Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis

AIM: To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score). METHODS: We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed. RESULTS: We identified 99 patients (53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity (62%), consideration of medication change (10%), assessment of medication efficacy (14%), and cancer screening (14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was moderate-substantial agreement between the two reviewers in assessing rectal Mayo scores (kappa = 0.54, 95%CI: 0.41-0.68). CONCLUSION: Endoscopic disease severity (Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies

A Screening Tool for Assessing Alcohol Use Risk among Medically Vulnerable Youth

Background: In an effort to reduce barriers to screening for alcohol use in pediatric primary care, the National Institute on Alcoholism and Alcohol Abuse (NIAAA) developed a two-question Youth Alcohol Screening Tool derived from population-based survey data. It is unknown whether this screening tool, designed for use with general populations, accurately identifies risk among youth with chronic medical conditions (YCMC). This growing population, which comprises nearly one in four youth in the US, faces a unique constellation of drinking-related risks. Method To validate the NIAAA Youth Alcohol Screening Tool in a population of YCMC, we performed a cross-sectional validation study with a sample of 388 youth ages 9–18 years presenting for routine subspecialty care at a large children’s hospital for type 1 diabetes, persistent asthma, cystic fibrosis, inflammatory bowel disease, or juvenile idiopathic arthritis. Participants self-administered the NIAAA Youth Alcohol Screening Tool and the Diagnostic Interview Schedule for Children as a criterion standard measure of alcohol use disorders (AUD). Receiver operating curve analysis was used to determine cut points for identifying youth at moderate and highest risk for an AUD. Results: Nearly one third of participants (n = 118; 30.4%) reported alcohol use in the past year; 86.4% (106) of past year drinkers did not endorse any AUD criteria, 6.8% (n = 8) of drinkers endorsed a single criterion, and 6.8% of drinkers met criteria for an AUD. Using the NIAAA tool, optimal cut points found to identify youth at moderate and highest risk for an AUD were ≥ 6 and ≥12 drinking days in the past year, respectively. Conclusions: The NIAAA Youth Alcohol Screening Tool is highly efficient for detecting alcohol use and discriminating disordered use among YCMC. This brief screen appears feasible for use in specialty care to ascertain alcohol-related risk that may impact adversely on health status and disease management

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical car

Protein-Losing Enteropathy in the Setting of Severe Iron Deficiency Anemia

A 20-month-old boy presented with a 2-week history of pallor and progressive abdominal distention. Nutritional history revealed long-standing excessive cow milk intake. He was subsequently found to be profoundly iron deficient and hypoproteinemic, with an elevated fecal α-1-antitrypsin level and occult blood positive stool, consistent with protein-losing enteropathy. He was treated with cow milk restriction and oral iron supplements, which resulted in resolution of his edema and laboratory anomalies. While small numbers of previous case reports have described the potential association between excessive cow milk intake and severe iron deficiency and protein-losing enteropathy, this constellation of clinical symptoms is infrequently recognized in clinical practice. As iron deficiency is recognized as the most common nutritional deficiency in the United States, it is important to keep excessive cow milk intake in mind when evaluating young children presenting with severe iron deficiency and protein-losing enteropathy

Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy

<div><p>Background and Aims</p><p>Morbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl^- secretion by blocking both cyclic nucleotide- and Ca²⁺-gated K⁺ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na⁺-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na⁺-coupled glucose uptake.</p><p>Materials and Methods</p><p>Short-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers.</p><p>Results</p><p>Treatment of small intestinal tissue with clotrimazole inhibited the Cl^- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca²⁺-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90).</p><p>Conclusion</p><p>Treatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca²⁺-dependent agonists as expected, but did not affect Na⁺-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.</p></div

Clotrimazole treatment does not inhibit the function of SGLT1.

<p><b>(A)</b> Equivalent changes in Isc following apical administration of 30 mM 3-O-methyl glucose (3-OMG) rule out an inhibitory effect on SGLT1 from 30 μM CLT. (<b>B</b>) Phloridzin (PHL)-mediated SGLT1 blockade decreases Isc changes in response to 3-O-methyl glucose but does not affect Cl^- secretion in response to VIP, with individual data points at t = 5 depicted in (<b>C</b>). (<b>D</b>) ΔIsc elicited by apical administration of 10 mM glucose is partially blocked by PHL treatment. Pooled data from 2 independent experiments in A and single experiments in B-D. Error bars represent SEM. *p<0.05; **p<0.01; NS not significant as assessed by student t-test on the ΔIsc following addition of described stimulus at the indicated time points.</p