Fecal Microbiota Transplantation: How important is the BMI of the stool donor?

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Currently fecal microbiota transplantation (FMT) “best practices” exclude obese stool donors based on a report of germ-free mice gaining weight after FMT from mice with obesity and based on a case report of an individual with 34 pound weight gain after FMT.

A recent report (M Fischer et al. Clin Gastroenterol Hepatol 2018; 16: 1351-3) suggests that the the BMI of the stool donor does not affect recipient weight after a single FMT procedure for C difficile infection.

This analysis included 173 patients with a mean age of 57 years.  One group of 103 were from a randomized control trial; in this group, 66 (64%) received FMT from a normal weight (BMI 18-24.9) donor and 37 (36%) received FMT from an overweight (BMI 25-29.9) donor. Among an additional 70 individuals from an observational cohort, 25 received FMT from normal weight donor, 30 received FMT from overweight donor, and 15 received FMT from an obese donor.

Key finding:

  • There was no significant difference in BMI among the FMT recipients up to 48 weeks after a single FMT.  Based on data from Figure 1, patients who received FMT from normal weight donor had slightly higher mean weight gain at 48 weeks afterwards (not statistically-significant)

The authors caution that a prospective study is required to confirm these findings and in the interim, they recommend exclusion of obese/overweight FMT donors.

My take: There are plenty of willing stool donors –so who knows if this will ever be examined adequately.  This study challenges the idea that FMT from an obese donor will result in recipient obesity, presumably via changes in the microbiome.

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Exclusive Enteral Nutrition for Crohn’s Disease -Less Effective in Those with Isolated Colonic Disease

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A recent study (Y Xu. Clinical Nutrition 2018; https://doi.org/10.1016/j.clnu.2018.08.022) showed that exclusive enteral nutrition (EEN) is less effective in patient’s with Crohn’s disease with isolated colonic disease.

Abstract Link: Isolated Colonic Crohn’s Disease is Associated with a Reduced Response to Exclusive Enteral Nutrition Compared to Ileal or Ileocolonic Disease

This was a retrospective study of 241 adults: 52 patients in the cCD (isolated colonic disease) group and 189 patients in the non-cCD group.

Key findings:

  • “The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2 –6.23], P = 0.016).”
  • “Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group.”

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This Makes Me Mad…Immigration Policy

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When our government takes actions on behalf of our country, this reflects on all of our values.  So, earlier this year I was disgusted and angry when I learned that as part of a ‘zero tolerance’ rule, young children were separated from their parents and placed in something akin to cages.  For me, this is a stain on our country’s history that could be compared to other atrocities like the Tuskegee experiments and Japanese internment during WWII.  While this policy was more short-lived, there are still children separated from their parents and for the children involved the consequences could be life-long.  Sadly, our entire country is responsible because we elected this administration which adopted these policies.

Now, this administration which seems incapable of any shame, is planning more steps that should make decent persons upset. Additional threats to lawful immigrants are being devised (KM Perreira et al. NEJM 2018; 379: 901-3).

“Under current guidelines, persons labeled as potential public charges can be denied legal entry to the United States” and in some cases deported.  Public-charge guidelines aim to keep immigrants from relying on public charges (eg. cash-assistance programs like welfare) for the first 5 years after admission to the U.S.

“The Trump administration is proposing sweeping changes to these [public-charge] guidelines.”  One of these proposed expansions of public-charge determination is including enrollment for Obamacare, which is legally mandated and which can include subsidies.  Another target is the Children’s Health Insurance Program.  As a consequence of these guideline changes, instead of ~3% of lawful immigrants being considered as receiving a public charge, if adopted, this would increase to a range from 32% to 47%.

If these policies are adopted, this is likely to have a lot of adverse health consequences.  Immigrants, including U.S.-born children, will be less likely to receive health care and more likely to be food insecure; 25% of U.S.-born children of immigrants currently receive SNAP (supplemental nutrition assistance program) benefits. Health consequences will affect millions and include an increase in low birth infants, increased infant mortality, and increased maternal morbidity.

For health care providers and institutions, implementation of these policies is likely to result in higher costs from uncompensated care.

In related commentaries (BL Grace et al. NEJM 2018; 379: 904-5, M Martin. NEJM 2018; 379: 906-7), the authors note the following points:

  • “Current immigration policies are undermining trust in U.S institutions…and changing the way immigrants and refugees seek health care.”  Many are worried that seeking health care could lead directly or indirectly (after providing information) to deportation
  • “Even naturalized citizens fear that their status is no longer secure.”
  • “I feel sad that my colleague’s 6-year-old patient has nightmares and urinary incontinence because she is terrified her parents will be deported.  Sad that my patients fear coming to the hospital despite grave illness out of panic that someone will ask about their immigration status.”

My take: We are all accomplices (many unwitting) in the roll out of these detrimental policies that are now affecting lawful immigrants..

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“If this was celiac, why didn’t it stop when she cut out gluten?”

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Here’s a link to a well-described case report. Her Searing Gut Pain Suggested Celiac Disease. Why Didn’t Cutting Out Gluten Help?

This 57 year old with ‘presumptive’ celiac disease did not improve with a gluten-free diet.  After an initial self-diagnosis and subsequently an endoscopy that also suggested celiac disease, she did not improve.  While the doctors involved in her care had labeled her ‘noncompliant,’ it turns out she did NOT have celiac disease and improved after the right diagnosis (diagnosis noted at bottom of this post).

My take: There are several entities that can mimic celiac disease (even histologically), including Crohn’s disease, Autoimmune enteropathy, CTLA4 deficiency, and Whipple’s disease (the diagnosis in this case).  When someone is not getting better, the diagnosis needs to be reconsidered.

