Gastrointestinal Hemangiomas in Infancy

Posted on November 2, 2015 by gutsandgrowth

A brief study (IW Soukoulis et al. JPGN 2015; 61: 415-20) makes several useful points about gastrointestinal infantile hemangiomas. This study retrospectively analyzed 16 children (14 less than 1 yr) and described the presentation and management of gastrointestinal hemangiomas.

Key points:

Most were female (14/16)
Melana, hematochezia and anemia were typical presentations, usually within the first 4 months of life
9/16 also ahd some cutaneous hemangiomas. These lesions were located predominantly in the midgut in the distribution of the SMA. Thus, endoscopy (EGD/colonoscopy) is mainly to exclude other etiologies.
Imaging usually will detect these lesions (High-resolution Ultrasound, CT, or MRI)
1st line treatment: Propranolol and/or corticosteroids

Related blog post:

Infantile Hemangioma –Propranolol Effective | gutsandgrowth

Sandy Springs

“More People Than Ever Want To Be Doctors”

Posted on November 1, 2015 by gutsandgrowth

From NBC News: “More People Than Ever Want To Be Doctors”

More people than ever want to be doctors, a new survey shows. Enrollment is up 25 percent this year over 2002, with more black applicants and Hispanic applicants being accepted.

More than 52,000 people applied to medical school in 2015 — up more than 56 percent from 2002 — the survey by the Association of American Medical Colleges (AAMC) found…And 20,630 were enrolled, a 25 percent increase over the 16,488 enrolled in 2002….

“The number of Hispanic or Latino enrollees increased by 6.9 percent to 1,988, and the number of applicants increased by 10.3 percent to 4,839,” the AAMC said in a statement.

“African-American enrollees rose 11.6 percent to 1,576, while the number of applicants increased by 16.8 percent to a total of 4,661.”

NY Times: Cutting Sugar Improves Children’s Health in Just 10 Days

Posted on October 31, 2015 by gutsandgrowth

Perhaps this is not the best day of the year for this topic….

A recent small study of 43 children is summarized by the NY Times: Cutting Sugar Improves Children’s Health in Just 10 Days

An excerpt:

Obese children who cut back on their sugar intake see improvements in their blood pressure, cholesterol readings and other markers of health after just 10 days, a rigorous new study found.

The new research may help shed light on a question scientists have long debated: Is sugar itself harming health, or is the weight gain that comes from consuming sugary drinks and foods mainly what contributes to illness over the long term?

In the new study, which was financed by the National Institutes of Health and published Tuesday in the journal Obesity, scientists designed a clinical experiment to attempt to answer this question. They removed foods with added sugar from a group of children’s diets and replaced them with other types of carbohydrates so that the subjects’ weight and overall calorie intake remained roughly the same.

After 10 days, the children showed dramatic improvements, despite losing little or no weight. The findings add to the argument that all calories are not created equal, and they suggest that those from sugar are especially likely to contribute to Type 2 diabetes and other metabolic diseases, which are on the rise in children, said the study’s lead author, Dr. Robert Lustig, a pediatric endocrinologist at the Benioff Children’s Hospital of the University of California, San Francisco.

My take: For a long time, I have been telling patients that if they make only one change, I would start by eliminating sugar-sweetened beverages. While this is a small study, it reinforces the view that sugar intake needs to be limited.

This post included last year’s pumpkin (Halloween 2014): NASPGHAN Postgraduate Course 2014 -Liver Module – gutsandgrow

This year’s pumpkin:

Why the Genetics of Inflammatory Bowel Diseases Matter Now

Posted on October 30, 2015 by gutsandgrowth

A terrific update on the genetics of inflammatory bowel diseases (DPB McGovern, S Kugathasan, JH Cho. Gastroenterol 2015; 149: 1163-76) explains why and how this information matters right now. The article is a little difficult to read due to its review of highly technical material.

Here’s what I think were the key points:

Big advances in understanding the genetics started with the first genome-wide association studies (GWAS) using genome-wide single nucleotide polymorphisms (SNP) chips in 2005. “The conceptual basis of GWAS is that most complex (ie, not single-gene Mendelian) genetic disorders are polygenic, being driven by multiple common genetic polymorphisms.”
“Early GWAS identified the most significant loci.” Now, more than 200 loci associated with IBD have been identified with GWAS and Immunochip data. Table 1 lists these loci over 4 pages. About 2/3rds of these are associated with Crohn’s disease (CD) and ulcerative colitis (UC) whereas the remaining 1/3rd are unique to either CD or UC.
These loci provide insight into disease mechanisms. NOD2 mutations result in “impaired activation of NF-κB” This supported “the general concept that deficiencies of innate immune cell function represent a central factor in Crohn’s disease, distinguishing it from ulcerative colitis.”
ATG16L1 gene mutation “establish the fact that the CD risk allele is correlated with impaired autophagy.” This is leading directly into treatment efforts.
IL23R. “The most significant association is Arg381Gln…confers a 2- to 3-fold protection against development of IBD.” The protective effect is thought to be due to “decreased numbers of interleukin (IL)-23 dependent CD4+ Th17 and CD8+ Tc17 cells…decreasing IL-23 signaling, such as through monoclonal antibody blockade of anti-p40 or anit-p19 may be beneficial.”
FUT2 mutations. These mutations affect the mucus layer in Crohn’s disease.
Studies in non-Caucasians highlight other susceptibility regions.
“Currently, sequencing of the whole exome has become not only a practical method but also a cost-effective option to identify functionally relevant variants in the protein encoding regions of the genome.”

