Current literature consolidates the view of Crohn's disease (CD) as a form of immunodeficiency highlighting dysregulation of intestinal innate immunity in the pathogenesis of CD. Intestinal ...macrophages derived from blood monocytes play a key role in sustaining the innate immune homeostasis in the intestine, suggesting that the monocyte/macrophage compartment might be an attractive therapeutic target for the management of CD. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that also promotes myeloid cell activation, proliferation, and differentiation. GM-CSF has a protective effect in human CD and mouse models of colitis. However, the role of GM-CSF in immune and inflammatory reactions in the intestine is not well defined. Beneficial effects exerted by GM-CSF during intestinal inflammation could relate to modulation of the mucosal barrier function in the intestine, including epithelial cell proliferation, survival, restitution, and immunomodulatory actions. The aim of this review is to summarize potential mechanistic roles of GM-CSF in intestinal innate immune cell homeostasis and to highlight its central role in maintenance of the intestinal immune barrier in the context of immunodeficiency in CD.
Immunooncology is still a growing area in cancer therapy. Drugs within this therapeutic approach do not directly target/attack the tumor but interfere with immune checkpoints and target or reprogram ...key metabolic pathways critical for anti-cancer immune defense. Indolamine 2,3-dioxygenase 1 (IDO1) and the tryptophan (TRP)-kynurenine pathway were identified as critical mechanisms in cancer immune escape and their inhibition as an approach with promising therapeutic potential. Particularly, a multitude of IDO1 inhibiting tryptophan analogs are widely applied in several clinical trials. However, this therapy results in a variety of implications for the patient's physiology. This is not only due to the inhibition of an enzyme important in almost every organ and tissue in the body but also because of the general nature of the inhibitor as an analog of a proteinogenic amino acid as well as the initiation of cellular detoxification known to affect inflammatory pathways. In this review we provide a deeper insight into the physiological consequences of an IDO1 inhibiting therapy based on TRP related molecules. We discuss potential side and off-target effects that contribute to the interpretation of unexpected positive as well as negative results of ongoing or discontinued clinical studies while we also highlight the potential of these inhibitors independent of the IDO1 signaling pathway.
We aimed to evaluate the long-term clinical and socioeconomic outcome of structured transition care in adolescents with inflammatory bowel disease (IBD).
We compared the clinical long-term course of ...24 patients with and 11 patients without structured transition care within 24 months before and 24 months after transfer from paediatric to adult health care. Socio-economic parameters and quality of life were assessed by IBD Questionnaire (IBDQ-32) and additional items. Treatment costs were calculated for medication, surgery and hospitalisation.
The percentage of transfer group patients with an IBD-related intestinal complication was higher compared to the transition group (64% vs. 21%, p = 0.022). We also found a tendency towards a higher number of IBD-related surgery in the transfer group compared to the transition group (46% vs. 13%, p = 0.077). Transfer group patients received higher mean cumulated doses of radiation compared with the transition group (4.2 ± 5.3 mSv vs. 0.01 ± 0.01 mSv, p = 0.036). Delayed puberty was only noted in the transfer group (27%, p = 0.025). Mean expenditures for surgeries and hospitalisation tended to be lower in the transition group compared to transfer group patients (744 ± 630€ vs. 2,691 ± 4,150€, p = 0.050). Sexual life satisfaction was significantly higher (p = 0.023) and rates of loose bowel movements tended to be lower (p = 0.053) in the transition group.
Structured transition of adolescents with IBD from paediatric into adult health care can lead to important clinical and economic benefits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and ...a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.
Racecadotril is a guideline-recommended option for the treatment of acute diarrhea in children but existing guidelines and previous reviews of the field are based on a small fraction of published ...evidence. Therefore, we have performed a systematic search for randomized controlled trials evaluating racecadotril as add-on or in comparison to other treatments.
A search was performed in PubMed, Scopus and Google Scholar without limits about country of origin or reporting language. A meta-analysis was conducted for the five most frequently used efficacy parameters.
