Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed.
Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited
The utility may be operator-dependent as well
My take: Due to low upfront costs, IUS would be appealing adjunct to current monitoring. However, one could envision IUS leading to more downstream studies (& costs), especially if its sensitivity and specificity are not very high.
In this internet-based cohort of 9-17 yr olds (n=159, 96% white), the authors found no association between baseline PROMIS Pediatric anxiety score and subsequent sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric −0.89; 95% CI −4.81 to 3.03). This study is in contrast to studies in adults which have shown a bidirectional relationship between anxiety/depression and IBD activity.
My take: It is difficult to know with certainty whether anxiety/depression may trigger IBD activity; more studies are needed. Treatment of mental health is important regardless of its effects on IBD activity.
An excerpt: “The Crohn’s & Colitis Foundation…launched the We Can’t Wait app, which provides an interactive map that allows users to find a restroom near them across the U.S. Driven by crowd-sourced submissions and major retail and restaurant partners that contributed their restroom location data, the app empowers IBD patients – and all users – with a tool to find restrooms more easily, both in emergency and everyday situations. The app is free and available for download now.
This is a case series of six pediatric patients and young adults who developed hypersensitivity reactions during intravenous infusion with ustekinumab (UST).
Key findings:
Hypersensitivity reactions during intravenous (IV) induction dose of UST, ranging from mild allergic reactions to anaphylaxis, with no antibodies detected in the two who had testing
Reactions occurred 0-30 minutes after start of infusion
Management was with methylprednisolone in 5 of 6 patients, diphendyramine in 3 of 6, and epinephrine in 1. One patient was managed with IV diphenhydramine alone.
Four of six continued with UST subcutaneously without reactions. ***Change of formulation of UST from IV to subcutaneous was done in a controlled hospital-based setting. The other two 33% were switched to another biologic due to physician preference and were never exposed to the subcutaneous formulation
Although the exact pathogenesis of this infusion reaction remains unknown, it has been attributed to EDTA
My take: It appears that patients with UST hypersensitivity reactions can be changed to SC formulation. The authors recommend to trial a subcutaneous dose of UST in a controlled setting; in addition, they suggest testing with skin prick testing or specific IgE levels to EDTA done by allergy and immunology.
Key finding: In 3 large adult US prospective cohorts (n=208,280), gluten intake was not associated with risk of CD or UC in 5,115,265 person-years of follow-up evaluation.
My take (from authors): These ” findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.”
This editorial helps provide needed context on the associated observational study by Xia et al (B Xia, M Yang et al. Gastroenterol 2021; 161: 1842-1852. Open Access. Regular use of proton pump inhibitor and the risk of inflammatory bowel disease: pooled analysis of 3 prospective cohorts) which showed a mild increase risk of IBD among PPI users. While the PPI users were at 42% increased risk of IBD compared to nonusers, if correct, “the absolute risk associated with PPI use is modest. Number needed to harm is 3770, meaning that when 3770 individuals are treated with PPIs for 1 year, 1 additional case of IBD is observed.”
Despite the efforts of the study authors to minimize confounders, the editorial focuses on the work of Austin Bradford Hill (Proc R Soc Med. 1965;58: 295-300. The environment and disease: association or causation?) who “realized making causal inferences on observational data was challenging and outlined a list of factors that would make this interpretation more or less likely….strength of association, dose response, and consistency are important and often not commented on in observational studies.”
In a previous “a double-blind, randomized clinical trial comparing pantoprazole with placebo over 3 years with more than 53,000 patient years follow-up found there was no association” with IBD identified…Interestingly, this trial reported a slightly higher risk of enteric infections, and this is the underlying mechanism proposed for how PPI therapy may increase the risk of IBD.”
My take (borrowed from editorial): “Most associations for PPI and harm are likely to be residual or unmeasured confounding, whether this is also true for IBD will only be determined by further study.”
