BackgroundThere are limited data about the range of diseases, natural history, age-appropriate endpoints and optimal care for children with pulmonary hypertension (PH), including the need for developing high quality patient registries of children with diverse forms of PH to enhance care and research.ObjectiveTo characterise the distribution and clinical features of diseases associated with pediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the WSPH Classification.Methods1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of 8 interdisciplinary PH programs.ResultsWSPH Groups 1 (PAH) and 3 (lung disease) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were BPD and CDH. Group 1 disease was predominantly associated with congenital heart disease (60%) and idiopathic (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (HR=3.1, p<0.001), tended to be younger at diagnosis (0.3 (0.0,0.6) versus 1.6 (0.1,6.9) years (median (IQR); p<0.001), and were more often male (57% versus. 45%, p<0.001). Down syndrome (DS), the most common genetic syndrome in the registry, constituted 11% of the entire PH cohort.ConclusionsWe find a striking proportion of pediatric PH patients with Group 3 disorders, reflecting the growing recognition of PH in diverse developmental lung diseases. Greater precision of clinical phenotyping based on disease-specific characterization may further enhance care and research of pediatric PH.

Clinical research investigates mechanisms of human disease, interventions, or new technologies, but pregnant women are often excluded from clinical studies. Few studies, beyond research on pregnancy, are designed to address questions relevant to pregnant women. A recent National Institutes of Health workshop considered the barriers and opportunities in conducting clinical research studies enrolling pregnant women.

Ventricular assist devices (VADs) are an increasingly common therapy for end-stage heart failure across all ages as a bridge to recovery or transplant and more recently as destination therapy. With increasing experience and difficulties with establishing therapeutic heparin levels, we have begun to explore the effectiveness of direct thrombin inhibitors in this patient population. This is a retrospective review of all long-term VAD patients, both adult and pediatric, who were anticoagulated with bivalirudin between January 2009 and January 2016. The starting dose was 0.3 mg/kg/hr, and dose was titrated for a goal partial thromboplastin time (PTT) of 70–100. There were 14 patients (13 males, 5 ≤18 years) with 17 episodes of bivalirudin therapy. The median age on initiation was 45 years (range, 15 days–67 years) with 10 episodes associated with a HeartWare HVAD, five a HeartMate II, and two with a Berlin Heart EXCOR. The predominant indication of bivalirudin therapy was suspected pump thrombosis (13/17). The median time from VAD insertion to initiation of bivalirudin was 116 days (range, 3–1,870) with the median duration of therapy being 21 days (range, 3–113). In patients with pump thrombosis, the mean baseline lactate dehydrogenase (LDH) was 229 ± 64 U/L, peak 690 ± 380 U/L, and decreased to 330 ± 243 U/L when bivalirudin was stopped. The outcomes following suspected pump thrombosis included: transitioned to warfarin (n = 7), death in two destination therapy patients who did not undergo pump exchange, transplantation (n = 2), and pump exchange (n = 2). A major bleeding complication occurred in only one patient. Our experience highlights the potential use of bivalirudin in a heterogenous VAD population. Although these initial results suggest some potential role for direct thrombin inhibitors for use in long-term VADs, larger prospective studies are required to support these preliminary observations and to determine who may benefit from direct thrombin inhibitors (DTIs) and the side effect profile in this patient population.

Abstract:Background: Mycophenolate mofetil (MMF, CellCept Õ ) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). Objective: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex Õ at 30 mcg) in relapsingremitting MS (RRMS). Methods: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. Results: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. Conclusions:The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.

