Long-Term Outcomes of Pediatric Patients with Sclerosing Cholangitis in the Setting of Inflammatory Bowel Disease

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KO Hensel et al. J Pediatr 2021; 238: 50-56. Sclerosing Cholangitis in Pediatric Inflammatory Bowel Disease: Early Diagnosis and Management Affect Clinical Outcome

This was a retrospective study of 82 pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years who were followed up for a mean of 6.8 ± 3.3 years. Tests for SC included immunoglobulins and serology (ANA, ASMA, LKM-1, and SLA). Patients with ASC were maintained on low dose prednisolone (5 mg/day) and azathioprine (up to 2 mg/kg/day).

Key findings:

  • Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%
  • Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis

The discussion notes generally better outcomes in this cohort than in previous studies. The authors note that this may be due to earlier diagnosis (though lead-time bias could be a factor as well). To increase earlier diagnosis, the gastroenterology diagnostic pathway at one institution (CUH) includes mandatory assessment of liver function and a low threshold for performing a liver biopsy (with initial panendoscopy). Diagnosis of ASC was based on the ESPGHAN diagnostic score for AILD (JPGN 2018; 66: 345-360, related post has image with scoring: Aspen Webinar 2021 Part 5 -Autoimmune Liver Disease & PSC). Also, they note that SCOPE score “seemed to overestimate the risk for developing complications.”

My take: In those with IBD and abnormal liver enzymes/GGT, looking for SC/ASC may improve outcomes.

Related blog posts:

Chattahoochee River, Atlanta

Why I Care About Another Biomarker for Pancreatitis Severity

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PR Farrell et al. J Pediatr 2021; 238: 33-41. Open Access: Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children

Methods: In this single center pediatric study, interleukin 6 (IL -6), monocyte chemotactic protein-1 (MCP-1) and CRP were obtained within 48 hours of admission in 66 subjects (20 controls, 36 with mild acute pancreatitis (AP), and 10 with severe AP) in a derivation cohort. and then in a validation cohort with 35 subjects (10 controls, 19 mild AP and 6 severe AP)

Key findings:

  • In both the derivation and vaildation cohorts, IL-6 (P = 0.02, P= 0.02 respectively) and MCP-1 (P= 0.02, P = .007) were found to differentiate mild acute pancreatitis from severe acute pancreatitis.
  • CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CRP were stratifed into 3 distinct groups, <0.4 mg/dL, 0.4-2.5 mg/dL, and >2.5 mg/dL

The discussion notes a few points:

  1. “BUN as part of a standard initial clinical biochemical evaluation on admission, as well as the response of the patient’s BUN to fluid resuscitation can help predict disease severity with high specificity and a high negative predictive value which can help to determine those patients least likely to progress to severe disease”
  2. “There is adult literature showing the benefit of placing patients at highest risk of progression to severe disease on Cox-2 inhibitors and monitoring, among other measures, the response of IL-6. Patients who received the investigational drug had significantly lower levels of IL-6, and the therapy was associated with an almost 50% reduction in the progression of patients to severe disease.”

My take: In clinical practice, both elevated CRP and BUN are associated with a higher risk of progression to severe pancreatitis. The reason why I was interested in this study was the potential for targeting IL-6 to improve outcomes.

Related blog posts:

Siesta Key, FL

Time to Change the Medical Treatment and Attitudes Directed at Obesity?

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NPR: New podcast examines wellness trends and beliefs, like what weight means about health. Interview with Aubrey Gordon and Michael Hobbes who co-host the podcast “Maintenance Phase.”

This interview has a lot of useful ‘food for thought.’

