Persistently Abnormal Celiac Labs =High Likelihood of Celiac Disease

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CM Trovato et al JPGN 2021; 72: 712-717. Diagnostic Value of Persistently Low Positive TGA-IgA Titers in Symptomatic Children With Suspected Celiac Disease

This retrospective study provides insight into the predictive value of persistently abnormal celiac labs in symptomatic children.

Inclusion criteria:  not eligible for a non-biopsy diagnosis AND children with at least 2 TGA-IgA measurements, endomysial antibody (EMA) assessment and esophagogastroduodenoscopy with biopsies

Methods: Patients were classified in groups according to median TGA-IgA values: Group A (TGA-IgA>1 ≤ 5 × ULN; defined as “low-positive”), Group B (TGA-IgA > 5 < 10 × ULN; “moderate-positive”), and C (controls).

Key findings:

  • In group A, CD was diagnosed in 142/162 (87.7%)
  •  In group B, all 62 children (100%) received a CD diagnosis

My take: In individuals with mild elevation of celiac serology, it is reasonable to recheck prior to confirming with endoscopy. However, those with persistently abnormal values are very likely to have celiac disease.

Related blog posts:

  • If TTG IgA at 1-fold ULN, then PPV 61%, NPV 98%, Sens 90%, Spec 90%
  • If TTG IgA at 2-fold ULN, then PPV 79%, NPV 97%, Sens 82%, Spec 96%
  • If TTG IgA at 5-fold ULN, then PPV 93%, NPV 94%, Sens 62%, Spec 99%
  • If TTG IgA at 7-fold ULN, then PPV 96%, NPV 91%, Sens 41%, Spec 100%
Near Hahn Woods, Atlanta

AGA Guidelines: Pre-endoscopy COVID-19 Testing No Longer Needed

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May 20, 2021: AGA Guideline–Summary: New AGA guidance: stop COVID-19 testing prior to endoscopy (for U.S.)

Full report (48 pages): AGA Rapid Review and Guideline for SARS-CoV2 Testing and Endoscopy PostVaccination: 2021 Update

“AGA has now updated its July 2020 recommendations regarding pre-procedure testing. Based on the latest available data, routine COVID-19 testing prior to endoscopy is no longer needed to perform endoscopy safely.

Read on for four key points from AGA’s newest, evidence-based COVID-19 clinical guidance. Review the full Rapid Recommendations document ahead of print — it will be published soon in Gastroenterology.

Key guidance for gastroenterologists:

  • Routine SARS-CoV-2 testing prior to endoscopy is no longer needed to perform endoscopy safely: Our systematic review found that there is little benefit in routine testing, given very low rates of infection (i.e. asymptomatic prevalence and transmission) during endoscopy to both patients and staff (0-0.5% across representative studies), with potential significant burden, including delays in care, impact of cancer burden, cost, health disparities and reduced endoscopy efficiency. Previously identified benefits of testing, including informed rationing of personal protective equipment (PPE) and patient and staff reassurance, have less relevance given adequate supply of PPE and reduced anxiety in later stages of the pandemic.
  • Vaccination status should not dictate decision-making for implementing pre-procedure SARS-CoV-2 testing: The studies included in our review were conducted prior to vaccination and show minimal benefit of testing as outlined above. While indirect data show that vaccination reduces that risk even further, the available evidence supports eliminating pre-procedure testing regardless of vaccination status of patients.
  • All patients should receive symptom screening prior to endoscopy: Centers should continue to implement universal screening of patients for COVID-19 symptoms, using a screening checklist, and follow universal precautions, including physical distancing, masks and hand hygiene in the endoscopy unit. For patients who have a positive symptom screen, pre-procedure testing can then be utilized for further triage.
  • For centers that value the small benefits (patient and staff reassurance or anxiety) over the downsides (delays care, potential exacerbation of health disparities, endoscopy efficiency, downstream consequences of false negatives and false positives), pre-procedure testing with rapid PCR tests can be considered: Rapid RT-PCR tests that can be performed on the day of endoscopy are preferable as they pose less burden to patients. In the pre-procedure setting, there is limited utility of rapid isothermal tests or antigen tests. There is no role for antibody tests in this context.”

These recommendations are only applicable IF:

My take: This is great news for our patients and hopefully will be widely adopted.