This study utilized the Swedish nationwide health registry (2002-2017; n = 5767 with IBD) and controls from the general population (n= 58,418). One reason for this study is the increased frequency and changing patterns of immunosuppressive medications that are being used in pediatric IBD. Key findings:
672 serious infections (38.6/1000 person-years) occurred among the children with IBD compared with 778 serious infections in the control group (4.0/1000 person years; adjusted HR 9.46 ). HRs were increased for children with ulcerative colitis 8.48, Crohn’s disease 9.30, and IBD unclassified 12.1
Particularly high HRs were also seen in the first year of diagnosis with HR of 12.1 and n children with IBD undergoing surgery, HR 17.1. This 17-fold risk translates to an average of 6 per 100 children having a serious infection among those with operations.
340 of the 672 serious infections were gastrointestinal, including 34 due to Clostridium difficile
20 opportunistic infections were identified during 19,000 person-years
Potential risk factors for infection, besides medications, include malnutrition, chronic inflammation, impaired response to vaccination, and dysregulation of immune responses. A limitation of this study is ascertainment bias as families/patients with underlying disease may be more likely to seek medical attention for otherwise self-limited infections.
My take: This report confirms and quantitates daily clinical practice: children with IBD are more frequently hospitalized due to infections.
Best Practice Advice 1: Precancerous colorectal lesions in inflammatory bowel disease should be described as either polypoid (≥2.5 mm tall), nonpolypoid (<2.5 mm), or invisible (detected on nontargeted biopsy), using a modified Paris Classification. The older terms dysplasia-associated lesion or mass, adenoma-like mass, and flat dysplasia (when referring to dysplasia detected in nontargeted biopsies) should be abandoned.
Best Practice Advice 3: Initial colonoscopy screening for dysplasia should be performed at 8–10 years after disease diagnosis in all people with colonic inflammatory bowel disease, and immediately on diagnosis of primary sclerosing cholangitis. Staging biopsies should be taken from multiple colonic segments to assess histologic disease activity and extent and to help guide future surveillance intervals.
Best Practice Advice 8: Extensive nontargeted biopsies (roughly 4 adequately spaced biopsies every 10 cm) should be taken from flat colorectal mucosa in areas previously affected by colitis when white light endoscopy is used without dye spray chromoendoscopy or virtual chromoendoscopy. Additional biopsies should be taken from areas of prior dysplasia or poor mucosal visibility. Nontargeted biopsies are not routinely required if dye spray chromoendoscopy or virtual chromoendoscopy is performed using a high-defintion endoscope, but should be considered if there is a history of dysplasia or primary sclerosing cholangitis.
In this study of 27,321 patients enrolled in the ImproveCareNow (ICN) learning health system, key findings:
Corticosteroid use decreased from 28% (2007) to 12% (2018)
Black patients received corticosteroids more commonly than white patients. This disparity improved as corticosteroid use decreased in both groups
Anti-tumor necrosis factor-alpha medication use <120 days after diagnosis was associated with a reduction in corticosteroid use
As corticosteroid use decreased, steroid-sparing therapy use increased and height and weight z scores improved, particularly among children with Crohn disease
27 centers (31%) had a significant reduction in steroid use, 5 (6%) had a significant increase, and 45 (52%) had variability in steroid use. 9 centers (11%) had <2 years of data.
My take: These findings are expected but nice to see. Patients in the ICN are using less steroids and growing better. Given the variation in care among centers, there is more work needed.
Methods: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index–matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed.
Key findings:
No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins.
Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively.
Discussion: “The gut microbiome composition of individuals at increased risk of developing IBD (i.e. healthy cotwins from IBD-discordant twin pairs) displays IBD-like signatures on a species and pathway level…The overlap in gut microbial features between healthy cotwins at increased risk of developing IBD and related and unrelated IBD patients suggests that these IBD-like microbiome signatures might precede the onset of IBD. This potentially opens new avenues for diagnosis and therapy in individuals with pre-symptomatic IBD.”
My take This study indicates that the microbiome changes in persons with IBD are also found in their healthy twins. In many ways, this is similar to the frequent finding of abnormal serology in Crohn’s disease; ASCA antibodies were considered much less helpful as a diagnostic test after the realization that ~20% of healthy first degree relatives also have detectable levels.
Figure 4 (pg 1979) shows the relative abundance of a selection of IBD-associated species and highlights similarities between the healthy cotwins and IBD twins.
gutsandgrowth 