Category Archives: Pediatric Gastroenterology Intestinal Disorder

Esophagus! & Nutritional/GI Outcomes with Esophageal Atresia

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In 8th grade, our English teacher would say ‘Esophagus, recite that poem.’  He would say this to everybody.  It is possible that the flask that he carried could have influenced his word choice.

That anecdote came to mind as reading a recent article (K Birketvedt et al. J Pediatr 2020; 218: 130-7) which showed that a large number of adolescents with history of esophageal disease (esophageal atresia [EA]) had a high likelihood of suboptimal nutritional parameters. In this study with 68 pediatric subjects, extensive investigations including 4-day diet records, blood tests, pH measuring, EAT (eating assessment test) questionnaire, and interviews. Median age at follow-up was 16 years.

Key findings:

  • Median height-for-age Z score was -0.6. 10 patients (15%) were considered stunted (height-for-age Z score <-2).
  • More than two-thirds reported symptoms of dysphagia (EAT score ≥3) and avoided specific foods.
  • 48 (71%) had suboptimal energy intake on diet records –intake below age-appropriate recommendations.  Many had low vitamin D and iron intake.
  • 13 of 68 patients had VACTERL association and 17 (25%) had congenital heart disease

My take: If your esophagus is not working right, it definitely can impair one’s nutritional status.  Some patients have other reasons (other comorbidities) that could influence these reported results.

As for the anecdote, I still remember some of the poems we had to recite.  The one I remember best:

To An Athlete Dying Young  A. E. Housman – 1859-1936 

The time you won your town the race
We chaired you through the market-place; 
Man and boy stood cheering by, 
And home we brought you shoulder-high.  

To-day, the road all runners come,    
Shoulder-high we bring you home,  
And set you at your threshold down,  
Townsman of a stiller town.  

Smart lad, to slip betimes away  
From fields where glory does not stay, 
And early though the laurel grows  
It withers quicker than the rose.  

Eyes the shady night has shut  
Cannot see the record cut,  
And silence sounds no worse than cheers 
After earth has stopped the ears:  

Now you will not swell the rout  
Of lads that wore their honours out,  
Runners whom renown outran  
And the name died before the man. 

So set, before its echoes fade,  
The fleet foot on the sill of shade,  
And hold to the low lintel up  
The still-defended challenge-cup.  

And round that early-laurelled head
Will flock to gaze the strengthless dead,  
And find unwithered on its curls  
The garland briefer than a girl’s.

Related blog posts:

 

 

Ethical Dilemmas and Digestive Symptoms –Common with COVID-19

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Ethical Dilemmas:

Full link: NEJM: Facing Covid-19 in Italy — Ethics, Logistics, and Therapeutics on the Epidemic’s Front Line

That truth is rather grim. Though Italy’s health system is highly regarded and has 3.2 hospital beds per 1000 people (as compared with 2.8 in the United States), it has been impossible to meet the needs of so many critically ill patients simultaneously…

If protecting patients is difficult, so is protecting health care workers, including nurses, respiratory therapists, and those tasked to clean the rooms between patients…

Though approaches vary even within a single hospital, I sensed that age was often given the most weight.

In the midst of the outbreak’s peak in northern Italy, as physicians struggled to wean patients off ventilators while others developed severe respiratory decompensation, hospitals had to lower the age cutoff — from 80 to 75 at one hospital, for instance…

The first and most important is to separate clinicians providing care from those making triage decisions. The “triage officer,” backed by a team with expertise in nursing and respiratory therapy, would make resource-allocation decisions and communicate them to the clinical team, the patient, and the family.

Digestive Symptoms:

From ACG: Full Link: ACG Media Statement

Excerpt:  (March 18, 2020) – Digestive symptoms are common in COVID19, occurring as the chief complaint in nearly half of patients presenting to hospital according to a new
descriptive, cross-sectional multicenter study from China by investigators from the Wuhan Medical Treatment Expert Group for COVID-19 published today in The American Journal of Gastroenterology

Key findings:

  • Compared to COVID-19 patients without digestive symptoms, those with digestive symptoms have a longer time from onset to admission and a worse clinical outcome according to this analysis by investigators from several hospitals and research centers in China who gathered data on 204 patients with COVID-19 presenting to three
    hospitals in Hubei province from January 18, 2020 to February 28, 2020.
  • Patients with digestive symptoms had a variety of manifestations, such as anorexia (83 [83.8%] cases), diarrhea (29 [29.3%] cases), vomiting (8 [0.8%] cases), and abdominal pain (4 [0.4%] cases)
  • As the severity of the disease increased, digestive symptoms became more pronounced.
  • Link to study: Pan L, et al., Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study, Am J Gastroenterol 

 

More Advice on Coronavirus for Pediatric GIs: NASPGHAN and CCFA

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For Georgia:

NASPGHAN statement regarding Coronavirus (SARS-CoV-2) Associated Infectious Disease (COVID -19) and Pediatric GI Patient Care and Providers.

Dear Members,

In view of the COVID -19 pandemic, care of our pediatric GI patients and at the same time our pediatric GI providers (i.e. physicians and other members of the healthcare team) is an utmost priority at NASPGHAN. NASPGHAN is working on several initiatives concurrently, and we are writing at this time to make you aware.

1. The Endoscopy Committee and the Clinical Practice Committee are working on a statement regarding elective procedures for pediatric GI patients with respect to this highly contagious pathogen, COVID to both preserve Personal Protective Equipment (PPE) as well as limit potential exposure.

2. A task force of leaders from NASPGHAN, ESPGHAN, LASPGHAN, and Asia (Hangzhou, China) will be writing a commentary to be published in the JPGN, our journal, with what COVID-19 means to the pediatric gastroenterologist.

3. Mike Kappleman of UNC, ICN, NASPGHAN and in particular the IBD Committee, are launching a prospective, real-time monitoring study of COVID-19 in IBD patients. The study is IRB and HIPAA approved and will link its data with that collected by the European Porto group’s study of coronavirus in IBD patients in Europe and Asia, thereby allowing an operational real-time active surveillance network for children and adolescents with IBD (our patients).

4. Jason Silverman, Jennifer Lee, and Peter Lu are putting together a special episode of the Bowel Sounds Podcast™ including relevant up-to-date guidelines and information about COVID-19 as it relates to our members and our patients.

5. The Endoscopy Committee and Clinical Practice Committee are working on information and options for telemedicine and virtual health, given the more recent announcement by CMS and the White House/President Trump in terms of changes in reimbursement given the coronavirus pandemic.

6. Within the next 24 hours, the NASPGHAN Website, as well as GIKids.org will house resources and links to the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), Crohn’s and Colitis Foundation (CCF), the Canadian Association of Gastroenterology (CAG) and the Joint GI Societies Statement (adult-based), including ASGE, ACG, AGA on Endoscopic procedures in the face of COVID-19.

7. Finally, please feel free to send us suggestions that would help our pediatric GI community work towards creative solutions during this time.

Sincerely,

Karen F. Murray MD
President, NASPGHAN

James Heubi MD
Past President, NASPGHAN

Benjamin Gold MD
President Elect, NASPGHAN

Jeannie S. Huang MD
Secretary Treasurer, NASPGHAN

Rina Sanghavi MD

Underlying Genetic Disease in Pediatric Inflammatory Bowel Disease

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Link to text of accepted study (Gastroenterology, ahead of publication): Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated with Monogenic Variants, Identified by Whole-exome Sequencing in 1000 Children at a Single Center 

Abstract:

Background & Aims: A proportion of infants and young children with inflammatory bowel diseases (IBD) have subtypes associated with a single gene variant (monogenic IBD). We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with IBD.

Methods: We performed whole-exome sequencing analyses of blood samples from an
unselected cohort of 1005 children with IBD, 0–18 y old (median age at diagnosis, 11.96 y) at a single center in Canada and their family members (2305 samples total). Variants believed to cause IBD were validated using Sanger sequencing. Biopsies from patients were analyzed by immunofluorescence and histochemical analyses.

Results: We identified 40 rare variants associated with 21 monogenic genes among 31 of the 1005 children with IBD (including 5 variants in XIAP, 3 in DOCK8, and 2 each in FOXP3, GUCY2C, and LRBA). These variants occurred in 7.8% of children younger than 6 y and 2.3% of children 6–18 y old. Of the 17 patients with monogenic Crohn’s disease, 35% had abdominal pain, 24% had non-bloody loose stool, 18% had vomiting, 18% had weight loss, and 5% had intermittent bloody loose stool. The 14 patients with monogenic ulcerative colitis or IBD unclassified received their diagnosis at a younger age, and their most predominant feature was bloody loose stool (78%). Features associated with monogenic IBD, compared to cases of IBD not associated with a single variant, were age of onset younger than 2 y (odds ratio [OR], 6.30; P=.020), family history of autoimmune disease (OR, 5.12; P=.002), extraintestinal manifestations (OR, 15.36; P<.0001), and surgery (OR, 3.42; P=.042). Seventeen patients had variants in genes that could be corrected with allogeneic hematopoietic stem cell transplantation.

Conclusions: In whole-exome sequencing analyses of more than 1000 children with IBD at a single center, we found that 3% had rare variants in genes previously associated with pediatric IBD. These were associated with different IBD phenotypes, and 1% of the patients had variants that could be potentially corrected with allogeneic hematopoietic stem cell transplantation. Monogenic IBD is rare but should be considered in analysis of all patients with pediatric onset of IBD.
KEY WORDS: HSCT, genetics, risk factor, prevalence

 

VEO-IBD -Useful “Position” Paper is Really a Review

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A recent publication (Full text: NASPGHAN Position Paper on the Evaluation and Management for Patients with Very Early-onset Inflammatory Bowel Disease. JR Kelsen et al. JPGN 2020; 70: 389-403) is more of a review than a true position paper. A related upcoming study (highlighted tomorrow) indicates that ~8% of VEO-IBD patients have underlying monogenetic forms of IBD.

While the article makes numerous useful points, explicit recommendations are not clearly stated.

Key Points:

  • Epidemiology: 6-15% of pediatric IBD population presents at <6 years of age
  • Children with VEO-IBD need careful immunologic evaluation.  Some of the specific disorders that need to be considered include Chronic Granulomatous Disease (can check DHR) and XIAP (can check a flow cytometry-based assay).
  • Besides panendoscopy, the article recommends close collaboration with the pathologist to identify specific features of the numerous VEO-IBD disorders (most listed/described in Table 1)
  • Identification of VEO-IBD disorders with genetic testing (either whole exome or targeted gene panel) helps determine specific medical therapies and/or stem cell transplantation for disorders like CTLA4B deficiency, LRBA defects, IL-10 deficiency, XIAP, STXBP2, and FOXP3 deficiency.
  • Infliximab does not work as well in VEO-IBD patients.  A recent study found only 12% remained on infliximab 3 years after initiation.
  • VEO-IBD were much more likely to need surgery with rates of 50% for those with onset before 1 year and ~30% for those after 1 year of age.  Colectomy should be considered with caution due to the overlapping presentation of Crohn’s disease and ulcerative colitis in this age group.

One topic that was not discussed was the potential role for dietary therapy in this age group.

Related blog posts:

The following related images are from Eric Topol’s twitter feed and share figures from a Nature review.

Seen on Eric Benchimol’s twitter feed

Briefly Noted: Parent Preference: MiniONE over MIC-KEY

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In a prospective, randomized cross-over trial (RA Abdelhad et al. JPGN 2020; 70: 386-8) that compared two low profile gastrostomy buttons, caregiver preference favored AMT’s MiniONE over Avanos Medical’s MIC-KEY.  It is worth noting that the authors reported no conflict of interests.

Among 185 patients, 65 with MIC-KEY and 43 with MiniONE completed crossover study; GT buttons were placed laparoscopically.

  • In this group, 69% preferred MiniONE.
  • There were no differences in objective outcomes: adverse effects, emergency room/clinic visits, leavage, granulation tissue or dislodgements.
  • Caregiver preference was based on smaller size of external bolster and its ability to glow in the dark.

Some limitations of this study included a lack of long-term followup and an imbalance in the crossover groups completing the study.  Lack of blinding of the investigators and caregivers could have allowed bias to affect evaluations as well.

UNC Campus Pic (Chapel Hill)

 

Silent Anal Fistulas –Sounds Bad, Is It?

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A recent prospective study (PH Kim et al. Clin Gastroenterol Hepatol 2020; 18: 415-23) with 440 consecutive adults (mean age 29.6 years) with Crohn’s disease (CD) identified asymptomatic anal fistulas with MRE (including anal MRI) studies. 36 patients were newly diagnosed and the remainder had established CD.

Key findings:

  • In all of these patients, none of whom had clinical fistulas, an MRE identified “perianal tracts” in 53 (12%).
  • 37 of 290 (12.8%) of patients without a perianal fistula history and 16 of 150 (10.7%) with a history of healed perianal fistula had perianal tracts identified on MRE
  • No patients had any lesions that required treatment after examination by a surgeon
  • MRE detection of asymptomatic tracts was independently associated with later need for perianal treatment: 17.8% cumulative incidence at 37 months (aHR 3.06)

My take: Abnormal perianal tracts on MRE in asymptomatic patients indicate an increased risk of developing clinically-significant perianal disease –though most do not.

More on COVID19:

  • No children with IBD have been reported thus far from ESPGHAN which includes a 100 sites (mainly Europe) (as of March 10th); to report cases: ESPGHAN COVID19 Case Report Page
  • There is some discussion that biologic therapy for IBD may have some protective effects

 

 

Does Reflux Really Worsen After Gastrostomy Placement in Children?

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A recent prospective longitudinal cohort study (J Franken et al. JPGN 2020; 70: e41-47) examined the development of gastroesophageal reflux (GER) in 50 children  who underwent gastrostomy tube (GT) placement between 2012-2014.

Key findings:

  • GER symptoms were present before and after GT placement: in 44% and 40% respectively.

Among the 25 who underwent pre- and post-operative impedance-pH analysis

  • there was not a significant change in acid exposure: 6.2% vs. 6.1%
  • there was not a significant change in reflux episodes
  • Prior to GT placement, 18 of 25 (72%) had pathologic reflux.  Afterwards, 18 of 25 (72%) had pathologic reflux –though this included 4 with new onset reflux and 4 with resolved reflux

My take: This study shows that reflux symptoms and documented reflux are commonplace in children undergoing GT placement.  Based on this limited sample size, it appears that GER does not appreciably change following GT placement.

Related blog posts:

Island Ford, Sandy Springs

IBD Shorts March 2020

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Ustekinumab Predictor. At recent ACG meeting, PS Dulai presented data on 781 adult patients that was used to determine likelihood of ustekinumab response. Source: GIHepNews: New ustekinumab response predictor in Crohn’s called ‘brilliant’

Variable  & Points:

  • No prior anti-TNF agents:  2 points
  • No prior bowel surgery: 2 points
  • No smoking (current or prior): 1 point
  • No active fistulas: 1 point
  • Baseline albumin: >4.3    3 points, >3.9-4.3     2 points, >.3.2-3.9   0 points,     >2.5-3.2    -1 point, 2.5 or less   -3 points

Probability of Response Interpretation:

  • High if ≥5 points
  • Intermediate if 2-4 points
  • Low if 0 or 1 points

Infliximab outperformed golimumab for moderate-to-severe ulcerative colitis. S Singh et al. Clin Gastroenterol Hepatol 2020; 18: 424-31. Using data from three phase 3 trials (1793 patients), the authors found that infliximab worked more rapidly and with greater efficacy than golimumab.  At week 6, patient reported outcome of clinical remission was 50.0% and 38.9% (aOR 2.0).  After adjusting for patient variables, infliximab was superior in achieving clinical remission with aOR 3.01 (39% vs. 21%).

Increasing incidence of inflammatory bowel disease in Latin America and Caribbean. PG Kotze et al. Clin Gastroenterol Hepatol 2020; 18: 304-12. This systematic review examined incidence & prevalence of IBD over the last 30 years. In Brazil, for example, the incidence of Crohn’s disease jumped from 0.08 per 100,000 person-years in 1988 to 5.5 per 100,000 person-years in 2015.

IBD Passport Website: IBD Passport homepage. “IBD Passport is an award winning website that aims to provide comprehensive, practical and reliable information on all aspects of travelling with Crohn’s Disease or Ulcerative Colitis (Inflammatory Bowel Disease). IBD Passport is the first website to combine this information into one resource to make planning your trip easy. IBD Passport is a UK registered non-profit charity (Registered number: 1171268) with a global reach aimed to support IBD travellers of all nations and regions in the world.”

Adverse Effects of Low-Dose Methotrexate (≤20 mg/week). DH Solomon et al. Ann Intern Med. 2020. DOI: 10.7326/M19-3369. n=4786, median age 66 years. This was a secondary analyses of a double-blind, placebo-controlled, randomized trial. “With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs.” There were increased risks of gastrointestinal, infectious, pulmonary, and hematologic AE.

 

 

 

Could Immunotherapy (EPIT) Work For Eosinophilic Esophagitis? & Coronavirus Up-to-Date Tally

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A recent double-blind pilot study (n=20) (JM Spegel et al. Clin Gastroenterol Hepatol 2020; 18: 328-36) explored the use of epicutaneous immunotherapy (EPIT) in children with milk-induced eosinophilic esophagitis (EoE). 15 children received active treatment with a “Viaskin” milk allergen extract patch and 5 children received a placebo.

The premise of EPIT for EoE has been based on animal models (mouse & piglet) which have shown that epicutaneous desensitization to peanuts has been successful in preventing development of EoE.

The design of the study involved EPIT during a 9 month milk-free period followed by a milk-containing diet for 2 months.  Biopsies were taken and then there was an additional 11 month open-label phase in which all patients received EPIT.

Key findings:

  • No significant differences in mean eos/hpf in the two groups: 50 vs 48 in EPIT compared to placebo respectively.
  • There were 9 of 19 (47%) had a significant drop in eosinophil count with less than 15 eos/hpf at the end of the open-label phase.
  • Overall, adverse events were similar in both groups, though the EPIT group had more frequent GI adverse events than the placebo group (67% vs. 40%)

My take: The primary and secondary endpoints were not reached in this study.  However, based on the open-label phase response, further studies are warranted.

Related blog posts:

Also, from Johns Hopkins: COVID19 Caseload & Outcomes Worldwide

This screenshot was taken at 2:53 pm on 3/7/20