Moderate-to-severe Endoscopic Inflammation is Frequent After Clinical Remission in Pediatric Ulcerative Colitis.

OBJECTIVES: Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate-to-severe endoscopic activity is a risk factor for relapse while prospective evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if significant inflammation is common after clinical remission and could explain the high relapse rate in pediatric UC. METHODS: Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores <10, were prospectively assessed for mucosal healing by endoscopy 3 to 5 months after remission was documented. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Symptomatic patients before sigmoidoscopy were excluded. Sustained remission was assessed retrospectively at 18 months follow-up. RESULTS: Forty-two children were screened, 28 children in continuous clinical remission at time of sigmoidoscopy were included. Mayo 0 was present in 12/28 (42.86%), Mayo 1 in 2/28 (7.1%) and Mayo 2 to 3 in 14/28 (50.0%) endoscopies. Among 23 patients with follow-up through 18 months, remission was sustained in 6/12 (50.0%) with Mayo score 0 to 1 versus 2/11 (18.18%) of patients with Mayo 2 and 3. CONCLUSIONS: Over 50% of children assessed for mucosal healing 3 to 5 months after clinical remission is obtained, have endoscopic disease, primarily moderate-to-severe Mayo 2 to 3 inflammation, which was associated with lower sustained remission.

Vitamin A levels are comparable between children with newly diagnosed coeliac disease and non-coeliac controls.

AIM: Nutritional deficiencies associated with coeliac disease include iron, folic acid and fat-soluble vitamins. This study compared the prevalence and degree of vitamin A deficiency among newly diagnosed coeliac disease patients to controls in a developed country. METHODS: This prospective cohort study included all children evaluated by gastroscopy at Dana-Dwek Children's Hospital, Israel, between September 2014 and February 2017. Vitamin A, haemoglobin, C-reactive protein (CRP), ferritin, tissue transglutaminase, immunoglobulin A and vitamin D levels were measured. RESULTS: Of the 113 children (69% females), 47 were diagnosed with coeliac disease whereas the others were the controls (mean age of 8.2 ± 3.8 years and 12.4 ± 3.5 years, respectively). There was no group difference in vitamin A, vitamin D or CRP levels. Among coeliac children, two had true vitamin A deficiency compared with three controls, while 18 coeliac children had subclinical vitamin A deficiency compared with 25 controls (p > 0.05). CONCLUSION: Paediatric coeliac disease was not associated with increased prevalence of vitamin A deficiency. Children evaluated for gastrointestinal complaints in a developed country were found to have an unexpectedly high prevalence of subclinical vitamin A deficiency. Further prevalence and causality assessments of vitamin A deficiency in developed countries are needed.

Gluten-free diet may improve obstructive sleep apnea-related symptoms in children with celiac disease.

BACKGROUND: Enlarged tonsils and adenoids are the major etiology of obstructive sleep apnea (OSA) in children. Lymphatic hyperplasia is common to both OSA and celiac disease. We aimed to investigate the effect of a gluten-free diet on OSA symptoms in children with celiac disease. METHODS: Children with celiac disease aged 2-18 years were prospectively recruited before the initiation of a gluten-free diet. Children with negative celiac serology who underwent gastrointestinal endoscopies for other indications served as controls. All participants completed a validated OSA-related symptoms questionnaire and the pediatric sleep questionnaire (PSQ) at baseline and 6 months later. RESULTS: Thirty-four children with celiac disease (mean age 6.6 ± 3.5 years) and 24 controls (mean age 7.3 ± 4.6 years, P = 0.5) were recruited. There were no significant differences in gender, body mass index or season at recruitment between the two groups. The rate of positive PSQ scores was higher (more OSA-related symptoms) in the control group compared to the celiac group, both at recruitment and at the 6-month follow-up (33.3% vs. 11.8%, P = 0.046, and 16.7% vs. 0, P = 0.014, respectively). PSQ scores improved significantly in both groups at the 6-month follow-up (P < 0.001 for both). Improvement was significantly higher in the celiac group compared to controls (0.1 ± 0.09 vs.0.06 ± 0.06, respectively, P = 0.04). CONCLUSIONS: Children with celiac disease had fewer OSA-related symptoms than controls, but the degree of improvement following the initiation of a gluten-free diet was significantly higher. These findings suggest that a gluten-free diet may improve OSA-related symptoms in children with celiac disease.