We have retrieved 58 trials, from nine countries including six in comparison to placebo, 15 in comparison to various active treatments and 41 as add-on to various standard treatments (some multi-armed studies allowing more than one comparison). Trials used 45 distinct efficacy parameters, most often time to cure, % of cured children after 3 days of treatment, global efficacy and number of stools on second day of treatment. Racecadotril was superior to comparator treatments in outpatients and hospitalized patients with a high degree of consistency as confirmed by meta-analysis for the five most frequently used outcome parameters. For instance, it reduced time to cure from 106.2 h to 78.2 h (mean reduction 28.0 h; P < 0.0001 in 24 studies reporting on this parameter). Tolerability of racecadotril was comparable to that of placebo (10.4% vs. 10.6% adverse events incidence) or that of active comparator treatments other than loperamide (2.4% in both groups).
Based on a comprehensive review of the existing evidence, we conclude that racecadotril is more efficacious than other treatments except for loperamide and has a tolerability similar to placebo and better than loperamide. These findings support the use of racecadotril in the treatment of acute diarrhea in children.
Objective To determine whether longitudinal measurements of fecal S100A12, a fecal marker of intestinal inflammation, can identify very low birth weight infants at risk for necrotizing enterocolitis ...(NEC). Study design This prospective study included 145 preterm infants with birth weight <1500 g. Meconium and stool samples (n = 843) were collected prospectively on alternate days for 4 weeks, and fecal S100A12 and calprotectin were measured by enzyme-linked immunosorbent assay. Results Eighteen patients (12.4%) developed NEC. Gestational age and birth weight were significantly lower in the patients with NEC compared with unaffected reference infants. Fecal S100A12 levels were significantly higher in patients with severe NEC at onset of disease and also, in contrast to fecal calprotectin, at 4-10 days before onset of NEC compared with unaffected reference infants (ideal cutoff value, 65 μg/kg; sensitivity, 0.76; specificity, 0.56). Conclusions Fecal S100A12 level may be a helpful marker for predicting disease severity and early risk assessment for subsequent development of NEC. However, the use of fecal S100A12 as a predictive biomarker for NEC in very low birth weight infants may be limited due to a high interindividual and intraindividual variability in S100A12 fecal excretion.
CD8
T cells are involved in the pathogenesis of inflammatory bowel disease (IBD), a complex multifactorial chronic disease. Here, we present an overview of the current research with the controversial ...findings of CD8
T cell subsets and discuss some possible perspectives on their therapeutic value in IBD. Studies on the role of CD8
T cells in IBD have contradictory outcomes, which might be related to the heterogeneity of the cells. Recent data suggest that cytotoxic CD8
T cells (Tc1) and interleukin (IL) 17-producing CD8
(Tc17) cells contribute to the pathogenesis of IBD. Moreover, subsets of regulatory CD8
T cells are abundant at sites of inflammation and can exhibit pro-inflammatory features. Some subsets of tissue resident memory CD8
T cells (Trm) might be immunosuppressant, whereas others might be pro-inflammatory. Lastly, exhausted T cells might indicate a positive outcome for patients. The function and plasticity of different subsets of CD8
T cells in health and IBD remain to be further investigated in a challenging field due to the limited availability of mucosal samples and adequate controls.
Along with others, we have reported that neutralization of granulocyte macrophage colony-stimulating factor (GM-CSF) increases intestinal permeability and bacterial translocation, and reduces ...neutrophil bacterial killing and anti-microbial seroreactivity. The objective was to investigate the utility of serum GM-CSF auto-antibody (Ab) as a marker for confirmation of stable remission and prediction of relapses in patients with inflammatory bowel disease (IBD).
We consecutively included 181 adults and children with Crohn's disease (CD, n=61) or ulcerative colitis (UC, n=120). Over a 3-year period, we collected 861 serum samples and 610 stool samples during regular follow-up visits. GM-CSF Abs and fecal S100 proteins were measured by an enzyme-linked immunoassay.
