Category Archives: Pediatric Gastroenterology Intestinal Disorder

Catheter-Related Venous Thrombosis in Pediatric Patients with Inflammatory Bowel Disease

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A recent retrospective study (CE Diamond et al. J Pediatr 2018; 198: 53-9) examined the issue of catheter-related venous thrombosis in pediatric inflammatory bowel disease (IBD) patients (2015-17).

In total, 40 patients (47 hospitalizations, median age 14 yrs) with IBD were reviewed.  At the discretion of the treating physician, anticoagulation therapy (AT) with enoxaparin was administered in some children due to the recognized increase risk of venous thromboembolism (VTE).  This protocol did NOT evaluate for subclinical venous thrombotic events.  Detection of VTE was undertaken in those who became symptomatic (eg. pain or swelling).

AT protocol: 

  • In patients less than 40 kg, the starting dose of enoxaparin was 0.5 mg/kg/dose SC every 12 hrs with anti-factor Xa levels drawn 4-6 hours after the patient had received at least 2 doses with a target level of 0.1-0.3 U/mL. The first dose was administered on the same day as CVC placement but after placement.
  • In patients >40 kg, a fixed dose of 40 mg of enoxaparin SC every 24 hrs without laboratory monitoring

Key findings:

  • 5 of 23 (22%) hospitalizations without AT developed VTE; in contrast 0 of 24 with AT prophylaxis.  Mean duration of AT was 11 days.
  • All five who developed VTE had complete resolution after treatment with anticoagulation Rx. No cases of genetic thrombophilia were identified.
  • Bleeding issues were similar in the two groups –46% of those receiving AT Rx required at least one blood transfusion compared with 39% who did not receive AT Rx.

Overall, these groups (with and without AT Rx) had similar demographic features and had severe active IBD.  Most were receiving biologic therapy and the majority were receiving steroids.  The authors observed a trend towards more use of AT over the study period, “suggesting increased comfort levels of treating physician…even in the presence of rectal bleeding.”

My take: This relatively small study found that AT Rx reduced the rate of CVC-related venous thrombosis.  A larger prospective study is needed to confirm the potential benefit of AT treatment.

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Artwork near Azalea Drive/Chattahoochee river

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.

Liver Shorts August 2018

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M Yakoot et al. JPGN 2018; 67: 86-89. This prospective, open-label, unblinded study from Egypt indicated that 29 of 30 (96.7%) pediatric (12-17 yr) patients with HCV (genotype 4) attained an SVR12 with sofusbuvir/daclatasvir.  No serious adverse effects were evident.  The one patient who did not achieve SVR12 was lost to followup but had viral negativity after completing treatment.

Related blog post: New HCV Treatment Effective in Adolescents –Important Study Now Published Online

O El-Sherif, ZG Jiang et al. Gastroenterol 2018; 154: 2111-21. This study showed that a “BE3A Score” based on BMI <25, no Encephalopathy, no Ascites, Albumin >3.5 and ALT >60 IU/L could be used to discriminate the likelihood of reducing the Child-Pugh-Turcotte (CPT) score to class A in patients with hepatitis C virus-associated decompensated cirrhosis who received DAA therapy.  This retrospective  analysis was based on 4 trials of a sofusbuvir-therapy with 502 CPT class B and 120 CPT class C patients.

AH Ali et al. Hepatology 2018; 67: 2338-51.  This study convincingly shows that surveillance for hepatobiliary cancers improves outcomes in patients with primary sclerosing cholangitis.  Among their cohort of 830 patients (Mayo clinic), 79 developed malignancies.  Of those under surveillance (n=40), the 5-year survival was 68% compared to 20% for those who had not been under surveillance.  While the true cynic might ascribe some of the difference to ‘lead-time’ bias, this is unlikely to account for this difference at 5 years.

F Aberg et al. Hepatology 2018; 67: 2141-49.  This Finish-population prospective study, over an 11 year follow-up, using a nationally-representative cohort (n=6771) showed that even moderate alcohol consumption worsened outcomes (eg hepatic decompensation, hepatocellular carcinoma) in patients with nonalcoholic fatty liver disease.  In addition, the authors showed that diabetes the most significant predictor of poor outcome (HR 6.79). In a related commentary, pg 2072-73, the authors state that this article “put an end to the ongoing ddebate whether moderate alcohol drinking (less than 20 g of alcohol/day or 2 drinks per day) could be helpful.”

IBD Shorts August 2018

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Vitamin D Receptor Signaling in IBD. Inflamm Bowel Dis 2018; 24: 1149-54.  This article reviews the ways vitamin D/vitamin D receptor may contribute to the genetic, environmental, immune, and microbial aspects of IBD.

LY Chi et al. Inflamm Bowel Dis 2018; 24: 1344-51. This study with 223 pediatric patients & young adults found that current or prior combination therapy with infliximab, compared to monotherapy resulted in higher infliximab levels and lower antibody formation. Combination agent was mainly methotrexate (n=71) rather than thiopurine (n=13). In those with infliximab dose <10 mg/kg, those currently receiving combination therapy had median level of 11.1 compared with 7.0 for prior combination and 5.86 for monotherapy (never combination).

CM Johnson et al. Clin Gastroenterol Hepatol 2018; 16: 900-7.  In this retrospective study with 1466 patients with Crohn’s disease, the subset of patients with granulomas (n=187, 12.8%) were associated with a more aggressive phenotype and a younger age at diagnosis (23.6 years compared with 27.9 years; P= .0005). These patients had higher rates of steroid use, narcotic use, more stricturing and penetrating disease along with increase rates of surgery.

 

Declining Role of Fundoplication in Esophageal Atresia, Too

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A recent study (SA Pellegrino et al. J Pediatr 2018; 198: 60-6) examines the likelihood of redo fundoplication for esophageal atresia (EA) in comparison to redo fundoplication for other indications.

Key findings:

  • Among all EA cases, n=344 (1994-2013), 85 underwent fundoplication (single-center study from Melbourne)
  • Rates of fundoplication were declining over study period: there was a 37% drop from 2010-2013 compared to 1994-97.
  • Overall, 767 patients had a fundoplication (n=682 without EA).  The rates of redo fundoplication were similar 11/85 compared with 53/682, despite the fact that EA patients had earlier surgery with median ages of 7.2 months versus 23 months, respectively.

Factors leading to fewer fundoplications:

  • Improving medical therapies, including proton pump inhibitors and use of jejunal feedings
  • Awareness that fundoplication may not be curative and is associated with significant morbidity

Anecdotally, I have had some EA patients whose lives were transformed positively by fundoplication, though many are difficult operations due to anatomic factors like small gastric volumes and pulmonary issues.  Careful selection and surgical expertise are essential to good outcomes.

My take: The authors note that “this study challenges the assertion that fundoplicaiton is less successful in patients with EA.”

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Gibbs Gardens

Costs/Yield of Diagnosing Cyclic Vomiting Syndrome

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A recent retrospective study (CJ Lucia-Casadonte et al. JPGN 2018; 67: 13-17) examined the costs and yield of testing for Cyclic Vomiting Sydrome (CVS).

As a bonus –this is a study with CME available (& ABP MOC): NASPGHAN-JPGN CME The full text can be obtained at CME website.

This study looked at 503 charts from a single center using ICD-9 coding to identify patients. In this group, 165 (33%) had a diagnosis of CVS with 135 of this group (82%) meeting NASPGHAN diagnostic criteria with a mean age of 7.7 years.

Key findings:

  • 6 (4%) had a change in management based on CVS evaluation
  • The mean cost for screening was $6125.02 per patient
  • Atypical symptoms included bilious emesis in 9 (7%), abdominal pain in 67 (50%), attacks precipitated by fasting 1 (0.7%), and neurologic abnormalities in 3 (2%).
  • Brain MRI was performed in 68 patients and 10 were considered abnormal; though, only 1 (0.7%) had a change in management related to increased intracranial pressure (this patient had hx/o hydrocephalus). Other findings included Chiari I malformation, cerebral cyst, macrocephaly, and abnormal myelination pattern.
  • Other underlying diagnosis: UPJ obstruction (n=1), unspecified metabolic condition with carnitine deficiency (n=1), and eosinophilic esophagitis.
  • Given the costs involved, the authors reiterate NASPGHAN recommendations to avoid a ‘shotgun’ approach and note that it has previously been shown that “the most cost effective therapy in the management of CVS to be UGI with small bowel follow through (SBFT) with empiric treatment.”  Additional evaluation would be indicated for those with red flags and/or progressive or a changing pattern of vomiting episodes.
  • The authors indicate that endoscopy was the most costly evaluation tool at their institution ($11,500) and only used in 36 patients and was considered to have a low yield.