Driveline infections (DLIs) remain a major source of morbidity for patients requiring long-term ventricular assist device (VAD) support. We aimed to assess whether VAD driveline exit site (DLES) (abdomen versus chest wall) is associated with DLI. All adult patients who underwent insertion of a HeartWare HVAD or HeartMate II (HMII) between 2009 and 2016 were included. Driveline infection was defined as clinical evidence of DLI accompanied by a positive bacterial swab and need for antibiotics. Competing risks analysis was used to assess the association between patient characteristics and DLI. Ninety-two devices (59 HMII) were implanted in 85 patients (72 men; median age 57.4 years) for bridge to transplant or destination therapy. VAD DLES was chest in 28 (30.4%) devices. Median time on VAD support was 347.5 days (IQR 145.5, 757.5), with 28 transplants and 29 deaths (27 on device). DLI occurred in 24 patients (25 devices) at a median of 140 days (IQR 67, 314) from implant. Staphylococcus aureus accounted for 15 infections (60%). Freedom from infection was 72.8% (95% confidence interval [CI] 53.1-78.0%) at 1 year and 41.9% (95% CI 21.1-61.5%) at 3 years. In competing risks regression, abdominal DLES was not predictive of DLI (hazard ratio, HR 1.65 [95% CI 0.63, 4.29]), but body mass index (BMI) >30 kg/m was (HR 2.72 [95% CI 1.25, 5.92]). In conclusion, risk of DLI is high among patients on long-term VAD support, and a nonabdominal DLES does not reduce this risk. The only predictor of DLI in this series was an elevated BMI.

Higher risk of intubation was found in patients with parainfluenza as compared to RSV. The risk of intubation comparing parainfluenza virus to other viruses and for patients with multiple versus single virus needs to be further studied.

Pulmonary arterial hypertension (PAH) is a disease characterized by pathological remodeling of the pulmonary vasculature causing elevated pulmonary artery pressures and ultimately, right ventricular failure from chronic pressure overload. Heterozygous pathogenic GDF2 (encoding bone morphogenetic protein 9 (BMP9)) variants account for some (>1%) adult PAH cases. Only three pediatric PAH cases, harboring homozygous or compound heterozygous variants, are reported to date. Ultra-rare pathogenic GDF2 variants are reported in hereditary hemorrhagic telangiectasia and overlapping disorders characterized by telangiectasias and arteriovenous malformations (AVMs). Here, we present two siblings with PAH homozygous for a GDF2 mutation that impairs BMP9 proprotein processing and reduces growth factor domain availability. We confirm an absence of measurable plasma BMP9 whereas BMP10 levels are detectable and serum-dependent endothelial BMP activity is evident. This contrasts with the absence of activity which we reported in two children with homozygous pathogenic GDF2 nonsense variants, one with PAH and one with pulmonary AVMs, both with telangiectasias, suggesting loss of BMP10 and endothelial BMP activity in the latter may precipitate telangiectasia development. An absence of phenotype in related heterozygous GDF2 variant carriers suggests incomplete penetrance in PAH and AVM-related diseases, indicating that additional somatic and/or genetic modifiers may be necessary for disease precipitation.

BackgroundPost-operative infections in pediatric cardiac surgery are an ongoing clinical challenge, with rates between 1 and 20%. Perioperative antibiotics remain the standard for prevention of surgical-site infections, but the type of antibiotic and duration of administration remain poorly defined. Current levels of practice variation through informal surveys are very high. Rates of antibiotic-resistant organisms are increasing steadily around the world.Methods/designWe will identify all controlled observational studies and randomized controlled trials examining prophylactic antibiotic use in pediatric cardiac surgery. Data sources will include MEDLINE, EMBASE, CENTRAL, and proceedings from recent relevant scientific meetings. For each included study, we will conduct duplicate independent data extraction, risk of bias assessment, and evaluation of quality of evidence using the GRADE approach.DiscussionWe will report the results of this review in agreement with the PRISMA statement and disseminate our findings at relevant critical care and cardiology conferences and through publication in peer-reviewed journals. We will use this systematic review to inform clinical guidelines, which will be disseminated in a separate stand-alone publication.Study registration numberPROSPERO CRD42016052978C Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-017-0502-y) contains supplementary material, which is available to authorized users.