Is fasting needed before checking lipids?

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Not really.  According to a recent study involving 209,180 individuals, fasting times showed little association with lipid levels in a community-based population (Arch Intern Med 2012; 172: 1707-10).

Although current guidelines suggest obtaining lipid levels after fasting, lipid levels do not vary much between fasting and nonfasting states.  Furthermore, fasting may not be reflective of the patient’s typical metabolic state.

Design: cross-sectional study over a 6-month period in 2011 (Calgary) using a large community-based cohort.  The average age of the participants was 52.8 years.

Results: In tables 1 and 2, the authors provide the cholesterol values for fasting times that varied from 1 hour to 16 hour.  The vast majority fasted for 10 hours or more.  For example, less than 1% of the cohort fasted for only 1 hour.  However, fasting time showed little association with lipid subclass levels, suggesting that fasting for routine levels is not necessary.

There were several limitations of the study.  The meal choices in the nonfasting groups were not known and the study was not randomized.  In addition, LDL values were not calculated when triglycerides were >400 mg/dL; this represented 1.5% of the study population.  The authors recommend that in individuals with triglycerides >400 mg/dL that fasting lipid levels could be considered.

Related blog entries:

Microbiome and the risk of Kwashiokor

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On the way home from work, NPR highlighted a study that suggests that altered microbiome may increase the risk of Kwashiokor (Gut Microbes May Play Deadly Role In Malnutrition : Shots … – NPR).

Interestingly, a separate article indicates that antibiotics lowers the mortality in severe acute malnutrition (NEJM 2013; 368: 425-35).  In this study, 2767 children from 18 feeding clinics in Malawi (2009-2011) were enrolled in a randomized, double-blind, placebo-controlled trial.  Children were 6 to 59 months of age with severe acute malnutrition.  Those who received amoxicillin, cefdinir, and placebo recovered in 88.7%, 90.9%, and 85.1% respectively.  The relative risk of death in the placebo group was 1.55 compared to amoxicillin and 1.80 compared to cefdinir.  The children in the antibiotic group also had improved growth.

The authors suggest that the reason for improvement is likely to be due to fewer invasive bacterial infections.  These infections are frequent and thought to be related to translocation across compromised mucosal surfaces.  However, perhaps the antibiotics act by producing a more favorable microbiome which in turn promotes improvement.  As such, microbes have a role in contributing to obesity (Microbial transfer for metabolic syndrome? | gutsandgrowth) and to starvation.

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Physician narrative on gun control

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Recent commentaries offer several physician viewpoints on this problem (NEJM 2013; 368: 397-99, 399-400, 401-403).  For me, the following points were of most interest:

  • 88 Americans died every day from firearm violence in 2011; high-profile events like Sandy Hook, Aurora, Virginia Tech and Columbine are uncommon.
  • In California, background checks are required on all firearm purchases and this has been associated with a 23% reduction in firearm-related crime.  Though, this policy is hampered by neighboring state policies.  In Reno, Nevada, about 1/3rd of the cars at gun shows are from California.
  • In 2010, 6570 deaths in children/young persons (1-24 yrs) were due to gun-related injuries. Gun-related fatalities cause twice as many deaths as cancer, five times as many as heart disease, and fifteen times as many as infections.
  • Suicide attempts with drugs are lethal in <5% whereas 90% involving guns are lethal.
  • The authors advocate for better background checks, a ban on assault weapons, limits on ammunition capacity, and removing restrictions on the collection of public health data regarding gun-related injuries.

In a previous blog about the problem of obesity, I referenced the “issue-attention cycle” problem.  ”This pattern occurs when initial public alarm over the discovery of a problem and optimism about its quick resolution are replaced by the realization that solving the problem will require some public sacrifice and will displace powerful societal interests.”

Despite the high toll exacted by gun violence, will there be enough staying power to work on these incremental steps?

Where is the Journal Editor?

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A recent article is titled “Determination of Bone Age in Pediatric Patients with Crohn’s Disease Should Become Part of Routine Care” (Inflamm Bowel Dis 2013; 19: 61-65). (Thanks to Ben Gold for suggesting this reference.)

Does the study merit the authors’ conclusion that ‘determination of bone age (BA) should become the standard of care in pediatric Crohn’s disease (CD) patients, allowing clinically meaningful interpretation of growth…leading to improved treatment recommendations?’

No.  This small study (n=49, 84% Caucasian) simply showed that a lot of pediatric CD patients have a delayed bone age.  This is not a novel finding.