Very Early Onset IBD:

Whole exome sequencing (WES) identified XIAP (X-linked inhibitor of apoptosis) in a case of boy with very early onset (VEO) IBD. XIAP is a positive regulator of NOD2 function. WES has also identified FOXP3, and IL10RB genes.
“The VEO group experiences a more severe disease course and more frequently shows a positive family history for IBD in support of higher genetic load.” Table 2 lists ~40 genes associated with VEO. These genes are involved in epithelial barrier function, neutropenia/defects in phagocyte function, hype-and autoinflammation, and regulatory T cells and immune regulation.

Genetic Testing Will Impact Current Therapies and Help Explain Extraintestinal Manifestations:

Currently testing for TPMT variations is recommended prior to use of thiopurines due to concerns of toxicity in individuals with decreased metabolism of these medications. However, genetic testing can identify other individuals with propensity to leukopenia (eg. NUDT15 polymorphism) and those with increase risk for pancreatitis (eg. HAL-DQA1-HLA-DRB1)
Primary Sclerosing Cholangitis (PSC) is associated with numerous genetic loci as well. PSC “genetically is more similar to UC than to CD.” Most other extraintestinal manifestation studies have been underpowered.
IBD share more genetic similarity to spondyloarthropathy (SpA) than any other immune-mediated diseases. “The vast majority of shared susceptibility loci are concordant between IBD and SpA.”
With regard to psoriasis, the genetic relationship to IBD is complex. Anti-TNF agents can cause psoriaform lesions in IBD patients. In addition, anti-IL17a therapy, “so successful in psoriasis, appears to worsen Crohn’s disease” but not in those with a TNFSF15 variant. Specific genotyping may help identify which patients with CD are susceptible to psoriaform lesions and those who may improve with therapy typically given for psoriasis.

My take: This article shows how understanding genetics of IBD is providing insight into pathophysiology and more personalized treatment approaches.

Briefly noted: EM Stoffel, CR Boland. Gastroenterol 2015; 149: 1191-1203. Excellent review of the genetics and genetic testing for Hereditary Colorectal Cancer. The review includes polyposis syndromes and Lynch syndrome.

Atlanta Botanical Gardens

Single High-Dose Oral Vitamin D Therapy (Stoss) for Children with Inflammatory Bowel Disease

Posted on October 29, 2015 by gutsandgrowth

A retrospective study (D Shepherd et al. JPGN 2015; 61: 411-14) shows that a single high-dose oral vitamin D3 therapy can be effective for 6 months. This study involved treatment of 76 children between 2006-2010.

Stoss vitamin D dosing used in this study:

< 3 yrs 200,000 IU
3-12 yrs 400,000 IU
>12 800,000 IU

Followup levels of Vitamin D (25-OH) and calcium were checked at 1 week, 4 weeks, 3 months and 6 months..

Key finding:

25-OHD >50 nmol/L (=20 ng/mL) was seen in 96.6% at 3 months and 76.4% at 6 months. 63% had a level >75 nmol/L (=30 ng/mL) at 1 month.

Bottomline: Authors noted: “Stoss therapy safely and effectively achieved and maintained a level of 25OHD > 50 nmol/L during 6 months in these children with IBD.”

Related blog posts:

Atlanta Botanical Gardens

What is Your Infliximab Adherence Rate?

Posted on October 28, 2015 by gutsandgrowth

I started thinking about this question after a recent study (DS Vitale, et al. JPGN 2015; 61: 408-10) examined adherence at a single pediatric center (2010-2012). Adherence indicated “those who attended >80% of scheduled infusions.” Key findings:

91.4% adherence rate of patients (n=151 with >4 infusions)
Adherent patients (n=138) attended an average of 98% of their infusions. Nonadherent patients attended, on average, 76% of their infusions.
The study provided some preliminary evidence that there was greater acute care use in nonadherent patients.
There were no demographic features that could predict adherence pattern.

My take: One of the key advantages of infusion therapy is improved and documented adherence. Infusions also provide opportunities to assess patient in a scheduled manner. This study shows that subsets of patients with scheduled infusions have suboptimal adherence — another target for quality improvement!

