Explore the vast range of titles available.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP. In a 28-year-old woman with postpartum immune thrombotic thrombocytopenic purpura, plasma exchange was unsuccessful. Near death while receiving vasopressors, she was treated with recombinant ADAMTS13, and the disease abated.

Abstract Objectives The 2019 SCARED study developed the Biomedical Excellence for Safer Transfusion (BEST) criteria in an effort to standardize the decision to culture residual units in the context of suspected septic transfusion reactions (STRs). The goal of this study was to apply the BEST criteria to determine the effect on the transfusion reaction decision to culture. Methods This retrospective, single-center, cross-sectional study assessed adult transfusion reactions identified in calendar years 2013 to 2020. Reactions following transfusion of RBCs, platelets, and plasma were included, and the decisions to culture following strict application of BEST criteria were compared with decisions to culture in actual practice. Results In total, 1,068 transfusion reactions were reported and 200 (19%) suspected STRs were cultured, all with negative results; 303 (28%) reactions would have been cultured per strict application of the BEST criteria. Concordance between actual culture decision and BEST criteria recommendation was 62% for cultured components and 79% for components that were not cultured. Conclusions BEST criteria provide objective recommendations of when to culture residual units implicated in suspected STRs, but strict application of these criteria may result in increased culture rates. Clinical correlation to aid in the decision to culture is recommended.

Purpose Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children’s psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. Methods Participants were mother–child dyads in the ECHO-PATHWAYS consortium’s harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4–6-year-old child’s mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. Results Among 1948 dyads (child age M  = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children’s psychopathology: higher CTE and PSLE counts were related to higher total problems ([ß CTE  = 0.11, 95% CI [.06, .16]; ß SLE  = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (OR CTE  = 1.41; 95% CI [1.12, 1.78]; OR PSLE  = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. Conclusion Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women’s and their children’s health.

Accumulating evidence suggests that maternal exposure to objectively stressful events and subjective distress during pregnancy may have intergenerational impacts on children’s mental health, yet evidence is limited. In a multisite longitudinal cohort (N = 454), we used multi-variable linear regression models to evaluate the predictive value of exposure to stressful events and perceived distress in pregnancy for children’s internalizing problems, externalizing problems, and adaptive skills at age 4. We also explored two- and three-way interactions between stressful events, distress, and child sex. Both objective and subjective maternal stress independently predicted children’s behavior, with more stressful events and higher distress predicting more internalizing and externalizing problems and worse adaptability; stress types did not significantly interact. There was some evidence that more stressful events predicted higher externalizing behaviors only for girls. Three-way interactions were not significant. The current findings highlight the importance of considering the type of stress measurement being used (e.g., counts of objective event exposure or subjective perceptions), suggest prenatal stress effects may be transdiagnostic, and meet calls for rigor and reproducibility by confirming these independent main effects in a relatively large group of families across multiple U.S. regions. Results point to adversity prevention having a two-generation impact and that pre- and postnatal family-focused intervention targets may help curb the rising rates of children’s mental health problems.

ImportanceAccess to healthy and affordable foods may play a role in reducing inflammation and in healthy pulmonary immune system development.ObjectiveTo investigate the association between residing in a low-income and low-food-access (LILA) neighbourhood and risk of childhood asthma. A positive association was hypothesised.Design, setting and participantsThis prospective cohort study consists of 16 012 children from 35 longitudinal studies in the Environmental influences on Child Health Outcomes programme (children born 1998–2021) from across the contiguous USA. We conducted survival analyses adjusted for child sex, race/ethnicity, maternal education, gestational smoking, and parental history of asthma.Exposure(s)Several commonly used geospatial food access metrics were linked to residential locations including: LILA census tracts where the nearest supermarket is >1 mile in urban and >10 miles in rural areas (LILA1 and 10), >1 mile in urban and >20 miles in rural areas (LILA1 and 20), >0.5 mile in urban and >10 miles in rural areas (LILA0.5 and 10), and >0.5 mile without a vehicle or >20 miles (LILAvehicle). Each metric was linked to lifetime residential history timelines then dichotomised according to whether the child had spent at least 75% of their life living in a LILA area separately for birth through age 5 years (cumulative early childhood) and birth through age 11 years (cumulative middle childhood).Main outcomes(s) and measure(s)Asthma incidence in cumulative early and middle childhood.ResultsResiding in a LILA0.5 and 10 and LILAvehicleneighbourhood was associated with a higher asthma incidence in cumulative early and middle childhood. The LILA0.5 and 10 and LILAvehicle associations were stronger for asthma during cumulative early childhood, where we observed hazard ratios of 1.13 (95% CI 1.02 to 1.24) and 1.13 (95% CI 1.01 to 1.27), respectively. The associations were higher among children who were Hispanic, were female and had lower maternal education.Conclusion and relevanceLimited residential food access was associated with higher childhood asthma incidence, especially among female and Hispanic children and those with lower maternal education. Our findings support multipronged efforts to increase access to healthy and affordable food options and lower food insecurity in LILA neighbourhoods.

Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1-/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1-/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1. These data suggest that Elovl1 inhibition may have broader consequences in ABCD1-/y mice than correction of lipid homeostasis.Competing Interest StatementAll authors are Sanofi employees or were Sanofi employees when they contributed to this project