Gastrostomy Tube Placement in Extremely Low Birthweight Infants

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A recent analysis (MG Warren et al J Pediatr 2019; 214: 41-6) examined gastrostomy tube (GT) placement among 4569 extremely low birthweight (ELBW) infants (birth wt <1000 gm) who were enrolled in the National Instittue of Child Health and Human Development Neonatal Research Network (25 centers).

Key findings:

  • 333 (7.3%) underwent GT placement; 76% had GT placed postdischarge from NICU
  • Among patients with GT placement, 56% had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems
  • At last follow-up, 32% of infants who required GT placement were taking full oral feeds.
  • Rates of fundoplication varied widely between centers, ranging from 0% to 6.4% among the centers.

In the discussion, the authors note the well-recognized associations between feeding difficulties and language delays in ELBW infants.  In addition, “behavioral and emotional problems have …been described in children with feeding problems.”

The authors also state, without evidence, that the high rate of GT placement after discharge suggests that “a large proportion of ELBW infants were first discharged from the NICU orally feeding but could not maintain these skills.”  Alternative explanations include the following:

  • Many infants were sent home with NG (nasogastric) supplementation and after not making progress with oral feedings, elective GT placement was done when the infant was a more suitable candidate (eg. improved respiratory status, better nourished, etc.)
  • Problems with oral feeding became apparent after discharge including poor growth and aspiration.  In fact, the authors note that “orormotor dysfunction and avoidant feeding behaviors at 3 and 12 months corrected age” were nearly twice as likely in infants born <34 weeks
  • While this study did not fully capture data regarding home NG feedings, 14% of patients sent home with NG feedings eventually received a GT

My take: This study indicates that 7% of ELBW infants undergo GT placement and that about one-third out-grow the need for GT supplementation after ~2 years.

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Transnasal Endoscopy in Unsedated Children to Monitor Eosinophilic Esophagitis

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A recent retrospective study (N Nguyen et al. Clin Gastroenterol Hepatol 2019; 17: 2455-2462) describe the feasibility of unsedated transnasal endoscopy (TNE) for monitoring eosinophilic esophagitis (EoE) in children (n=190, subject ages 3-22 years).

TNE was facilitated by distraction with either video google or virtual reality (starting 2016).  NPO time was 2 hours before the TNE.

Key points:

  • Over 294 TNEs were completed from 300 attempts (98% success)
  • Cost of TNE was halved: $4393 compared to $9444 for EGD (does not count pathology costs)
  • Adverse events: 8 (2.7%) with vomiting, 9 (3.1%) spit up, 11 (3.7%) with epistaxis
  • By 2017, TNE accounted for 31.8% of upper endoscopies in 2017

The authors recommend that TNE be offered starting at age 5 years in those without a known stricture.

My take: I am looking forward to less invasive/less costly ways of monitoring treatment response in EoE.  I think TNE can lower costs –though I am a little surprised that the cost of TNE in their institution was still more than $4000.  In our outpatient endoscopy center, costs for an upper endoscopy/biopsy with anesthesia are typically about one-third the cost of an EGD in their study and about three-fourths the cost of a study TNE.

Related study: A Krigel et al. Clin Gastroenterol Hepatol 2019; 17: 2489-96. This study showed increasing use of anesthesia assistance (AA) for colonoscopy in adults from 16.7% in 2006 to 58.1% in 2015. This data was derived from the Premier Perspective database with more than 4.6 million patients who had an outpatient colonoscopy. AA was associated with a median increase in cost of $182 for patients with commercial insurance.

Related blog post: Waiting for the String Test for EoE

 

Celiac Disease: “”80 percent of success is just showing up”

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“80 percent of success is just showing up” —Woody Allen

Reading a recent (brief) study (BA Blansky et al. Clin Gastroenterol Hepatol 2019; 17: 2503-4) reminded me of the quote from Woody Allen.  This study of children with Celiac disease (CD) demonstrates a high rate of children who were lost to follow-up at a leading Children’s hospital.

