Fluid Convection, Generation and Reinfusion in Haemodiafiltration

Despite widespread use in clinical practice for over 30 years, many questions remain unanswered regarding fluid convection and reinfusion strategies in haemodiafiltration (HDF). Randomised controlled trials have failed to consistently demonstrate improved survival with convective therapies, but a dose-dependent improvement in outcome has been suggested. The ‘minimum’ and ‘ideal’ volumes of convection are undefined. Online generation of ultrapure dialysis fluid has allowed unprecedented convection volumes; however, delivery of fluid directly into the blood circuit requires strict monitoring. The replacement fluid may be reinfused at multiple points in the circuit. Post-dilution HDF is highly efficient in terms of solute clearance but is limited by haemoconcentration. Pre-dilution HDF prolongs filter life but requires significant convection volumes to achieve adequate solute clearance. Mid-dilution HDF utilises a specific dialyser, which is associated with additional cost and escalating transmembrane pressure. Mixed-dilution HDF appears to offer an attractive balance between solute clearance efficiency and haemoconcentration, however these findings need to be confirmed in large studies. The majority of trials comparing fluid reinfusion strategies have enrolled small numbers of patients over brief study periods. It is unclear whether high-quality evidence examining fluid convection and reinfusion will become available and practice may need to rely on observational data

Gastrointestinal and Psychiatric Symptoms Among Children and Adolescents With Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors. Identification of medical comorbidities that contribute to these concerns may elucidate mechanisms through which psychiatric concerns arise, as well as offer additional avenues for intervention. Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population. In this paper, we draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection to characterize the unique contributions of (1) autism symptoms, (2) psychosocial factors (child's age, sex, verbal and nonverbal IQ, adaptive behavior, race, and household income), and (3) GI concerns with respect to multiple psychiatric outcomes. Multiple regression models revealed unique contributions of ASD symptoms and multiple psychosocial factors such as verbal IQ, adaptive behavior, and family income to internalizing, externalizing, and self-injurious behavior. In general, higher levels of psychiatric symptoms were associated with more ASD symptoms, higher verbal IQ, lower adaptive behavior skills, and lower family income. Furthermore, levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD. Taken together, results indicate that the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD, and that treatment of GI conditions may be an important component in alleviating a broad array of mental health concerns in this group

MHCII-mediated dialog between group 2 innate lymphoid cells and CD4+ T cells potentiates type 2 immunity and promotes parasitic helminth expulsion

Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity