12 Year Data: Pros and Cons with Bariatric Surgery

Posted on November 30, 2017 by gutsandgrowth

A recent study (TD Adams et al. NEJM 2017; 377: 1143-55) examines outcomes of bariatric surgery after 12 years. The ‘skinny’ on this study is that the weight loss/improved metabolic measures associated with bariatric surgery were very durable but there was a small increased risk of suicide among those undergoing bariatric surgery.

In this study, there were three cohorts:

Surgery group: 418 patients
Nonsurgery group 1: 417 patients. This group had sought surgery but did not receive surgery (often due to insurance coverage) (147 underwent subsequent surgery)
Nonsurgery group 2: 321 patients. This group had not sought surgery (39 underwent subsequent surgery)

Key findings:

At 12 yrs, mean change from baseline body weight was -35 kg in surgery group, compared with -2.9 kg in nonsurgery group 1 and 0 kg in nonsurgery group 2
Of those with type 2 diabetes in the surgery group, type 2 diabetes remitted in 75% at 2 yrs and remained remitted in 51% at 12 yrs.
The surgery group had higher remission rates of hypertension and dyslipidemia as well.
7 deaths by suicide were noted -5 in the surgery group, and 2 in the nonsurgery 1 group but only after the patients had undergone subsequent bariatric surgery

My take: Weight loss and improved metabolic changes at 6 yrs were maintained over the following 6 yrs. It is troubling that the surgery and/or weight loss is associated with suicide in a small number of patients.

Related blog entries:

Crisis Developing in Blood Supply

Posted on November 29, 2017 by gutsandgrowth

As noted in a previous blog, Business of Blood in Decline, the number of transfusions are declining. While this is good news, there are a number of worrisome trends that indicate a crisis in the sustainability of the U.S. blood system (HG Klein et al. NEJM 2017; 1485-8).

Some background:

U.S. blood collectors draw 35,000 units a day
Blood transfusion is ordered in 10-15% of all hospitalizations
Less-invasive surgical techniques and other blood-management strategies have reduced demand for blood

So what is the problem?

The U.S. blood supply relies on nonprofit organizations which in turn have relied on blood as a major source of revenue. With reduction in blood demand and increased screening (e.g. for more infections), the cost per unit has increased; yet, due to stiff competition, there has not been a commiserate increase in reimbursement.

57.1% of America’s Blood Centers in December 2016 reported operating with negative margins
90% of the blood supply is estimated to be provided below cost
Due to cost constraints, blood suppliers are less likely to adopt additional measures which could improve patient and donor safety

The authors argue that human blood should not be treated as “just another consumer good.” Strict economic principles undervalues the need of having a safe, available blood supply. While there have not been clinical consequences thus far, the current model is not sustainable.

My take: The financial market of the blood supply is precarious. This needs to be addressed to ensure the availability of blood when we need it.

Briefly noted -related study: EA Gehrie et al. J Pediatr 2017; 189: 227-31. In this study, the authors tested 220 red blood cell units. 15 (6.8%) had detectable drugs:. opiates, benzodiazepines, stimulants, and barbituates. While none of these units would have been disallowed under current FDA regulations, it is possible that these levels could cause reactions in vulnerable populations, like neonates. The authors note that allergens, like peanuts and fish, in blood donations can result in anaphylactic transfusion reactions

IBD Short Takes -Fall 2017

Posted on November 28, 2017 by gutsandgrowth

From ImproveCareNow: Real-World Experience with Adalimumab

An excerpt:

A total of 174 children and adolescents were treated with adalimumab as their first anti-TNF therapy…The mean age at the time of Crohn’s disease diagnosis was 13 years and, on average, they started adalimumab at 14.5 years of age…

At 3 months after adalimumab was started, all 174 were still on the medication, and 69-71% were in steroid-free remission
At 6 months after adalimumab was started, of the 174 who had a clinic visit, 95% were still on the medication, and 75-77% were in steroid-free remission
At 12 months after adalimumab was started, of the 154 who had a clinic visit, 94% were still on the medication, and 79-80% were in steroid-free remission
At 24 months after adalimumab was started, of the 71 who had a clinic visit, 97% were still on the medication, and 91-94% were in steroid-free remission
At 36 months after adalimumab was started, of the 39 who had a clinic visit, 80-86% were still on the medication, and 81-86% were in steroid-free remission

No positive or negative effect on remission was seen with concomitant immunomodulator therapy. However, the number of patients studied during the retrospective analysis is too small to detect all but the greatest impact of this approach.

EC Maxwell et al. JPGN 2017; 65: 299-305 CHOP experience with diverting ileostomy for severe IBD (2000-2014).

