Learned Fear of Gastrointestinal Sensations Plus Two

Posted on December 14, 2016 by gutsandgrowth

Briefly noted: The authors of a recent study (E Ceunen et al. Clin Gastroenterol Hepatol 2016; 14: 1552-58) set out to study whether it is likely that healthy adults could learn to fear “innocuous visceral sensations.” Fifty-two healthy subjects received 2 types of esophageal balloon distentions –one that was perceptible and non-painful and one that was painful. Not surprisingly, when the researchers paired these two interventions in the experimental group, the experimental group learned to fear the innocuous stimulation as well as the painful distention. This study provides theoretical support for one mechanism that could trigger ongoing functional gastrointestinal symptoms and a potential rationale for therapies, like cognitive behavioral therapy, which attempt to extinguish these symptoms.

In a retrospective study (AM Moon et al. Clin Gastroenterol 2016; 14: 1629-37) with 6451 patients with cirrhosis (mean age 60.6 yrs), the authors note that use of antibiotics during upper gastrointestinal bleeding (which is currently recommended) is associated with reduced mortality by ~30% at 30 days. Despite its benefit, this intervention is often overlooked. In the current study, only 48.6% of admissions received timely antibiotics; however, during the course of the study, the rate of antibiotic use improved from 30.6% in 2005 to 58.1% in 2013.

A recent retrospective study (N Goossens et al. Clin Gastroenterol 2016; 14: 1619-28) with 492 subjects showed that histologic NASH (in 12% of cohort) was associated with increased risk of death in patients who underwent bariatric surgery compared to patients without NASH. Overall, bariatric surgery reduced the risk of death during the study period with HR of 0.54; the median follow-up was 10.2 years, with surgery taking place 1997-2004. However, in patients with NASH the HR 0.90 which indicated that there was not a significant reduction in the risk of death.

Bar Harbor, ME (low tide)

Is there a link between the microbes in your colon and depression?

Posted on December 13, 2016 by gutsandgrowth

A recent study (Y Liu et al. Clin Gastroenterol Hepatol 2016; 14: 1602-11) showed that fecal microbiota signatures were similar between patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and in patients with depression.

The authors analyzed stool samples from 100 Chinese subjects. In addition to analyzed stool microbiota, the authors evaluated visceral hypersensitivity with a barostat and assessed for mucosal disease with immunohistochemical analyses of sigmoid biopsies.

In both IBS-D patients and patients with depression, the stool diversity was much less than controls and had similar abundance of many alterations, including higher proportions of Bacteroides and Prevotella (see below).

My take: It is interesting to speculate on whether changes in our microbiome could trigger/be related to the pathogenesis of not only IBS-D but other non-GI disorders like depression.

In the screenshot below, the term “COMO” refers to the 25 subjects who had both IBS and depression.

The President-Elect and the Anti-Vaccine Crowd

Posted on December 12, 2016 by gutsandgrowth

Multiple sources have reported that the anti-vaccine crowd is pleased with the results of the 2016 presidential election.

From Slate (11/22/16): Trump reportedly assured vaccine skeptics of of his support

An excerpt:

The president-elect has a long history of vaccine misinformation; he first began to express his beliefs that there might be a relationship between vaccines and autism nearly a decade ago—years after this association was scientifically discredited. He’s repeated these ideas over the years, and he never found it necessary to correct or refine his position during the election…

Jennifer Larson, CEO of the autism-focused Holland Center, in which she explained that she and other vaccination skeptics discussed their concerns with Trump at a donor event in August. According to her account, Trump assured them that he’s on their side.

From StatNews (11/30/16): Meeting with Trump emboldens anti-vaccine activists, who see an ally in the Oval Office

An excerpt:

“For the first time in a long time, I feel very positive about this, because Donald Trump is not beholden to the pharmaceutical industry,” movement leader Andrew Wakefield told STAT in a phone interview…

A former doctor whose medical license was revoked, Wakefield launched the movement to question the safety of vaccines nearly two decades ago with a fraudulent study (which has since been retracted) suggesting that a widely administered vaccine against measles, mumps, and rubella can cause autism…

Those who seek to undercut trust in vaccines “see in Donald Trump a fellow traveler — someone who, like them, is willing to basically ignore scientific studies and say, ‘This is true. Vaccines cause autism because I believe it’s true,’” said Dr. Paul Offit, the head of the infectious diseases department at Children’s Hospital of Philadelphia.

My take: There is a reason anti-vaxxers see Donald Trump as a fellow traveler.

Related blog posts:

Acadia Natl Park

Nonpartisan Fear of GMOs

Posted on December 11, 2016 by gutsandgrowth

A recent NPR report: Americans Don’t Trust Scientists’ Take On Food Issues

This reports how frequently misinformed the US public is about is about food safety issues but at least this information is not associated with partisan political views.