Specifically, the mean BA Z score was -1.40 ± 1.5 in this population and 41% had a BA Z score of < -2.0.  This cross-sectional study was conducted between 2007-2009.  Patients were consecutively approached for enrollment during this time period.

Clinical factors associated with delayed bone age included Caucasian race, Tanner stage 1-3, history of steroid exposure, colonic disease location, azathioprine/6-mercaptopurine usage, and female sex.  Interestingly, these variables are not entirely consistent with prior studies in which male sex was associated with delayed bone age.

The reason why the conclusion is a far-reach is that there is no data in the study showing how bone age influences any clinical decision-making in these patients.  There is no information on cost-effectiveness of their proposed “standard of care.”  There is no longitudinal data to suggest that the delayed BA or the recognition of a delayed BA  resulted in a different outcome.

My conclusion:

Many pediatric patients with CD have delayed BA and some may benefit from a BA determination.  I think extrapolating a much broader conclusion from this study is not warranted.

Vitamin D deficiency and metabolism in pediatric Crohn’s disease

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As noted in previous blog posts (see links below), vitamin D has received a great deal of attention with a number of chronic diseases.  In this latest study from CHOP, the incidence and mechanisms of vitamin D deficiency in pediatric Crohn’s disease are explored (Inflamm Bowel Dis 2013; 19: 45-33).

At diagnosis (2002-2005), Crohn’s disease (CD) participants (n=78) had their serum vitamin D assays and parathyroid hormone (PTH) levels checked.  Then, these values were sequentially followed at 6 months, 12 months, and a median of 43 months later (n=52). The average age of the CD patients was 12.7 years.

Key findings:

  • 42% of CD participants were 25-OH D deficient (<20 ng/mL) with an odds ratio of 2.1 compared with controls.
  • Among patients with 25-OH D <30 ng/mL, CD patients had a lower PTH than controls.
  • At final visit, 3% remained 25-OH D deficient and PTH levels corrected.
  • Risk factors, besides CD, for vitamin D deficiency: black race (OR 10.4), visit in winter (OR 2.4), age 12 to <15 (OR 2.7), age >15 (OR 3.2).  Greater disease activity was associated with lower vitamin D levels at baseline.

Implications of this study:

  1. Vitamin D deficiency normally causes secondary hyperparathyroidism.  With newly-diagnosed CD, there was a relative hypoparathyroidism that resolved with therapy.  “It is conceivable that proinflammatory cytokines associated with CD …prevent an appropriate PTH response.”
  2. The authors state that ‘vitamin D deficiency likely contributes to the pathogenesis of CD through effects on T and B lymphocyte, macrophage, and dendritic cell regulation.”  Correcting vitamin D deficiency may improve CD treatment response in addition to potential improvements in bone health.

Related posts:

Checklists for Crisis and Daily Care

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Not surprisingly, a new study has shown that checklists were associated with improvement in the management of operating-room crisis (NEJM 2013;  368: 246-53).

Many people use a checklist just to go to the grocery store so they don’t forget something important.  In medicine, checklists offer the same opportunity.

In this particular study, 17 operating-room teams participated in 106 simulated surgical crisis scenarios.  When checklists were available, there was better adherence to lifesaving processes: only 6% of steps were missed with checklists compared with 23% when they were unavailable.  Every team performed better when the crisis checklists were available.  Furthermore, 97% of participants reported they would prefer to have a checklist in the event of a crisis.

There were many limitations of this study, particularly the absence of surgeons from most of the simulations (due to difficulty enlisting them as volunteers).  Nevertheless, “experts have long recognized the potential for human fallibility in complex systems…it has been nearly 100 years since the surgeon W. Wayne Babcock called for emergency protocols to be rehearsed and ‘posted on the walls of every operating room.'”

For a pediatric gastroenterologist, the implication of this study is much broader.  It is trying to develop a checklist for every patient.  For a patient with a GI bleed, that checklist may include a supply list for the endoscopy suite, having written instructions for the settings of the cautery equipment, checking the proper PPI dose, and drawing a specific set of labs.  Agreeing to a minimum and not-too-onerous checklist would be worthwhile for almost anybody.  If you have a checklist for any GI condition (or a mobile app), think about adding a comment to this posting. If something is important in day-to-day care of a specific condition, a “hardstop” can be incorporated into electronic records as a reminder.

Related blog entries (mostly guidelines –not really checklists for a few specific conditions):

A much more articulate spokesman for checklists would be Atul Gawande:

Limiting Cow’s Milk for EoE

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A small retrospective study suggests that eliminating cow’s milk, without other interventions, can be effective in the treatment of Eosinophilic Esophagitis (EoE) (JPGN 2012; 55: 711-16).

Out of 161 children with EoE, 17 patients were identified who excluded only cow’s milk from their diet.  Remission was noted in 65%.  Complete histologic remission (≤1 eosinophil/hpf) was noted in 7 patients (41%) and 4 (24%) had “significant remission” (defined as peak eosinophil count of 2-15/hpf).

This study, conducted in Chicago, took place between 2006-2011.  The majority of the patients treated at this institution are treated with dietary elimination: 61% with empiric elimination diet, 8% empiric elimination diet with topical steroids, and 7% with elemental diet.

The authors suggested that younger children may be more likely to benefit from this approach but cautioned against drawing firm conclusions due to the small ‘scope’ of this retrospective study.

 Related posts:

T-cell therapy for Crohn’s disease

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Data from the Crohn’s and Treg Cells Study (CATS1) are very preliminary but indicate that administration of antigen-specific T-regulatory cells (Tregs) to refractory Crohn’s disease (CD) patients could be effective (Gastroenterol 2012; 143: 1207-17).  Tregs are specialized subpopulations of T-cells.

In this study, the investigators, performed a 12-week open-label multicenter single injections study of 20 patients with refractory CD.  After withdrawing blood from patients, mononuclear cells were isolated and cultured.  Subsequently, T cells were cloned.  A specific subset with high IL-10/IL-13 production and low IL-4 production were selected.

Key findings:

  • 8 of 20 (40%) patients had a CDAI reponse at 5 and 8 weeks.  This was associated with a reduction in serum CRP and a trend of decreasing fecal calprotectin.
  • Remission was noted in 3 patients at week 5 and in 2 patients at week 8.
  • Overall, regardless of dose used, the safety profile was “in line” with severe active refractory CD.  Gastrointestinal adverse events were common.  7 patients had CD flares. One patient died due to suicide.

To understand this study more fully, an accompanying editorial is in the same issue (pages 1135-38).  A more complete discussion of the function of Treg cells is given, included their physiologic role of patrolling the gut lamina propia for antigens ‘derived from food and commensal flora.’  Circulating Treg cells may be deficient in IBD patients and thus contribute to the pathogenesis.

While injecting Treg cells may become a useful therapy, other ways of boosting Treg cells may be enhanced as an alternative.  Currently, granulocyte colony-stimulating factor (GCSF), anti-TNFα agents, and IL-2 all have the potential to enhance Treg cell function.  This supports the editorial’s conclusion that ‘Treg cells are rapidly moving from the bench to the bedside.’

Given the experimentation with stem cell therapy and bone marrow transplantation for CD, Treg cells show promise of a much more targeted effect on the immune system.

Additional references:

  • -Blood 2010; 116:6123-32.  Autologus stem cell transplantation in patients with refractory CD.
  • -Gut 2008; 57: 211-17.  Autologus stem cell transplantation for refractory CD.
  • -Gut 2010; 59: 1662-69.  Mesenchymal stromal cell treatment for luminal Crohn’s.

Could Cysteamine help NAFLD?

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Maybe (J Pediatr 2012; 161: 639-45, editorial p 579).

Cysteamine bitartrate has been used in cystinosis and reduces intralysosomal Cys accumulation.  It has potential antioxidant and antiapoptotic effects.  A pilot study has shown that cysteamine may improve NAFLD through unclear mechanisms and may reduce aminotransferase levels in the serum along with increasing adiponectin levels (reduced in NAFLD).

Adiponectin is produced by adipocytes and helps regulate glucose and lipid homeostasis.  It has insulin-sensitizing properties as well as anti-inflammatory effects. Adiponectin levels inversely correlate with degree of obesity and insulin resistance.

In this study of 10 children with biopsy-proven NAFLD, cysteamine therapy was administered for 24 weeks.

  • Following therapy, multimers of adiponectin were increased and total adiponectin level increased 49.3% (P = 0.05).
  • ALT dropped from a mean of 123 IU/L at baseline to 55 IU/L at 24 weeks.
  • AST dropped from a mean of 61 IU/L at baseline to 32 IU/L at 24 weeks.
  • Adiponectin values returned to baseline 16 weeks after completing treatment while aminotransferase values remained low.

The editorial notes that an NIH-funded NASH clinical research network study will investigate cysteamine in a much larger cohort.

Related blog entries: