Not Curing Obesity with Fecal Microbiota Transplantation & More on Remdesivir

A recent pilot (n=22) double-blind study (JR Allegrett et al. Clin Gastroenterol Hepatol 2020; 18: 855-63) pours cold water on the idea that repopulating one’s microbiome would be helpful in treating obesity.

In this study, the authors examined obese patients without diabetes, nonalcoholic steatohepatitis, or metabolic syndrome.  In the treatment group, patients received FMT by capsules: 30 capsules at week 4 and then a maintenance dose of 12 capsules at week 8.  All FMT was derived from a single lean donor.

Key findings:

  • There were no significant changes in mean BMI at week 12 in either group.
  • Patients in the FMT group had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001).  In addition, bile acid profiles became more similar to the donor.

My take: Though this was a small study, it suggests that changing the microbiome by itself is likely insufficient to result in significant weight loss.

Related blog posts:

JH Beigel et al. NEJM DOI: 10.1056/NEJMoa2007764 (May 22, 2020): Full text: Remdesivir for the Treatment of Covid-19 — Preliminary Report

This was a a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement (n=1063).

Key findings:

  • Faster recovery for remdesivir recipients: 11 days vs 15 days
  • Lower mortality rate: 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70, 95% CI, 0.47 to 1.04) (mortality difference did not reach statistical significance)

 

 

Celiac Studies -Increasing Prevalence (Italy) and Nonadherence Risks

S Gatti et al. Clin Gastroenterol Hepatol 2020; 18: 596-603.   The authors screened 4570 children (5-11 year olds) from 2015-16; this study included 80% of eligible children from two metropolitan areas in Italy.

Key findings:

  • 77 cases of children met diagnostic criteria for celiac disease (54 met criteria and 23 prior known cases)
  • Prevalence in this population, overall, was 1.58% (2015-16); in 1993-95, the adjusted prevalence was 0.88%
  • Celiac disease autoimmunity was noted in 96 .
  • 1960 (43%) had celiac disease associated haplotypes

A Myleus et al. Clin Gastroenterol Hepatol 2020; 18: 562-73.  In this systematic review, 49 studies (out of initial 703) were included in final analysis to determine risk factors and outcomes with nonadherence to treatment with gluten free diet.

Key findings:

  • Large range of adherence rates: 23% to 98% (median rates were 75-87%).
  • Adolescents were at increased risk of non-adherence
  • Children whose parents had good knowledge had higher adherence rates
  • There was not improved adherence over time, despite improvement in palatable gluten-free foods.

One of the other findings in the study was the lack of consensus about what defines strict adherence and how to measure it.

My take: The first study is in agreement with many others which have demonstrated higher prevalence of celiac disease now compared to previously.  The second study shows that adherence with treatment is highly variable and difficult to measure.

Related blog posts:

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UNC Campus Pic (Chapel Hill)

Using Spot Urine Sodiums

A recent study (AKN Pedersen et al. JPEN https://doi.org/10.1002/jpen.1593) shows the utility of obtaining urine spot sodiums in patients with an ileostomy. Thanks to Kipp Ellsworth for sharing this reference.

Full link: A Single Urine Sodium Measurement May Validly Estimate 24‐hour Urine Sodium Excretion in Patients With an Ileostomy

Background: Sodium deficiency in patients with an ileostomy is associated with chronic dehydration and may be difficult to detect. We aimed to investigate if the sodium concentration in a single spot urine sample may be used as a proxy for 24‐hour urine sodium excretion.

Design: In this prospective, observational study, we included 16 adult individuals: 8 stable patients with an ileostomy and 8 healthy volunteers with intact intestines

Key finding:

  • There was a high and statistically significant correlation between 24‐hour natriuresis and urine sodium concentrations in both morning spot samples (n = 8, Spearman’s rho [ρ] = 0.78, P = 0.03) and midday spot samples (n = 8, ρ = 0.82, P = 0.02) in the patients with an ileostomy.

My take: In patients with ileostomy (and also short bowel syndrome), periodic urine sodium values (from morning or mid-day) will help detect subclinical sodium depletion.

