Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

Prevalence of elevated liver enzymes and comorbidities in children and adolescents with overweight and obesity.

AIM: We investigated the prevalence of elevated liver aminotransferases (ALT) and additional comorbidities in a large cohort of Israeli children and adolescents with overweight and obesity. METHODS: This study included data from medical records of 2- to 18-year-old children and adolescents, with body mass index (BMI) in the overweight or obesity range (WHO definitions), for whom ALT testing was performed. RESULTS: Overweight was present in 50 418 (10.7%) and obesity in 70 515 (15.0%). Elevated ALT, above 30 IU/L (0.51 µkat/L), was reported in 2245 (7.2%) of children with overweight and 5475 (16.8%) of children with obesity (P < .0001). Compared to children with overweight and obesity and ALT within normal range, children with elevated ALT were older (11.9 ± 4.2 vs 10.9 ± 4.2, P < .001), mostly male (68.0% vs 49.4%, P < .001) and had higher BMI (27.3 ± 6.1vs 24.0 ± 4.8, P < .001). They also had a more unfavourable cardiometabolic profile with significantly higher either systolic or diastolic blood pressure, total cholesterol and triglycerides, and had more than three criteria defining metabolic syndrome. CONCLUSION: In this large cohort, abnormally elevated ALT was present in a high number of individuals with overweight or obesity. The children and adolescents with abnormal ALT had higher BMI, were older, male and had more cardiometabolic risk factors.

Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment for Respiratory Exacerbation.

OBJECTIVES: In all patients with cystic fibrosis (CF), gastrointestinal (GI) tract CF transmembrane conductance regulator dysfunction occurs early in life. The identical pathophysiological triad of obstruction, infection, and inflammation causes disease of the airways and in the intestinal tract (CF enteropathy). Mucus accumulation within GI tract is a niche for abnormal microbial colonization, leading to dysbiosis. Fecal calprotectin (FC) is a neutrophil cytosolic protein released during apoptosis and necrosis and reflects inflammatory status. Systemic antibiotic treatment for pulmonary exacerbations has been shown to improve systemic inflammatory markers and serum and sputum calprotectin. Antibiotic treatment aimed at pulmonary complaints may improve GI tract inflammatory status. We hypothesized that high levels of FC present during pulmonary exacerbation are due, in part, to multiorgan dysbiosis and thus should diminish with systemic antibiotic treatment. METHODS: This prospective pilot study enrolled 14 patients with CF, with no current GI symptoms. FC levels and lung function were measured at the beginning and end of systemic antibiotic treatment. RESULTS: Compared to preantibiotic treatment baseline values, end of treatment FC levels declined significantly after antibiotic treatment, P = 0.004 and similarly, there was significant improvement in forced expiratory volume in 1 second, P = 0.002. CONCLUSIONS: High levels of FC during respiratory exacerbation may reflect a systemic exacerbation rather than solely pulmonary. Antibiotic treatment lowered the FC levels possibly by its impact on the intestinal microbiome.

The role of infant nutrition in the prevention of future disease.

There is growing evidence that nutrition is part of the environmental factors affecting the incidence of various diseases. The effect starts in the prenatal life and affects fetal growth and continues in early life and throughout childhood. The effect has been shown on various disease states such as allergic diseases, hyperlipidemia and cardiovascular diseases, obesity, type II diabetes and metabolic syndrome, and immunologic diseases such as celiac disease and type 1 diabetes mellitus. It seems that the recommendations of exclusive breastfeeding until the age of 4 months and subsequently exposure to various solid foods has beneficial effect in terms of allergic, immunologic, and cardiovascular diseases prevention. Will these recommendations change the natural course of these diseases is unknown yet, but there is accumulating evidence that indeed this is the case. In this review, we review the evidence of early nutritional intervention and future disease prevention.

Zn/Ga-DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma.

BACKGROUND: Redox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma. OBJECTIVE: To examine the anti-inflammatory properties of a newly developed specific iron-chelating complex, Zn/Ga-DFO, in a mouse model of asthma. MATERIALS AND METHODS: Asthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga-DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga-DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted. RESULTS: The amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections. CONCLUSION: In this mouse model of allergic asthma, Zn/Ga-DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga-DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga-DFO.

Effect of dexamethasone on germ cell apoptosis in the contralateral testis after testicular ischemia-reperfusion injury in the rat.

OBJECTIVE: To evaluate the effect of dexamethasone on spermatogenesis and germ cell apoptosis in the ipsilateral and contralateral testis after testicular ischemia-reperfusion (IR) in rats. DESIGN: Laboratory study. SETTING: Medical research laboratory in a university setting. ANIMAL(S): Forty adult Sprague-Dawley rats weighing 250-280 g. INTERVENTION(S): Testicular IR, treatment with dexamethasone (10 mg per kilogram of body weight). MAIN OUTCOME MEASURE(S): Testicular germ cell apoptosis was assessed by deoxyuridine nick-end labeling immunohistochemical assay. RESULT(S): Testicular ischemia in rats led to histological damage in the ipsilateral testis. In the contralateral testis, minimal damage was observed. Germ cell apoptosis in both the ischemic and the contralateral testis increased significantly after IR. Treatment with dexamethasone did not change germ cell apoptosis in ischemic testis but decreased germ cell apoptosis in the contralateral testis. CONCLUSION(S): Glucocorticoids may be beneficial for spermatogenesis after testicular IR by decreasing germ cell apoptosis in the contralateral testis.