An excerpt:

39 percent of the survey participants believe that genetically modified foods are worse for your health than non-GM food. However, there’s essentially no scientific evidence to support that belief — a conclusion confirmed most recently by a National Academy of Sciences report…

Americans believe that there’s no scientific consensus on GMOs. Just over 50 percent of respondents believe that “about half or fewer” of scientists agree that GM foods are safe to eat. Only 14 percent’s beliefs match the reality — that “almost all” scientists agree that GM foods are safe to eat…

Roughly equal shares of Republicans and Democrats (39 percent versus 40 percent) feel that GMOs are worse for people’s health. More Democrats than Republicans (60 percent versus 50 percent) believe that organic foods are healthier. It’s significant, but not a huge difference….

Related posts:

Here’s another related link: NY Times Stop Bashing GMO Foods

Ft Knox, Maine

Truly Penicillin Allergic?

Posted on December 10, 2016 by gutsandgrowth

Here’s a link to the video story regarding misdiagnosis of penicillin allergy: Your Allergy to Penicillin May Be Non-Existent

Link to print version: Allergy to Penicillin?

An excerpt: Dr. Thanai Pongdee, an allergist at the Mayo Clinic in Jacksonville, Florida and colleagues tested 384 people who said they were allergic to penicillin. Tests showed 94 percent of them were in fact, not allergic.

Predicting Short Bowel Syndrome Enteral Autonomy: Small Bowel Diameter

Posted on December 9, 2016 by gutsandgrowth

In a small retrospective single-center study (GC Ives et al. J Pediatr 2016; 178: 275-7), the authors found that small bowel diameter, as measured on calibrated luminal contrast studies was predictive of enteral autonomy.

Measurements of >35 mm of bowel lumen was considered dilated. 29 patients had adequate imaging for the study. Necrotizing enterocolitis was the most common etiology of short bowel syndrome in this study. 16 (55%) of the intestinal failure group achieved enteral autonomy in an average of 1.3 years. 11 (38%) of patients underwent an intestinal lengthening procedure.

Key findings:

Small bowel diameter correlated negatively with residual small bowel length
Larger small bowel diameter predicted failure to achieve enteral autonomy. In fact, only one patient in this study with a dilated small bowel diameter achieved enteral autonomy.

My take: Bigger (diameter) is not better.

Related blog posts:

Lighthouse in Rockland

Weak Link in Liver Transplantation Survival

Posted on December 8, 2016 by gutsandgrowth

A recent article and editorial (DH Leung et al. Liver Transpl 2016; 22: 1584-92 & editorial by JC Bucuvalas, S Feng 1466-68) provides a better picture of long-term survival for pediatric patients facing the prospect of liver transplantation.

Among patients less than 2 years in the UNOS data sharing registry, there were 994 with biliary atresia (BA) and 221 with other chronic liver disease.

The key data:

The overall postlisting mortality was 19.6% with most of this due to wait-list mortality (12.4%). Posttransplant mortality was 8%.
The non-BA patients had a higher wait-list mortality compared with BA patients: 23.9% vs 9.8%
Risk factors for mortality included lack of exception points (HR 5.8), and initial creatinine >0.5. In addition, BA patients without prior abdominal surgery (eg Kasai) was higher (risk was 1.6 times greater) than in those with BA with presumed Kasai.

Reviewing the article, it is not clear to me if patients removed the waitlist (eg due to sepsis and other causes) are included in this analysis. Thus, the true postlisting mortality may be higher than 20% if all needy individuals are considered.

From the editorial -other aspects:

Only one-third of pediatric recipients have optimal outcomes which would include normal LFTs, maintained on monotherapy immunosuppression, normal growth, and free of comorbidity. In addition, even among those with ‘optimal’ outcomes, many would still have histologic injury.
The “incidence of nonstandard exception requests has increased 5-fold and is now used on behalf of 44% of wait-listed children.” Importantly, children with public insurance were less likely to have petitions for exception PELD points.

My take (with help from editorial): To improve outcomes, this means starting with candidate selection and working on each step: traversing wait-list management and optimizing posttransplant care.

Related blog posts:

Mural in Rockland, ME

Notable Briefs for IBD -December 2016

Posted on December 7, 2016 by gutsandgrowth

MI Abdalla et al. Inflamm Bowel Dis 2016; 22: 2658-64. This article reviewed the impact of an ostomy on QOL (quality of life) for Crohn’s disease patients. n=402 with ostomy compared with 4331 CD patients without.

Key findings:

Patients with ostomy were more likely to be in remission: 48.5% versus 31.35%.
Having an ostomy did not impact overall health-related quality of life but did reduce social role satisfaction.
Conclusion: “ostomy is well tolerated…particularly when clinical remission is achieved.”

WKM Liew et al. J Pediatr 2016; 178: 227-32. In this study with 16 patients (aged 6-24 years) who received thalidomide, more information on neuropathy is provided. “All subjects with cumulative doses greater than 60 g developed polyneuropathy.” 4 of 5 subjects receiving the drug for >20 months developed neuropathy. Two important points:

the severity of neuropathy plateaued (nonprogressive)
there are similar derivative drugs which do not appear to cause neuropathy: lenalidomide adnd pomalidomide
related blog posts: When nothing else is working | gutsandgrowth, Desperate measures in refractory IBD

V Collij et al. Inflamm Bowel Dis; 2016; 22: 2562-70. “We identified drugs that target the proteins encoded by IBD candidate genes.” Key finding: There were 113 drugs that could potentially be used in IBD treatment, including 14 known IBD drugs, 48 drugs that are/have been tested for IBD, 19 being tested for other inflammatory diseases, and 32 new investigational medications.

from one of the best days all year on board “Bufflehead”

Latest on Vedolizumab

Posted on December 6, 2016 by gutsandgrowth

A Amiot et al. Clin Gastroenterol Hepatol November 2016 Volume 14, Issue 11, Pages 1593–1601.

Abstract:

Background & Aims

Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn’s disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy.

Methods

From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey–Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase.

Results

Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma).

Conclusions

In a cohort of patients with CD or UC who failed previous anti–tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

Related Blog Posts:

Are Followup Biopsies Necessary for Celiac Disease? Look Beyond the Headline

Posted on December 5, 2016 by gutsandgrowth

A retrospective study from Boston has gained attention for suggesting that repeat biopsies may be needed for celiac disease (published online, MM Leonard et al JPGN, doi: 10.1097/MPG.0000000000001460). In my view, this may be a little early for that recommendation for asymptomatic patients with normal serology.

Full Abstract:

Value of IgA tTG in Predicting Mucosal Recovery in Children with Celiac Disease on a Gluten Free Diet.

Objective: Our objective was to determine the rate of mucosal recovery in pediatric patients with celiac disease on a gluten free diet. We also sought to determine whether IgA tissue transglutaminase (tTG) correlates with mucosal damage at the time of a repeat endoscopy with duodenal biopsy in these patients.

Methods: We performed a retrospective chart review of one-hundred and three pediatric patients, under 21 years of age, with a diagnosis of celiac disease defined as Marsh 3 histology, and who underwent a repeat endoscopy with duodenal biopsy at least twelve months after initiating a gluten free diet.

Results: We found that 19% of pediatric patients treated with a gluten free diet had persistent enteropathy. At the time of the repeat biopsy, tTG was elevated in 43% of cases with persistent enteropathy and 32% of cases in which there was mucosal recovery. Overall the positive predictive value of the autoantibody tissue transglutaminase was 25% and the negative predictive value was 83% in patients on a gluten free diet for a median of 2.4 years.

Conclusions: Nearly one in five children with celiac disease in our population had persistent enteropathy despite maintaining a gluten free diet and IgA tTG was not an accurate marker of mucosal recovery. Neither the presence of symptoms nor positive serology were predictive of a patient’s histology at the time of repeat biopsy. These findings suggest a revisitation of monitoring and management criteria of celiac disease in childhood.

Link to full text: A few other key points:

The most common indications for repeat endoscopy were due to persistent symptoms (43%) and new gastrointestinal symptoms (27%). Twenty-four subjects (34%) had persistently elevated serology at the time of the repeat biopsy.
19% exhibited persistent enteropathy consistent with a Marsh 3 lesion at the time of the repeat endoscopy.
Only 71 patients had serology within 4 months of repeat endoscopy, limiting the interpretation of the concordance of tTG value to histology

My take: I think it is premature to recommend routine followup biopsies in asymptomatic patients with normal serology. I think a prospective study will be helpful; the majority of patients in this study who underwent repeat biopsy were symptomatic and 9% were not adherent to their diet. Thus, this may not reflect a typical patient with celiac disease at followup. In addition, it would be helpful with regard to whether persistent histological findings have clinical significance.

Despite these limitations –this is how this article is being reported (from news-medical.net), here’s an excerpt from a recent summary:

Study finds 1 in 5 pediatric celiac disease patients on gluten-free diet sustain persistent intestinal damage

Alessio Fasano, MD, director of the MGHfC center and co-senior author of the study, was also surprised by the results, which were based on a retrospective examination of the biopsy and medical records of 103 children with celiac disease treated at MGHfC or BCH. The children had been on the gluten-free diet for at least one year and were determined by dietitians and other hospital health care practitioners to have complied well with the diet. But repeat biopsies found persistent intestinal damage in 19 percent of them. “The number of children who don’t heal on the gluten-free diet was much higher than what I expected,” Fasano says.