[Anxiety dyspnea].

BACKGROUND: Patients complaining about chronic dyspnea, in whom the dyspnea remains unexplained following a thorough diagnostic evaluation, will be defined as having unexplained psychogenic or anxiety dyspnea. AIM: To evaluate the clinical picture of patients with anxiety dyspnea, to evaluate their state of anxiety and whether their dyspnea is related to higher than normal perception of dyspnea. PATIENTS AND METHODS: Forty-six patients with continuous complaints of dyspnea, with no obvious cause of dyspnea, were recruited for the study. The perception of dyspnea (POD) and their anxiety state (using the HADS questionnaire) were evaluated. RESULTS: Dyspnea that is not related to effort (100% of the patients), difficulties in filling the lung (93%), the need for occasional sigh breathing (93%), and the need for occasional yawns in order to fill the lung (83%) were the most characteristic symptoms. Thirty-two patients (70%) were positive for anxiety states and surprisingly had lower than normal POD. CONCLUSIONS: Our study suggests that patients with anxiety dyspnea have characteristic clinical presentation: dyspnea that is not related to effort, difficulties in filling the lung, and need for occasional sighs and/or yawns in order to be able to fill the lung. If baseline evaluation is negative for an organic cause of dyspnea, the diagnosis of anxiety dyspnea can be established with no further costly diagnostic procedures.

Chronic valproic acid intoxication.

Valproic acid intoxication may be associated with cerebral, cardiovascular, respiratory, gastrointestinal, and hematologic complications. We report a case of a 7-year-old girl, epilepsy-treated chronically with valproic acid, sulthiame, and clonazepam, who presented to the emergency room because of a global deterioration during the preceding 2 months, including poorer feeding and worsened general responsiveness. The girl was later diagnosed to have chronic valproic acid intoxication.

[Chronic obstructive pulmonary disorder (COPD) patients with the syndrome of combined pulmonary fibrosis and emphysema, compared to patients with emphysema alone].

BACKGROUND: In recent years the syndrome of combined puLmonary fibrosis and emphysema (CPFE) was recognized as a unique disorder. The diagnosis of CPFE is based on the pulmonary findings of High ResoLution Computed Tomography (HRCT) of the Lung. Patients with this entity have reLativeLy preserved lung volumes and spirometry but marked reductions in diffusing capacity on pulmonary function testing. OBJECTIVES: Since dyspnea is the main symptom that limits daily activities in patients with COPD, we wanted to compare the clinical features, exercise tolerance, quality of life and dyspnea of patient with CPFE to patients with emphysema alone. METHODS: A total of 14 patients with CPFE were compared to 16 patients with COPD and emphysema alone. All patients had HRCT, spirometery, body ptethysmography, CO diffusion capacity, 6 minute walk test, inspiratory muscle strength, measurements of the perception of dyspnea at rest and following effort, and they completed a questionnaire on quality of Life aspects. RESULTS: Patients with CPFE were a littLe younger, had a similar smoking history, had milder airway obstruction, smaller RV and FRC, and more severe reductions in diffusing capacity. They had more dyspnea at rest and following effort, and their exercise tolerance and quality of life were significantly reduced compared to patients with emphysema alone. CONCLUSIONS: The group of patients with combined pulmonary fibrosis and emphysema (CPFE), based on the HRCT, is characterized by relatively preserved lung volumes and spirometry but marked reductions in diffusing capacity, exercise tolerance, quality of life and higher perception of dyspnea, compared to patients with emphysema alone.

Dual biologic therapy with Vedolizumab and Ustekinumab for refractory Crohn's disease in children.

There is a paucity of treatment options for patients who have failed multiple biologics. A drawback of biologic therapies is their selectivity in targeting a single pathway. We report the use of dual biologic therapy with vedolizumab and ustekinumab for three highly refractory patients who previously failed both of these medications as monotherapy. The dual biologic therapy led to the closure of a recto-vaginal fistula and restoration of continuity after takedown of a stoma.

A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study.

BACKGROUND: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. METHODS: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8-19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. RESULTS: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30-40) at baseline to 12.5 (5-30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0-1880.0) µg/g at baseline to 592.0 (140.7-1555.0) µg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. CONCLUSION: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn's disease.

BACKGROUND: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. AIM: To develop predictive models for early relapse following first remission. METHODS: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. RESULTS: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. CONCLUSIONS: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.