Don’t Go Nuts over Nuts

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A recent study (NEJM 2013; 369: 2001-11) showed that nut consumption was associated with a lower mortality rate among more than 115,000 people in two large independent cohorts.  Nut consumption had significant inverse associations with deaths due to cancer, heart disease, and respiratory disease.  Those who ate nuts most frequently (7 or more times per week) had a 20% lower hazard ratio for death. However, the individuals who consumed nuts may have been more likely to have other healthy habits, though this was not identified in the study.

This study is explained more fully in the following video (less than 3 minutes):  nej.md/1aSbuY4 

Have you seen the Duodenal-Jejunal Bypass Liner?

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A recent article (Clin Gastroenterol Hepatol 2013; 11: 1517-20) reports on the effects of the duodenal-jejunal bypass liner (DJBL) on improvement in parameters of nonalcoholic liver disease (NAFLD).  The study enrolled 17 patients who had obesity and type 2 diabetes mellitus.

The following link provides more details on this technique (from a 2009 study) and provides a picture (Figure 2) of the 60 cm sleeve that is placed endoscopically:

Radiographic appearance of endoscopic duodenal … – GI Dynamics

These studies indicate that less invasive approaches may develop as alternatives to bariatric surgery.

Related blog links:

Explaining the Vitamin D Paradox

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For a long time, there has not been a satisfying explanation for the fact that blacks have higher bone mineral density but lower 25-hydroxy-vitamin D levels than whites.  New research (NEJM 2013; 369: 1991-2000, editorial 22047-48) helps explain this paradox.

This study examined a community cohort of 2085 individuals in the “Healthy Aging in Neighborhoods of Diversity across the Life Span” study.

Key Findings:

  • Blacks had higher bone mineral density and lower 25-hydroxy-vitamin D levels than whites
  • The calculated bioavailable levels of 25-hydroxy-vitamin D were similar to whites.

The editorial notes that the similar bioavailability is due to differences in the vitamin D-binding protein (aka GC-globulin).  “GC1F is the most abundant form in persons of African ancestry whereas GC1S is most abundant in European populations.”  Thus, it has been hypothesized that the vitamin D-binding protein in blacks has “increased affinity for vitamin D3, and thus able to transport vitamin D3 more efficiently from the skin to the liver for its metabolism to 25-hydroxy-vitamin D.”

Bottomline: This research in vitamin D metabolism may impact on how we determine vitamin D deficiency.  The measurement of vitamin D-binding protein may need to be incorporated into the assessment.

Related posts:

Progression of Hepatitis C in Children

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A retrospective study (Hepatology 2013; 58: 1580-86) of liver biopsies from treatment-naive children enrolled in the PEDS-C study confirm the perception that hepatitis C histologic progression is typically slow.

This study examined 35 pediatric patients (84% genotype 1) who had at least two liver biopsies more than a year a part at eight different centers.  For this study, all of the liver histology was scored by a single pathologist.  Mean age at first and final biopsy were 8.6 and 14.5 years.  Mode of transmission: 57% vertical and 39% transfusion.

Results:

  • Inflammation was minimal in about 50% at both timepoints.
  • Fibrosis was absent in 16% at both timepoints.  Fibrosis was limited to portal/periportal in 73% at first biopsy and 64% at second.
  • Proportion of patients who had bridging fibrosis/cirrhosis at second timepoint increased from 11% to 20%.  Overall, 29.5% (n=13) showed an increase in severity of fibrosis.
  • In aggregate, “this cohort did not show significant histologic progression of liver disease over 5 years.”

Implications for treatment per authors: “It may be argued that treatment of a slowly progressing disease in an asymptomatic child may be deferred given the side effects and limitations of the currently available therapy. On the other hand, some might favor early treatment…a liver biopsy …may influence decisions regarding therapy.”

Related blog posts:

Reclassifying Biliary Atresia -Three Subtypes

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Using a large prospective multicenter cohort (ChiLREN study group), a recent study examined 289 infants and identified three subtypes of biliary atresia (BA) enrolled in PROBE (Hepatology 2013; 58: 1724-31).

Previously, BA has been considered to have two presentations:

  • Acquired/nonsyndromic ~90%
  • Embryonic/syndromic ~10%

However, this study suggests the following:

  • Group 1 -nonsyndromic, isolated BA. n=242 (84%)
  • Group 2 -BA with major malformation but without laterality defect. n=17 (6%)
  • Group 3 -syndromic, with laterality defect. n=30 (10%)

Group 3 BA defects included splenic abnormalities (eg. asplenia, polysplenia, right-sided spleen), cardiovascular anomalies (eg. dextrocardia, TAPVR, interrupted IVC) and gastrointestinal anomalies (eg. “abdominal heterotaxy,” malrotation, annular pancreas).

In contrast, Group 2 BA had frequent genitourinary problems (cystic kidney and hydronephrosis) along with different cardiovascular anomalies and gastrointestinal anomalies which included esophageal/duodenal/jejunal atresia and imperforate anus.

Other points:

  • The frequency of cardiac problems is particularly important to recognize as this could make differentiation from Alagille syndrome more difficult.
  • One other interesting finding was the high incidence of autoimmunity in first-degree relatives of all BA groups (~44%).

Bottomline: there are at least 3 subtypes of BA.

Related posts:

Intermittent Abdominal Pain and Intestinal Swelling –a Mystery?

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A recent “Think Like a Doctor”  -full link to the solved case: nyti.ms/1aJtxFK 

First an except from the challenge:

The Patient’s History

It started nearly two years earlier, the woman told Dr. Merai. She had been at work — she was a clerk in a bank then — and had suddenly started vomiting. As she made her way back to her desk, she felt weak and unsteady and fainted. Or that’s what everybody told her, because the next thing she knew, she was in an ambulance on the way to the hospital.

There, a CT scan showed that her small intestines were inflamed. The doctors said she might have Crohn’s disease. But after a couple of days, she started to feel better and went home. Because she felt O.K., she never followed up.

And then, it happened again — nine months later. Again she was rushed to the hospital. Again a CT scan showed an abnormality in the small intestines. This time the doctors were so worried they took her straight into the operating room.

“They thought my guts were tangled up in knots,” she told the doctor. But when she woke up, the surgeon told her that he was amazed to see that her insides were pristine. There was swelling and a lot of fluid in her belly, but no twisting, and no infection. And nothing to take out.

At that hospital she had an endoscopy so doctors could look at her stomach and upper G.I. tract and a colonoscopy to look at the other end. Those exams were normal.

And now the answer (an excerpt):

The correct diagnosis is…

Intestinal angioedema, triggered by lisinopril, the ACE inhibitor the patient took for her high blood pressure.

The Diagnosis:

Angioedema is a localized type of swelling usually involving the mouth, tongue or upper airways. It can be part of a typical allergic reaction, with hives and itching, or it can be isolated, with swelling as the only notable finding. While there is an inherited form of this disease, most cases are acquired. And medications are the most common cause of this form of the syndrome…

his patient had a rare form of the problem that arose not in the face but in the intestine. When swelling occurs in the gut, it can block off the intestinal lumen and bring digestion to a screeching halt, causing the terrible pain and vomiting this patient experienced.

Remarkably, no matter where in the body the swelling occurs, or how severe it gets, it always resolves quickly – often within hours – even if the patient continues to take the medication.

When the angioedema happens in the G.I. tract, the diagnosis can be delayed for months or years because so many doctors don’t know that this kind of reaction is even possible. When the medication is stopped, the episodic reaction also finally stops…

the resident on call that day at the University of Chicago Medical Center, and told her that he thought this was a reaction to the patient’s blood pressure medication.

He also recommended that the patient be tested for the inherited version of the disease.

Related blog post: 

Overlooking Important Detail$ in Hereditary Angioedema Treatment …

Long-term Outcomes with Pediatric PEG Placement

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As noted about a week ago in this blog, gastrostomy tube (gtube) placement in children is much different from gtube placement in adults.

A retrospective study from Boston Children’s followed 138 patients who had PEG tube placed between 1999-2000 (JPGN 2013; 57: 663-67).  The median followup was approximately 5 years.

Results:

  • Median time to elective tube removal was 10.2 years.
  • ~50% of patients continued with gastrostomy tube 10 years after placement.
  • 11% (n=15) had at least 1 major complication related to gastrostomy placement.  Major complication was defined as any unplanned adverse events requiring hospitalization, surgery (eg. fundoplication) or interventional radiology (eg. gastrojejunal tube placement). Most major complications occurred during the first 6-12 months following placement with the most common being cellulitis (n=10).
  • 18% of the cohort died during the 10-year study period because of non-gastrostomy-related issues.  No deaths were attributed to gastrostomy tube placement.

Bottomline: The need for gastrostomy tube placement is associated with frequent comorbidities.  A significant number of patients undergoing gastrostomy tube placement experience major complications.

Also noted:

JPGN 2013; 57: 659-62. This prospective study of 69 patients showed that early reintroduction of feedings after gastrostomy placement, 4 hours postoperatively, was safe and compared favorably to those fed 12 hours postoperatively.  Early feedings were associated with hospital duration, on average, of 6.7 hours. At this center, prophylactic antibiotics were not administered without apparent increase in infections.

JPGN 2013; 57: 668-72. This retrospective study of 77 children with feeding disorders showed that inpatient behavioral interventions are effective in transitioning children from gastrostomy tube feeding to oral feeding.

Related blog entries:

Autism Earlier -Gazing for Clues

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From NY Times twitter feed, http://t.co/smZBQimdUY:

Scientists are reporting the earliest behavioral sign to date that a child is likely to develop autism: when and how long a baby looks at other people’s eyes.

In a study published Wednesday, researchers using eye-tracking technology found that 3-year-olds diagnosed with autism looked less at people’s eyes when they were babies than children who did not develop autism.

But contrary to what the researchers expected, the difference was not apparent at birth. It emerged when babies were two to six months old, and autism experts said that may suggest a window during which the progression toward autism can be halted or slowed.

The study, published online in the journal Nature, found that infants later diagnosed with autism began spending less time looking at people’s eyes between two and six months of age and paid less and less attention to eyes as they grew older. By contrast, babies who did not develop autism looked increasingly at people’s eyes until about nine months old, and then kept their attention to eyes fairly constant into toddlerhood.

“This paper is a major leap forward,” said Dr. Lonnie Zwaigenbaum, a pediatrician and autism researcher at the University of Alberta, who was not involved in the study. “Documenting that there’s a developmental difference between two and six months is a major, major finding.”

The authors, Warren R. Jones and Ami Klin, both of the Marcus Autism Center and Emory University, also found that babies who showed the steepest decline in looking at people’s eyes over time developed the most severe autism….

Dr. Jones and Dr. Klin, who directs the autism center, studied two groups of babies. One group was at high risk for autism, with a 20 times greater likelihood of developing it because they had siblings with the disorder. The other group was at low risk, with no relatives with autism.

The researchers assessed 110 children, from two months to two years of age, ten times while watching videos of friendly women acting like playful caregivers. Eye-tracking technology traced when the babies looked at the women’s eyes, mouths and bodies, as well as toys or other objects in the background. At age three, the children were evaluated for autism. Ultimately, researchers used data from 36 boys, 11 of whom developed autism. (They excluded data from girls because only two developed autism.)

Related post:

“Too many vaccines and autism” is debunked | gutsandgrowth

Suffering

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I was intrigued by the title “The Word That Shall Not Be Spoken” (NEJM 2013; 369; 177-78).

According to the author the word is “suffering.”  He notes that clinicians do not like to use this word. Some of the reasons:

  • It is not “actionable”..it is “too heterogeneous, too complicated”
  • It reminds us that we are “powerless against so many of our patients’ problems”
  • Because “the idea of taking responsibility for it overwhelms us as individuals –and we are already overwhelmed by our other duties and obligations

His conclusion: “in truth, I’m less interested in the words we use than in what we actually do, and what we organize ourselves to do. Collectively, we should not shy away from work that can never be completed.  For our organizations, relief of suffering does seem like the right goal, endless though the work might be.”

Microscopic, Lymphocytic and Collagenous Colitis

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Microscopic Colitis (MC) is a rare pediatric problems and occurs when chronic diarrhea occurs in the presence of a normal-appearing endoscopic exam but with abnormal histology.  In adult populations, microscopic colitis is seen more frequently and can be confused with irritable bowel syndrome.  The two subtypes:

  • Lymphocytic Colitis (LC):  >20 intraepithelial lymphocytes/100 colonocytes
  • Collagenous Colitis (CC): thickened subeptihelial collagen band in addition to changes seen with LC

In a recent study (JPGN 2013; 57: 557-61), 27 MC cases were identified from a pathology database between 1995-2011.  5 were excluded due to an enteric infection.  Among the 22 other cases, 19 had LC and 3 had CC.  Association with celiac disease was evident in 4 patients and many had preceding drug exposures.

Treatment included steroids, melamine, an bismuth.

Additional references:

  • -JPGN 2011; 53: 579. lymphocytic colitis case report
  • -Clincal Gastro & Hep 2011; 9: 13.  Celaic with persistent symptoms: consider poor adherence**, SBBO*, pancreatic insufficiency*, refractory celiac (rare), PLE, giardia, malignancy, lactose intolerance, functional d/o*, microscopic colitis, Crohn’s*, NSAIDs
  • -Gut 2009; 58: 68-72. Collagenous colitis: Budesonide at 6mg/day maintained remission in ~25%.
  • Gastro 2008; 135: 1510.  Budesonide effective for collagenous colitis; n=48, 9mg/day.
  • -Gastro 2011; 140: 1155. Review of microscopic colitis/collagenous colitis.
  • -Am J Gastroenterol 2010; 105: 859-865.  n=466 & 451 controls.  Microscopic colitis present in 1.5% of IBS patients.  IBS pts with lower incidence of adenomas (7.7.% vs 26%).  9% had diverticulosis (lower).
  • -Clin Gastro & hep 2009; 7: 1210. 4.3% of pts w microscopic colitis had celiac. 44/1009.