In this retrospective study, a diverting ileostomy in 24 patients had improvement: 71% –>22% on chronic steroids, improved growth, hemoglobin, blood transfusion and hospitalization.
10 patients underwent subsequent colectomy, 7 had successful reanastomosis, and 7 remain diverted.
Diversion allowed a definitive diagnosis in 7 subjects (initially 13 patients were considered IBD-U).
Surgical complications were common (n=13 in 7 subjects) and included stoma obstruction, stoma prolapse, and resection of ischemic bowel.
One notable feature regarding this cohort was that 50% were 5 or younger when diagnosed with IBD.
The authors conclude that a diverting ileostomy can induce clinical stability and allow time to clarify diagnosis.

A Assa et al. JPGN 2017; 65: 293-98. In this study involving findings from 234 patients extracted from the ImageKids database (prospective multicenter cohort), the authors found that pediatric patients with perianal Crohn’s disease have a greater inflammatory burden; however, this was driven mainly by those who had fistulizing disease.

L Lian et al. Clin Gastroenterol Hepatol 2017; 15: 1226-31. This retrospective study from the Cleveland Clinic compared outcomes of endoscopic balloon dilation (EBD) (n=176) or surgery (n=131) for Crohn’s disease-related strictures (1998-2013). Patients who had EBD had an “average time to surgery delayed by 6.45 years.” Immediate success rate for EBD was 91.3%; the perforation rate was 1.1%.. Ultimately, 52% of patients who had EBD required surgery. Earlier surgery lowered the risk of further surgery but also was associated with significant perioperative complications. In the operative group, 8.8% of patients experienced complications, mainly intra-abdominal abscesses and enterocutaneous fistula. Thus, in the right hands and with careful selection, EBD may be useful.

I Lawrance et al. Clin Gastroenterol Hepatol 2017; 15: 1248-55. This study reported the results of 11 patients who received rectal tacrolimus for resistant ulcerative proctitis. Dosing: The concentration of tacrolimus was 0.5 mg/mL and 3 mL was administered twice a day.Clinical response, using the Mayo Clinic score, was achieved in 73% of tacrolimus subjects compared with 10% (n=1) of placebo-treated subjects. Mucosal healing at week 8 was noted in 73% of tacrolimus-treated patients, as well.

Soapes Creek Trail

Therapeutic Drug Monitoring: Ustekinumab (Stelara)

Posted on November 27, 2017 by gutsandgrowth

The ability to measure drug levels has changed how we think about refractory medical disease, particularly in patients with inflammatory bowel disease. Prior to the availability of therapeutic drug monitoring (TDM), in some situations poor response to therapy could be ascribed to variability in host immune response. Now, it is clear that many cases of refractory medical disease are due to insufficient drug level. TDM allows for dose individualization to target the right amount of medication.

TDM has an accepted role in anti-TNF therapy. Now, a study (R Battat et al. Clin Gastroenterol Hepatol 2017; 15: 1427-34) extends the concept of TDM to ustekinumab. This study which took place between 2014-2015 examined ustekinumab use in 62 patients with refractory Crohn’s disease (CD). Ustekinumab dosing: 90 mg SC at weeks 0, 1, and 2 for induction, then 90 mg every 4 or 8 weeks for maintenance.

Key findings:

At week 26, 80.7% of patients had a clinical response, 66.1% had a clinical remission, and 58.9% had an endoscopic response.
In those with an endoscopic response, the mean trough concentration of ustekinumab was 4.7 mcg/mL compared with 3.8 mcg/mL those without an endoscopic response.
Using a trough threshold of 4.5 mcg/mL at week ≥26, 75.9% had an endoscopic response whereas those with a level below this trough had a 40.7% endoscopic response
The authors did not detect antibodies to ustekinumab in any patient. The authors note that ustekinumab has low immunogenicity and prior UNITI studies indicated antibody formation in 0.2% after induction and 2.3% at 1 year.
Unlike combination therapy with anti-TNF therapy, “concurrent immunosuppressive therapy does not explain low immunogenicity, as only 25.8% of patients received these and had neither improved clinical outcomes nor higher drug concentrations.”

Thus far, no clinical studies have demonstrated improved clinical outcomes with dose escalation in the setting of low ustekinumab levels. A prospective trial would be helpful.

My take: This study shows promising results for ustekinumab for refractory CD. The low immunogenicity indicates that monotherapy is likely appropriate. A target level of >4.5 mcg/mL indicates a higher likelihood of response.

Related blog posts:

#NASPGHAN17 Celiac Disease and Mucosal Healing

Posted on November 26, 2017 by gutsandgrowth

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Celiac disease: treat to target! Where should we aim and how do we get there?

Ivor Hill Nationwide Children’s Hospital

Key point:

Dr. Hill asserted that long-term outcomes are related to ongoing intestinal inflammation and thus our goal should be mucosal healing rather than normalized symptoms/normalized serology

At this lecture, I asked Dr. Hill what he would recommend for an asymptomatic pediatric patient with ongoing intestinal inflammation who was strictly adherent to a gluten-free diet, who had no other recognizable diseases, and who had normalized their serology on treatment. His response was that in adults that ~50% of patients improve with better attention to diet. Thus, currently besides further dietary scrutiny, it is unclear what should be done in the pediatric population should one find ongoing mucosal disease in an asymptomatic adherent patient.

My take: Until prospective pediatric studies are published to determine the frequency of ongoing intestinal inflammation in those on a strictly GFD in asymptomatic patients and until we have additional management options, it does not make sense to look for mucosal healing. “Don’t hunt what you cannot kill.”

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. 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.

#NASPGHAN17 Therapeutic Drug Monitoring Associated with Increased Clinical Remission

Posted on November 25, 2017 by gutsandgrowth

In support of Dr. Baldassano’s talk (NASPGHAN17: Treat to Target and Tight Control), this poster from the Cincinnati group (A Mulgand et al) showed that therapeutic drug monitoring has been associated with improved clinical remission scores (80% to 87%). Correlation with a more objective marker of remission along with longer followup is now needed. One of the authors, Dana Dykes, has joined our group in Atlanta!

Related blog posts:

#NASPGHAN 17 More Abstracts

Posted on November 24, 2017 by gutsandgrowth

This link for the NASPGHAN abstracts :NASPGHAN 2017 Scientific Abstracts

The following slides are from some of the abstract posters. This first poster (next 5 pics) showed that symptom association with meals is not predictive of aspiration among a selected group of children who underwent swallow study evaluations. In the figures, the blue bars are children who passed the swallow study whereas the red bars indicate the children who failed the swallow study.

This next slide demonstrated that a six food diet for EoE could be administered blenderized via a gastrostomy tube.

The next slide showed that irritable bowel syndrome was more frequent (overall hazard ratio of 1.52) following a urinary tract infection in the first year of life.

The next pictures are from a poster discussing high rates of recurrent C difficile infection following fecal microbial transplantation in pediatric patients with inflammatory bowel disease (mainly ulcerative colitis). An inference from this study would be that many cases of C difficile that were attributed as causing symptoms could in fact have been from a flare up of their IBD. More details about the diagnosis of C difficile (based on PCR or ELISA) would be helpful

The next poster provides data from CHOP experience with Ustekinumab. Overall, in this highly-selected (refrcactory) population the long term improvement was low; while one-third had steroid-free remission at week 8, this was not maintained at week 16 and week 24. In addition, among the 22 patients, one developed transverse myelitis.

This study that follows (next two pics) documented the relative safety of liver biopsies (mainly percutaneous without interventional radiology) in the post-transplant period. The two most serious adverse events, cholangitis and bile leak, helped identify biliary strictures.

The following collaborative study examined the neurocognitive status of children with Alagille syndrome. Overall, this study shows that children with Alagille syndrome are at increased risk of low IQ compared to children with other cholestatic diseases.

#NASPGHAN17 Selected Abstracts

Posted on November 23, 2017 by gutsandgrowth

Some of the abstracts that were presented at this year’s meeting –see below. For a listing of the titles/authors presented, use this link: NASPGHAN Annual Mtg 2017

For complete abstracts: NASPGHAN 2017 Scientific Abstracts

Using a standardized approach along with a protocol for oral cleanouts and saline enemas if needed, the authors showed a marked decline in admissions for fecal impaction:

In this study, the authors found that low risk patients had a 91% likelihood of a negative scope. However, on closer inspection, this rate OVERESTIMATES the likelihood of finding anything significant. Most findings in the low risk group had questionable benefit from being identified on endoscopy including “acute colitis,” and H pylori.

The following abstract showed that in patients with EoE and not PPI-REE that topical steroids alone were as effective as PPI with topical steroids.

The following slides indicate the development of A4250, a bile acid transporter, which reduces pruritus. The presenter stated that this drug essentially is a chemical diversion which could replace biliary diversion for pruritic conditions like PFIC and Alagille syndrome.

Changing the Dietary Approach with Eosinophilic Esophagitis

Posted on November 22, 2017 by gutsandgrowth

A recent study (AF Kagalwalla, JB Wechsler, K Amsen, S Schwartz, M Makhija, A Olive, CM Davis, M Manuel-Rubio, Seth Marcus et al. Clin Gastroenterol Hepaot, 2017; 1698-1701) is going to help shake up the dietary management of eosinophilic esophagitis (EoE). Our group GI Care for Kids, led by Seth Marcus, was one of the four centers which participated in this study of a four food elimination diet (FFED or 4-FED).

