Johns Hopkins All Children's Hospital

Identifying and preventing patient safety events is a goal for institutions that provide quality care; understanding and mitigating disparities in care is another. The mainstay of safety event detection, voluntary event reporting (VER), is prone to bias and under-reporting; previous research suggests this creates disparities in reported events. We aim to explore disparities in voluntary event reporting that may exist in a large, academic health system. We conducted a retrospective review of inpatient-associated safety events submitted to our health system's VER system from April 2021 to July 2022 and compared the cohort's demographics to those of all admitted patients during the same period. Pediatric patients, who are over-represented in the overall VER system (23% vs. 20%, P<0.001), are under-represented among most harmful events (P<0.001). Female patients, who are under-represented in the VER system (50.1% vs. 56.5%, P<0.001), remain so only in lower harm events. Other groups are over-represented in the VER system, including patients who are English-speaking (93.8% vs. 92.9%), non-Hispanic or Latino (88.9% vs. 82.4%), Black/African American (33.3% vs. 28.7%), and from areas of high neighborhood deprivation (23.5% vs. 18.9%) (all P<0.001). Disparities in VER were observed in a large academic health system. We conducted a broad analysis, including novel variables that have yet to be evaluated robustly in the literature, and we do find important disparities in these variables. Further research is needed to understand the mechanism for disparities to mitigate bias in reporting. Implementation of more objective methods of event detection may help reduce disparities.

How is postural orthostatic tachycardia syndrome (POTS) diagnosed? What about adolescents who seem to have POTS but do not meet the diagnostic criteria? How can we treat POTS and related conditions? How can we best respond to common questions of frustrated patients and parents and guardians? This article provides evidence- and expert-based answers to questions that frequently arise when caring for patients with POTS and related conditions.

The clinical focus of haemophilia has expanded beyond bleeding outcomes to encompass long-term comorbidities such as cardiovascular disease (CVD). However, it remains unclear when vascular changes begin in this population. Carotid intima-media thickness (cIMT), a validated, non-invasive marker of subclinical atherosclerosis, may help detect early vascular remodelling in youth with haemophilia, even in the absence of conventional CVD risk factors. This single-centre, cross-sectional study compared adolescent males (ages 10-21 years) with severe haemophilia (FVIII or IX <1%) to age-matched healthy controls. Bilateral carotid ultrasonography was performed, and right-sided cIMT was the prespecified primary endpoint. Conventional CVD clinical risk factors were also collected. Thirty-eight participants were enrolled, 22 with haemophilia and 16 controls. Median right cIMT was higher in the haemophilia group (0.40mm, SD 0.08 range 0.35-0.47) versus the control group (0.38mm, SD 0.06 range 0.32-0.39;p = 0.009). When referenced to age-and-height specific nomograms, cIMT percentiles were also elevated in the haemophilia group (6.5% vs. 1.6%;p = 0.026 and 12.9%vs. 1.7%;p= 0.018; respectively). HDL-cholesterol was significantly lower in the haemophilia group (48.9 SD 9.9 vs. 60.2 SD 14.9mg/dL;p = 0.012). No correlations were found between cIMT and any CVD risk factors. Adolescent males with severe haemophilia show early arterial thickening, suggesting that vascular remodelling in this population may begin in adolescence. Incorporating cIMT and CVD risk assessment into routine haemophilia care may support timely interventions and reduce long-term cardiovascular complications.

We sought to perform multi-variable modeling to assess the independent value of the CVPS in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD). CVPS was assessed at a core lab using the first and last echocardiograms during gestation. A receiver operating characteristic (ROC) curve analysis was conducted. Changes in the CVPS from the first to the last echo were assessed with Wilcoxon signed-rank tests. There were 164 fetuses with EA/TVD with complete CVPS at the first echo. Nearly half, 48.8% (n=80), had intrauterine fetal demise (IUFD) or died neonatally. At the first echo, median gestational age (GA) was 27.6weeks (IQR: 23.0-31.0) and median CVPS was 7 (IQR: 6-8). The optimal cut-point for classification of perinatal survival was observed at CVPS ≥ 6.5 (Youden index=0.46). After adjustment, there remained a significant independent association between every 1-point increase in the CVPS at first echo and the odds of perinatal survival (adjusted odds ratio: 2.0, 95% CI: 1.3 to 3.2, and p=0.003). The CVPS at the last echo decreased by a median of 1 point among both survivors (p<0.01) and non-survivors (p<0.001). Among fetuses with EA/TVD, the CVPS may be used as an additional tool to assess perinatal survival throughout gestation.

Hofbauer cells (HBCs) are fetal macrophages located in the placenta that contribute to antimicrobial defense, angiogenesis, tissue remodeling, and metabolic processes within the chorionic villi. Although their roles in placental biology are increasingly recognized, the mechanisms that regulate HBC identity and function are not yet fully defined. This study aimed to define the core transcriptomic and epigenomic features of HBCs in term placentas and to examine their capacity for transcriptional responsiveness and phenotypic variation. Using chromatin accessibility profiling and bulk RNA-seq, we found that HBCs exhibit a unique gene expression and chromatin accessibility profile compared with other fetal and adult macrophages. We identified a coordinated transcriptional network involving nuclear receptors (NRs) NR4A1-3, the glucocorticoid receptor, and RFX family members (RFX1, RFX2, RFX5) that appears to shape HBC identity, particularly through pathways linked to lipid metabolism and angiogenesis. Although exploratory in nature, in vitro stimulation studies showed that HBCs exhibited increased transcriptional activity in response to combined IL-4 and rosiglitazone treatment, including induction of the lipid transporter CD36. Mass cytometry analysis revealed surface markers indicative of both immature and mature macrophage states. These results together indicate that HBCs are a distinct and diverse population of macrophages with a specialized, adaptable regulatory program in the human placenta.

To assess the predictive validity of neurodevelopmental screening in toddlers and preschool children with sickle cell disease (SCD) using the Ages and Stages Questionnaire (ASQ). We expected screening in preschool children to predict academic problems in elementary school and future stroke risk. Using a longitudinal cohort design, academic problems (e.g. grade retention, failing a subject) and increases in stroke risk (e.g. abnormal transcranial Doppler exam) were assessed for a 6-year period after neurodevelopmental screening in 2-year-olds ('toddlers') and 4-year-olds ('preschool children') using medical record review, which included annual information from parents about school functioning. Biopsychosocial variables were examined as alternate predictors. In total, 30% of toddlers and 34% of preschool children had positive screenings. For toddlers (n=111), positive screenings on the ASQ predicted academic problems (p=0.009), but not increased stroke risk (p=0.938). For preschool children (n=110), positive screenings predicted academic problems (p < 0.001) and increased stroke risk (p=0.018). The ASQ independently predicted academic outcomes across cohorts; baseline biomedical factors were unique predictors of stroke across cohorts. Screening with the ASQ allows for risk stratification for neurodevelopmental outcomes in SCD. Screening in preschool children is important because of changing risk factors with age.