IBD Updates: Microbiome afer surgery, Anti-TNF agents NOT changing hospitalizations/surgeries, Biobanking Genetics

X Fang et al. Inflamm Bowel Dis 2021; 27: 603-616. Full Text: Gastrointestinal Surgery for Inflammatory Bowel Disease Persistently Lowers Microbiome and Metabolome Diversity

  • Methods: The UC San Diego IBD Biobank was used to prospectively collect 332 stool samples (every 6 months) from 129 subjects (50 ulcerative colitis; 79 Crohn’s disease). Of these, 21 with Crohn’s disease had ileocolonic resections, and 17 had colectomies.
  • Key finding: Intestinal surgeries in IBD patients seem to reduce the diversity of the gut microbiome and metabolome in IBD patients. Colectomy has a larger effect than ileocolonic resection.
  • Limitations: Confounding variables (eg. antibiotics) and selection bias (patients with more severe disease

C Verdon et al. Inflamm Bowel Dis 2021; 27: 655-661. No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015

Key findings:

  • 34,644 newly diagnosed patients with IBD (CD = 59.5%)
  • The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs. However, the authors note that “in the present study, biologics use under the public reimbursement plan was 13% in patients with UC and 16% in patients with CD.”
  • My take: This study is provocative but probably misleading; it is quite likely that use of anti-TNF agents do lower the risk of hospitalization and surgery.

K Gettler et al. Gastroenterol 2021; 160: 1546-1557. Full text PDF: Common and Rare Variant Prediction and Penetrance of IBD in a Large, Multi-ethnic, Health System-based Biobank Cohort

  • Methods: The authors used the Mount Sinai BioMe Biobank, which contains genetic data on
    32,595 patients. After rigorous phenotype validation, 19,541 individuals were retained, of whom 339 were IBD patients (273 CD, 28 UC, and 37 individuals who were classified as both) and 19,202 were controls
  • Key findings: In this study, the authors identified several rare VEO-IBD variants with high genetic penetrance using the biobank samples and then replicated results in large case control African American and European data sets.
  • One of the variants with the highest genetic penetrance located in the gene LRBA was predicted to result in a deleterious change to the amino acid structure. Reduced expression of CTLA-4 secondary to the variants we identified in LRBA may result in autoinflammation that contributes to IBD. “Targeting reduced CTLA-4 expression is an exciting treatment venue, because expression of CTLA-4 has been shown to be increased by chloroquine treatment in vitro.”
  • Enteropathy is present in 63% of all known individuals with LRBA deficiency, with 27% having chronic diarrhea as the presenting symptom

Mangroves in John Pennekamp State Park (Key Largo)

COVID: Schools & Age-Related Morbidity and Mortality

JF Ludvigsson et al NEJM 2021; 384: 669-671. Full text: Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden In this letter to the editor, the authors report on outcomes in Sweden, which kept schools open during the pandemic; time period: from March 1-June 30, 2020 (schools end around June 10th). Key findings:

  • Among 1-16 years of age (~1.95 million in total), 15 required ICU admission; there were no deaths in this age group
  • “Fewer than 10 pre-school teachers [1-6 years] and 20 schoolteachers received ICU care up to June 30, 2020.” Excluding health care workers, the occupational risk was similar to other occupations, with relative risk of 1.10 (0.49-2.49, 95% CI) and 0.43 (0.28-0.68, 95% CI) for preschool and school teachers respectively.

My take: This study suggests that school teachers are at similar risk for COVID-19 infection as other essential workers. In Sweden, during this timeframe, distancing but not masking was recommended. Thus, transmission rates could be lowered further.

Related article: SR Kadire et al. NEJM 2021; 384: DOI: 10.1056/NEJMclde2101987. Full text: Delayed Second Dose versus Standard Regimen for Covid-19 Vaccination This article provides rationale for both vaccine options.

Related blog posts:

Does Gastrostomy Tube Placement Lower Rates of Hospitalization?

Yes. But maybe for the reasons one might expect.

In this retrospective study from Australia (P Jacoby et al J Pediatr 2020; 217: 131-8.), the authors analyzed two cohorts with total of 673 children with disabilities who had undergone gastrostomy tube (GT) placement.

Key findings:

  • All-cause hospitalizations declined at 5 years after procedure with combined (both cohorts) incidence rate ratio of 0.63
  • Admissions for lower respiratory tract infections did not change appreciably
  • Admissions for epilepsy were generally decreased (see Table V) –this drop is mainly what accounts for the lower hospitalization rates.
  • Fundoplication (which occurred in ~30% with GT insertion) “seemed to decrease the relative incidence of acute LRTI admissions in the combined cohort”
  • The specific numbers for hospitalizations are listed in Table V.

In their discussion, the authors noted that in the year prior to GT placement, there had been an elevated number of hospitalizations.  With regard to fundoplication, the authors note uncertain benefit for respiratory complications.  In previous studies of neonates and children with neurologic impairment and GT placement, there was similar gastrointestinal and respiratory related admissions with or without fundoplication.

My take: GT placement facilitates care for children with disabilities including provision of medication and nutrition.  This study confirms subsequent improvement in hospitalization rates but does not show a clear benefit with regard to respiratory infections.

Related blog posts:

Do Anti-TNF Agents Reduce Surgeries and Hospitalizations?

Briefly noted:

A recent study (http://dx.doi.org/10.1136/gutjnl-2019-318440; SK Murthy et al. BMJ indicates that anti-TNF therapy has not been effective in significantly lowering CD-related hospitalizations or surgeries.

Full Text Link (from Eric Benchimol twitter feed): Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study)

My take: While big changes in the frequency of these outcomes were not demonstrated in this large study, prior studies, including the RISK study, have shown that anti-TNF therapy can be disease-modifying and reduce the risk of penetrating disease in Crohn’s disease.

Related blog post: CCFA Updates in IBD