Missing Bacteria in Refractory Malnutrition

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A recent article in the NY Times reports on a Nature study (Link: Bacteria and Malnutrition) which showed that certain bacteria were essential in resolving malnutrition.  Here is an excerpt:

“When children are starving, the bacteria that live in their intestines may determine whether they can be saved, scientists working in Bangladesh are reporting. And they say it may become imperative to find a way to give children bacteria as well as food.

The study, done by researchers from Washington University School of Medicine in St. Louis and the International Center for Diarrheal Disease Research in Dhaka, the Bangladeshi capital, was published by Nature last week…stool samples showed that severely malnourished children often lack the needed species and do not acquire them even when they are fed nutrition-dense therapeutic foods like the peanut-based Plumpy’Nut or lentil-based porridges for weeks. As a result, they may remain stunted and mentally handicapped although they are getting enough calories to live.“

Another “chilling” story from NY Times describes E.P.R. (Link: “Emergency Preservation and Resuscitation“) which involves rapidly chilling catastrophic trauma victims by draining their blood and replacing with cold salt water.  This has the potential to dramatically improve survival and has been effective in animal models.

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Are Biopsies Needed with a Normal-appearing Colonoscopy?

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“Colonoscopy in children routinely includes the practice of obtaining multiple biopsy samples even in the absence of gross mucosal abnormalities.”  This is the beginning of a recent report (JPGN 2014; 58: 773-78) which shows good agreement between endoscopic and histologic findings in a retrospective study of 390 colonoscopies.

Key findings:

  • “A known diagnosis of inflammatory bowel disease was a strong predictor of abnormal histology (OR 6.4 P<0.0001)”
  • 20 of 172 patients with a reportedly normal-appearing colonic mucosa had abnormal histology.  8 had a known diagnosis of IBD, 4 had symptoms/bloodwork highly suspicious for IBD, and another 3 were immunosuppressed.
  • The agreement rate (normal vs. abnormal) between pathologist and endoscopist was 84% with most of the disagreement when the endoscopist reported an abnormal finding whereas the pathologist reported normal histology.  This occurred in 11% of colonoscopies.

The authors “believe our data support the use of a combination of endoscopic appearance and evidence-based risk stratification to…reduce the number of biopsies obtained.”  “The symptom of abdominal pain as a primary indication for performing the procedure was an extremely strong negative predictor of histopathology. ”

Take-home message: If the colon appears normal and there is no prior evidence of IBD/along with reassuring laboratory studies, taking fewer biopsies is appropriate with colonoscopy in children.

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.  Endoscopy decisions should be determined by your 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.

Another Reason for Inflammatory Bowel Disease Patients to Take Vitamin D

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According to a recent study (Clin Gastroenterol Hepatol 2014; 12: 821-27), “in a large mulit-institutional IBD cohort, a low plasma level of 25(OH)D was associated with an increased risk of cancer, especially colorectal cancer.”  The study reviewed data from 2809 patients who vitamin D levels check (total cohort 11,028 persons with IBD); nearly a third had vitamin [25(OH)D] levels less than 20 ng/mL.  The median followup was 11 years.  During this period, 7% developed cancer (excluding nonmelanoma skin cancer).  Vitamin D deficiency was associated with an adjusted odds ratio of 1.82 of increased cancer risk.

Like so many other studies, this study is another reason for vitamin D manufacturers to feel pretty good.  The associated editorial provides some helpful context (pgs 828-30). The evidence regarding vitamin D dates back to at least 1980 when there was an observed higher incidence of colorectal cancer (CRC) mortality in regions with low solar radiation levels.  Similar findings were noted with breast cancer.

There is biologic plausibility to the importance of vitamin D with regard to cancer as it is involved in “cell signaling, cell proliferation, cell apoptosis, cell adhesion, angiogenesis and it can up-regulate tumor suppressor genes.” A number of reviews have shown an inverse relationship to vitamin D levels and CRC risk.

The editorial points out a number of potential flaws.  “For instance, those who had vitamin D measured may have been among the more ill patients…they may have been the most malnourished.”  “Whether patients had concurrent …primary sclerosing cholangitis was also omitted.”

Take-home message (from editorial): “Although the authors have identified an association, for several reasons it may be spurious…the jury is still out as to what impact maintaining normal vitamin D levels may have on reducing inflammation and modulating cancer risk in chronic inflammatory diseases. However, it is healthful to have adequate vitamin D.” In Manitoba, the authors recommend that all of their patients receive vitamin D supplementation.  In areas with more sun, checking levels may be worthwhile.

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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.

Gastric Emphysema -A Quick Pic

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A recent image (available online only N Engl J Med 2014; 370:e33) shows a clearcut case of gastric emphysema and the narrative explains the differential diagnosis:

“The differential diagnosis included infection, ischemia, and gastric-outlet obstruction due to volvulus, annular pancreas, intestinal malrotation, and duodenal hematoma or stenosis. Laparotomy revealed diffuse gastric and omental emphysema resulting from duodenal stenosis.”

Rotavirus Vaccine: 4-year Savings One Billion Dollars and Preventing Lots of Suffering

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A report from USA Today on the success of vaccination against rotavirus (Link: Pediatrics Rotavirus Study), here’s an excerpt:

“Vaccines against a common cause of infant diarrhea have kept hundreds of thousands of children out of the hospital, saving nearly $1 billion in their first four years, a new study shows.

The study is one of three reports in today’s Pediatrics that show the far-ranging impact of childhood vaccinations. The papers are being published as the USA faces its largest number of measles cases – 334 – in two decades. Current measles outbreaks are being fueled by parents who skip vaccines or avoid them altogether, according to the Centers for Disease Control and Prevention.

The first of the new studies focuses on rotavirus, which causes severe diarrhea and dehydration. In the first four years they were available, vaccines against rotavirus prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million doctor’s visits among children under 5, the study says. The vaccines saved an estimated $924 million during the same period, 2007 to 2011, according to the CDC study.”

While this study is not likely to change the ingrained beliefs of many who are opposed to vaccines (Parental Immunity (to Education) and Vaccine Decision …), perhaps humor will be more successful.  Here’s a terrific link from The Daily Show’s Samantha Bee: An Outbreak of Liberal Idiocy – The Daily Show – Video Clip …

Related blog post: Alan Alda (aka Hawkeye Pierce) on Communicating Science

ESPGHAN IBD Diagnostic Practice Recommendations -Revised Porto Criteria

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Recently ESPGHAN assembled an international group of European experts in pediatric inflammatory bowel disease (PIBD) to establish practice recommendations (JPGN 2014; 58: 795-806).  Their aim was “to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD.”

Before detailing some of their recommendations, I want to state my main criticism: these recommendations do not consider cost or cost-effectiveness. This is important since we do not live in a world where costs are irrelevant.

Some specific recommendations/observations:

1. “We recommend performing small bowel imaging in all suspected cases of IBD at diagnosis; this may be deferred in typical UC.”  In addition, all suspected cases of IBD should undergo esophagogastroduodenoscopy (EGD) and ileocolonoscopy.  “The diagnostic yield of an EGD to diagnose Crohn’s disease (CD) in patients with an otherwise normal workup [ileocolonoscopy/small bowel imaging] is ~7.5%. ”

2. The authors clarify the use of IBD-unclassified (IBD-U). “IBD-U should be …for patients with colitis and highly atypical findings.” Atypical findings for ulcerative colitis: include rectal sparing, and cecal patch (present in 2% of pediatric patients with left-sided colitis).  Table 3 suggests that if at least one “class 2” (rare feature) exists or at least 2 “class 3” (uncommon) feature exists, then labeling IBD-U is appropriate.

Rare (Class 2):

  • significant growth delay
  • histologic and gross sparing of rectum
  • transmural inflammation in the absence of severe colitis
  • duodenal or esophageal ulcers (not due to other causes)
  • multiple aphthous ulcerations in the stomach (not due to other causes)
  • positive ASCA in the presence of negative pANCA
  • mucosal inflammation more severe in proximal colon

Uncommon (Class 3):

  • severe scalloping of stomach or duodenum (not due to other causes)
  • focal chronic duodenitis (not due to other causes)
  • aphthous ulcerations in the colon

3. Crohn’s disease, according to Table 3, should be diagnosed with any of the following:

  • well-formed granulomas anywhere in the GI tract, remote from a ruptured crypt
  • deep serpentine ulcerations, cobblestoning or stenosis anywhere in the small bowel
  • fistulizing disease
  • ileal inflammation in the presence of normal cecum

4. “Normal blood tests do not exclude the diagnosis of IBD”… Fecal markers (eg. calprotectin) are “extremely sensitive in the detection of mucosal inflammation but are not specific for IBD.”

5.”Although small bowel imaging is encouraged in all of the patients with suspected IBD, it is essential in pediatric patients with CD, IBD-U, or atypical UC.”  Magnetic resonance enterography (MRE) is currently the imaging modality of choice in PIBD.  Wireless capsule endoscopy (WCE) is a “useful alternative.”  The authors advocate for imaging because it may “detect small intestinal involvement…and identify disease complications.”

6. Evaluation for primary immune deficiency should be performed in all cases of PIBD  diagnosed <2 years of age.

While the authors acknowledge that “clinical considerations may require taking a course of action that varies from these criteria,” nevertheless, they are likely to influence clinical practice.  My personal belief is that there are many situations in which small bowel imaging will not result in changes in clinical care.  Furthermore, many patients, especially younger patients, would require anesthesia in order to complete a MRE which is an added burden.  In addition, with the added emphasis on assessing response to therapy, one could envision that some patients would be better served with imaging after implementing treatment.

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Another Study Supporting Enteral Therapy for Crohn’s Disease

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Here’s the link (Enteral Nutrition Study) from a summary of the study in Healio Gastroenterology (from their twitter feed) and an excerpt:

Frivolt K. Aliment Pharmacol Ther. 2014;39:1398-1407.

A retrospective study of all pediatric Crohn’s disease (CD) patients treated with exclusive enteral nutrition (EEN) at a children’s hospital in Munich between January 2004 and June 2011. Fifty-two included patients (mean age, 13.2 years; 59.6% male) had newly diagnosed CD (n=40) or had relapsed (n=12) while maintaining treatment for at least 3 months….The first course of EEN showed a higher median starting wPCDAI score compared with the second (59 vs. 40; P<.0001), as well as higher remission rates after 3 months (92% vs. 77%). Relapse rates after 1 year were comparable (67% vs. 70%), but fewer relapses occurred in the first 120 days after the first EEN course compared with the second (25% vs. 45%).

Of 48 patients with NOD2 genotype, 44 went into remission with EEN; 11 of 12 patients carrying R702W or G908R genotype relapsed within 1 year; and there were significantly lower rates of relapse in patients with wild-type (60%) or 1007fs (50%) mutations.

 

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Change the Name: “Functional” is Lousy

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A recent commentary explains why “functional” pain is such a lousy term (JAMA Pediatr. Published online June 02, 2014. doi:10.1001/jamapediatrics.2014.530 –thanks to Ben Gold for this reference).  In pediatric GI practice, functional gastrointestinal disorders (FGIDs) constitute a large part of clinical work.

The author, Neil Schechter from the Chronic Pain Program in Boston, makes several important observations:

  • “There is general dissatisfaction with the terminology.”  This stems from the fact that “in common parlance today, functional disorders are typically assumed to be a product of psychological distress.” Yet, parents/patients are “not ready to accept a strictly psychological explanation.”
  • The idea that functional pain is solely a psychological disturbance is inaccurate.  Though, anxiety and depression are common associated problems which often contribute to symptoms.  He states that “hyperexcitability” of the nervous system is “the core biological link and final common pathway for the creation of functional pain disorders.”
  • This category should be labeled dysfunctional pain.  “In effect, calling pain ‘functional’ is like calling disease, ‘ease.'”
  • These disorders frequently respond to centrally acting therapies including antidepressants, anticonvulsants, exercise, cognitive behavioral therapy, and acupuncture.
  • “The search for an appropriate term for these pain problems is far more than semantic…[a patient’s] understanding of their illness is clearly linked to their compliance with medical advice…it may stem their desire for additional costly investigation.”
  • Dr. Schechter proposes the term “primary pain disorder.”  “Unlike Shakespeare’s rose, functional pain would benefit from a new name.”

Take-home message: I wish I had written this commentary.  Explaining “functional” pain and “irritable bowel syndrome” are Sisyphean tasks.  Better nomenclature could ease the burden.  Join me in abandoning the use of the word “functional.”

In the same issue, an editorial on the “Role of Celiac Disease Screening for Children with Functional Gastrointestinal Disorders” (JAMA Pediatr. 2014;168(6):514-515. doi:10.1001/jamapediatrics.2013.5418) comments on a study (JAMA Pediatr. 2014; 168(6):555-60) in the same issue which reports a 4-fold higher prevalence of celiac disease among children who meet clinical criteria for irritable bowel syndrome.  The study reports the results from a cohort of 992 children identified with recurrent abdominal pain in a primary care setting.  In the editorial, the authors note:  “When grouped together, the prevalence rate of celiac disease among all children with FGIDs (IBS included) approaches 2%.  Celiac disease screening in this population would result in a positive tTG-IgA test result in 4%…However, 53% of all positive test results would be falsely elevated.”  As such the editorial advocates in favor of screening for celiac disease in children with IBS but not all FGIDs.