Key findings:

  • From a randomly selected retrospective cohort (2010-2014) with 241 eligible subjects, one-fourth of children were lost to follow-up within a year of diagnosis. 22 (9%) had NO GI visits after their diagnostic procedure.
  • Risk factors for loss of follow-up: sibling with CD (HR 1.90), Medicaid insurance (HR 2.19), and older age at diagnosis; those with adherence had median age at diagnosis of 8.7 years compared with 11.4 years for those lost to follow-up.
  • Median time to tissue transglutaminase (TTG) IgA normalization was 17 months.  Of 141 who had recommended follow-up, 25% had elevated TTG IgA at last GI visit.

My take: These numbers should not be surprising to most clinicians.  If clinicians want to improve follow-up and outcomes, then families will need more nudging; EMRs can be configured to help in this task.

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Quebec City

Easy Advice for Pediatric Hepatologists: PSC Surveillance Recommendations

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A recent clinical practice update (CL Bowlus et al. Clin Gastroenterol Hepatol 2019; 17: 2416-22) makes several recommendations on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis (PSC).

Full Text Link: AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review

I will highlight the most important recommendation for pediatric hepatologists:

  • Best practice advice 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20.

In the text, the authors note that “in pediatric PSC patients, cholangiocarcinoma is very rare, with only 8 of 781 (1%) …developing cholangiocarcinoma” (MR Deneau et al. Hepatology 2017; 66: 518-27)

Here are the other recommendations:

  • Best practice advice 1  Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age.
  • Best practice advice 2 Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months
  • Best practice advice 3  Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC.
  • Best practice advice 4  Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture.
  • Best practice advice 5  Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma.
  • Best practice advice 7 The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm.
  • Best practice advice 8  Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.

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From The Onion

 

20-Year Follow-up of Statins in Children

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A recent study (IK Luirink et al. NEJM 2019; 381: 1547-56) examined the effects of statin therapy in children with familial hypercholesterolemia (FH) who were followed for 20 years. At baseline, the median age was 13 years in the treated cohort and in their sibling control group.  184 of 214 (86%) of patients with FH were seen in follow-up and 77 of 95 (81%) of siblings.

Key findings:

  • The mean LDL cholesterol had decreased from 237 to 161 mg/dL
  • LDL target of <100 mg/dL was achieved in 37 patients (20%)
  • Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm/year in patients with FH and 0.0057 mm/year in sibling controls
  • The cumulative incidence of cardiovascular events and death from cardiovascular causes at age 39 years was lower in the treated group compared to  their affected parents: 1% vs. 26% and 0% vs. 7% respectively

Discussion:

“This makes a strong case for not only ‘the lower the better’ but also for ‘the younger the better” as atherosclerotic disease is determined not only by the LDL level but also by cumulative exposure.

My take: This study provides convincing data that statin therapy prolongs health and life in patients with familial hypercholesterolemia.

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IBD Updates December 2019

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SR Gupta et al. JPGN 2019; 69: 544-50.  This article reports on preliminary experience in 54 children who received external (non-hospital) infliximab infusions. The average age was 17.6 years. The authors noted no serious safety concerns.  Prior to arranging these infusions, the authors insisted on the following:

  • Infusion services had to guarantee pediatric trained nurses with PALS certification
  • Emergency medications had to be available
  • A plan for emergency communication was arranged
  • Postinfusion communication would occur with each infusion

BN Limketkai et al. Inflamm Bowel Dis 2019; 25: 1828-37.  This study, using Truven Health MarketScan database (2007-16) reviewed proactive or reactive mucosal monitoring after biologic initiation in IBD.  Early (< 6 months) proactive monitoring (88% endoscopy-based) was performed in 11% (n=2195/19,899) of patients with Crohn’s and 12.8% (925/7247) of patients with ulcerative colitis.

  • “Early proactive monitoring was associated with a reduction in disease-related complications for CD (aHR 0.90) and UC (aHR 0.87) and predominantly driven by a reduction in corticosteroid use.”
  • Another interesting finding was that ~40% of patients had biologic therapy initiated without assessment of mucosal disease activity within 6 months.
  • The authors state that disease monitoring is typically more useful in CD than UC because with the latter, cessation of bleeding and diarrhea appear to be adequate surrogates.
  • This study was not able to assess whether a biomarker like fecal calprotectin would be suitable due to its low utilization.

RZ Cohen, BT Schoen, S Kugathasan, CG Sauer. JPGN 2019; 69: 551-6. In this chart review, the authors identified anti-drug antibodies (ADA) in 24.8% (n=58) of patients undergoing therapeutic drug monitoring (n=234) with both infliximab and adalimumab.  54% of this group had antibody suppression with dose optimization. Of note, 37 patients had detectable ADA at time of initial drug monitoring. Dose optimization was 10 mg/kg every 4 weeks with infliximab or 40 mg weekly with adalimumab. Patients who were switched to a second anti-TNF agent (n=23) were not more likely to develop ADA to the second agent (small sample size). Also, the authors caution that in the five patients with ADA levels (>10 U/mL), dose optimization failed and patients required a therapeutic switch. My take: This study provides some useful information about the frequency of ADA.  My view is that the actual drug level is more critical than the presence of ADA; though, the presence of high ADA often precludes the ability to deliver a therapeutic drug level.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

More Details on Drug-Resistant E coli Transmitted by Fecal Microbiota Transplant

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In June 2019, the FDA delivered a warning about the potential danger of transmitting drug-resistant E coli with fecal microbiota tranplantaion (FMT).  (FDA Warning for FMT)

A report on this issue has now been published: Z DeFilipp et al. NEJM 381: 2043-50, editorial M Blaser pgs 264-6.

The authors describe two patients, a 69 year-old with cirrhosis and a 73 year-old sp stem cell transplantation, who developed bacteremia due to transmission of a drug-resistant (extended-spectrum beta-lactamase [ESBL]) E coli following FMT which was delivered by oral capsules. The latter patient died from sepsis. The two patients had a genomicly-identical strain isolated that was also found in the donated aliquot.

In the commentary, a couple of important points:

  • “Up to now, the complications have been infrequent [from FMT], and for recurrent C difficile infection, the benefits of FMT clearly outweigh the risks; however, as the use of FMT is broadened and more compromised patients are treated, complications may be more frequently observed.”
  • “In the short term, improved and uniform screening of FMT material is needed to reduce the risks.”

My take: Both of these patients who became developed bacteremia were at risk for more severe infections.  However, we need to remain aware that severe complications can and do occur with FMT.  In context, though, there are risks of severe complications from routine use of antibiotics as well.

Frontenac Hotel, Quebec City

Only 3% Make It Through the Donor Screening Process for Fecal Microbiota Transplantation

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A recent letter (Z Kassam et al. NEJM 2019; 381: 2070-2) describes the arduous process involved in being selected as a stool donor for fecal microbiota transplantation (FMT).

In a previous blog (2015), it appeared that 17% of donors were accepted for FMT: Rejected! Most Stool is Not Good Enough for FMT This current review of the donor program from a stool bank (OpenBiome) prospectively evaluated 15,317 donor candidates from 2014-2018.

