The impact of Narcotrend™ EEG-guided propofol administration on the speed of recovery from pediatric procedural sedation—A randomized controlled trial

Background: Propofol is often used for procedural sedation in children undergoing gastrointestinal endoscopy. Reliable assessment of the depth of hypnosis during the endoscopic procedure is challenging. Processed electroencephalography using the Narcotrend Index can help titrating propofol to a predefined sedation level. Aims: The aim of this trial was to investigate the impact of Narcotrend Index-guided titration of propofol delivery on the speed of recovery. Methods: Children, aged 12-17 years, undergoing gastrointestinal endoscopy under procedural sedation, had propofol delivered via target controlled infusion either based on Narcotrend Index guidance (group NI) or standard clinical parameters (group C). Sedation was augmented with remifentanil in both study groups. The primary endpoint of this study was to compare the speed of fulfilling discharge criteria from the operating room between study groups. Major secondary endpoints were propofol consumption, discharge readiness from the recovery room, hypnotic depth as measured by the Narcotrend Index, and adverse events. Results: Of the 40 children included, data were obtainable from 37. The time until discharge readiness from the operating room was shorter in group NI than in group C, with a difference between medians of 4.76 minutes [95%CI 2.6 to 7.4 minutes]. The same accounts for recovery room discharge times; difference between medians 4.03 minutes [95%CI 0.81 to 7.61 minutes]. Propofol consumption and the percentage of EEG traces indicating oversedation were higher in group C than in group NI. There were no significant adverse events in either study group. Conclusion: Narcotrend Index guidance of propofol delivery for deep sedation in children aged 12-17 years, underdoing gastrointestinal endoscopy results in faster recovery, less drug consumption, and fewer episodes of oversedation than dosing propofol according to clinical surrogate parameters of depth of hypnosis. The results of this study provide additional evidence in favor of the safety profile of propofol/remifentanil for procedural sedation in adequately selected pediatric patients

Value of an outpatient transition clinic for young people with inflammatory bowel disease: A mixed-methods evaluation

Objective: Developing and evaluating effective transition interventions for young people (16-25 years) with inflammatory bowel disease (IBD) is a high priority. While transition clinics (TCs) have been recommended, little is known about their operating structures and outcomes. This study aimed to gain insight into the value of a TC compared with direct handover care. Design: Controlled mixed-methods evaluation of process outcomes, clinical outcomes and patient-reported outcomes. Setting: Two outpatient IBD clinics in the Netherlands. Participants: Data collection included: semistructured interviews with professionals (n=8), observations during consultations with young people (5×4 hours), medical chart reviews of patients transferred 2 to 4 years prior to data collection (n=56 in TC group; n=54 in control group) and patient questionnaires (n=14 in TC group; n=19 in control group). Outcomes: Data were collected on service structures and daily routines of the TC, experienced barriers, facilitators and benefits, healthcare use, clinical outcomes, self-management outcomes and experiences and satisfaction of young people with IBD. Results: At the TC, multidisciplinary team meetings and alignment of care between paediatric and adult care providers were standard practice. Non-medical topics received more attention during consultations with young people at the TC. Barriers experienced by professionals were time restrictions, planning difficulties, limited involvement of adult care providers and insufficient financial coverag

Development and Function of Immune Cells in an Adolescent Patient with a Deficiency in the Interleukin-10 Receptor

OBJECTIVE:: Monogenic defects in the interleukin-10 (IL-10) pathway are extremely rare and cause infantile-onset inflammatory bowel disease (IBD)-like pathology. Understanding how immune responses are dysregulated in monogenic IBD-like diseases can provide valuable insight in “classical” IBD pathogenesis. Here, we studied long-term immune cell development and function in an adolescent IL-10 receptor (IL10RA)-deficient patient who presented in infancy with severe colitis and fistulizing perianal disease and is currently treated with immune suppressants. METHODS:: Biomaterial was collected from the IL10RA-deficient patient, pediatric IBD patients and healthy controls. The frequency and phenotype of immune cells were determined in peripheral blood and intestinal biopsies by flow cytometry and immunohistochemistry. Functional changes in monocyte-derived dendritic cells and T cells were assessed by in vitro activation assays. RESULTS:: The IL10RA-deficient immune system developed normally with respect to numbers and phenotype of circulating immune cells. Despite normal co-stimulatory molecule expression, bacterial lipopolysaccharide-stimulated monocyte-derived dendritic cells from the IL10RA-deficient patient released increased amounts of TNFα compared to healthy controls. Upon T-cell receptor ligation, IL10RA-deficient peripheral blood mononuclear cells released increased amounts of T cell cytokines IFNγ and IL-17 agreeing with high numbers of T-bet and IL-17 cells in intestinal biopsies taken at disease onset. In vitro, the immunosuppressive drug thalidomide used to treat the patient decreased peripheral blood mononuclear cell-derived TNFα production. CONCLUSIONS:: With time and during immunosuppressive treatment the IL10RA- deficient immune system develops relatively normally. Upon activation, IL-10 is crucial for controlling excessive inflammatory cytokine release by dendritic cells and preventing IFNγ and IL-17-mediated T-cell responses

First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: An open-label multicentre randomised controlled trial

Objective: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. Design: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. Results: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was no

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction b