Gut Microbiome, Crohn’s Disease and Effect of Diet

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At this past year’s NASPGHAN conference, Bob Baldassano indicated that a low-residue diet probably does not makes sense for the majority of patients with Crohn’s disease because it would not promote a ‘healthy’ gut microbiome.  Another article (Walter SS, Quiros A, et al. SOJ Microbiol Infect Dis 2014; 2: 1-13) supporting this argument has been published. (Thanks to Ben Gold for giving me this reference.)

In this study, the authors examined the gut microbiome from two healthy volunteers and compared them to six patients with Crohn’s disease (CD) (ages 16-50).  The CD cohort were in clinical remission and were not receiving probiotics.  Subjects were randomized to either a low-residue diet (LRD) or a specific carbohydrate diet (SCD).

Besides having some cool figures to explain their results, the key points:

  • The complexity of the gut microbiome was lower in IBD patients compared to healthy controls
  • Bacteroides fragilis was increased in fecal samples of IBD positive patients
  • There was a temporal response of gut microbiome to SCD with increased microbial diversity while the LRD diet was associated with a reduced diversity of the microbiome in patients with CD

While the number of patients participating in this study are low, the affects of these diets can still be measured due to the trillions of microbes in the gut microbiome.

Also noted: Church PC, Turner D, et al. Aliment Phamacol There 2015; 41: 153-66. “Systematic review with meta-analysis: magnetic resonance enterography for the detection of inflammation and intestinal damage in Crohn’s disease.”

How the gut micro biome may affect other diseases including Multiple Sclerosis: Study Hints Gut Microbiome Plays a Role in Multiple Sclerosis (Link to Gastroenterology & Endoscopy News)

Related blog posts:

From NASPGHAN:  Introducing New Website for Teens with Inflammatory Bowel Diseases: JustLikeMeIBD.org  PRESS RELEASE

New York, NY- January 20, 2015 – The number of inflammatory bowel disease (IBD) patients in the U.S. has now increased to an estimated 1.6 million, with approximately 5 percent of that patient population under the age of 18. In response to the growing number of kids with IBD, the Crohn’s & Colitis Foundation of America (CCFA) along with the NASPGHAN Foundation for Children’s Digestive Health and Nutrition, has launched a new website called “Just Like Me” for teenagers with Crohn’s disease and ulcerative colitis.

The interactive site will feature stories and videos from teens with IBD as well as information on school, dating, stress, diet, and research.

 

 

How Bilingual Studies Reflect a Deeper Scientific Flaw

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A recent story on NPR explored the purported advantages of bilingual acquisition.  Previous reports have suggested that individuals with bilingual education attain other advantages in learning and “executive” function.  This may be a bunch of bunk and more related to scientific journals bias of reporting “positive” studies.  If you listen to the report (link below), consider how the problem of reporting bias affects so many fields in medicine and science.

Link: Bilingual Studies Reveal Flaw In How Info Reaches Mainstream

Somewhat related post:

 

The Best Way to Handle Vaccine Skeptics

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According to a recent NY Times editorial, the best way to improve vaccination rates is not to mandate universal vaccination or to label ‘anti-vaxxer’ parents as ignorant.  The best way is to make it more difficult to receive personal exemptions –this is something the government can be quite good at.

Here’s the link: How to Handle Vaccine Skeptics -NY Times

Here’s an excerpt:

They [States} can require parents to write a letter elaborating on the reason their child should be exempt. They can require that the letter be notarized. They can insist that parents read and sign a form that discusses the risks of nonvaccination. Better yet, they should mandate in-person counseling so that the decision not to vaccinate is truly informed.

States can also require that parents obtain an exemption form by specifically requesting one from the state or local health department, rather than downloading it online. They can insist that these parents acknowledge that they will be responsible for keeping the children away from school during outbreaks. Moreover, they should have procedures to review each request for exemption rather than automatically approving them, as many states do now. And they should require parents with exemptions to apply annually for renewal…

 In a 2012 study, which my colleagues and I [Saad Omer] published in The New England Journal of Medicine, nonmedical exemption rates were 2.3 times higher in states with easy administrative policies for granting exemptions (like Connecticut, Missouri and Wisconsin) than in states with difficult policies (like Florida, Minnesota and Texas). Moreover, the annual rate of increase in nonmedical exemptions was about 60 percent higher in states with easy exemption policies compared with states with difficult policies.

“Origins of Cystic Fibrosis Lung Disease”

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Origins of Cystic Fibrosis Lung Disease — NEJM (NEJM 2015; 372: 351-62) is a good read.  The authors note that the basic defect in Cystic Fibrosis (CF), the loss of the cystic fibrosis transmembrane conductance regulator (CFTR), has been recognized for a long time.  However, the connection between this defect and the progressive lung disease/inflammation has remained uncertain.

Now, new animal models have provided a wealth of information that closes the knowledge gap.

Here are the key points:

  • CF affects the lungs very early: Bronchiectasis is present in nearly one in three children with CF by 3 years of age and CT scans are abnormal in most babies with CF as early as 3 months of age.
  • Infection precedes inflammation: “During the first hours after birth, piglets with CF show no evidence of inflammation in their airways…yet,…they fail to eradicate bacteria as well…[which] can initiate a cascade of airway inflammation and airway remodeling.”
  • There are multiple “hits” on the airways.  While many have suggested that increased sodium leads to a ‘dehydrated’ state, this does not seem to be correct.
  • More recent studies point to loss of bicarbonate secretion as a crucial factor.  This results in a reduced pH which in turn leaves the lungs more vulnerable to infection.  Lower acidity reduces the effectiveness of a “complex soup of antimicrobial peptides, proteins, and lipids in airway-surface liquid.”
  • Poor mucociliary transport, “which guards the lungs by trapping invading pathogens and particulates in mucus,” is another important “hit” on the lungs.

Implications:

  • CF needs to be diagnosed early and treated early
  • Improving even one of these defects in host defenses is likely to be beneficial.
  • Animal models remain important in understanding pathophysiology.  They allow “investigating the disease at its genesis and before the onset of secondary manifestations.”

Related blog posts:

Progress in Cystic Fibrosis over 18 Years

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A recent study (J Pediatr 2014; 165: 1091-7) showed significant improvement in lung function among 6-year-olds with Cystic Fibrosis (CF) between 1994-2012.

Using the Cystic Fibrosis Foundation Patient Registry with a total of 11,670 children, the authors found that the mean FEV1 and FVC z-scores increased significantly over the period in the entire cohort.  In addition, the height-for-age (HFA) also improved.  These results are easy to see graphically in Figures 1 & Figure 2.  The authors note that in 2012, children who were identified by screening had improved HFA, FEV1, and FVC compared to children who were not identified by screening.

Take-home points:

  • These data show impressive improvement in lung function and growth over the past two decades
  • These values are going to improve further now that all 50 states mandate newborn screening for CF
  • While there is improvement, 6-year-olds with CF still have measurable pulmonary dysfunction; thus, more work is needed, perhaps with novel therapies.

Related blog posts:

What We Know Now: Therapeutic Drug Monitoring for Inflammatory Bowel Disease

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This blog has discussed the utility of obtaining drug levels for both biologic agents and thiopurines.  A recent article (Inflamm Bowel Dis 2015; 21: 182-97) provides a concise up-to-date review.

Here are the key points:

  • Primary nonresponse to anti-TNF therapy (PNR) “is most commonly defined as lack of improvement of clinical signs and symptoms after the induction phase leading to discontinuation of the drug.”
  • “We think that patients who respond but fail to achieve remission…are likely almost all due to insufficient drug.”
  • Table 2 provides a list of predicting factors, both negative and positive, for PNR.  This list includes genetic mutations (e.g.. IL23R, NOD2/CARD15 variant), mucosal gene expression, clinical factors (e.g. young age, isolated colitis, smoking, nonstricturing disease, concomitant immunomodulators) and serologic (eg. CRP, hemoglobin, and presence of pANCA).
  • Patients with PNR to a TNF antagonist, “despite therapeutic concentrations of drug and no anti-drug antibodies (ADA), would likely benefit from a switch to an alternative drug with a different mechanism of action.”
  • “Patients with a high baseline inflammatory load…and increased clearance of drug because of a high turnover would likely benefit from higher induction doses.”  This hypothesis has been proven in rheumatoid arthritis patients in which patients with high TNF concentrations had a clinical response to 10 mg/kg that was “significantly better than the response to 3 and 6 mg/kg of infliximab.”
  • Patients (with ADA) with an “early immunogenic response against the TNF antagonist are unlikely to respond to dose escalation and thus should be switched to another TNF antagonist, and it should be considered to give higher induction doses in combination with an IMM [immunomodulator] to reduce the risk of immunogenicity.”

Take-home message: New definition of primary nonresponse to anti-TNF agent: “a lack of improvement of objectively assessed signs of active inflammation at baseline, after the induction phase despite the presence of adequate concentrations of drug and the absence of anti drug antibodies.”

Also noted: “Surgical management of ulcerative colitis in the era of biologicals” Inflamm Bowel Dis 2015; 21: 208-10. Key point: “Sacrificing the non responsive diseased colon is an underused or unnecessarily delayed chance to normalize ..health and life.”  “Deconditioning of patient with unreasonably long escalations of ineffective medications adds to the morbidity of surgical intervention.”

“Automimmune Features are Associated with Chronic Antibiotic-refractory Pouchitis”Inflamm Bowel Dis 2015; 21: 110-20. Key point: “Microsomal antibody expression and elevated IgG4-positive plasma cell infiltration were independent risk factors” for chronic antibiotic-refractory pouchitis.”

Update on MOC (recent blog:Resistance to Maintenance of Certification | gutsandgrowth) American Board of Internal Medicine “We Got It Wrong” “We launched programs that weren’t ready and we didn’t deliver an MOC program that physicians found meaningful. We want to change that.”

Related blog posts:

“Using Drugs to Discriminate”

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A recent commentary (Jacobs DB, Sommers BD, NEJM 2015; 372; 399-402) highlighted a growing problem.  Many insurers are using drug benefit plans to dissuade sicker people from enrolling in their plans.

Prior to the Affordable Care Act (ACA), insurers charged high premiums to people with chronic conditions.  The ACA attempted to address this problem; in fact, the “individual mandate” was necessary to make sure that insurance companies had enough healthy people in their insurance pool to make it financially feasible.

Yet, insurance companies make more money if they can limit insuring sicker, chronically-ill people.  One way this is happening is through “Adverse Tiering” which substantially increases out-of-pocket expenses for individuals with HIV, cancer, diabetes, mental illness, and arthritis. The difference in out-of-pocket costs, for example, with for each HIV drug was more than $3000 (on average) between adverse-tiered plans and those that were not adverse-tiered.  Even for generic drugs, the cost was nearly a $2000 difference.

A few problems with this approach:

  • Insurer’s drug prices are not usually available to public when choosing a plan; thus, these higher out-of-pocket costs are often unanticipated. (*Price transparency could accelerate rather than hinder this process.)
  • If sicker patients flock to plans without “adverse tiering,” this could make these non-adverse-tiered plans lose money and result in similar design to avoid “adverse selection.”

Conclusion: “Preventing [this adverse tiering and] other forms of financial discrimination on the basis of health status — with the attendant risks of adverse selection in the marketplace –will require ongoing oversight.”

Here’s the NY Times Report on this study: Study Finds HIV Drugs Priced Out of Reach

Related blog post:

 

“Weekend Effect” –From the Other Side of the Bed

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Many times when I’m working at the hospital on a weekend I’ve wondered how long hospitals can continue to offer fewer services during weekends than during the work week.  Usually if I’m there, I don’t want to hear that something has to wait until Monday.  It also puts me in the uncomfortable position of deciding whether something is urgent enough that on-call staff (eg. radiology, anesthesiology) need to be called in.  At the same time, some services in the hospital, for example, interventional radiology may have only one or two people who are qualified and it is unrealistic to expect them to be available 24/7/365.

A recent commentary (Klass P, NEJM 2015; 372: 402-405) helps provide a family’s perspective regarding this situation. Here are some of the key points:

  • “It can be shocking to hear, over and over, about the ways that weekends are slower and things don’t get done.”
  • Often many services are absent like physical therapy and psychiatry.  Most other services are understaffed and “cross-covering” patients with less familiarity.
  • For many conditions, morbidity and mortality are higher on weekends. (J Pediart Surg 2014; 49: 1087-91, NEJM 2001; 345: 1580, JAMA 2008; 299: 785-92))
  • “When you’re sick and scared, Sunday is the same as Tuesday.”

Bottomline: This commentary makes a strong case for saying “the hospital is not actually about patients. It’s about doctors and nurses, physical therapists and nutritionists.”

Question: Do you think weekend staffing should change or will change to address these shortcomings?

Related blog post:

Related link:

 

Cool Mirror at High Museum

Cool Mirror at High Museum

What to Fear in 2015

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From Parade Magazine,  What to Fear in 2015:

An excerpt:

Here are a few of the things you should and should not fear in 2015:

  • Flu not Ebola
  • Domestic violence not serial killers, pedophiles
  • Heart disease not Mercury in fish
  • Not getting enough dietary fiber not gluten
  • The re-appearance of measles, whooping cough, and other preventable diseases not vaccine side effects
  • Texting while driving not air travel
  • Malware on your cell phone not bulk password theft
  • Gun violence among young people not school shootings/mass murders
  • Sitting too much not heart attacks during exercise

Another link on the measles epidemic from NY Times: Vaccine Critics Defensive. Another editorial remarked on how Ebola which is much less contagious than the measles alarmed so many people in this country; it stated that if a terrorist, rather than parents refusing vaccinations, had unleashed a highly contagious virus on our communities, many would be calling for military retaliation. Unfortunately, it takes a measles epidemic to provide a passionate argument for immunizations. Related blog post: 1400 Different Immunization Schedules -What Could Go Wrong …

From NBC News Measles Vaccine FAQ

Leptin Deficiency and Early-Onset Extreme Obesity

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A brief report (NEJM 2015; 372: 48-54) details a case of 2.5 year old who weighed 33.7 kg (>99.9% and z score of 7.2) and had BMI of 38.6 (>99.9% and z score of 5.8).

Link to article (and picture/growth curve)

The authors determined that he had a mutation which caused biologically inactive leptin.  Subsequently, treatment with metreleptin injections, improved eating behavior and resulted in substantial weight loss.

Key points:

  • “Current clinical recommendations advise that leptin serum concentrations be measured in children who have rapid weight gain in the first months of life.” (“The severely obese patient –a genetic work-up.” Nat Clin Pract Endocrinol Metab 2006; 2: 172-7)
  • This case report demonstrates that normal circulating levels of the hormone “do not rule out disease-causing mutations in the gene encoding leptin.”

Related blog posts:

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