Category Archives: Uncategorized

Impact of Adalimumab Levels on Fistula Healing in Crohn’s Disease

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K Papamichael et al.Clin Gastroenterol Hepatol 2024; 22: 2134-2136.
Higher Adalimumab Concentration Is Associated With Complete Fistula Healing in Patients With Perianal Fistulizing Crohn’s Disease

In this multicenter retrospective review with 183 patients, the adalimumab (ADM) levels were examined with respect to healing of perianal fistulas. Most patients (82%) had complex perianal fistulizing CD.

Key findings:

  • 87 patients (48%) received intensified dosing at the time of therapeutic drug monitoring (TDM)
  • Patients with complete fistula healing (CFH) had higher median ADM levels: 12.9 compared to 6.1 for those witout CFH
  • “Optimal ADM concentration associated with CFH was 12.2 mcg/mL” which had positive predictive value of 64% and negative predictive value of 80%. Among those with ADM >12.1, CFH was achieved in 64% compared to 20.5% in those with concentrations <12.1 (Odds ratio, 5.7). “Even higher drug levels may be needed.”
There were 46 patients in each drug level category

My take: There is a lot of data supporting TDM, including proactive TDM, with anti-TNF agents like adalimumab and infliximab. This study shows that with fistulizing disease higher drug levels are needed to achieve better outcomes.

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Update on Norovirus — November 2024 from Caitlyn Rivers

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From Caitlyn Rivers Newsletter, Force of Infection 11/4/24:

Norovirus is high and increasing right now. Nationally, test positivity is at nearly 12%. To put this in context, the peak last year was 13.6%. Rates are particularly high in the Southern region.

Source: CDC

A reminder as cases increase: norovirus causes stomach pains, diarrhea, and vomiting. It is extremely transmissible via bodily fluids and through contaminated surfaces, food, and water.

  • To reduce your odds of getting sick, remember to wash your hands frequently with soap and water for at least 30 seconds (norovirus is able to withstand hand sanitizer).
  • If you or someone in your household becomes sick, wash hard surfaces with soap and water or a diluted bleach mixture, and wash soiled clothing and linens in hot water and then dry on high heat.
  • Norovirus is still highly transmissible for several days after symptoms improve or go away. As such, insofar as is possible, avoid preparing food for others for at least 72 hours after symptoms end. Longer is better: it can spread up to two weeks after symptoms end, though it is most transmissible during those first few days of illness and after symptoms resolve.

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Here’s the Data: Endocrine Insufficiency After Acute Pancreatitis in Children

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M Abu-El-Haija et al. Clin Gastroenterol Hepatol 2024; 22: 2033-2043. Open Access! The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children

In this observational prospective cohort with 114 children (after excluding 6), outcomes following the first episode of acute pancreatitis (AP) were determined. In addition, pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15.

Pre-DM was defined as follows: fasting blood glucose ≥100 mg/dL and <126 mg/dL, or hemoglobin A1C ≥5.7% and <6.5%

Key findings:

  • 95/114 (83%) remained normoglycemic and 19/114 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM) 12 months after the first episode of AP
  • Sixty-three subjects (52.5%) had at least 1 reportable variant identified
  • Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group
  • CFTR (53%), SPINK1 (13%), PRSS1 (10%), and UBR1 (9%) accounted for the majority of variants identified

My take: 3.5% of this cohort developed diabetes and 13% developed prediabetes. The risk is increased in those with severe acute pancreatitis and underlying genetic variants. As noted recently with Dr. Freeman’s lecture (summarized on prior blog posts), it is worthwhile for patients to follow-up after an episode of acute pancreatitis.

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Firearm Deaths: A U.S. Crisis Compared to Other Nations

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10/30/24 The Guardian, Jessica Glenza: Some US states have firearm death rates comparable to countries in conflict, report says

An excerpt:

“A new report by the Commonwealth Fund finds some US states have firearm death rates comparable to countries in conflict…For instance, Mississippi’s rate of firearm-related violence (28.5 per 100,000 people) was nearly double that of Haiti (15.1 per 100,000) in 2021…

Rhode Island, which has the lowest firearm death rate in the US (three per 100,000) is still 23 times higher than the United Kingdom (0.13 per 100,000) and nearly 1.3 times higher than France (2.3 per 100,000).

The US overall is in the 93rd percentile of all countries and territories for overall firearm mortality, at 13.5 deaths per 100,000 people…

In another example, Mississippi, Louisiana, Alabama and New Mexico all have higher firearm mortality rates than Mexico, where decades of violence between state forces and rival drug cartels has caused hundreds of thousands of deaths and left more than 115,000 people missing…

More than half of all firearm-related deaths (56.1%) in 2022 were from suicide…the rate of firearm deaths among American children is 72 times higher in the US than in the UK (36.4 deaths per million versus 0.5 deaths per million)

Related: The Commonwealth Fund Report (10/30/24): Comparing Deaths from Gun Violence in the U.S. with Other Countries. The report has many charts showing U.S and each states data.