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Treating to Target

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As alluded to in a previous post (CCFA Conference Notes 2014 (part 2) | gutsandgrowth), there has been increasing discussion and efforts aimed at mucosal healing (MH) because it is associated with improved clinical outcomes in patient’s with Crohn’s disease (CD).  Even before its print publication, this study (Clin Gastroenterol Hepatol 2014; 12: 978-85) by William Sandborn’s group has influenced the discussion.

This retrospective study analyzed 67 patients with CD (2011-2012).  These 67 were selected from a population of 510 patients seen at UCSD who had at least several endoscopies and ulcers  seen at the initial procedure.  In this cohort of 67 patients, the median disease duration was 9.8 years.  Only 26 (38.8%) were naive to both immunosuppressives and biologics at referral.

Key findings:

  • Only half of the patients achieved MH.  “After a median follow-up of 62 weeks, 50.7% had MH and 61.1% had endoscopic improvement.”  79% of those who underwent adjustments achieved MH.
  • Clinical symptoms do not correlate with MH. “40.9% of patients experienced clinical symptoms despite MH and 18.8% of patients without clinical symptoms had significant endoscopic lesions.”
  • Biomarkers may be effective at predicting MH. “None of the patients with MH had an increased concentration of CRP.”
  • Adjusting treatment is needed if abnormal endoscopy; this is inherent in the philosophy of treating-to-target.

The authors conclude that “serial endoscopic procedures to guide treatment to the goal of MH is feasible in clinical practice.” Ultimately the goal is to influence the natural history of Crohn’s disease.

Study limitations:

  • retrospective study
  • small number of highly-selected patients
  • lack of randomization
  • definition of MH remains debated
  • no cost data
  • lack of data on stool biomarkers (e.g. calprotectin) which could serve as alternative
  • no answer to the question of what to do for the patient without MH who is receiving ‘maximal medical treatment’

From Dr. Sandborn: (from Healio Gastro summary):

“Evidence has accumulated that the complications of Crohn’s disease [CD] … are due to chronic inflammation that has not been fully treated,” William J. Sandborn, MD, chief of the gastroenterology division and director at the University of California, San Diego, IBD Center, told Healio.com. “This in turn has led to the concept of ‘treat to target’ in which patients are assessed with endoscopy for active inflammation prior to making important changes in therapy, and then reassessed with endoscopy within 4 to 6 months to ensure that the therapy change healed the bowel and resolved the inflammation.

“If active disease persists at endoscopy, even in the absence of clinical symptoms, then therapy is intensified and this cycle is repeated until mucosal healing (MH) is achieved.”

Take-home message: This study is one of many that are likely to influence the practice of clinicians to prove that the treatment is exerting a biologic effect and not solely improvement in clinical scoring indices.  With the emergence of multiple modalities to assess improvement, including biomarkers and imaging, it is not clear that repeated endoscopy will be the best assessment tool.

Related blog post: EXTEND & MUSIC: Optimizing Crohn Disease Care …

Also noted:

Clin Gastroenterol Hepatol 2014; 12: 986-94.  “Association Between Telephone Activity and Features of Patients with Inflammatory Bowel Disease.”  The authors found that 15% of patients were responsible for half of all telephone calls.  These patients were more likely to be seen in ED and hospitalized.

Clin Gastroenterol Hepatol 2014; 12: 929-34. “Histologic Remission: The Ultimate Therapeutic Goal in Ulcerative Colitis?” This article reviews definitions for histologic remission and highlights questions that need to be addressed before histologic remission is used more widely as a clinical endpoint in trials and in practice.

Antibiotics, Oral Contraceptives, and IBD

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Briefly noted:

“Physician Knowledge Regarding Concomitant Antibiotic and Oral Contraceptive Use in Patients with IBD.” Gastroenterology & Hepatology 2014; 10: 302-06.

Key finding:

  • IBD specialists and gynecologists were more likely to be aware that no evidence exists to support a link between a decrease in oral contraceptive pill (OCP) efficacy and concomitant use of ciprofloxacin or metronidazole.

Previous studies suggested that antibiotics reduced OCP efficacy.  The authors note that “more recent, prospective, pharmacokinetic studies in women demonstrate no evidence of an interaction between OCPs and most antibiotics, with the exception of rifampin.” (J Am Acad Dermatol 2002; 46: 917-23)

 

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.