Atlanta Botanical Gardens, Bruce Munro Exhibit

Be Aggressive! Treating Anemia Associated with Inflammatory Bowel Disease

Posted on October 27, 2015 by gutsandgrowth

A number of recent publications have made the point that anemia is a biomarker for severe inflammatory bowel disease and undertreatment affects quality of life. Reading one of the more recent studies (IE Koutroubakis et al. Clin Gastroenterol Hepatol 2015; 13: 1760-66) brought to mind the high school football cheer: Be Aggressive!

This particular retrospective study involved 410 patients (245 with Crohn’s disease, 165 with ulcerative colitis) from 2009-2013. This study is from the same group that published data on a somewhat smaller cohort and showed that IBD treatment alone often will not resolve anemia (Koutroubakis, IE et al. Inflamm Bowel Dis 2015; 21: 1587-93–see previous blog links).

Key findings:

Prevalence of anemia: 37.2% in 2009 and 33.2% in 2013
Anemia was associated with increased hospitalizations (P<.01), clinic visits (P<.001), telephone calls (P<.004), surgeries for IBD (P=.001), and lower quality of life scores (P<.03)

The associated editorial (pgs 1767-69) suggests that IBD-related anemia, if mild (w/in 1 g/L below normal) to treat with oral iron replacement and if moderate-to-severe, then to replace intravenously (using Ganzoni’s formula calculator). In addition, if anemia is not improving, looking for alternative explanations (e.g. vitamin B12 or folate deficiency) is recommended.

Ganzoni Equation: Total Iron Deficit = Weight {kg} x (Target Hb – Actual Hb) {g/l} x 2.4 + Iron stores {mg}. Iron stores: { 500 if W > 35kg } & { 15 mg/kg if W < 35kg }

My take: Anemia is a biomarker for severe disease. While treating the underlying inflammatory bowel disease, don’t forget to make sure the patient’s anemia is addressed.

Related blog posts:

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.

Central Park

Biosimilars -Position Statement

Posted on October 26, 2015 by gutsandgrowth

Briefly noted:

“Use of Biosimilars in Paediatric Inflammatory Bowel Disease” Position Statement. JPGN 2015; 61: 503-08. Conclusions:

“IBD Porto group advocates giving high priority to performing paediatric trials with long-term followup to support” the use of biosimilars (97% agreement)
“Treatment of a child with sustained remission on a specific medication should not be switched to a biosimilar until clinical trials in IBD are available to support the safety and efficacy of such a change” (94% agreement)
“Postmarketing surveillance…in children with IBD should be a mandatory requirement.” (100% agreement)

My take: Keep this reference handy. The lower expected costs (>30% reduction) could create pressure to change treatment before the safety/efficacy is proven.

Atlanta Botanical Gardens

NY Times: Frequent Antibiotics May Make Children Fatter

Posted on October 25, 2015 by gutsandgrowth

The topic of antibiotics and obesity has been discussed several times on this blog (see links below). More information on this topic has been published and is summarized by the NY Times: Frequent Antibiotics May Make Children Fatter

Children who regularly use antibiotics gain weight faster than those who have never taken the drugs, according to new research that suggests childhood antibiotics may have a lasting effect on body weight well into adulthood.

The study, published in the International Journal of Obesity, examined the electronic medical records of 163,820 children ages 3 to 18, counting antibiotic prescriptions, body weight and height. The records, which covered pediatric exams from 2001 through 2012, showed that one in five — over 30,000 children — had been prescribed antibiotics seven or more times. By the time those children reached age 15, they weighed, on average, about 3 pounds more than children who had received no antibiotics.

While earlier studies have suggested a link between antibiotics and childhood weight gain, they typically have relied on a mother’s memories of her child’s antibiotic use. The new research is significant because it’s based on documented use of antibiotics in a child’s medical record.

This story was covered by Time: Too many antibiotics may make children heavier

My Take: More evidence that antibiotics could contribute to obesity. Perhaps this will help with antimicrobial stewardship.

Related blog posts:

Lack of Survival Benefit With MELD Exception Points in Hepatocellular Carcinoma

Posted on October 24, 2015 by gutsandgrowth

Briefly noted:

Another study also looks at transplant utility by showing the use of MELD exception points for hepatocellular carcinoma provides almost no survival benefit: K Berry, GN Ioannou. Gastroenterol 2015; 149: 669-80, editorial 531-34. The article states that the “survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score…a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient).”

How is this possible?

When patients are transplanted at lesser illness acuity, it takes longer to achieve a transplant benefit because they can live longer without a transplant. In essence, the survival clock starts ticking much later than the transplant date.

Why this is important (from editorial):

The proportion of patients undergoing liver transplantation for HCC has increased from “4.6% before the introduction of MELD exception to 16.5% currently.” And, “the results, put simply, suggest that allocating donor livers and performing liver transplantation in patients with HCC MELD exception points produces almost no survival benefit.”

My take: Liver allocation policies need to be modified. This study suggests that prioritizing HCC patients does not make much sense.

Atlanta Botanical Garden