Low Fiber Diet During Bowel Prep

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A recent prospective, randomized trial (A Mytyk et al. JPGN 2018; 66: 720-24) compared a low fiber diet with a clear liquid diet during a polyethyylene glycol prep prior to colonoscopy. N=184, Median age 15 yrs (range 6-18 yrs).

Low fiber diet included milk, dairy products, some soups, bread and rolls, sandwiches, meat, fish, eggs, pasta, and honey.

Children in both groups were asked to fast for a minimum of 6 hours prior to colonoscopy and their bowel prep was assessed with the Boston Bowel Preparation Scale (BBPS). Bowel prep consisted of PEG 4000 with electrolytes dosed at 66 mL/kg to max of 4 liters.

Key findings:

  • There was no significant difference in BBPS between the two groups
  • Overall, 95.4% of patients had good bowel cleanness (BBPS ≥5)

My take: This study indicates that with a good volume of bowel prep, a less-rigorous diet change may be effective for a cleanout.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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Big Creek Greenway -not far from McFarland

 

ADMIRE Study: Use of Stem Cell Therapy for Complex Perianal Fistulas in Crohn’s Disease

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A recent phase 3 randomized, double-blind, placebo-controlled study (J Panes et al. Gastroenterol 2018; 154: 1334-42) examined the use of stem cell therapy for the treatment of complex perianal fistulas in Crohn’s disease (CD).

They used a single local injection of 120 million Cx601, a suspension of allogeneic expanded adipose-derived stem cells, and compared to a placebo injection.  This study comprised 212 patients from 49 centers. The primary endpoint, labelled “combined remission,” was based on absence of draining fistulas and MRI findings.

Key Findings:

  • As noted in Figure 1 (below), combined remission occurred in 51.5% of Cx601-Rx patients compared with 35.6% for placebo at week 24; at week 52, combined remission occurred in 56.3% of Cx601-Rx patients compared with 38.6%

My take: This local therapy improved outcomes for 1 year after a single injection and appears promising for refractory perianal fistulas.  It may help avoid surgery or systemic immunosuppression.

 

Closer Look at Data Then Image Below

Expert Actuary is Overcharged by the Hospital in ‘Collusion’ with the Insurance Company– Guess Who Wins

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From NPR Why Your Health Insurer Doesn’t Care About Your Big Bills

This is a terrific article that explains a lot about what is wrong with our health system’s economics.  This article details how an expert actuary is overcharged by Aetna and NYU Langone for a partial hip replacement and how insurance companies are NOT good financial representatives for patients.

Some excerpts:

Widely perceived as fierce guardians of health care dollars, insurers, in many cases, aren’t. In fact, they often agree to pay high prices, then, one way or another, pass those high prices on to patients — all while raking in healthy profits…

Before Frank’s hip operation, he asked NYU Langone for an estimate. It told him to call Aetna, which referred him back to the hospital. He never did get a price…

For one item in his bill the implant, Aetna said NYU Langone paid a “member rate” of $26,068 for “supply/implants.” But., the maker of his implant, … told him the hospital would have paid about $1,500…

Turns out, insurers don’t have to decrease spending to make money. They just have to accurately predict how much the people they insure will cost. That way they can set premiums to cover those costs — adding about 20 percent for their administration and profit…

It’s as if a mom told her son he could have 3 percent of a bowl of ice cream. A clever child would say, “Make it a bigger bowl.”

Wonks call this a “perverse incentive.”…

After the hearing, Nugent said a technicality might have doomed their case. New York defendants routinely lose in court if they have not contested a bill in writing within 30 days, he said. Frank had contested the bill over the phone with NYU Langone and in writing within 30 days with Aetna. But he did not dispute it in writing to the hospital within 30 days.

My take: While I’m no expert, I have had a similar experience where I was convinced that my insurance company would want to look into their agreement with a local hospital (Northside Hospital) because I was charged exorbitantly for the processing of a pathology specimen.  Further aggravating the situation was that I had no idea that this specimen, obtained from an outpatient visit, would be sent to a hospital system, rather than an outpatient pathology group.  It turns out that the insurance company had no interest in looking into this matter, even though the cumulative effect of these types of pathology charges were enormous.

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Laying to Rest a Breast-Feeding Myth

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A recent study (VJ Flaherman et al. J Pediatr 2018; 196: 84-90) examines whether early limited formula feeding undermines breastfeeding.

Background: The authors note that women have been discouraged from using formulas for newborns during the birth hospitalization due to concerns that this will diminish the frequency/success of breastfeeding.

Besides the concern that supplemental formula could increase the risk of breastfeeding cessation, some have expressed concern that supplemental formula could undermine benefits of breastmilk on the intestinal microbiome.  In addition, some have worried that if mothers perceived formula-feeding to be easier, that this could lower satisfaction with breastfeeding.

Yet, on the other side of the ledger, there are “about 80,000 newborns who require readmission after discharge” with the majority related to dehydration and hyperbilirubinemia.  Both of these conditions could be ameliorated by formula supplementation.  Thus, to address whether supplemental formula may be of benefit, the authors devised an “early limited formula” (ELF) trial.  The authors only enrolled infants >2500 gm and who had a weight loss >75th percentile on The Newborn Weight Tool (www.newbornweight.org). The authors excluded those with >10% of their birth weight due to routine practice of supplementation.

Methods: 163 mother-infant pairs were randomly assigned to either ELF along with breastfeeding or breastfeeding exclusively.  ELF involved giving infants 10 mL of a hydrolysate formula with a feeding syringe after each breastfeeding until the onset of copious breast milk

Key findings:

  • Mothers using ELF averaged 5.4 times/day for a median of 2 days.
  • Breastfeeding rates at one month of age: 86.5% of ELF group and 89.7% of controls; 54.6% of ELF and 65.8% of controls were breastfeeding exclusively at 1 month of age.
  • Readmission occurred in 4 (4.8%) of control infants and none of the infants in the ELF cohort (P=.06)
  • Using a subset of 15 (8 with ELF), the authors did not identify significant changes in microbiome of ELF group compared with the exclusively fed group when examined at 1 week and 1 month (as well as baseline)

Limitations of this study include the relatively small number of participants.  Furthermore, some populations that are at increased risk for breastfeeding cessation, namely mothers <25 years and African-American mothers were underrepresented.

My take: This study indicates that ELF is safe and does not appear to significantly increase breastfeeding cessation.

Related blog posts:

“A Guide to Gutsy Living”

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A recent article ( David JG, Jofriet A, Seid M, et al. “A Guide to Gutsy Living”: Patient-Driven Development of a Pediatric Ostomy Toolkit. Pediatrics. 2018;141(5): e20172789) describes “A Guide to Gutsy Living”: Patient-Driven Development of a Pediatric Ostomy Toolkit (Full Text)

From ImproveCareNow: Download a free copy of the Ostomy Toolkit

Background:

The education we received about our ostomy surgery was brief and focused only on basic skills regarding caring for an ostomy, including changing and emptying the bag, but did not address concerns we had about living with ostomies as part of our everyday lives. This educational void placed the burden on us as patients to find resources on our own, decide if the information was appropriate, and determine if it was reliable and accurate.

In this article, we describe how we, as patients, harnessed the capacity of a collaborative chronic care network1 and were supported to develop a resource that patients needed.

Methods:

We started a national task force of interested patients and parents who had experiences with ostomies to develop a pediatric ostomy toolkit. The task force was composed entirely of patients and parents and consisted of 7 patients and parents

After a literature review, we asked task force members to identify questions and topics related to living with an ostomy, including questions members had preoperatively, immediately postoperatively, and in the extended time since their surgeries. From this prompt, our group generated a list of topics all patients and parents agreed on based on the shared concerns, insights, or questions our task force members had around ostomy surgery… After the creation of the toolkit, we reached out to clinicians to provide clinical review.

Results:

Our final 19-page, colorful toolkit included topics relating to friends, school, travel, ostomy supplies, clothing, playing sports, using humor to cope, emergency kits, educational issues (eg, 504 plans), “Gastronauts” (Gastronauts are freely available puppets with ostomies), and ostomy medical language…The pediatric ostomy toolkit was posted on the ICN Exchange platform

My take (borrowed from authors): In our patient- and parent-led toolkit project, we demonstrate how patients and families can self-organize and ask clinicians to consult to create needed resources within a network

Resources:

  • The Oley Foundation website is a good link for patients with enteral tubes, ostomies, and central lines. http://oley.org/
  • From ImproveCareNow: Download a free copy of the Ostomy Toolkit

View from Pine Mountain

 

Point-of-Care Calprotectin Values in Preterm Infants at Risk for Necrotizing Enterocolitis

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It doesn’t look like calprotectin measurement in newborns is going to be terribly useful for detecting necrotizing enterocolitis.  A recent study (W Nakayuenyongsuk et al. J Pediatr 2018; 196: 98-103) showed a great deal of variability in the calprotectin values in their cohort of 62 infants.

Methods:

  • All infants had a birth weight of <1500 g
  • Stools collected daily (first stool of the day) either for 30 days or postmenstrual age of 32 weeks (whichever was longer)

Results: Calprotectin Values in microgram/gram

  • 1st week of life: All patients: Mean 637 +/- 638, Median 273
  • 2nd week of life: All patients: Mean 349 +/- 414, Median 180
  • 3rd week of life: All patients: Mean 486 +/- 470, Median 316
  • 4th week of life: All patients: Mean 488 +/- 385, Median 412
  • 5th week of life: All patients: Mean 358 +/- 339, Median 226
  • 6th week of life: All patients: Mean 370 +/- 334, Median 295
  • 7th week of life: All patients: Mean 240 +/- 191, Median 184
  • 8th week of life: All patients: Mean 445 +/- 110, Median 466

The highest subset scores for calprotectin was noted in the 1st week of life among preterm infants with gestational age >30 weeks.  In this group, the mean value was 799 +/- 651 and the median value was 718.

There were only two patients who developed necrotizing enterocolitis, both of whom did have an early rise in calprotectin

My take: This data shows elevated and highly variable calprotectin values in the neonatal period.  There was also a trend towards higher values among those with postnatal age >30 weeks.

Related blog post: Fecal calprotectin values in first years of life

 

 

Eosinophilic Esophagitis -Three Subtypes

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Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study

T Shoda et al. The Lancet Gastroenterology & Hepatology, published online May 2, 2018. DOI: https://doi.org/10.1016/S2468-1253(18)30096-7

Abstract:

Background

Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical–pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states.

Methods

We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis.

Findings

The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36–0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32–0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1–3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04–10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09–0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11–6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84–34·64; p=0·0013) and adult onset (2·22, 1·19–4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm.

Interpretation

Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis.

Related blog entries:

Comprehensive 2018 AASLD Guidance for Chronic Hepatitis B

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NA Terrault et al. Hepatology 2018; 67: 1560-99. Here’s the full link: Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance

Some of the key points:

Table 4 (pg 1565): provides a refresher on interpretation of serology

Table 5 (pg 1567): Children and Adults Who Are HBsAg Positive:

  • Can participate in all activities, including contact sports
  • Should not be excluded from daycare or school participation and should not be isolated from other children
  • Can share food and utensils and kiss others

Figure 1 (pg 1571) Treatment algorithms.

  • For both HBsAg-positive/HBeAg-positive and HBsAg-positive/HBeAg-negative patients, treatment is recommended if ALT ≥2 x ULN.
  • For both groups, treatment is NOT recommended for those with ALT ≤ULN and low HBV DNA levels (<20,000 IU/mL for HBeAg-positive and <2,000 IU/mL for HBeAg-negative).
  • In those who do not fall into these categories, ongoing monitoring is recommended

Figure 1 from AASLD Guidance Link

Guidance Statements for HCC Screening in HBsAg‐Positive Persons

  • All HBsAg‐positive patients and high risk adults (see page 1574) with cirrhosis should be screened with US examination with or without AFP every 6 months.
  • There are insufficient data to identify high‐risk groups for HCC in children. However, it is reasonable to screen HBsAg‐positive children and adolescents with advanced fibrosis (F3) or cirrhosis and those with a first‐degree family member with HCC using US examination with or without AFP every 6 months.

Treatment: 

  • In adults: The AASLD recommends peg‐IFN, entecavir, or tenofovir (TDF) as preferred initial therapy for adults with immune‐active CHB
  • In children: The AASLD suggests antiviral therapy in HBeAg‐positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV‐DNA levels, with the goal of achieving sustained HBeAg seroconversion.

Perinatal transmission:

  • The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg‐positive pregnant women with an HBV‐DNA level >200,000 IU/mL..The only antivirals studied in pregnant women are lamivudine, telbivudine, and TDF. Of these 3 options, TDF is preferred to minimize the risk of emergence of viral resistance during treatment. Interim studies show high efficacy of TDF in preventing mother‐to‐child transmission.
  • The infants of all HBsAg‐positive women should receive immunoprophylaxis (HBV vaccination with or without hepatitis B immunoglobulin, per World Heath Organization and Centers for Disease Control and Prevention recommendations)

Treatment & prevention of HBV reactivation in patients receiving immunosuppressive or cytotoxic drugs (section 6 pages 1577-9)

  • HBsAg and anti‐HBc (total or immunoglobulin G) testing should be performed in all persons before initiation of any immunosuppressive, cytotoxic, or immunomodulatory therapy.
  • HBsAg‐positive, anti‐HBc–positive patients should initiate anti‐HBV prophylaxis before immunosuppressive or cytotoxic therapy.
  • HBsAg‐negative, anti‐HBc–positive patients could be carefully monitored with ALT, HBV DNA, and HBsAg with the intent for on‐demand therapy, except for patients receiving anti‐CD20 antibody therapy (e.g., rituximab) or undergoing stem cell transplantation, for whom anti‐HBV prophylaxis is recommended.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Sub-Analysis of DIAMOND Study

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K Watanabe et al. Clin Gastroenterol Hepatol 2018; 16: 542-9.

The DIAMOND study evaluated monotherapy with adalimumab (n=85) compared with combination therapy of adalimumab with azathioprine (n=91).

Key findings:

  • In this subanalysis of patients with moderate and severe Crohn’s disease (CD), endoscopic response (defined by SES-CD drop of at least 8 points or SES-CD <4) was significantly higher at week 26: 71.6% vs 54.4%. The OR for endoscopic response was 2.12 at week 26 with combination therapy.
  • At week 52 the endoscopic response difference was not statistically significant: 60% vs. 50%.
  • Similarly, mucosal healing was more common (but not statistically significant) in the combination group compared with monotherapy: 20.9% vs 103% at week 26, and 21.5% vs 12.2% at week 52.
  •  While not statistically significant, the combination group had ADA trough that was higher (7.6 compared with 6.5).

My take: The results described above for endoscopic responses and mucosal healing rates are depicted in figure 2 (I do not have a digital copy of figure or permission to use).  After one looks at this figure, depicting the data noted above, there certainly appears to be an advantage for the use of combination therapy in patients with moderate-to-severe CD.

Related blog posts:

 

 

I have not independently verified the claims on this tweet

Don’t Forget the Kidneys in Children with Intestinal Failure

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Increasingly, kidney problems are recognized in children with intestinal failure/short bowel syndrome who receive long-term parenteral nutrition.  A recent study (H Billing et al JPGN 2018; 66: 751-54) highlights the experience with this issue at a pediatric intestinal rehabilitation center in Germany.

Key findings:

  • Among 50 patients with a median age of 4.2 years, 76% had proteinuria
  • 30% had chronic kidney disease –indicated by reduced creatinine clearance of <90 min (1.73 squared)/min
  • Hypercalciuria was identified in 30 patients (60%)
  • Nephrocalcinosis was identified in 9 patients (18%)

The authors note that end-stage renal failure has not been reported in association with intestinal failure, though proteinuria is associated as a risk factor.

My take: This observational study shows a high frequency of kidney issues in children with intestinal failure. With improvements in survival, chronic kidney disease could become a more significant clinical issue.

 

Tweet below indicates need for careful nutrition input when children are placed on unusual diets, including the ketogenic diet.