Effects of Surgical Shunts on Liver Atrophy in Patients with Noncirrhotic Portal Vein Thrombosis

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A recent study (AS Elnaggar et al. Liver Transplantation 2018; 24: 881-87; editorial 868-9) examine the effect of different types of surgical shunts in the setting of portal vein thrombosis (PVT).  The authors examined surgical shunts from 1998-2011 in their institution (senior author: Jean Emond).

  • 40 patients received “portal flow-preserving shunts”: 32 mesoportal and 8 selective splenorenal
  • 24 received portal flow-diverting shunts (16 nonselective splenorenal and 8 mesocaval)
  • Of these 64 patients, only 39 had preoperative and postoperative cross-sectional imaging.   In addition, only 11 patients who had mesoportal shunt (7 children and 4 adults) had preoperative and postoperative cross-sectional imaging allowing for volume comparison.

Key finding:

  • In patients receiving portal flow-preserving shunts (mainly mesoportal), this was associated with liver volume expansion (886 versus 1131 cm to the third), whereas diverting shunts were not.

The authors note that liver atrophy, especially in children, can have a “significant effect on cognitive function and somatic growth.”  Thus, restoring portal flow may improve adverse effects that PVT has caused.

Limitations:

  • Lack of validation of their formula to calculate liver volumes in the pediatric age group
  • Relatively short follow-up:5.7 months in the portal-preserving group and 11 months in the other group
  • Small numbers of patients..

Long-term followup of patients who have needed surgical shunts is needed.  For mesoportal shunts, strictures have been noted in the hepatic end in 15% of patients.

My take: This study shows that portal blood flow, which was interrupted by PVT and restored by mesoportal (Rex) shunt, is important in maintaining liver mass. So, while all shunts may stop upper GI bleeding, mesoportal shunt is likely to improve other adverse effects of PVT.

Virginia Museum of Fine Arts (Richmond) has acquired Chihuly’s Red Reeds

Are We Making Progress on Infant Sleep-Related Deaths? (Not anymore)

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An interesting commentary (KP Quinlan. JAMA Pediatrics; 2018; 172: 714-6) points out the need for better surveillance and prevention efforts for sudden unexpected infant deaths (SUIDs).

Key points:

  • Since the late 1990s, there has NOT been significant improvement in SUID.  In 1999, there were 3716 SUIDs compared with 3684 in 2015.
  • This rate of SUID is 9 times the rate of deaths to motor vehicle crashes for an 18 year-old driver.  The author notes the driving-related fatalities have declined by ~50% for persons younger than 20 years since 2000.
  • Promotion of safer sleeping habits is important. Bed sharing raises the SUID risk but is commonly practiced by parents from all backgrounds.
  • There is very little publicity of this problem and there is not a systematic surveillance system.  . How often do we here about a teenager involved in a crash and how often do we here about an infant with SUID? If there was more awareness of this danger, it is likely that there would be more actions taken

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Useful website: Charlieskids.org This website has a book called “Sleep Baby Safe and Snug” which incorporates updated recommendations on safe sleep practices.

Children should sleep in the same room but on a separate surface from their parents for at least the first six months of their lives, and ideally the first year. They say that this can halve the risk of SIDS…You can read the AAP’s full guidance here. These are a few more of the pediatricians’ recommendations:

  • Infants under a year old should always sleep lying on their backs. Side sleeping “is not safe and is not advised,” the AAP says.
  • Infants should always sleep on a firm surface covered by only a flat sheet. That’s because soft mattresses “could create a pocket … and increase the chance of rebreathing or suffocation if the infant is placed in or rolls over to the prone position.”
  • Any other bedding or soft objects, like pillows or stuffed animals, could obstruct a child’s airway and increase the risk of SIDS and suffocation, according to the AAP.
  • The pediatricians say breastfeeding reduces the risk of SIDS.
  • The same goes for pacifiers at nap time and bedtime, although the doctors say the “mechanism is yet unclear.” They add that “the protective effect is observed even if the pacifier falls out of the infant’s mouth.”
  • Smoking – both during pregnancy and around the infant after birth – can increase the risk of SIDS. Alcohol and illicit drugs during pregnancy can also contribute to SIDS, and “parental alcohol and/or illicit drug use in combination with bed-sharing places the infant at particularly high risk of SIDS,” the pediatricians say.

Pain in Children with Severe Neurologic Impairment

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A recent commentary (JM Hauer JAMA Pediatrics; 2018. doi: 10.1001/jamapediatrics.2018.1531) addresses a common misconception regarding children with severe neurologic impairment (SNI):

“we don’t think she experiences pain”

She notes that literature since 2002 has challenged this assumption and that this is addressed in a new AAP clinical report as well (Hauer J, Houtrow AJ. Pediatrics 2017; 139: e20171002).

Key points:

  • Children with SNI may have moaning, grimacing, changes in tone/body position in reaction to pain and treatment can make them comfortable.
  • “We can never prove that such a child does not feel pain…When parents of children with hydranencephaly were asked whether their child felt pain, 96% indicated yes.”
  • Pain can trigger changes in catecholamines, cortisol and stress hormones.  “These considerations suggest that untreated chronic pain is more harmful to the well-being of children with SNI than is treatment used for pain.”
  • Sometimes no source for pain is identified.  This may be related to a CNS etiology (alteration of CNS) and may benefit from treatment.
  • “It is time to do away with the question of whether these children feel pain and focus on how we as individuals” identify/consider pain

My take: Reframing this issue is important; pain can occur in children with SNI.  At the same time, we have to be careful that some “palliative” measures could paradoxically prolong suffering in some children.

Related blog post: Suffering