Nonpharmacological treatment of rumination syndrome in childhood: A systematic review of the literature

Rumination syndrome (RS) is a complex functional disorder characterized by recurrent, repetitive regurgitation of recently swallowed food. RS may have medical and psychosocial implications, compromising the quality of life and causing high rates of school absenteeism. Pediatric RS has been poorly studied and little evidence regarding its treatment is available. This systematic review aims to evaluate the literature on the nonpharmacological treatment of RS in childhood. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, from 2000 to 2023. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different designs of study, and the risk of bias was evaluated with the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). Five hundred ninety-six studies were screened, and 7 studies were included in the review. Diaphragmatic breathing was the most used nonpharmacological treatment, and it was always combined with other therapeutic strategies. The vast heterogeneity of the physical or mental comorbidities and the methodology adopted in the publications did not allow a comparative analysis of the different treatments. Regardless of the type of treatment, high-intensity therapeutic programs and specific operators' training emerged as the most influencing factors for patients' outcomes. According to the available evidence, there is not enough high-quality evidence to suggest a defined therapeutic strategy. Large observational studies on selected patients accounting for possible confounders, with adequate follow-up times, and with clearly defined treatment regimens are needed to identify the best therapeutic approach

Enteral bleeding in a former preterm girl with short bowel syndrome: Do not miss the diagnosis

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Atomic Force Microscopy Application for the Measurement of Infliximab Concentration in Healthy Donors and Pediatric Patients with Inflammatory Bowel Disease

The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of influximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients (p-value < 0.05), demonstrating the promising use of AFM nanoassay in TDM

A child with green urine after a diagnostic enema: Answers

No abstract availabl

The Risks of Phosphate Enemas in Toddlers: A Life-Threatening Unawareness

Background: While oral laxatives represent the first-line treatment of fecal impaction, enemas are frequently used in clinical practice in pediatric emergency departments (PEDs) and by family pediatricians (FPs). Objectives: Phosphate-containing enemas (PcEs) are commonly employed, even causing the risk of rare but lethal toxicity. We investigated pediatricians' awareness of PcE risks. Methods: We conducted an online survey by sending a multiple-choice questionnaire to the referents of 51 PEDs and 101 FPs. We collected and compared the answers with recommendations reported by the Italian Drug Agency (AIFA) and the available literature about PcE administration. Results: Of the institutions and pediatricians receiving the questionnaire, 23 PEDs (45%) and 63 FP (62.3%) participated in the survey. Of PEDs, 95% and 33.0% of FPs treated fecal impaction with PcE. Moreover, 54% of PEDs and 86.0% of FPs did not provide treatment according to the AIFA recommendations for the daily dose. Conclusions: This study shows limited pediatricians' awareness of the potential risks related to PcE

Impact of the first COVID-19 lockdown on the relationship with parents and peers in a cohort of adolescents with somatic symptom disorder

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group

Expression profiles of the lncRNA antisense GAS5-AS1 in colon biopsies from pediatric inflammatory bowel disease patients and its role in regulating sense transcript GAS5

The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this study aims to detect whether GAS5-AS1 and GAS5 levels are related to IBD clinical parameters and investigate their correlation in vitro. Twenty-six IBD pediatric patients were enrolled; paired inflamed and non-inflamed intestinal biopsies were collected. We evaluated GAS5 and GAS5-AS1 levels by real-time PCR. The role of GAS5 and GAS5-AS1 was assessed in vitro by transient silencing in THP1-derived macrophages. GAS5-AS1 and GAS5 levels were associated with patients' clinical parameters; GAS5-AS1 expression was downregulated in inflamed tissues and inversely correlated with disease activity. A positive correlation between GAS5-AS1 and GAS5 levels was observed in non-inflamed biopsies. On THP1-derived macrophages, a reduced amount of both GAS5-AS1 and GAS5 was observed; accordingly, matrix metalloproteinase (MMP) 9 was increased. After GAS5-AS1 silencing, a downregulation of GAS5 was found, whereas no effect was detected on GAS5-AS1 after GAS5 silencing. Conclusion: This study provided for the first time new insights into the potential role of GAS5-AS1 in IBD. GAS5-AS1 modulates GAS5 levels in vitro and may serve as a potential IBD diagnostic biomarker

PACSIN2 as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells

PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve auto-phagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of in-flammatory bowel disease pediatric patients at diagnosis. PAC-SIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein- protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cyto-toxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy

Diagnostic accuracy and applicability of intestinal auto-antibodies in the wide clinical spectrum of coeliac disease

BACKGROUND: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. METHODS: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. FINDINGS: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n\u202f=\u202f178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n\u202f=\u202f16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n\u202f=\u202f14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). INTERPRETATION: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations

Transcriptomic profiling of white blood cells reveals new insights into the molecular mechanisms of thalidomide in children with inflammatory bowel disease

Thalidomide has emerged as an effective immunomodulator in the treatment of pediatric patients with inflammatory bowel disease (IBD) refractory to standard therapies. Cereblon, a component of E3 protein ligase complex that mediates ubiquitination and proteasomal degradation of target proteins, has been identified as the primary target of thalidomide. Cereblon plays a crucial role in thalidomide teratogenicity, however it is unclear whether it is also involved in the therapeutic effects in IBD patients. This study aimed at identifying the mechanisms underpinning thalidomide action in pediatric IBD. Ten IBD pediatric patients clinically responsive to thalidomide were prospectively enrolled. RNA-sequencing and functional enrichment analysis was carried out on peripheral blood mononuclear cells obtained before and after treatment with thalidomide. RNA-sequencing analysis revealed 378 differentially expressed genes after treatment with thalidomide. The most deregulated pathways were cytosolic calcium ion concentration, cAMP-mediated signaling, eicosanoid signaling and inhibition of matrix metalloproteinases. Neuronal signaling mechanisms such as CREB signaling in neurons and axonal guidance signaling also emerged. Connectivity Map analysis revealed that thalidomide gene expression changes were similar to those induced by MLN4924, an inhibitor of NEDD8 activating enzyme, suggesting that thalidomide exerts its immunomodulatory effects by acting on the ubiquitin-proteasome pathway. In vitro experiments on cell lines confirmed the effect of thalidomide on altered candidate pathways observed in patients. These results represent a unique resource for enhanced understanding of thalidomide mechanism in patients with IBD, providing novel potential targets associated with drug response.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202