This prospective study enrolled 78 patients. IN those who did not respond to twice daily proton pump inhibitor therapy, subjects were instructed to restrict cow’s milk, wheat, egg, and soy. Patients underwent serial challenges (8 week for a challenge) with followup upper endoscopy to each food to determine response; 25 patients completed the challenge to all four foods. Key findings:

64% (n=50) had remission (Eos <15/hpf) with the FFED
Symptom scores decreased in 91% of the histologic responders
Among those who completed additional challenges: 22/26 (85%) had reactions to cow’s milk, 10/30 (33%) had reactions to wheat, 14/40 (35%) had reactions to eggs, and 8/43 (19%) had reactions to soy
Among those (n=25) who completed challenges to all four foods, reactions to food: 84% milk, 28% wheat, 8% eggs, 8% wheat
Among those (n=25) who completed challenges to all four foods, reactions occurred to a single food-groups in 64%, two food-groups in 20%, three-food groups in 8%, and four-food groups in 8%. Thus 36% had more than a single-food group reaction.

This study shows that the FFED provides similar efficacy to the six-food elimination diet (SFED) and is less restrictive. It offers the prospect of less time to complete food reintroduction and fewer upper endoscopies

Limitations: nonrandomization, absence of control group, selection bias. The fact that 24 patients dropped our before completing reintroduction highlights the difficulty of maintaining these diets in clinical practice.

In the associated editorial (S Eluri, ES Dellon, pages: 1668-9), the authors reiterate that the SFED (or 6-FED), which includes nuts and seafood, had histologic response rates typically between 69%-72% and that this study shows a similar response. They note that dairy elimination alone has had response rates ranging from 43% to 65%.

In addition, they discuss a 2-food elimination diet (milk and wheat). In a recent study (J Molina-Infante, et al. Gastroenterol 2017; 152: S207), the authors started with a 2-FED with histologic response of 43% and if not responding would advance to 4-FED and 6-FED. This approach was more efficient and further limited endoscopies.

My take: In those patients who are treated with a dietary approach, the 4-FED is a sensible initial therapeutic approach and an improvement from the 6-FED. Though there is slightly higher initial response to 6-FED, the 4-FED allows more efficiency at identifying the trigger foods and lessened patient burdens with regard to endoscopy, diet complexity, and cost.

Related study: EA Erwin et al. JPGN 2017; 65: 520-5. This study showed that patients multiple IgE antibodies (≥ 0.1 IU/mL) to foods correlated with the likelihood of identifying eosionphilic esophagitis (≥ 15 eos/hpf):

In this cohort, among males, positive IgE antibodies to zero foods had a positive predictive value of 22%, 1-3 foods 52%, and 4-5 foods of 77%
In this cohort, among females, positive IgE antibodies to zero foods had a positive predictive value of 10%, 1-3 foods 29%, and 4-5 foods of 56%

Related blog posts:

#NASPGHAN17 Eosinophilic Esophagitis Session

Posted on November 21, 2017 by gutsandgrowth

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This is a long post –highlighting four separate talks on eosinophilic esophagitis.

PPI Use in Esophageal Eosinophilia: Recommendations from the recent AGREE conference

Glenn Furuta Children’s Hospital of Colorado

Key points:

The term PPI-REE (proton pump inhibitor-responsive eosinophilic esophagitis) may not be needed. PPI-REE is quite similar to eosinophilic esophagitis based on molecular and clinical features. The main difference being that this subset responds to PPI therapy.

Characterization of CYP2C19*17 Polymporphisms Among Children with PPI Responsive EoE and EoE

James Franciosis et al. Nemours Children’s Hospital Orlando

My take: This cool presentation offered a potential explanation of why some patients respond to PPIs (so called “PPI-REE”) from those with EoE that does not respond to PPIs. This is pertinent because on a molecular basis the disease appears to be the same. The difference in PPI-REE from EoE may be how the patient metabolizes PPI. Those EoE patients who metabolize PPIs “extensively” are much less likely to respond to this therapy.

Eosinophilic esophagitis: Now an “Oldie” -But with increased interest and new research, a “Goodie”

Chris Liacouras Children’s Hospital of Philadelphia

This lecture covered an enormous amount of material. Here are a few slides.

Final Lecture (from November 3rd presentation):

Key points:

Endoflip is a new tool that helps determine esophageal distensibility. Improved distensibility indicates less fibrostenotic disease which is one long-term goal.
Response to treatment has been correlated in improvement in Endoflip measurements.
There are no FDA approved medications at this point for EoE, though topical steroids may be approved soon.