Related blog posts:

 

Atlanta Botanical Gardens

FMT Warning & “Get Your Butt in Gear” –Less Than 10% of Kids Meeting Guidelines for Healthy Movement

To lessen obesity, three health risk behaviors have been targeted:

  • Sedentary behavior -goal is to limit to 2 hours of screen time in 24 hours
  • Physical activity -goal is 1 hour (or more) of moderate to vigorous activity
  • Sleep duration -goal is 9-12 hours (ages 6-12 years) and 8-10 hours (13-18 years)

A recent study (X Zhu et al. J Pediatr 2020; 218: 204-9) shows that <10% of U.S. kids meet these goals.  The authors examined data (2016-17) from the National Survey of Children’s Health (NSCH) dataset (n=71,811)

Key findings:

  • 80.9% did NOT meet physical activity goal
  • 76.2% did meet screen time goal
  • 581% did meet sleep goal
  • However, only 9.4% met all 3 goals
  • Not meeting these ‘movement’ guidelines was associated with obesity, particularly in females (aOR 4.97 compared to aOR 3.99 for males)

My take: We are all made to be different shapes and sizes.  Nevertheless, we should strive for healthy behaviors and healthy eating which could improve outcomes.

Iron Injectables

At bottom of post, more information on COVID-19.

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At a recent Pharmacy, Nutrition, and Therapeutics (PNT) meeting, one of the topics that we reviewed was injectable iron agents, primarily iron sucrose (Venofer ®) and ferric carboxymaltose (Injectafer®).  Iron dextran is mainly used as a supplement in parenteral nutrition in our patient population.

Also, this topic is reviewed in Practical Gastroenterology Jan 2020 (M Auerbach et al. January 2020 • Volume XLIV, Issue 1: Treatment of Iron Deficiency in Gastroenterology: A New Paradigm

Key points:

  • Venofer® is much less expensive and currently has an FDA indication for children. To provide 1500 mg, Venofer®, 5 doses of 300 mg (~$75/dose)~$375. Injectafer®, 2 doses of 750 mg (~$600/dose) ~1200.  This does not include potential travel and other ancillary costs.
  • Dosing: Injectafer® can give large amounts of iron; in adults, typical dose is 750 mg given 7 days apart (in children 15 mg/kg/dose with 750 mg max).  FDA approved method is to administer over 15 minutes. Venofer® in children is 5-7 mg/kg/dose with 300 mg max per dose.
  • Injectafer® has been associated with hypophosphatemia (in 27%, <2 mg/dL); Hypophosphatemia has also been reported with iron sucrose.  The reported incidence of hypophosphatemia is higher with ferric carboxymaltose vs iron sucrose.
  • Other Adverse Effects
Iron Sucrose (Venofer®) Ferric Carboxy (Injectafer®)
Nausea 8.6% 7.2%
Vomiting 5% 1.7%
Diarrhea 7.2% <1%
Dizziness 6.5% 2%
Hypertension 6.5% 3.8%

Oral vs IV Iron for IBD: Auerbach et al recommends that “iron should only be given orally to IBD patients with inactive disease, mild anemia, and good tolerance of oral iron; in patients with active IBD oral iron should be avoided.”  They state that “oral iron has been shown to exacerbate intestinal inflammation of IBD independent of anemia, and cause luminal changes in microbiota and bacterial metabolism, which may negatively alter the microbiome.” (Has IV iron’s effect on the microbiome been studied/compared to oral iron?)

Safety of intravenous iron: “In a recent meta-analysis, the results of more than 10,000 patients who were treated with intravenous iron were reported. Compared to oral iron, placebo, and even intramuscular iron (which should never be given), while minor infusion reactions were observed with IV iron, there was no increase in serious adverse events compared to any comparator including placebo.”

My take: Injectafer® is likely preferable to Venofer® in the outpatient setting as adequate dosing can be given in 1 or 2 infusions.

Related blog posts:

Trail on Blood Mountain

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

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Here’s a link to Financial Times COVID-19 Tracker –includes logrithmic charts plotting the rates of reported infection and deaths and allows quick comparison between countries and high-volume locations (eg. Madrid, Lombardia, NY City).  Some figures from March 23, 2100 GMT noted below; unfortunately, the U.S is likely to the world leader in number of reported cases quite soon.

Other relevant tweets:

 

It’s Complicated: The Relationship Between Milk and Health

  • GutsandGrowth Milestone: this is the 3000th blog post
  • New COVID19/IBD worldwide registry (so far zero cases reported.  Can report cases at the following: SECURE-IBD Registry

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A provocative review (WC Willett, DS Ludwig. NEJM 2020; 182: 644-54) provides a rationale for why a healthy diet may not need milk.

Key points:

  • “The current recommendation to greatly increase consumption of dairy foods to 3 or more servings per day does not appear to be justified.”
  • All the nutrients in milk can be obtained from other sources (including calcium and vitamin D). If diet quality is low, especially for children, dairy foods can improve nutrition. “If diet quality is high, increased intake is unlikely to provide substantial benefits, and harms are possible.”
  • Overall evidence does not support high dairy consumption will reduce fractures
  • Total dairy consumption has not been clearly related to weight control or to risks of diabetes or cardiovascular disease
  • The reported health benefits of milk depend strongly on what food it is being compared to; dairy intake is generally more favorable than processed red meat or sugar-sweetened beverages but less compared to plant-protein sources (eg. nuts)
  • No clear benefit of consuming reduced-fat milk compared to whole milk
  • Milk intake in childhood is associated with greater attained height which confers both risks and benefits

More details:

The authors review the composition of cow’s milk and compare it to human milk and cheddar cheese (Table 1). They note that cows have been bred to produce higher levels of insulin-like growth factor 1 (IGF-1) and that they are pregnant for most of the time they are milked; this greatly increases hormones like progestins and estrogens in milk.

The authors review how milk can promote growth and development in children.  Tall stature, associated with milk intake, is associated with lower risks of cardiovascular disease but with higher risks of many cancers, hip fractures, and pulmonary emboli.

Bone health and fracture risk: “paradoxically, countries with the highest intakes of milk and calcium tend to have the highest rates of hip fractures;” this, however, may not be causal as their are a lot of confounding factors (eg. Vitamin D status, ethnicity).  The authors also note that U.S. studies have shown calcium intake was unrelated to bone mineral density in the hip.  Further, the authors point out the discrepancies between U.S. and U.K with regard to daily calcium requirements; at age 4-8 yrs, U.S RDA is 1000 mg per day compared to 450-550 mg in UK.  Estimation of the calcium requirement is “problematic.”

Body weight and obesity.  “Studies of milk consumption and body weight in children are few and are subject to confounding and reverse causation.”  Available studies, however, have shown that whole milk and 2% milk are associated with lower risk of obesity than low-fat or skim milk.

Blood pressure, lipids, and cardiovascular disease in relation to milk consumption:  Ultimately, whether milk is beneficial is mainly related to the comparison foods.

Milk and the development of diabetes:  intake of dairy products has been associated with a modestly lower risk of type 2 diabetes.  Despite some hypothetical risks for type 1 diabetes, children weaned to “hydrolyzed protein instead of cow’s milk did not have fewer autoantibodies to beta cells after 7 years than children who drank cow’s milk.”

Milk intake and cancer.  Milk consumption is associated with a lower risk of colorectal cancer (likely due to its high calcium intake) and an increased risk of breast cancer, prostate cancer, and endometrial cancer; these effects may be mediated by the sex-hormones in milk.

Allergies to milk may affect up to 4% of infants.  In addition, lactose intolerance “limits consumption of milk worldwide.”

Total mortality and its association with milk intake:  “in a meta-analysis that included 29 cohort studies, intake of milk (total, high-fat, and low-fat) were not associated with overall mortality.”  Again, the risk is related to what food is substituted for milk intake.

Organic/grass-fed production and potential detrimental environmental effects from milk production; the latter includes pollution, antibiotic resistance, and greenhouse gas production.

My take: These authors are not going to get any funding from the dairy industry.  Dairy is typically an important nutrient source in children. Particularly in adults, lower intakes of dairy may be warranted.

Related blog posts:

 

Island Ford, Sandy Springs

Clinical Practice Advice: Pancreatic Necrosis

Recently the AGA published expert practice advice for pancreatic necrosis: TH Baron et al. Gastroenterol 2020; 158: 67-75.

Link to full-text PDF:  American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis.  The link includes 5 figures which provide algorithms based on their recommendations.

I’ve copied their 15 best practice advice below and highlighted the most useful.  Early in the course of pancreatic necrosis, it can be difficult to discern if an infection is present due to a robust inflammatory response; some findings suggestive of infection include gas in the collection, bacteremia, sepsis, or clinical deterioration.  Generally, surgical, endoscopic or radiologic intervention is more optimal when there is a walled-off pancreatic necrosis (WON) which typically takes 4 weeks or more.

Best Practice Advice 1

Pancreatic necrosis is associated with substantial morbidity and mortality and optimal management requires a multidisciplinary approach, including gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition. In situations where clinical expertise may be limited, consideration should be given to transferring patients with significant pancreatic necrosis to an appropriate tertiary-care center.

Best Practice Advice 2

Antimicrobial therapy is best indicated for culture-proven infection in pancreatic necrosis or when infection is strongly suspected (ie, gas in the collection, bacteremia, sepsis, or clinical deterioration). Routine use of prophylactic antibiotics to prevent infection of sterile necrosis is not recommended.

Best Practice Advice 3

When infected necrosis is suspected, broad-spectrum intravenous antibiotics with ability to penetrate pancreatic necrosis should be favored (eg, carbapenems, quinolones, and metronidazole). Routine use of antifungal agents is not recommended. Computed tomography–guided fine-needle aspiration for Gram stain and cultures is unnecessary in the majority of cases.

Best Practice Advice 4

In patients with pancreatic necrosis, enteral feeding should be initiated early to decrease the risk of infected necrosis. A trial of oral nutrition is recommended immediately in patients in whom there is absence of nausea and vomiting and no signs of severe ileus or gastrointestinal luminal obstruction. When oral nutrition is not feasible, enteral nutrition by either nasogastric/duodenal or nasojejunal tube should be initiated as soon as possible. Total parenteral nutrition should be considered only in cases where oral or enteral feeds are not feasible or tolerated.

Best Practice Advice 5

Drainage and/or debridement of pancreatic necrosis is indicated in patients with infected necrosis. Drainage and/or debridement may be required in patients with sterile pancreatic necrosis and persistent unwellness marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications, including gastrointestinal luminal obstruction; biliary obstruction; recurrent acute pancreatitis; fistulas; or persistent systemic inflammatory response syndrome.

Best Practice Advice 6

Pancreatic debridement should be avoided in the early, acute period (first 2 weeks), as it has been associated with increased morbidity and mortality. Debridement should be optimally delayed for 4 weeks and performed earlier only when there is an organized collection and a strong indication.

Best Practice Advice 7

Percutaneous drainage and transmural endoscopic drainage are both appropriate first-line, nonsurgical approaches in managing patients with walled-off pancreatic necrosis (WON). Endoscopic therapy through transmural drainage of WON may be preferred, as it avoids the risk of forming a pancreatocutaneous fistula.

Best Practice Advice 8

Percutaneous drainage of pancreatic necrosis should be considered in patients with infected or symptomatic necrotic collections in the early, acute period (<2 weeks), and in those with WON who are too ill to undergo endoscopic or surgical intervention. Percutaneous drainage should be strongly considered as an adjunct to endoscopic drainage for WON with deep extension into the paracolic gutters and pelvis or for salvage therapy after endoscopic or surgical debridement with residual necrosis burden.

Best Practice Advice 9

Self-expanding metal stents in the form of lumen-apposing metal stents appear to be superior to plastic stents for endoscopic transmural drainage of necrosis.

Best Practice Advice 10

The use of direct endoscopic necrosectomy should be reserved for those patients with limited necrosis who do not adequately respond to endoscopic transmural drainage using large-bore, self-expanding metal stents/lumen-apposing metal stents alone or plastic stents combined with irrigation. Direct endoscopic necrosectomy is a therapeutic option in patients with large amounts of infected necrosis, but should be performed at referral centers with the necessary endoscopic expertise and interventional radiology and surgical backup.

Best Practice Advice 11

Minimally invasive operative approaches to the debridement of acute necrotizing pancreatitis are preferred to open surgical necrosectomy when possible, given lower morbidity.

Best Practice Advice 12

Multiple minimally invasive surgical techniques are feasible and effective, including videoscopic-assisted retroperitoneal debridement, laparoscopic transgastric debridement, and open transgastric debridement. Selection of approach is best determined by pattern of disease, physiology of the patient, experience and expertise of the multidisciplinary team, and available resources.

Best Practice Advice 13

Open operative debridement maintains a role in the modern management of acute necrotizing pancreatitis in cases not amenable to less invasive endoscopic and/or surgical procedures.

Best Practice Advice 14

For patients with disconnected left pancreatic remnant after acute necrotizing mid-body necrosis, definitive surgical management with distal pancreatectomy should be undertaken in patients with reasonable operative candidacy. Insufficient evidence exists to support the management of the disconnected left pancreatic remnant with long-term transenteric endoscopic stenting.

Best Practice Advice 15

A step-up approach consisting of percutaneous drainage or endoscopic transmural drainage using either plastic stents and irrigation or self-expanding metal stents/lumen-apposing metal stents alone, followed by direct endoscopic necrosectomy, and then surgical debridement is reasonable, although approaches may vary based on the available clinical expertise.

Related blog post: NASPGHAN 2017 Postgraduate Course Part 1 -includes slides on pancreatic fluid collection management