Key finding:

  • Only 3% (n=386) made it through all the steps to become donors

Reasons for exclusion:

Stage 1: common reasons for exclusion:

  • geographical -living too far away to donate regularly
  • BMI >30
  • social history
  • travel history
  • not in age range

Stage 2: “failing” the 200-item clinical assessment –common reasons for exclusion:

  • lost to followup
  • allergic disorders/asthma
  • receiving medications/supplements
  • mental health concerns
  • infectious disease history
  • social history/sexual history/other reasons

Stage 3: “failing” the stool and nasal screening which included (in 2016) carbapenem-resistant Enterobacteriacea (CRE), extended-spectrum beta-lactamase-producing organisms (ESBL) and MRSA. –common reasons for exclusion:

  • lost to followup
  • infectious disorders (including C diff in 7 patients)

Stage 4: “failing” serological screening

  • lost to followup
  • abnormal LFTs, CBC or infection

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Island Ford, Sandy Springs, GA

How Genetics Influence Response to PPIs in Eosinophilic Esophagitis

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About two years ago, James Franciosi presented research at NASPGHAN meeting indicating that the main difference between children with eosiniophilic esophagitis (EoE) who respond to proton pump inhibitiors (PPIs) compared to those who do not was related to their metabolism of PPIs and not related to the nature of their underlying EoE.

Related blog: #NASPGHAN17 Eosionophilic Esophagitis Session

Now, more has been published on this topic: EB Mougey et al. JPGN 2019; 69: 581-7.

In this study with 92 patients, data was collected from participants in a prospective clinical trial of high-dose PPI for EoE.

Key findings:

  • 57 (62%) were responsive to PPIs and 35 (38%) were not responsive to PPIs
  • Carriage of STAT6 allele variant rs1059513 predicted responsiveness to PPIs with OR of 6.16
  • Carriage of STAT6 rs324011 synergizes with CYP2C19*17 to predict PPI-nonresponsive EoE

Discussion: 

  • Carriers of CYP2C19*17 are more likely to fail PPIs for EoE.  Children with CYP2C19*17 gain of function “have a 7.7 fold better odds of failing PPI therapy” than noncarriers.
  • CYP2C19*17 effects “appears to be exerted within a specific range of PPI doses…and does not appear to exert influence at the low and high ends of this dose range.”
  • STAT6, which in this study is a cofactor, “upregulates transcription of CCL26 (eostaxin-3) 53-fold in esophageal eosinophilia relative to levels in peptic esophagitis and 490-fold over levels found in normal esophageal biopsies.”
  • PPIs effectiveness “does not correlate with esophageal” acid exposure; thus, its effects are mediated via an anti-inflammatory mechanism.

My take: This study indicates that genotype-guided dosing of PPIs for the treatment of EoE is likely to be worthwhile.

 

View from Yonah Mountain, GA

How Bad is Reflux in Children with Esophageal Atresia?

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A recent retrospective study (FWT Vergouwe et al. JPGN 2019; 69: 515-22) with 57 children with esophageal atresia (EA) found most children have a normal reflux index.

This study, analyzing data between 2012-2017, reviewed all 24-hour pH-impedance (MII) studies in children at ≤18 months and 8 year olds with EA.  “All children with EA born in our hospital are offered a 24-hour pH-MII study at the age of 0.5 years and 8 years.”  In this institution, PPI treatment is given for at least 6 months after surgery. Of the 57 in the cohort, 20 had completed pH-MII at <18 months of age and 32 at age 8 years.

Key findings:

  • In children ≤18 months of age, median reflux index was 2.6% (abnormal in 2), median number of retrograde boluses was 61 (62% nonacid, 58% mixed)
  • In the older cohort (~8 years of age), median reflux index was 0.3% (abnormal in 4) and median number of retrograde boluses was 21 (64% nonacid, 75% mixed)
  • Overall, 10 of 57 children (17.5%) had GERD with reflux index >7% (n=6) or positive SI/SAP (n=4).  The authors note that much higher rates of GERD have been found in prior studies.  If they included children with fundoplication who were considered as having GERD (prior to fundoplication), then the GERD rate was 32%.

My take: This study showed that reflux in this cohort of children with EA was similar to the general population and likely indicates that a substantial portion of patients with EA do not need indefinite PPI therapy.  In children with more complex EA, PPI therapy is likely to be more beneficial.

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Recent (November 4th) GI-Related Tweets: