Real Foods in Short Gut Kids

Posted on September 9, 2016 by gutsandgrowth

Reference from Kipp Ellsworth:

Transition to a Tube Feeding Formula With Real Food Ingredients in Pediatric Patients With Intestinal Failure K Samela et al. NCP: Published online before print August 4, 2016, doi:10.1177/0884533616661011

Abstract: Due to concerns related primarily to allergic response and malabsorption, enteral nutrition therapy has traditionally relied on the use of elemental formulas in children with intestinal failure (IF). Blended food diets via a gastrostomy tube have been reported to improve feeding tolerance in pediatric populations receiving long-term enteral nutrition therapy. Complex macronutrients have been shown to stimulate intestinal adaptation in animal models. We report on our experience in children with IF who had an overall improvement in stool output when transitioned from an elemental formula to a tube feeding formula with real food ingredients (TFRF). Data were collected in a retrospective chart review of children with IF, >1 year of age, who were receiving enteral nutrition via continuous infusion, bolus feeding, or both. Indications for the TFRF trial were diarrhea or inconsistent stooling patterns. Ten children with a mean small bowel length of 48.3 cm were trialed on TFRF. Nine of 10 (90%) children tolerated the transition to 100% TFRF, of which 7 of 9 (78%) had their entire colon in continuity. The average age at successful transition was 29.2 months, and the average length of time to transition to 100% TFRF was 67.3 days. TFRF is well tolerated in children >1 year of age with IF; it also improves their stooling patterns. A commercially available TFRF is a cost-effective and nutritionally adequate means of providing nutrition to this patient population.

If I ever see an infant with Congenital Sodium Diarrhea

Posted on September 8, 2016 by gutsandgrowth

If I ever see an infant with Congenital Sodium Diarrhea (CSD), I will revisit: AR Janecke et al JPGN 2016; 63: 170-6.

A couple of pointers from this article:

CSD represents a group of clinical conditions with high fecal sodium losses at birth Three mutations: SPINT2, GUCY2C, and SLC9A3 account for the majority of cases.
IBD occurs in some of these children.
GUCY2C causes a secondary loss of sodium-proton antiporter 3 function related to mutations in the receptor for guanylate cyclase C (GC-C). (I find this particularly interesting due to work in my fellowship with guanylin which binds to GC-C.)
SPINT2 is associated with a syndromic CSD which may include choanal/intestinal atresias, cleft palate, hypertelorism, and polydactaly. Unlike classical CSD (due to SLC9A3), this form of CSD is characterized by associated villous atropy and some characteristic tufts.
Table 1 lists other causes on the differential diagnosis including microvillus inclusion disease and epthelial dysplasia (tufting enteropathy)

Hepatocellular Carcinoma Still Occurs in Patients who Clear HBsAg

Posted on September 7, 2016 by gutsandgrowth

Briefly noted:

Editorial: MH Nathanson, N Terrault Hepatology 2016; 64: 328-29. This very unusual editorial explains a published erratum of 2010 paper reversing a claim that patients with Hepatitis B who had achieved HBsAg clearance had markedly decreased rates of hepatocellular carcinoma (37 cases per 100,000 person-years). After correction of the arithmetic error, the rate of HCC in this population was actually 442 cases per 100,000 person-years. The editorial does reiterate that studies have shown lower HCC among those with low HBV DNA which is a prerequisite for HBsAg clearance. Exact risk is difficult in this population due to infrequent development of HBsAg loss and infrequent development of HCC. The message: While loss of HBsAg may lower HCC risk, there remains a need for HCC surveillance.

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Wild Goose Island, Glacier Natl Park

Competition and Costs in HCV Market

Posted on September 6, 2016 by gutsandgrowth

Following FDA approval of Zepatier (Elbasvir/Grazopresvir) (related blog post:In brief: Pediatric HCV trial, Exercise for NAFLD, and … – gutsandgrowth), it is gratifying to see reductions in the cost of HCV treatment. Merck has priced Zepatier at $54,600 for a 12-week course which is substantially lower than Sovaldi ($84.000), Harvoni ($94.500), and Viekira Pak ($83,000).

Zepatier is indicated for genotypes 1 and 4 and can be used in patients with severe renal impairment, including dialysis. It is likely that this will pressure rival drug companies to lower their prices as well.

More information: Will Zepatier Shake Up the HCV Market? This link is to an issue of “Specialty Pharmacy Continuum” but interestingly this same story (?verbatim) was published months later by “Gastroenterology and Endoscopy New” (August 2016) without acknowledging the previous publication (by same author).

Grinnell Glacier Trail, Glacier Nat’l Park

Safety of Fluticasone for Eosinophilic Esophagitis (Abstract)

Posted on September 5, 2016 by gutsandgrowth

Doerthe A Andreae et al. The American Journal of Gastroenterology 111, 1187-1197 (August 2016) | doi:10.1038/ajg.2016.238

METHODS:

In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2–4 years: 44, 5–11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4–12 months, 13–24 months, and >24 months. Growth and adverse effects were monitored.

RESULTS:

We enrolled 54 patients, 80% male, median age 6.5 years (range 2–17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4–12 months: 1.75, 13–24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4–12 months: 50, 13–24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4–12 months: 0.17, 13–24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4–12 months: 0.11, 13–24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves.

CONCLUSIONS:

We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

My take: This post, from an abstract, shows a single-center’s experience with fluticasone. This study provides some reassurance regarding safety & efficacy when used as a maintenance medication. However, as noted in links below, higher doses of fluticasone have been associated with adrenal insufficiency.

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Bioequivalence of Biosimilars

Posted on September 3, 2016 by gutsandgrowth

From Annals of Internal Medicine: Bioequivalence of Biosimilar TNF-α Inhibitors

Ann Intern Med. Published online 2 August 2016 doi:10.7326/M16-0428

Abstract:

Background: Biosimilars are of growing clinical, regulatory, and commercial importance.

Purpose: To summarize evidence about the bioequivalence between biosimilar and reference tumor necrosis factor-α (TNF-α) inhibitors.

Data Sources: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS from inception through 13 April 2016 and ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, U.S. Food and Drug Administration, and European Medicines Agency from inception through 30 April 2016.

Study Selection: Published English-language studies of any size or design that compared the pharmacokinetics, clinical efficacy, adverse events, or immunogenicity of a biosimilar TNF-α inhibitor with a reference biologic in humans.

Data Extraction: Two reviewers independently screened titles and abstracts, extracted data from selected studies, and assessed study quality.

Data Synthesis: Of 19 eligible studies, 8 were phase 1 randomized trials, 5 were phase 3 randomized trials, and 6 were observational studies. Most phase 1 trials (n = 7) involved healthy volunteers, phase 3 trials involved patients with rheumatoid arthritis, and observational studies involved those with rheumatoid arthritis or inflammatory bowel disease. All phase 1 trials showed that pharmacokinetic parameters of the biosimilar and respective biologic were within the prespecified equivalence margin of 80% to 125%. Phase 3 trials suggested similar clinical responses and adverse events. Adverse events were usually of mild to moderate severity. Two cross-sectional observational studies showed cross-reactivity between products, whereas 4 cohort studies of patients switched from reference to biosimilar products suggested similar efficacy and safety outcomes.

Limitation: Possible publication bias, small sample sizes of many studies, and lack of published studies for several biosimilars.

Conclusion: Preliminary evidence supports the biosimilarity and interchangeability of biosimilar and reference TNF-α inhibitors.

Does Reflux Lead to Increased Aspiration Pneumonia?

Posted on September 3, 2016 by gutsandgrowth

This post’s title question turns out to be quite tricky. According to a recent study (RL Rosen et al. JPGN 2016; 63: 210-17), reflux burden, even in children that aspirate did not correlate with increased hospitalization.

Here are the details:

Methods: Prospectively recruited cohort of 116 children who had both pH-impedance testing along with modified barium swallow. The authors considered pathologic reflux to have at least 73 episodes on pH-impedance or if pH<4 for >6% of study period.

Key findings:

There was no statistical correlation between pH-impedance study results and total number of admissions even with or without adjusting for aspiration status (and neurologic complications).

When the authors tried to reconcile these findings, they offered three competing potential explanations for these results:

Reflux has little impact on hospitalziations
Our methods for measuring reflux are not good
Even “normal” reflux can be a problem for those prone to complications; therefore, reflux burden is not consequential.

What is clear is that pH-impedance studies cannot predict which patients are at risk for increased complications. This is supported by data showing that ‘reflux-related’ hospitalizations may not improve after fundoplication (Pediatrics 2006; 118: 2326-33; J Pediatr Surg 2008; 43: 59-63). One particularly important limitation was that the cause of hospitalizations was determined by medical record review.

My take: A simple algorithm for preventing aspiration pneumonia does not exist. Even the role of reflux testing is uncertain.