Some excerpts:

  • Every year, millions of Americans go on a diet. Americans also spend billions of dollars on weight loss products. So why, despite all of that, are obesity rates in the U.S. are continuing to rise?….
  • There’s a very clear correlation between weight and bad health outcomes, but weight is not the only thing that’s correlated with health. We know that poverty has a devastating effect on people’s health. The life expectancy in various counties in America can be up to 20 years of difference…And yet, weirdly, when it comes to obesity, it’s like, oh, no, no, we know that the obesity is causing this, right? Like, people have kind of jumped to this causal explanation…
  • Paradoxically, and unfortunately, what we have seen in the years since that redefinition [of obesity as a disease] is a skyrocketing of bias against fat people. That has happened amongst health care providers. It has happened amongst social workers. It has happened amongst the general public in the United States…
  • I think we would all do ourselves a really significant service by actually just focusing on the health markers and not the proxy for the health markers, which is weight…
  • What we find is really consistent stories from fat people of going into the doctor with a migraine headache and their doctor tells them to lose weight. They go in with a car accident, their doctor tells them to lose weight. They go in with a tumor, their doctor tells them to lose weight. This is something that is, like, really, really devastating to the health of fat people that essentially people don’t listen to them.

My take: Diets for weight loss have very low rates of success. Focusing on healthy eating habits (eg. food/beverage composition, eating together) along with encouraging healthy activity levels is likely to be most beneficial for long-term outcomes. .

Related blog posts:

Siesta Key, FL

Improving Outcomes with Proactive Therapeutic Drug Monitoring + Swiss COVID-19 Data

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Another recent study showing the benefits of proactive therapeutic drug monitoring (pTDM):

SW Syverson et al. JAMA. 2021;326(23):2375-2384. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases (The article is only 10 pages; however, the supplementary material (which I did not read) is an additional 258 pages.) Thanks to Ben Gold for sharing article reference. Also, this study was reviewed in Healio Gastro: Link: Therapeutic drug monitoring sustains disease control during infliximab maintenance

Methods: Randomized, parallel-group, open-label clinical trial including 458 adults (mean age, 44.8 years; 49.8% women) with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis (n=81), Crohn disease (n=66), or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospital

Key finding:

  • Sustained disease control without worsening was evident in 73.9% of pTDM group compared with 55.9% in standard infliximab group

Some limitations of this study:

  1. The open-label study was not powered to detect the difference of pTDM in each of the six diseases
  2. The therapeutic goal for maintenance infliximab was 3 to 8 mg/L, which is a little lower than current goals (ACG expert panel suggests a level of at least 5-10)

My take: This study supports recent expert guidance (see blog post below) on the benefit of pTDM as part of evidence-based care. It is likely that pTDM is even more important in children/teens due to growth.

Time to Disease Worsening

Related blog posts:

Also data from Switzerland:

Acid Suppression for Laryngomalacia -Handed This Article to My ENT Colleagues

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DR Duncan et al. J Pediatr 2021; 238: 42-49. Acid Suppression Does Not Improve Laryngomalacia Outcomes but Treatment for Oropharyngeal Dysphagia Might Be Protective

This retrospective cohort study with 236 subjects (55% received acid blockers) provides a compelling argument that acid suppression is unlikely to be beneficial in infants with laryngomalacia and to consider the possibility of aspiration in them as well. Among all subjects, 27% received H2RA, 11% received PPI, and 17% received both.

Key findings:

  • Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates
  • Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment.
  • Subjects with moderate-to-severe laryngomalacia were more likely to have aspiration on a video fluoroscopic swallow study (VFSS)
  • Of the 40 patients who had a supraglottoplasty, only 4 (10%) had a VFSS before and afterwards. All repeat VFSS showed improvement at a mean of 4.7 months after supraglottoplasty

It is noted that 36% of subjects underwent a VFSS and 40% had a clinical feeding evaluation. The authors note that other studies have found “a high rate of silent aspiration in laryngomalacia.”

My take:

  1. Acid blockers are unlikely to be beneficial in infants with laryngomalacia and are potentially detrimental (findings limited by retrospective design in a tertiary care setting)
  2. Symptoms in children with laryngomalacia may be due to aspiration and evaluation is needed in those with significant symptoms

Related blog posts:

WSJ 1/2/22: Why Cloth Masks Might Not Be Enough as Omicron Spreads

Best of IBD in Gastroenterology 2021 from AIBD

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The following link is the same as the QR code below (from twitter feed) and provides PDF access to ~30 influential articles from the journal, Gastroenterology, this past year (many reviewed on this blog previously):

Link: Best of Gastroenterology 2021 AIBD

I’ve included screenshots of many of the articles below.

