Blind Men and The Elephant: Lasting Consequences of Enteric Infections

Recently, Ben Gold handed me a supplement which alluded to the case of “the blind men and the elephant.”  So, of course, I wanted to know more about this.

According to Wikipedia:

In various versions of the tale, a group of blind men (or men in the dark) touch an elephant to learn what it is like. Each one feels a different part, but only one part, such as the side or the tusk. They then compare notes and learn that they are in complete disagreement. The stories differ primarily in how the elephant’s body parts are described, how violent the conflict becomes and how (or if) the conflict among the men and their perspectives is resolved.  In some versions, they stop talking, start listening and collaborate to “see” the full elephant. When a sighted man walks by and sees the entire elephant all at once, the blind men also learn they are all blind. While one’s subjective experience is true, it may not be the totality of truth. If the sighted man were deaf, he would not hear the elephant bellow.

It has been used to illustrate a range of truths and fallacies; broadly, the parable implies that one’s subjective experience can be true, but that such experience is inherently limited by its failure to account for other truths or a totality of truth. At various times the parable has provided insight into the relativism, opaqueness or inexpressible nature of truth, the behavior of experts in fields where there is a deficit or inaccessibility of information, the need for communication, and respect for different perspectives.

The rest of the supplement regarding chronic health consequences following acute enteric infections was less interesting but probably more important than learning a new anecdote.

The introduction notes that nearly 600,000 children under 5 years die from dehydrating diarrhea each year.  Many more suffer from consequences of disease-associated malnutrition with both physical and cognitive deficits.

Articles in supplement:

  • Am J Gastroenterol Suppl 2016; 3: 4-11. –details diarrhea-associated years lived with disability 51 per 100,000 in developed regions compared with 685 in developing regions.
  • Am J Gastroenterol Suppl 2016; 3: 12-23. –details the likelihood of consequences following enteric infections, including functional GI disorders, inflammatory bowel disease, celiac disease (data limited), Guillain-Barré syndrome, hemolytic uremic syndrome, chronic fatigue, and neurologic sequelae.
  • Other articles in the supplement describe changes in the microbiome, the micorbiome-gut-brain axis, and the relationship between autoimmunity and irritable bowel.

 

IBD Updates -January 2017

L Beswick et al. Inflamm Bowel Dis 2016; 22: 2966-2976. The authors provide an algorithm for diagnosis and management of CMV in the setting of inflammatory bowel disease which primarily in the setting of steroid-refractory colitis.  Despite conferring a worse prognosis, the authors note that in most cases the virus is nonpathogenic and thus antiviral is usually ineffective.  Figure 1 outlines their algorithm, in those with high density inclusions on tissue (≥5 per biopsy) and/or high blood CMV PCR, the authors recommend treatment (including ganciclovir).  The details of this figure are too complex to easily summarize and if faced with this clinical scenario, I recommend reviewing source article.

KA Dunn et al.  Inflamm Bowel Dis 2016; 22: 2853-62. Fecal samples from 10 patients & 5 controls (age 10-16) showed that microbial diversity was lower in Crohn’s and lowest in patients who did not achieve SR.

EL Barnes, R Burakoff. Inflamm Bowel Dis 2016; 22: 2956-65. New biomarkers for diagnosing inflammatory bowel disease: biomarker signatures, gene expression analysis, protein profiling and microRNA

Primary Sclerosing Cholangitis (PSC) –Natural History Study

Last week, I posted an blog referencing new guidelines for peanut introduction.  A more detailed explanation of these guidelines: New Guidelines: Early Introduction of Peanut to Prevent Peanut Allergy from David Stukus (Thanks to Kipp Ellsworth for sharing this information)

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A recent study (PL Valentino et al. JPGN 2016; 63: 603-09) follows “the largest reported pediatric PSC cohort” to determine the natural history.

Study characteristics:

This retrospective study followed 120 children (1-21 yrs) with a median age of 14 years.  27% had autoimmune sclerosing cholangitis (ASC), 63% had PSC; 24% (n=29) of entire cohort had exclusive small duct PSC. Median followup was 3.7 years.

Key findings:

  • 81% of PSC patients had inflammatory bowel disease; most (72/97) had ulcerative/indeterminant coliits. 40/72 had pancolitis.
  • PSC-IBD was more common than ASC-IBD (85% vs 68%).
  • 10-year transplant-free survival in this cohort was 89%; there were 6 liver transplants.
  • The rate of cirrhosis was lower in the group who had IBD preceding PSC (15% vs 31%,P=0.05).
  • PSC is clinically silent in the majority of patients; 64% presented with abnormal chemistries and no other symptoms.
  • ERCP therapeutic intervention was low, 3% for stenting and 7% for balloon dilatation.

The authors speculate that one reason for milder PSC-IBD disease could relate to the fact that IBD patients undergo frequent chemistries.  In those without IBD, subacute PSC could be present for a much longer period before detection.  The authors note that PSC in children presents as a milder disease with only 10% having cirrhossi compared with 30% in studies with adult patients.

My take: We have a lot to learn about PSC including which patients are likely to develop clinically significant liver disease and whether most patients benefit from treatment.

Related blog post: Should we care about subclinical PSC? (This post has links to others related to PSC)

Thunder Hole, Acadia Nat'l Park

Thunder Hole, Acadia Nat’l Park

Better Hydration May Lead to Better Outcomes For Hemolytic Uremic Syndrome due to E coli

According to a recent meta-analysis of 8 studies (1511 children), better hydration may reduce the risk of bad outcomes for hemolytic uremic syndrome (HUS): From JAMA Pediatrics: Shiga Toxin-Producing E coli, Hydration Status and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coliA Systematic Review and Meta-analysis

ReferenceJAMA Pediatr. Published online November 28, 2016. doi:10.1001/jamapediatrics.2016.2952

Results: A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]).

Conclusion from abstract: Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

This study is in agreement with a prior study referenced on this blog: Changing Paradigm in Hemolytic Uremic Syndrome

acadia5

 

Improved Understanding 18 Years Later

A deeply painful experience for me occurred 18 years ago when a child that I cared for had a complication following an endoscopy.  Now, a recent publication (A Sierra et al. JPGN 2016; 63: 627-32) provides relevant information.  To be clear, this article would not have averted the complication but may help explain why it happened.

This retrospective study from 2010-2014 identified 7 cases of biopsy-induced intraduodenal hematoma (IDH) from a total of 2705 nontherapeutic upper endoscopies and 1163 duodenal biopsies.

Key findings:

  • 6 of 7 children had undergone a bone marrow transplantation and were at risk for graft-versus-host disease (GVHD)
  • 1 had Noonan syndrome
  • Thrombocytopenia was NOT correlated with IDH
  • No early perforations were associated with IDH

As part of this study, the authors reviewed the entirety of published IDH in children, 47 cases.  One prior author, Sahn et al (JPGN 2015; 60: 69-74) suggested that any organ transplant could increase the risk of IDH.  In this series, 29% of their patients had undergone transplantation (2 liver, 1 heart, 1 BMT).  Interestingly, among the entire 47 cases, there had been another report of a child with Noonan syndrome, suggesting some underlying susceptibility in the coagulation or platelet function pathways.

Clinical features of IDH:

  • Following endoscopy, particularly the first 3 days, signs/symptoms included epigastric pain, abdominal tenderness, and vomiting
  • Imaging including U/S, CT and MRI can confirm diagnosis
  • Resolution can take 2-3 weeks, during which parenteral nutrition is needed
  • IDH can cause acute pancreatitis or obstructive cholestasis
  • In trauma-induced IDH, surgery is much more likely than with endoscopic/biopsy-induced IDH

My take: BMT (and other types of transplantation) markedly increase the risk of biospy-induced duodenal hematoma. In this series, 7% of BMT patients had IDH compared with 0.1% of all others.

Related blog posts:

Jones Bridge & Chattahoochee River

Jones Bridge & Chattahoochee River

Liver Briefs 2017

Briefly noted:

RJ Fontana et al. Hepatology 2016; 64: 1870-80.  In this study of 681 adults with acute liver failure in U.S., only 3 had detectable anti-HEV IgM and all three were negative for HEV-RNA.  In addition, other putative causes of acute liver failure were present in all three.  My take: Hepatitis E is very rare explanation for acute liver failure in the U.S.

RA Rosencrantz et al. Hepatology 2016; 64: 2253-6. Case report of 2.5 yr old with autoimmune sclerosing cholangitis with Kawasaki disease. This was a well-described case with MRCP and liver histology. My take: In patients with Kawasaki with protracted liver disease, another etiology to consider.

Related blog posts:

St Maarten

St Maarten

Top Posts 2016

The following posts are the ones that I think are most useful from 2016.

Gastroenterology:

Liver:

General:

Doctoring:

IBD:

Nutrition:

truth-johnpohl

Bad Combination? Lansoprazole and Ceftriaxone

From Gastroenterology & Endoscopy News Nov 2016: Giving PPIs and Antibiotics Together May Disrupt Heart Rhythm

An excerpt:

Taking two common drugs—an over-the-counter proton pump inhibitor (PPI) and an antibiotic—together was associated with an increased risk for life-threatening arrhythmia (J Am Coll Cardiol 2016 Oct 10. [Epub ahead of print]).

New York researchers scanned data from two independent databases to investigate possible QT interval–prolonging drug–drug interactions: 1.8 million adverse event reports from the FDA’s Adverse Event Reporting System and 1.6 million ECGs from 382,221 patients treated at NewYork-Presbyterian Hospital/Columbia University Medical Center, in New York City, between 1996 and 2014…

In the study, patients taking ceftriaxone, a cephalosporin antibiotic, and the PPI lansoprazole were 40% more likely to have a QT interval above 500 milliseconds, the current FDA-stated threshold of clinical concern. Among men taking the two drugs, QT intervals were 12 milliseconds longer than men who took either drug alone…

The interaction identified in the data analysis was specific to lansoprazole and ceftriaxone, but not other cephalosporins.

My take: The magnitude of this risk is very low for a single individual but is important when one considers how many patients could be taking this combination of medications.

Easily Overlooked Esophageal Inlet Patch

Background: In numerous articles, it is stated that an esophageal inlet patch (IP) is often missed during routine endoscopy.  IP, a salmon-colored, velvet-appearing, distinct area of heterotopic gastric mucosa, typically is located just distal to the upper esophageal sphincter and is usually a single lesion ranging from a few millimeters to >5 cm.  Estimates on prevalence ranges from 0.1% to 10%.

A recent study (G Di Nardo et al. J Pediatr 2016; 176: 99-104) examined 1000 consecutive patients <18 years. Symptoms often attributed to IP include chronic cough, sore throat, dysphagia, globus pharyngeus, hoarseness, and vocal cord dysfunction.

Key findings:

  • The authors noted an IP incidence of 6.3%.
  • 35 of the 63 patients were asymptomatic.
  • The authors state that 17 of the 63 patients had chronic IP-related symptoms and all 17 were unresponsive to PPI therapy.  All were treated “successfully” with argon plasma coagulation (APC)
  • Median size was 13.3 mm.
  • The authors state that they did not find any acid-independent episodes related to IP, though pH-MII studies did help identify several patients with underlying GERD.

My take: Since the treatment of IP was not randomized/blinded and many patient’s with IP are asymptomatic, it remains unclear to me how many patients with IP truly benefit from APC treatment.

acadiaharbo