My take: This study underscores the low yield and expense involved in the evaluation of pediatric CVS; yet, it remains difficult to balance this with the concern of overlooking some anatomic and metabolic problems which can benefit from a timely diagnosis.

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Gibbs Gardens 2018

 

Dietary Patterns in First Year of Life May Increase Risk of Celiac Autoimmunity

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M Barroso et al. Gastroenterol 2018; 154: 2087-96.

Background: “Western-like diets –mainly characterized by high intake of red and processed meats, refined grains, simple sugars, and saturated fats and low intake of fruits, vegetables, and whole grains– have been associated with low-grade chronic inflammation, which is involved in the etiology of inflammatory conditions.” Ref: Br J Nutr 2015; 114: 999-1012.

To examine how diet may influence the development of celiac autoimmunity, defined by TG2A positivity, the authors examined a subset of patients (n=1997) from the prospective Generation R study (Netherlands); 27 in this cohort developed celiac autoimmunity (1.4%).

Key finding:

  • Higher adherence to a “prudent” diet which had a higher intake of vegetables, vegetable oils, pasta, and grains and low consumption of refined cereals and sweet beverages at 1 year of age was associated with a lower odds of celiac autoimmunity at 6 years of age with an odds ratio of 0.67.

This study is limited by the relatively low number who had celiac autoimmunity and by its use of a food questionnaire.

My take: This study indicates that diet plays a role in the development of celiac along with other disease, but this likely involves a complex mix of components rather than a single toxic agent.

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How Many Eosinophils Indicate Eosinophilic Gastroenteritis or Colitis?

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A recent study (Z Kiss et al. JPGN 2018; 67: 6-12) provides more data on normative values for eosinophil counts in the GI tract.  For their report, the authors reviewed 3 databases for a systematic search of the literature. They screened 1316 abstracts but found only 8 articles with complete/relevant data.  Among these 8 articles, data regarding each segment of the GI tract was present in as few as 3 articles and as many as 6 articles. The authors provide confidence intervals (CIs) and prediction intervals (PIs); the latter account for the wider uncertainty due to insufficient data.

Key points:

Normal eosinophil cell number per high-power field (HPF area = 0.2 mm squared):

  • Duodenum 8.26 with CI 4.71-11.8 and PI of 0 to 20.57
  • Terminal ileum 11.52 with CI 7.21-15.83 and PI of 0 to 60.64
  • Cecum 14.12 with CI 9.05-19.19 and PI of 0 to 38.64
  • Ascending colon 13.25 with CI 8.65-17.86 and PI of 0 to 35.42
  • Transverse colon 11.52 with CI 7.80-15.23 and PI of 0 to 25.85
  • Descending colon 10.32 with CI 7.22-13.42 and PI of 0 to 49.10
  • Sigmoid colon 8.80 with CI 6.82-10.77 and PI of 0 to 32.49
  • Rectum 7.39 with CI 4.20-10.59 and PI of 0 to 22.33

Other points:

  • The authors note that eos/HPFis a flawed measurement due to technical parameters of the microscope.  Some HPFs are bigger than others –this could affect eosinophil count up to 5-fold.  The authors specify an HPF to be =0.2 mm squared.
  • Obtaining appropriate mucosal samples for normal number of eosinophil counts can be difficult.  Even patients with functional disorders like irritable bowel syndrome and nonulcer dyspepsia could have abnormal numbers of eosinophils.

My take: These numbers of expected eosinophil counts for pediatric histology are a good starting point.  The prediction intervals remain large due to insufficient data.

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MRE Does Not Fare Well at Detecting Lesions Evident on Upper Endoscopy

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A recent study (PC Church et al. JPGN 2018; 67: 53-8) examined how well EGD findings were detected by MRE in 188 children (mean age 14 years).

Key findings:

  • EGD was macroscopically abnormal in 93 (49%) with ulcerations being the most common abnormality in 66 (35%).
  • In contrast, the local radiologist identified UGI inflammation in 7 (4%) and the central radiologists identied UGI inflammation in 20 (22%).  “There was no agreement between local and central radiologists when examining the UGI as a whole (κ=-0.02, P-0.59)”
  • The local radiologists “correctly identified only 5 of 93 (8%) patients with UGI findings on EGD.”  The central radiologists “correctly identified 9 of 45 (30%) patients with UGI findings on EGD.”

The authors state that “the Porto criteria mandate the performance of EGD for all pediatric patients suspected of having IBD. Our study has demonstrated that MRE cannot be relied upon as the sole method of evaluating the UGI.”

My take: For those who take care of children with IBD, this study will not come as a surprise as many of the UGI findings (found at endoscopy) are subtle.  This study does quantify the much higher sensitivity of endoscopic evaluation and is similar to studies that have compared capsule endoscopy to MRE.

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Cumberland Island 2018

Pediatric Pancreatitis -Working Group Nutritional Recommendations

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Abstract Link: Nutritional Considerations in Pediatric Pancreatitis: A Position Paper from the NASPHAN Pancreas Committee and ESPHAN Cystic Fibrosis/Pancreas Working Group.

M Abu-El-Haija et al. JPGN 2018; 67: 131-43.  This working group made ~27 recommendations (summarized in Table 1) and indicated the quality of evidence supporting the recommendation as well as the agreement among team members –virtually all received at least 12 of 13 votes.

Here are the ones that grabbed my attention:

For Acute Pancreatitis (AP):

  • 1a & 1aa. Children with mild AP should be started on a regular diet –preferably via mouth as compared to nasogastric route
  • 1b. Enteral nutrition (EN) should be attempted in children with severe AP within 72 hours from presentation, once deemed hemodynamically stable.
  • 1.4 Even in severe AP, jejunal tube feeding should be reserved for those unable to tolerate oral or NG tube feeding

For Acute Recurrent Pancreatitis (ARP):

  • 2.1a & 2.1b. Children should receive a regular-fat diet in between bouts of ARP and a regular-fat diet can safely be started within 1 week after the onset of a bout of AP (except in those with very elevated triglycerids (>1000 mg/dL)
  • 2.2a & 2.3a. PERT is NOT recommended in children with ARP without eocrine pancreatic insufficiency (EPI). Antioxidants are NOT recommended (insufficient supporting evidence)

For Chronic Pancreatitis (CP):

  • 3.1b & 3.12a. Recommends routine followup every 3-6 months and a regular diet
  • 3.3a, 3.4a, & 3.5a Monitoring: recommends checking fat-soluble vitamin levels every 6 to 12 months, checking for EPI with elastase (or 72 hr fecal fat) every 6-12 months, and BMD (bone mineral density) if CP and malnutrition (especially if Vit D deficiency or hx/o fractures)

My take: This report provides a methodical approach for the care of children with these pancreatic disorders.

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Tide pools and wide beach at Cumberland Island 2018

Serology Titers Associated with Clinical Expression of Ulcerative Colitis in Children

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Briefly noted: A recent study (EA Spencer et al.Inflamm Bowel Dis 2018; 24: 1335-42) examined phenotype and serology in 399 children with newly diagnosed ulcerative colitis (PROTECT study).

Key findings:

  • 65% had positive serology for pANCA; 62% in those <12 and 66% in those ≥12 years
  • 19% had positive serology for anti-CBir1; 32% in those <12 and 14% in those ≥12 years
  • High titer (≥ 100)) pANCA positivity was associated with more extensive disease but not with PUCAI values or Mayo endoscopic subscores.

My take: The serology titers for IBD, in my view, have academic interest but do not routinely enhance patient care.

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