My take: The fact that the U.S firearm mortality rates can be compared unfavorably to places with violent reputations like Haiti and Mexico is awful. What’s worse is the capitulation by most to not even try to improve the situation.

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Potential Bias with Interpreting Rumination Outcomes

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MR Jia et al. J Pediatr Gastroenterol Nutr. 2024;79:850–854. Delay in diagnosis is associated with decreased treatment effectiveness in children with rumination syndrome

In this retrospective single-center study with 247 patients, the authors evaluated whether the time from symptom onset to diagnosis over time and whether it was associated with symptom resolution.

Key findings:

  • The median age at symptom onset was 11 years and median age at diagnosis was13 years
  • Among the 164 children with outcome data, 47 (29%) met criteria for symptom resolution after treatment
  • A longer time to diagnosis was associated with a lower likelihood of symptom resolution after treatment (p = 0.01)

In the discussion, the authors note that “we suspect that one contributing factor to worse outcomes associated with diagnostic delays is the excessive testing leading to over‐medicalization of DGBIs…Our findings are the first to show that diagnostic delay contributes to poorer outcomes in children with RS, which highlights the importance of a timely diagnosis.” In fairness to the authors, other parts of the manuscript state that the delay in diagnosis is associated with worse outcomes but does not attribute causality.

Limitations:

  • The patient cohort is derived from a specialized referral center (Nationwide Children’s)
  • Recall bias

My take:

  1. While I concur that a timely diagnosis of rumination syndrome is useful, it is unproven that a delayed diagnosis contributes to a worse outcome. The outcome differences could more easily be explained by a selection bias. Patients who never recovered from rumination symptoms previously may be less likely to respond to treatment regardless of when treatment is instituted. Perhaps attributing poor outcomes to delayed diagnosis, rather than a selection bias, is due to a confirmation bias.
  2. Another important finding is that the more than 70% of patients did NOT have resolution of their symptoms. Realizing that many patients have some symptoms after treatment helps gastroenterologists set reasonable goals.

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LIBERTY Trials for Subcutaneous Infliximab

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SB Hanauer, BE Sands, et al. Gastroenterology 2024;167: 919-923. Open Access PDF! Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY)

Methods: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. 

Key findings:

  • At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC–treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001)
  • In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001).
  • CT-P13 SC was well tolerated, with no new safety signals identified.
  • The mean serum infliximab trough concentrations at weeks 14 and 54 were 13.2 and 14.8 mcg/mL with CD study and 14.6 and 16.3 with UC study, respectively.
Proportions of patients achieving co-primary and key secondary end points
at week 54 in the CD study (all randomized population)
Proportions of patients achieving primary and key secondary efficacy end
points at week 54 in the UC study (all randomized population)

Discussion:

  • “The present findings are generally comparable with or numerically better than those observed in previous clinical trials that evaluated IV infliximab in patients with CD or UC…At week 50 in the SONIC trial, 35% of patients receiving infliximab achieved corticosteroid-free clinical remission,30 compared with 40% of patients in the CT-P13 SC group in the current study.”
  • “In terms of UC, the ACT 1 study4 found that patients receiving infliximab 5 mg/kg and 10 mg/kg were more likely to achieve clinical remission based on total Mayo score after 54 weeks (34.7% and 34.4%, respectively) compared with participants receiving placebo (16.5%), and in the current study, 43.2% and 20.8% of patients, all of whom had responded to induction therapy, achieved clinical remission at week 54 in the CT-P13 SC and placebo groups, respectively.”
  • This study had a high rate of antidrug antibody detection (63.8%–65.1%)…” likely due to the use of highly sensitive, next-generation ADA assays, which have improved sensitivity compared with those used in historical studies… This suggests that route of administration of CT-P13 does not affect rates of ADA formation, and that the observed incidence of ADA is not unexpected.”
  • “The decision to initiate CT-P13 SC maintenance therapy at week 10, 4 weeks after finishing CT-P13 IV induction therapy, was based on results of PK or pharmacodynamic model simulation.”

My take: These studies suggest that SC infliximab is likely to have similar efficacy as IV infliximab

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When and How to Pursue Ileal Diversion in Crohn’s Disease

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A Simard et al. J Pediatr Gastroenterol Nutr. 2024;79:800–806. Role of ileal diversion in pediatric inflammatory bowel disease

Indications:

  • Severe, medically refractory colitis
  • Complex and medically refractory perianal disease
  • In combination with bowel resection for irreversible bowel damage (e.g., fistulae, abscesses, or strictures)

Diversion “provides the opportunity to reduce steroid use, improve growth and observe the natural history of the disease in a more controlled manner. It may also enhance quality of life”

My take: This is a handy article when considering ileal diversion in a patient with medically-refractory inflammatory bowel disease.

