IMPORTANCE Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children.OBJECTIVE To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. DESIGN, SETTING, AND PATIENTS Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. INTERVENTIONS Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. MAIN OUTCOMES AND MEASURES Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by Ն25% or Ն75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. RESULTS Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI,]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event.CONCLUSIONS AND RELEVANCE In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment.

In newly diagnosed CD, some variability of histological lesions can be found, even within the same duodenal biopsy, in which areas of apparently normal mucosa with increased IEL number often exist. We also confirm our previous findings that duodenal lesions may vary among different biopsies; lesion severity has a proximal-to-distal gradient, but no patient has entirely normal duodenal biopsies. The awareness of such histological variability may help establish a correct diagnosis of CD.

This cross-sectional survey aimed to evaluate the prevalence of burnout and estimated psychiatric disorders among haematooncology healthcare professionals in Italy. The aspects of work that respondents perceive as stressful and satisfying have also been examined. The assessments were made using the Maslach Burnout Inventory (MBI), General Health Questionnaire and a studyspecific questionnaire. Logistic regression models were applied to show associations between different sources of work-related stress and burnout. Three hundred and eighty-seven out of 440 (87.95%) returned their questionnaires. The scores on MBI subscales indicate a high level of emotional exhaustion in 32.2% of the physicians and 31.9% of the nurses; a high level of Depersonalisation in 29.8 and 23.6%, respectively; and a low level of personal accomplishment in 12.4 and 15.3% respectively. The estimated prevalence of psychiatric disorders was 36.4% in physicians and 28.8% in nurses. Statistical analysis confirmed age, sex, personal dissatisfaction, physical tiredness and working with demanding patients to be associated with burnout. In conclusion, haemato-oncology healthcare professionals report a level of burnout and estimated psychiatric morbidity comparable to other oncological areas. Knowledge of the mechanisms of burnout and preventing and dealing with them is therefore a fundamental requirement for the improvement of quality in health services and job satisfaction.

Cow's milk protein-induced proctocolitis presents with overt rectal bleeding in otherwise healthy infants and is characterized by an eosinophilic infiltrate of the left colonic mucosa. Although it is the most common cause of proctocolitis in infancy, dietary protein-induced proctocolitis had hardly ever been reported in childhood so far. We hereby report 16 otherwise healthy children aged 2-14 yr, who presented over a 6-yr period with persistent or recurrent rectal bleeding related to a mild form of left-sided colitis characterized by a prominent eosinophilic infiltration, focal lymphoid follicle hyperplasia, and a prompt clinical and histological response to a cow's milk-free diet. No patient had a history of food-induced proctocolitis during infancy, and most patients did not show an IgE-mediated response to cow's milk protein. Half of the patients did have other gastrointestinal symptoms, but no systemic symptoms were present and other causes of colitis were excluded by appropriate investigation. Tolerance to cow's milk protein developed in half of the patients within a year. Dietary protein-induced proctocolitis is a relatively common cause of overt rectal bleeding in childhood, and its features are remarkably similar to those of dietary protein-induced proctocolitis of infancy.

SUMMARY BackgroundThere is recent evidence that mast cells may play important roles in the gut, especially concerning visceral hypersensitivity and motor activity. However, most data are only available for clinical conditions characterised by diarrhoea, where MC have chiefly investigated in the mucosal layer of the colon and there is almost no information concerning constipation.