Polyethylene Glycol in the First Two Years of Life

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A recent retrospective study (D Roy et al. JPGN 2021; 72: 683-689. Full text: Utilisation and Safety of Polyethylene Glycol 3350 With Electrolytes in Children Under 2 Years) provides some reassurance that use of polyethylene glycol 3350 (PEG) (aka Miralax) was well-tolerated in children <2 years of age.

From an initial cohort of 20,861 from the Clinical Practice Research Datalink (CPRD) GOLD, the authors identified 13,235 patients with a constipation indication and 40 patients with fecal impaction indication for PEG.

Key finding:

  • The safety aspect of this study did not identify any signals of concern in the constipation cohort.
  • The mean duration of exposure, in the first treatment episode, was 88.9 days.
  • 9380 patients (70.9%) were aged between 12 and <24 months, with a further 3855 patients (29.1%) aged <12months. Also, PEG 3350+E was used in 477 patients (3.6%) who were <6 months of age

This type of retrospective study is less capable of detecting adverse events than a prospective study and is limited by how carefully the primary care provider elicits and documents them.

My take: This large study confirms the widespread usage of PEG in young children without apparent adverse reactions.

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Near Lullwater Park, Atlanta

Olive Oil Enemas for Constipation

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Briefly noted: A recent retrospective study (A Yokoi, N Kamata. J Pediatr Surg 2021; https://doi.org/10.1016/j.jpedsurg.2021.03.024 The usefulness of olive oil enema in children with severe chronic constipation) showed the potential utility of olive oil enemas for children (n=115) with constipation.

Treatment regimen: “A 1–2 ml/kg olive oil enema was given either alone or followed several hours later by a glycerin enema.”

Study population: “Forty-nine had functional constipation; 43 had anorectal malformation; 40 had Hirschsprung disease; 12 had spina bifida; and 10 had other maladies.”

  • Key finding: Olive oil enema was considered effective in treating fecal impaction in 77.6% of patients

My take: I don’t have any personal experience with olive oil but expect it would work similar to mineral oil.

Mural on beltline near Ansley Park

Increased Cancers with Fatty Liver Disease

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Z Wang et al. Clin Gastroenterol Hepatol 2021; 19: 788-796. Associations Between Nonalcoholic Fatty Liver Disease and Cancers in a Large Cohort in China

It is well-recognized that obesity/overweight increases the risk of cancer (related blog post: Cancer due to Overweight/Obesity). Wang et al provide data regarding cancer risk due specifically to nonalcoholic fatty liver disease (NAFLD) from a large prospective adult cohort (n=54,187). Key findings:

  • Prevalence of NAFLD, based on ultrasonography, was 32.3%.
  • NAFLD was associated with increased risk of all cancers (hazard ratio [HR], 1.22; 95% CI, 1.10–1.36; P = .0001), thyroid cancer (HR, 2.79; 95% CI, 1.25–6.21; P = .01), and lung cancer (HR, 1.23; 95% CI, 1.02–1.49; P = .03).
  • Increased risk for colorectal cancer (HR, 1.96) and lung cancer (HR, 1.38) was demonstrated only in smokers.  An association between NAFLD and kidney cancer (HR, 1.57; 95% CI, 1.03–2.40) was only observed in men without diabetes.
  • Risk of hepatocellular carcinoma was increased only in those with elevated ALT values of 80 U/L or more (HR 8.08)

My take: This study shows that NAFLD increases the risk of cancer; much of this risk may be due to obesity/metabolic syndrome and associated chronic inflammation. Overall, cardiovascular disease in patients with NAFLD represents a higher risk for morbidity and mortality.

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Peonies

Trial by Diet Approach for Crohn’s Disease in Children

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RS Boneh et al. Clin Gastroenterol Hepato 2021; 19: 752-759. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn’s Disease

The authors collected  data from a multicenter randomized trial of the CD exclusion diet (CDED) in children (mean age, 14.2 ± 2.7 y) with Crohn’s disease who were randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (PEN) (n = 39). 

The CDED has been discussed previously on this blog; it aims to avoid animal and saturated fat, milk fat, gluten, specific emulsifiers, taurine, red (reduced heme) and processed meat, and certain fibers from some fruits and vegetables. In addition to excluding patients who received competing therapies (eg. steroids, immunomodulators, and biologics), the authors excluded patients with isolated large bowel disease (L2).