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Near-Death Experience from a Button Battery

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MR Smetak, LJ Wilcox. N Engl J Med 2024;391:1139. Button-Battery Ingestion

An excerpt:

A previously healthy 11-month-old girl presented to the emergency department with a 2-week history of progressively worsening dysphagia and cough..A chest radiograph showed a foreign body with a “halo” or “double-ring” sign. Approximately 10 hours after endoscopic removal, “torrential hematemesis and hemorrhagic shock developed. During emergency surgical exploration, no source of bleeding was initially identified, but intraoperative angiography revealed a fistula between the esophagus, which was dilated, and the left common carotid artery (Panel B, arrow). The artery was ligated, and hemostasis was achieved.” The patient was discharged 32 days after admission without neurologic or functional deficits.

My take: Even in children in the hospital, massive bleeding due to a coronary artery to esophagus fistula carries an extremely high mortality rate.

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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.

How to Upgrade Pancreas Care –Jay Freeman MD (Part 2)

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We had a great pancreas update lecture from Dr. Jay Freeman. In my view, a great lecture involves a well-delivered informative lecture that likely leads to an improvement in clinical practice. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

  • Currently there are NO recommendations for medications that can prevent progression of chronic pancreatitis
  • Use of neuromodulators (eg. TCAs, Gabapentin) are often given to reduce pain
  • Cognitive behavioral therapy has been used in chronic pancreatitis with significant improvement
  • Pain management is working towards objective pain markers
  • Changes in pancreatic function are associated with risk of pancreatitis
  • CF drugs have changed pancreatic function in the CF population and may be helpful in other populations
  • Pancreatic enzymes (PERT) may decrease the risk of pancreatitis. Based on the PAUSE study, a double-blind study is needed to determine if PERT can reduce pancreatitis with ARP or CP
  • From Nationwide Children’s Summary: “The researchers found that nearly 17% of children with pancreatic-sufficient ARP and CP were treated with pancreatic enzymes. Children started on pancreatic enzyme therapy experienced fewer AP episodes annually, and approximately 40% of children on pancreatic enzyme therapy had no additional AP episodes [during a mean 2.1 years of follow-up] over approximately two years of follow-up. Children with a SPINK1 mutation and those with ARP (compared with CP) were less likely to have an AP episode after initiating pancreatic enzyme therapy… a randomized, placebo-controlled clinical trial is necessary to evaluate the true impact of pancreatic enzymes for these patients.” Freeman AJ, et al. American Journal of Gastroenterology. 2024 Apr 18. DOI: 10.14309/ajg.0000000000002772. Epub ahead of print.Open Access! Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE. “After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001).”
  • The TACTIC study showed that an oral serine protease inhibitor reduced daily pain; however, the 4-week change was similar to placebo. This study shows why placebo-controlled studies are needed
  • There are other treatment approaches that are being studied in adults including antifibrotics, simvastatin, and paracalcitol

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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.

How to Upgrade Pancreas Care –Jay Freeman MD (Part 1)

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We had a great pancreas update lecture from Dr. Jay Freeman. In my view, a great lecture involves a well-delivered informative lecture that likely leads to an improvement in clinical practice. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

  • About 10% of patients with acute pancreatitis already have damage indicating chronicity
  • Severe pancreatitis is often defined by degree of organ dysfunction (eg. cardiac, pulmonary, renal). A practical definition of severe pancreatitis in children is whether the patient requires admission to an ICU
  • The term “position paper” is typically used instead of “guidelines” due to lack of definitive data and reliance on expert opinion
  • While the guidelines suggest 1.5-2.0 x maintenance fluid volumes, the benefit of this additional IVFs is not clear. Dr. Freeman’s clinical practice is often to start with 1.5 x maintenance rate and to try to transition to enteral diet
  • Aggressive fluid resuscitation of acute pancreatitis in adults is associated with increased risk of fluid overload. Lactated ringer’s is generally fluid of choice.
  • In this study with 211 pediatric patients, starting with a narcotic increases the likelihood of continuing with narcotics. Many patients can respond to acetaminophen and NSAIDs. Using narcotics, may increase the risk of sensitization to pain (lowering pain threshold)
  • In this study with adults (Not Randomized), use of PCA was associated with longer hospitalizations, slower start to enteral nutrition and increased narcotic use at discharge
  • A single episode of acute pancreatitis, even mild cases, is associated with long-term risks including risk of exocrine pancreatic insufficiency (often transient), increased risk of diabetes mellitus and even pancreatic cancer.
  • Restricting fat in the diet for 1-2 weeks after an episode may reduce some symptoms
  • Because of risk of complications, Dr. Freeman recommends follow up after hospitalization (after a few months) and for up to 5 years (at least for 2 years)
  • Dr. Freeman indicated that he recommends checking genetic tests for pancreatitis if a patient has had more than one episode. If a patient is less than 5 years of age or has a significant family history, checking for genetic predisposition should be considered with the first bout of pancreatitis.

Key points: Even patients with acute pancreatitis need follow-up. Consider using non-narcotic medicines as the first line, especially in patients who have not ‘failed’ these medications.

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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.