Serum GM-CSF Ab levels correlated with disease activity, location, and extent. Time course analysis before and after relapse showed a clear increase of GM-CSF Ab concentrations up to 6 months before clinical relapse. At 1.7 μg/ml (CD) and 0.5 μg/ml (UC), the sensitivity and specificity of GM-CSF Ab for predicting relapse already 2-6 months earlier were 88% and 95% in CD and 62% and 68% in UC, respectively. A baseline GM-CSF Ab level of >1.7 μg/ml was significantly associated with relapse of CD within 18 months.
As GM-CSF is required for myeloid cell antimicrobial functions and homeostatic responses to tissue injury, serum GM-CSF Ab levels might reflect the degree of bowel permeability and bacterial translocation. Therefore, GM-CSF Ab might identify IBD patients at risk of disease relapse at an early stage, which makes the test a potential tool for monitoring disease activity and optimizing therapy.
The number of children and adolescents with inflammatory bowel disease (IBD) is increasing. Many chronically ill children and adolescents have low health literacy. Patient empowerment (PE) enables ...positive changes and control over one's disease through specific activities, information, and counseling. The CEDNA (IBD Needs Assessment) Survey aimed to provide the necessary data to improve PE in pediatric IBD (PIBD).
Questionnaires were distributed to adolescent IBD patients and parents of children and adolescents with IBD throughout Germany. The answers were given anonymously. Based on the available data, a subgroup analysis was conducted in relation to the age of the patients and the period since diagnosis. For the parents' responses, the same age groups were analyzed for comparison with the patients' responses.
From October 2021 to April 2022, 2810 questionnaires were distributed and 1158 questionnaires were completed (
= 708 parents 61.1%,
= 450 patients 38.9%). The results indicate that health literacy in children with IBD is low. Significant gaps in knowledge of important IBD topics were identified, and a comparison of responses regarding preferred methods and timing of obtaining information revealed differences between patient and parent preferences. The greatest need for knowledge on IBD topics was found in the group of 16-17-year-old patients on transition (
= 214, 31.8%) and in the group of patients diagnosed 1-2 years ago on the causes of IBD (
= 288, 17.4%). The willingness to seek advice was unexpectedly low.
The analysis of all findings according to the patient's age structure and duration since diagnosis can be used to enable age-appropriate communication at certain stages of the disease. This tailored information should increase patients' health literacy, improve their management of the disease, and reduce the burden on their families.
The incidence/prevalence of pediatric inflammatory bowel disease (IBD) is increasing. IBD places a significant burden on young patients during important developmental stages and affects their ...families. Children and adolescents with IBD require increased support from health care services. However, little is known about the additional support needed and how to provide it. Therefore, a large survey was conducted with a focus on patient empowerment.
For the anonymous survey, called CEDNA, a patient questionnaire for adolescents with IBD and a questionnaire for parents of children and adolescents with IBD were made available throughout Germany (distributed n = 2810). Questions covered various aspects of coping with the disease, utilization of care, use and need of information and communication services, and how information should be provided.
From October 2021 to April 2022, 1158 (n = 708 parents (61.1%), n = 450 patients (38.9%)) questionnaires were completed. The results show a deficit in pediatric IBD care and revealed a large gap in knowledge about core IBD topics (e.g., 74.8% of patients feel poorly informed about transition, 62.4% know little about patient organizations and self-help groups, and 54.7% have little information about preventive health measures), indicating a low level of health literacy among affected children and adolescents.
Pediatric IBD poses significant challenges for patients, their families, and healthcare teams. By empowering patients and families, and providing targeted information and communication tailored to the age of the child or adolescent and the needs of the parents, care can be improved and better adapted to the needs of patients. Actions would include providing quality information online through scientific societies and patient organizations and facilitating self-management in adolescents.
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