Key findings:

  • At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a dietary response or remission. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001)
  • Among the 49 patients in remission at week 6, 46 patients (94%) had had a diet response or remission by week 3 and 81% were in clinical remission by week 3

The authors note that the rapid response to dietary therapy suggests a role for a ‘trial by diet’. As such, dietary therapy could be used as monotherapy, for patients failing other therapies, or as a bridge to biological therapy. The authors note that the exact reasons for response to dietary therapy are unsettled and could be “due to both foods excluded and foods enriched in the diet.” In addition, they note that diet appears to be a trigger for inflammation and that reintroduction of foods leads to rebound in inflammation (eg. higher calprotectin) and dysbiosis.

My take: This study shows that dietary therapy works quickly. In this small study, the effectiveness of combined CDED with 50% PEN was similar to EEN.

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Rhododendrum

Patient Information on Irritable Bowel Syndrome From Rome Foundation

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More information from Rome Foundation:

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Related humor: YouTube Link: SNL IBS Ad (4/10/21) Very funny!

Can We Learn to Live With Germs Again?

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Correction made on blog post on 5/12/21 Humira Dosing Guidelines. For Crohn’s induction >/= 40kg, there is not an 80mg dose on day 8, just 160mg day 1 and 80mg day 15. Blog post: Ustekinumab for Refractory Pediatric Ulcerative Colitis and Updated Adalimumab Dosing

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NY Times: Can We Learn to Live With Germs Again? (4/23/21)

An excerpt:

Almost everything we know about the microbiome is uncertain, including how our activities and environments influence its makeup...

Despite the now consensus recognition that air transmission, …we continue to annihilate every microbe in our midst, even though most are harmless…

Excessive hygiene practices, inappropriate antibiotic use and lifestyle changes such as distancing may weaken those [microbial] communities going forward in ways that promote sickness and imperil our immune systems. By sterilizing our bodies and spaces, they argue, we may be doing more harm than good…

Dr. Graham Rook, an emeritus professor of medical microbiology at University College London, likens the immune system to a computer. He says that the microbes we encounter in daily life — on other people and in our spaces — are the data that the immune system relies on to program and regulate its operations.

Deprived of these exposures, especially at the start of life, the immune system is prone to malfunction. The result can be allergies, asthma, autoimmune disorders, obesity, Type 2 diabetes and other chronic medical conditions...

 “Even before the pandemic, we know that half of antibiotic use was inappropriate.”…

For those who aren’t yet able to mix and mingle — and right now, that’s most of us — there are other ways to support microbial health. “If you want to do something proactive right now, I would put eating a healthy diet high on your list,” says Dr. Emeran Mayer… plant foods (legumes, greens, whole fruits, a variety of vegetables), as well as fermented foods, support the richness and diversity of the gut microbiome. So, too, does limiting one’s intake of processed and fast foods, especially those that contain added sugar…

Before the pandemic, only one of the top 10 causes of death in America — influenza — was attributable to an infectious disease that someone could “catch.” Nearly all the rest, such as heart disease and stroke, cancer, brain disease and diabetes, are associated with poor microbiome health or dysfunction.

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World Obesity Day was March 4, 2021

AGA: Best Practice Advice for Refractory H pylori

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SC Shah et al. Gastroenterol 2021;  160: 1831-1841. Full text: AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review

Key recommendations:

  • Best Practice Advice 4: If bismuth quadruple therapy failed as a first-line treatment, shared decision making between providers and patients should guide selection between (a) levofloxacin- or rifabutin-based triple-therapy regimens with high-dose dual proton pump inhibitor (PPI) and amoxicillin, and (b) an alternative bismuth-containing quadruple therapy, as second-line options
  • Best Practice Advice 5: When using metronidazole-containing regimens, providers should consider adequate dosing of metronidazole (1.5–2 g daily in divided doses) with concomitant bismuth therapy, because this may improve eradication success rates irrespective of observed in vitro metronidazole resistance.
  • Best Practice Advice 6: In the absence of a history of anaphylaxis, penicillin allergy testing should be considered in a patient labeled as having this allergy in order to delist penicillin as an allergy and potentially enable its use. Amoxicillin should be used at a daily dose of at least 2 g divided 3 times per day or 4 times per day to avoid low trough levels.
  • Best Practice Advice 8:Longer treatment durations provide higher eradication success rates compared with shorter durations (eg, 14 days vs 7 days). Whenever appropriate, longer treatment durations should be selected for treating refractory H pylori infection.
  • Best Practice Advice 10: After 2 failed therapies with confirmed patient adherence, H pylori susceptibility testing should be considered to guide the selection of subsequent regimens.
  • Table 1 in report details specific regimens

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