Prevalence of Diabetes with Pediatric NAFLD

Posted on September 2, 2016 by gutsandgrowth

Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease (JAMA Pediatr. Published online August 01, 2016. doi:10.1001/jamapediatrics.2016.1971)

According to a a multicenter, cross-sectional study at 12 pediatric clinical centers across the United States participating in the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network and with 675 participants (mean age 12.6 yrs):

Is a Gluten-Free Diet a Healthy Diet for Those without Celiac Disease?

Posted on September 1, 2016 by gutsandgrowth

A helpful commentary (NR Reilly. J Pediatr 2016; 175: 206-10) on the gluten-free diet (GFD) tries to separate fact from fiction. A few key points:

There are some health problems that can occur with a GFD, particularly when the diet is started without the support of an experienced dietician. GFD foods frequently contain a greater density of fat and sugar and can contribute to obesity and metabolic syndrome. A GFD may lead to nutrient deficiencies in B vitamins, folate, and iron. GFD without sufficient dietary diversity may contain increase in toxin exposures (eg. arsenic, and mercury).
Gluten is not toxic. “There are no data to support the theory of an intrinsically toxic property of gluten for otherwise-healthy and asymptomatic adults and children, and certain studies have specifically demonstrated a lack of toxic effects.“
Most individuals with NonCeliac Gluten Sensitivity (NCGS) do not have NCGS! First of all, many receive a GFD without proper testing to exclude celiac disease. Secondly, most will tolerate gluten reintroduction. In an Italian study, “only 6.6% of consecutive patients with presumed gluten sensitivity…actually had NCGS. 86% did not experience symptoms when gluten was reintroduced.”
Timing of gluten introduction: “The most current understanding…in at-risk infants is that neither delaying gluten introduction from the recommended 6 months of age to 1 year, nor introducing at 4 months of age alters long-term CD risk estimates.”

My take: This is an excellent commentary. While many people (without celiac disease) perceive benefit from a GFD, only a minority are likely to derive better health or improved quality of life. Those who stick with a GFD should seek the help of a well-qualified dietician.

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How helpful are serologies in pediatric inflammatory bowel disease?

Posted on August 31, 2016 by gutsandgrowth

For quite some time, I have been unimpressed with the utility of serologies in distinguishing Crohn’s disease and Ulcerative Colitis. While some of these tests claim some usefulness, when one excludes the obvious cases of Crohn’s disease (eg. perianal disease, fistulizing disease, small bowel disease), these claims seem quite dubious Another study backs up my interpretation: L Birimberg-Schwartz et al. Inflamm Bowel Dis 2016; 22: 1908-14

This longitudinal report from the IBD Porto Group examined a multicenter retrospective cohort of 406 children with isolated colonic disease. These children had a mean age of 10.5 years. 117 had Crohn’s colitis, 143 had ulcerative colitis, and 146 had IBD-unclassified (IBDU).

Key findings:

Among those with IBDU, the most prevalent serologic profile was pANCA neg/ASCA neg (41%). 34% had pANCA pos/ASCA neg, and 17% and pANCA neg/ASCA pos.
ANCA+: present in 43% of patients with IBDU, 64% of patients with UC, and 30% of patients with Crohn’s.
ASCA+ (IgA or IgG): present in 26% of patients with IBDU, 6% of patients with UC, and 40% of patients with Crohn’s.
pANCA neg/ASCA pos did help differentiate Crohn’s colitis versus IBDU with 83% specificity, 96% positive predictive value; however the sensitivity was only 33% and the negative predictive value was only 13%.
pANCA neg/ASCA pos also differentiated Crohn’s colitis compared with ulcerative colitis with 97% specificity, and 90% positive predictive value however the sensitivity was only 33% and the negative predictive value was only 40%.
pANCA pos/ASCA neg did NOT differentiate well. For IBDU versus UC, the specificity was 66%, the positive predictive value was 94%; the sensitivity was 65% and the negative predictive value was 38%.

In short, these tests generally have poor sensitivity. If ASCA antibodies are present, which occurred in only 23%, the serology performs better but still usually not well-enough to help with big decisions. The presence of positive serology was associated with an increased likelihood of more severe disease.

Before you order IBD serology, you may want to consider whether you might use the money for this costly test in a better way.

My take (borrowed from authors): “Serology cannot routinely be recommended for differentiating between IBDU versus CC or UC as a sole diagnostic criterion given its low diagnostic utility.”

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