D Turner, SB Hanauer. Editorial on DINE-CD study
Krugliak et al. In press.

Also, recent data indicate that the omicron strain of SARS-CoV-2 is much less likely to affect sense of smell or taste but more likely to cause a sore throat –from Eric Topol twitter feed:

2-Fold Risk of Urolithiasis in Patients with Inflammatory Bowel Disease

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H Dimke et al. Clin Gastroenterol Hepatol 2021; 19: 2532-2540. Risk of Urolithiasis in Patients With Inflammatory Bowel Disease: A Nationwide Danish Cohort Study 1977–2018

Using national registries, the authors identified all patients with IBD (>15 years of age) and all cases of urolithiasis in Denmark during 1977-2018. Key findings:

  • 2,549 (3%) of 75,236 IBD patients and 11,258 (2%) of 767,403 non-IBD individuals developed urolithiasis, resulting in a 2-fold increased risk of urolithiasis (HR, 2.27; 95% CI, 2.17-2.38) in patients with IBD
  • The authors note that a small risk of urolithiasis preceded the diagnosis of IBD: with OR, 1.42; 95% CI: 1.34-1.50 prior to diagnosis
  • After IBD diagnosis, risk of urolithiasis was associated with anti-TNF therapy and surgery (increased disease severity appears to be associated with increased risk). Anti-TNF therapy had a RR of 2.68 in patients with ulcerative colitis and a RR of 3.56 in patients with Crohn’s disease; for surgery, the RR were 3.14 and 2.74 respectively
  • One limitation is detection bias as patients with IBD may have more asymptomatic stones identified due to more frequent imaging

My take: This confirms an increased risk of urolithiaiss in patients with IBD and is a good reminder to consider this when patients present with severe abdominal pain/possible flare-up.

Siesta Key, FL

IBD Shorts: Fecal Calprotectin in UC & Medication Withdrawal, Outcome of Biosimilar Reverse Switches, Vedolizumab after Anti-TNF Therapy

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TW Stevens et al. Inflamm Bowel Dis 2021; 19: 2333-2342. Open Access. Diagnostic Accuracy of Fecal Calprotectin Concentration in Evaluating Therapeutic Outcomes of Patients With Ulcerative Colitis

Key finding: A post hoc analysis of data from a phase 4 trial (the MOMENTUM trial) found that, even in patients (n=593 at week 8, n=305 at week 52) with complete endoscopic healing of UC, FC concentration can be used to discriminate patients with ongoing microscopic inflammation from patients with histologic remission.  The optimal FC cut-off concentrations for identification of patients with histologic remission were 75 μg/g at week 8 and 99 μg/g at week 52.

A Cassinotti et al. Clin Gastroenterol Hepatol 2021; 19: 2293-2301. Noninvasive Monitoring After Azathioprine Withdrawal in Patients With Inflammatory Bowel Disease in Deep Remission

Key finding: In this prospective study, 57 patients in deep remission stopped azathioprine after a median of 7 years. 26 (46%) relapsed within a median of 15 months. Fecal calprotectin (FC) levels were >50 mcg/g in all patients with relapse (FC specificity 100%) but the sensitivity was only 50%. Thus, having a normal FC does not preclude relapse but elevated FC is associated with relapse.

S Mahmmod et al. Inflamm Bowel Dis 2021; 27: 1954-1962. Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease

In this retrospective study, 75 patients, 9.9% of all patients, who had been changed from originator infliximab to a biosimilar had clinical worsening. Key finding: Improvement of reported symptoms was seen in 73.3% of patients after reverse switching back to originator infliximab; alsor 7 out of 9 patients (77.8%) with loss of response regained response

J Kim et al. Inflamm Bowel Dis 2021; 27: 1931-1941. Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study

Key finding: Clinical remission rates with vedolizumab among patients with CD (n=80) and patients with UC (n=78) were 44.1% and 44.0%. Among patients with UC, the endoscopic remission rate was 32.4%

Double Whammy: Coexistent IBD and Celiac Disease in Children

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Merriam-Webster: Double Whammy Definition: “a combination of two usually adverse forces, circumstances, or effects”

M Bramuzzo et al. Inflamm Bowel Dis 2021; 27: 1881-1888. Open Access: Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease

Methods: This was a retrospective case-control study based on a national registry. Cases included children diagnosed with both IBD and Celiac Disease (CeD). Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case.

Key findings:

  • Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. CeD was diagnosed before IBD in 37 (75.5%)
  • Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97–8.37; P = 0.04) (mainly thyroiditis 6.1% vs 0%)
  • Children with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%); however, this was based on a small number (3 surgeries out of 23 patients)
  • Anti-TNF biologics (46.2% vs 69.2%) were less commonly administered in patients with Crohn’s disease and CeD than in patients with Crohn’s disease alone
  • Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24)

The discussion emphasizes the need to consider the risk of developing IBD in children with CeD and to recognize the increased risk of autoimmune diseases. Children with both UC and CeD may have a more severe phenotype. The authors recognize the possibility of misdiagnosis of CeD as patients with IBD could present with similar upper GI findings; however, this is likely infrequent as most cases of CeD preceded the diagnosis of IBD.

My take: One point that the authors neglect is the need to consider an underlying monogenetic disorder (eg. CTLA4B) in children with multiple immune-mediated diseases. The main message for children with this double whammy, though, is to consider the need for more aggressive treatment (especially with UC) and the need to screen for other autoimmune conditions (especially thyroiditis).

Related blog posts:

Huntingdon Lake, Sandy Springs, GA -Foggy New Year’s Eve (12/31/21)

NY Times: Year in Health Articles

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Personal item: If any blog follower has experience using biologics (eg mepolizumab, benralizumab) in a young child (1 yo) with eosinophilic colitis and marked eosinophilia, please send me a personal email: jjhochman@gmail.com.

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NY Times: The Year in Fitness: Shorter Workouts, Greater Clarity, Longer Lives
By Gretchen Reynolds

Key points:

  • “Another series of studies from the University of Texas found that four seconds — yes, seconds — of ferocious bicycle pedaling, repeated several times, was enough to raise adults’ strength and endurance, whatever their age or health when they started.”
  • “As I wrote in July, the familiar goal of 10,000 daily steps, deeply embedded in our activity trackers and collective consciousness, has little scientific validity. It is a myth that grew out of a marketing accident, and a study published this summer further debunked it, finding that people who took between 7,000 and 8,000 steps a day, or a little more than three miles, generally lived longer than those strolling less or accumulating more than 10,000 steps.”
  • “Exercise also has a disproportionate impact on our odds of enjoying a long, healthy life. According to one of the most inspiring studies this year, overweight people who started working out lowered their risk of premature death by about 30 percent even if they remained overweight, with exercise providing about twice as much benefit as weight loss might…Exercise enhances our brain power, too, according to other, memorable experiments from this year”
  • “In the study, which I wrote about in May, active people reported a stronger sense of purpose in their lives than inactive people….In effect, the more people felt their lives had meaning, the more they wound up moving, and the more they moved, the more meaningful they found their lives.

NY Times: The Secrets to Successful Aging in 2022

Key points:

  • For successful aging, recognize one’s issues and adapt accordingly. “Sooner or later, we all must recognize what is no longer possible and find alternatives,” says Jane Brody (Personal Health columnist) –“Inspired by Steven Petrow’s book, “Stupid Things I Won’t Do When I Get Old.”
  • Learning from ‘Super-Agers’ — “past research has revealed lifestyle factors that contribute to resilience such as obtaining a high level of quality education; holding occupations that deal with complex facts and data; consuming a Mediterranean-style diet; engaging in leisure activities; socializing with other people; and exercising regularly”
  • The sweet spot for longevity lies around 7,000 steps a day (or 30 minutes of exercise).

NY Times: How to Improve Your Mental Health in 2022 By Dani Blum and Farah Miller

NY Times: Favorite Pieces of Advice (7 tips) includes being kind to yourself and advice to learn/do new things

The Legacy Trail -Sarasota County, FL