‒Dwass test. Results: The median age of the patients was 15 months, and of the total patients, 140 were boys (55.5%). The types of foreign bodies ingested were as follows, in order of frequency: cigarettes (n = 44, 17%, median age: 12 months), plastics (n = 43, 17%, median age: 11 months), chemicals (n = 27, 11%, median age: 13 months), internal medicines (n = 26, 10%, median age: 33 months), and metals (n = 26, 10%, median age: 35 months). The median age was significantly different among the types of causative foreign bodies (p < 0.01). The patient age for the ingestion of cigarettes was significantly younger than that for ingesting metals or coins. The age for ingesting internal medicines was significantly older than that for ingesting plastics, cigarettes, paper, or chemicals (p < 0.01). Conclusions: The causative foreign body ingested differed according to age. This will be valuable information for physicians that encounter pediatric patients who may have ingested an unknown foreign body in Japanese pediatric emergency or general practice settings.

Impact of persistent left ventricular regional wall motion abnormalities in childhood cancer survivors after anthracycline therapy: Assessment of global left ventricular myocardial performance by 3D speckle-tracking echocardiography.

AIMS: To identify left ventricular (LV) mechanical impairment by 3D speckle-tracking echocardiography (3DSTE) in long-term childhood cancer survivors after anthracycline therapy with or without persistent LV regional diastolic wall motion abnormalities (WMA) and a preserved LV ejection fraction (EF >53%). METHODS AND RESULTS: Thirty-two patients (median: 14.6 years) and 12 age-matched controls were studied. The patients were divided into two groups according to the existence of WMA: Group 1 (with WMA: n=14), Group 2 (without WMA: n=18). 3DSTE was performed to assess LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS), LV torsion, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV). LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of time to peak strain of the 16 segments divided by the RR interval. There was no significant difference in LVEDV, LVESV, GLS, torsion, or SDI derived from LS, CS, or AS among the 3 groups. In contrast, there were significant differences in GRS, GCS, and GAS, and SDI derived from RS among the 3 groups. Compared with group 2, group 1 had significantly reduced GRS (p<0.001), GCS (p<0.01), GAS (p<0.01), and greater SDI derived from GRS (p<0.01). Moreover, the existence of WMA was correlated with GRS (p<0.001), SDI derived from GRS (p<0.001), and LVEF (p=0.036). Multiple linear regression analysis identified GRS as a significant determinant of the existence of WMA (ß=0.751, p=0.001). CONCLUSION: Childhood cancer survivors with persistent LV regional WMA show a reduced LV myocardial performance compared with those without WMA, despite a preserved LVEF.

Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: a single institution experience.

INTRODUCTION: Recombinant thrombomodulin (rTM), which degrades factors Va and VIIIa by activating protein C, has been developed as a new drug for treating disseminated intravascular coagulation (DIC). MATERIALS AND METHODS: Since July 2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130 U/kg/day for newborns) as a first-line therapy. Median duration of rTM administration was 5 consecutive days (range, 2-13 days). We employed DIC criteria of the Japan Welfare and Health Ministry. The first day on which rTM treatment was given was defined as day 1. RESULTS: Median patients age was 3 years. Underlying diseases were hematological disorders (n=13) and severe infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7 and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009). Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU; antithrombin, 112%; protein C, 105%) were significantly improved compared to results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU; antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and serious bleeding events were observed in 2 newborns. CONCLUSION: The efficacy of rTM cannot be assessed from the present dataset, due to several limitations such as the small heterogenous patient cohort, and the lack of age- and disease-matched controls. Nevertheless, this case-series remains important in terms of enabling further prospective control studies to evaluate the efficacy of rTM in children.