Autoimmune disorders of platelet function: systematic review of cases of acquired Glanzmann thrombasthenia and acquired delta storage pool disease

Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbβ3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immune-mediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.     

Updated Meal Patterns in the Child and Adult Care Food Program and Changes in Quality of Food and Beverages Served: A Natural Experimental Study

With diet-related chronic diseases being the largest contributors to U.S. morbidity and mortality, identifying population-level strategies to promote healthier diets is essential. Intervention during early childhood may be particularly important. The Child and Adult Care Food Program (CACFP), a federal nutrition assistance program in the U.S. that supports serving meals and snacks in child care settings, reaches millions of U.S. children. Recent 2017 updates to CACFP’s meal patterns were meant to improve the nutritional quality of food served through CACFP by providing more whole grains, fruit, and vegetables. In this study, we used a natural experimental, longitudinal study of child care centers participating in CACFP compared to nonparticipating centers to assess whether the quality of food and beverages served (per menu analysis) improved following the CACFP meal pattern changes. While we found that CACFP centers were more likely to meet several key nutrition standards in comparison to non-CACFP centers overall, there were no differences in menu quality from before to after the 2017 standards change between CACFP and non-CACFP centers. Nutrition standards for CACFP may need to be further strengthened with adequate financial and technical support given to child care programs for effective implementation.     

Alternative Healthy Eating Index-2010 and Incident Non-Communicable Diseases: Findings from a 15-Year Follow Up of Women from the 1973–78 Cohort of the Australian Longitudinal Study on Women’s Health

Non-communicable diseases (NCDs) and multimorbidity (≥two chronic conditions), are increasing globally. Diet is a risk factor for some NCDs. We aimed to investigate the association between diet quality (DQ) and incident NCDs. Participants were from the Australian Longitudinal Study on Women’s Health 1973–78 cohort with no NCD and completed dietary data at survey 3 (2003, aged 25–30 years) who responded to at least one survey between survey 4 (2006) and survey 8 (2018). DQ was measured by the Alternative Healthy Eating Index-2010 (AHEI-2010). Outcomes included coronary heart disease (CHD), hypertension (HT), asthma, cancer (excluding skin cancer), diabetes mellitus (DM), depression and/or anxiety, multimorbidity, and all-cause mortality. Repeated cross-sectional multivariate logistic regressions were performed to investigate the association between baseline DQ and NCDs over 15 years. The AHEI-2010 mean (±sd) for participants (n = 8017) was 51.6 ± 11.0 (range: 19–91). There was an inverse association between AHEI-2010 and incident asthma at survey 4 (OR_Q5–Q1: 0.75, 95% CI: 0.57, 0.99). Baseline DQ did not predict the occurrence of any NCDs or multimorbidity between the ages of 25–45 years. Further well-planned, large prospective studies conducted in young women are needed to explore dietary risk factors before the establishment of NCDs.     

Induction of natural IgE by glucocorticoids

IgE mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of foreign allergens; yet the origin, regulation, and functions of such “natural” IgE still remain largely unknown. Here, we find that glucocorticoids enhance the production of IgE in B cells both in vivo and ex vivo without antigenic challenge. Such IgE production is promoted by B cell–intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis, such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent pathogenic anaphylaxis. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.     

Epstein-Barr virus-associated smooth muscle tumors in immunocompromised patients: Six case reports

BACKGROUNDEpstein-Barr virus associated smooth muscle tumor (EBV-SMT) is a rare oncological entity. However, there is an increasing incidence of EBV-SMTs, as the frequency of organ transplantation and immunosuppression grows. EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder (PTLD). There is no clear consensus on the treatment of EBV-SMTs. However, surgical resection, chemotherapy, radiation therapy, and immunosuppression reduction have been explored with varying degrees of success. CASE SUMMARYOur case series includes six cases of EBV-SMTs across different age groups, with different treatment modalities, adding to the limited existing literature on this rare tumor. The median latency time between immunosuppression and disease diagnosis is four years. EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency.CONCLUSIONIt is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.     

Infant brain imaging using magnetoencephalography: Challenges,solutions, and best practices

The excellent temporal resolution and advanced spatial resolution of magnetoencephalography (MEG) makes it an excellent tool to study the neural dynamics underlying cognitive processes in the developing brain. Nonetheless, a number of challenges exist when using MEG to image infant populations. There is a persistent belief that collecting MEG data with infants presents a number of limitations and challenges that are difficult to overcome. Due to this notion, many researchers either avoid conducting infant MEG research or believe that, in order to collect high‐quality data, they must impose limiting restrictions on the infant or the experimental paradigm. In this article, we discuss the various challenges unique to imaging awake infants and young children with MEG, and share general best‐practice guidelines and recommendations for data collection, acquisition, preprocessing, and analysis. The current article is focused on methodology that allows investigators to test the sensory, perceptual, and cognitive capacities of awake and moving infants. We believe that such methodology opens the pathway for using MEG to provide mechanistic explanations for the complex behavior observed in awake, sentient, and dynamically interacting infants, thus addressing core topics in developmental cognitive neuroscience.