Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available. Experimental Design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study. Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli–Leydig cell tumor at a median age of 14 years (range: 11 months–66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli–Leydig cell tumors were diagnosed before 4 years of age. Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

Hospital-acquired bloodstream infections have a definite impact on patient encounters and cause increased length of stay, costs, and mortality. However, methods for estimating these effects are potentially biased, especially if the time of infection is not incorporated into the estimation strategy. We focused on matching patient encounters in which a hospital-acquired infection occurred to comparable encounters in which an infection did not occur. This matching strategy is susceptible to a selection bias because inpatients that stay longer in the hospital are more likely to acquire an infection and thus also are more likely to have longer and more costly stays. Instead, we have proposed risk-set matching, which matches infected encounters to similar encounters still at risk for infection at the corresponding time of infection. Matching on the one-dimensional propensity score can create comparable pairs for a large number of characteristics; an analogous propensity score is described for risk-set matching. We have presented dramatically different estimates using these 2 approaches with data from a pediatric cohort from the Premier Healthcare Database, United States, 2009-2016. The results suggest that estimates that did not incorporate time of infection exaggerated the impact of hospital-acquired infections with regard to attributed length of stay and costs.

Introduction: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. Objective: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. Methods: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010–June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. Results: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. Conclusions: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.

BACKGROUND: Thrombosis is a major complication after cardiac surgery in children with congenital heart disease. The mechanisms underlying thrombosis development remain poorly understood. We aimed to identify novel circulating metabolites before cardiac surgery that are associated with thrombosis after surgery in children with congenital heart disease. METHODS: In this prospective cohort study, all blood samples were drawn right before surgical incision and after the induction of anesthesia, and plasma was separated immediately under 4 °C. Untargeted metabolomic data were measured by Metabolon in plasma from children (age range, 0 days–18 years) with congenital heart disease undergoing cardiac surgery. The primary outcome was thrombosis within 30 days of surgery or before discharge. Associations of individual metabolites with thrombosis were assessed with logistic regression with false discovery rate correction for multiple comparison and adjustment for clinical characteristics; elastic net regression was used to select a prediction model. RESULTS: Out of 1115 metabolites measured in samples from 203 children, 776 met the quality control criteria. In total, 25 children (12.3%) developed thrombosis. Among the 776 metabolites, 175 were significantly associated with thrombosis (false discovery rate Q <0.05). The top 3 metabolites showing the strongest associations with thrombosis were eicosapentaenoate, stearidonate, and andro steroid monosulfate C ₁₉ H ₂₈ O ₆ S (false discovery rate, 0.01 for all). Pathway analysis showed that the pathways of nicotinate and nicotinamide metabolism and glycerophospholipid metabolism were enriched (false discovery rate, 0.003 for both) and had significant impact on the development of thrombosis. In elastic net regression analysis, the area under the receiver operating-characteristic curve of a prediction model for thrombosis was 0.969 in the training sample (70% of the total sample) and 0.833 in the testing sample (the remaining 30%). CONCLUSIONS: We have identified promising novel metabolites and metabolic pathways associated with thrombosis. Future studies are warranted to confirm these findings and examine the mechanistic pathways to thrombosis.